Long term outcomes of pharmacological treatments for opioid dependence: does methadone still lead the pack?

The aim of this review was to update and summarize the scientific knowledge on the long term outcomes of the different pharmacological treatment options for opioid dependence currently available and to provide a critical discussion on the different treatment options based on these results. We performed a literature search using the PubMed databases and the reference lists of the identified articles. Data from research show that the three pharmacological options reviewed are effective treatments for opioid dependence with positive long term outcomes. However, each one has its specific target population and setting. While methadone and buprenorphine are first line options, heroin-assisted treatment is a second line option for those patients refractory to treatment with methadone with concomitant severe physical, mental, social and/or functional problems. Buprenorphine seems to be the best option for use in primary care offices. The field of opioid dependence treatment is poised to undergo a process of reinforcement and transformation. Further efforts from researchers, clinicians and authorities should be made to turn new pharmacological options into clinical reality and to overcome the structural and functional obstacles that maintenance programmes face in combatting opioid dependence.     

Experimental Analysis of the Enzymatic Degradation of Polycaprolactone: Microcrystalline Cellulose Composites and Numerical Method for the Prediction of the Degraded Geometry

The degradation rate of polycaprolactone (PCL) is a key issue when using this material in Tissue Engineering or eco-friendly packaging sectors. Although different PCL-based composite materials have been suggested in the literature and extensively tested in terms of processability by material extrusion additive manufacturing, little attention has been paid to the influence of the fillers on the mechanical properties of the material during degradation. This work analyses the possibility of tuning the degradation rate of PCL-based filaments by the introduction of microcrystalline cellulose into the polymer matrix. The enzymatic degradation of the composite and pure PCL materials were compared in terms of mass loss, mechanical properties, morphology and infrared spectra. The results showed an increased degradation rate of the composite material due to the presence of the filler (enhanced interaction with the enzymes). Additionally, a new numerical method for the prediction of the degraded geometry was developed. The method, based on the Monte Carlo Method in an iterative process, adjusts the degradation probability according to the exposure of each discretized element to the degradation media. This probability is also amplified depending on the corresponding experimental mass loss, thus allowing a good fit to the experimental data in relatively few iterations.     

Crystal structure and functional analysis of tetracenomycin ARO/CYC: implications for cyclization specificity of aromatic polyketides

Polyketides are a class of natural products with highly diverse chemical structures and pharmaceutical activities. Polyketide cyclization, promoted by the aromatase/cyclase (ARO/CYC), helps diversify aromatic polyketides. How the ARO/CYC promotes highly specific cyclization is not well understood because of the lack of a first-ring ARO/CYC structure. The 1.9 A crystal structure of Tcm ARO/CYC reveals that the enzyme belongs to the Bet v1-like superfamily (or STAR domain family) with a helix-grip fold, and contains a highly conserved interior pocket. Docking, mutagenesis, and an in vivo assay show that the size, shape, and composition of the pocket are important to orient and specifically fold the polyketide chain for C9-C14 first-ring and C7-C16 second-ring cyclizations. Two pocket residues, R69 and Y35, were found to be essential for promoting first- and second-ring cyclization specificity. Different pocket residue mutations affected the polyketide product distribution. A mechanism is proposed based on the structure-mutation-docking results. These results strongly suggest that the regiospecific cyclizations of the first two rings and subsequent aromatizations take place in the interior pocket. The chemical insights gleaned from this work pave the foundation toward defining the molecular rules for the ARO/CYC cyclization specificity, whose rational control will be important for future endeavors in the engineered biosynthesis of novel anticancer and antibiotic aromatic polyketides.     

Comparative study of all-ceramic crowns obtained from conventional and digital impressions: clinical findings

Objective

To compare clinical aspects of all-ceramic crowns fabricated from conventional and digital impressions.

Methods

Thirty patients with 30 posterior teeth with the need of a crown restoration were selected. Zirconia-based ceramic crowns were made using an intraoral digital impression system (TRIOS®, 3shape) and two-step silicone impression technique. Two external blinded operators evaluated the all-ceramic crowns. Five selection items were assessed of which four were clinical: “marginal fit,” “occlusal contacts,” “interproximal contact points,” and “primary retention.” Then, the last selection item “final selection” was assessed when the operators considering all the variables had to select which of the digital or conventional crown had the best clinical conditions. Data was analyzed using Kappa index test and the Pearson’s chi-square test (α = 0.05).

Results

For the items marginal fit and interproximal contact points, moderate agreement between the two operators was described and significant differences were found between the two study groups. Conversely, for the variables primary retention and occlusal contacts, the agreement between the operators was fair and no significant differences were found. For the final selection, a substantial agreement was reached between the two operators and significant differences were found between the two groups (p < 0.05).

Conclusion

In most cases and in a significant way, the digital crowns had better clinical conditions according to both evaluators. The digital crowns were statistically superior for the interproximal contact points and marginal fit. For the variables occlusal contacts and primary retention, no difference between the two groups was observed.

Clinical significance

Digital intraoral impressions can be used for manufacturing ceramic crowns, with the same or better clinical results as conventional impressions.

     

Alpha‐Tocopherol during lactation and after weaning alters the programming effect of prenatal high salt intake on cardiac and renal functions of adult male offspring

Maternal salt overload programs cardiovascular and renal alterations in the offspring. However, beneficial and harmful effects of high dose vitamin E supplementation have been described in humans and animals. We investigated the hypothesis as to whether cardiac and renal alterations can be programmed by gestational salt overload, and can become further modified during lactation and after weaning. Male Wistar rats were used, being the offspring of mothers that drank either tap water or 0.3 mol/L NaCl for 20 days before and during pregnancy. α‐Tocopherol (0.35 g/kg) was administered to mothers daily during lactation or to their offspring for 3 weeks post‐weaning. Systolic blood pressure (tcSBP) was measured in juvenile rats aged 210 days. The response of mean arterial pressure (MAP) and heart rate (HR) to intravenous infusion of angiotensin II (Ang II) was also examined. Left ventricle plasma membrane (PMCA) and sarcoplasmic reticulum Ca²⁺‐ATPase (SERCA) activities, and certain parameters of renal function, were measured. Maternal saline programmed for increased body mass and kidney mass/body mass ratio, increased tcSBP, increased mean arterial pressure and heart rate with anomalous response to infused Ang II. In the heart, saline increased PMCA and α‐Tocopherol per se increased PMCA/SERCA. In the kidney, the most remarkable result was the silent saline programming of Cr_Cl, which was sensitized for a sharp decrease after α‐Tocopherol. In conclusion, the combination of maternal saline overload and high α‐Tocopherol immediately after birth leads to simultaneous cardiovascular and renal alterations in the young offspring, like those encountered in type V cardiorenal syndrome.     

Factors associated with reporting of abuse against children and adolescents by nurses within Primary Health Care

OBJECTIVE:

to analyze the factors associated with the underreporting on the part of nurses within Primary Health Care of abuse against children and adolescents.

METHOD:

cross-sectional study with 616 nurses. A questionnaire addressed socio-demographic data, profession, instrumentation and knowledge on the topic, identification and reporting of abuse cases. Bivariate and multivariate logistic regression was used.

RESULTS:

female nurses, aged between 21 and 32 years old, not married, with five or more years since graduation, with graduate studies, and working for five or more years in PHC predominated. The final regression model showed that factors such as working for five or more years, having a reporting form within the PHC unit, and believing that reporting within Primary Health Care is an advantage, facilitate reporting.

CONCLUSION:

the study''s results may, in addition to sensitizing nurses, support management professionals in establishing strategies intended to produce compliance with reporting as a legal device that ensures the rights of children and adolescents.     

Screening for autism spectrum disorders: state of the art in Europe

A large number of studies have reported on the validity of autism spectrum disorder (ASD) screening procedures. An overall understanding of these studies’ findings cannot be based solely on the level of internal validity of each, since screening instruments might perform differently according to certain factors in different settings. Europe has led the field with the development of the first screening tool and first prospective screening study of autism. This paper seeks to provide an overview of ASD screening studies and ongoing programmes across Europe, and identify variables that have influenced the outcomes of such studies. Results show that, to date, over 70,000 children have been screened in Europe using 18 different screening procedures. Differences among findings across studies have enabled us to identify ten factors that may influence screening results. Although it is impossible to draw firm conclusions as to which screening procedure is most effective, this analysis might facilitate the choice of a screening method that best fits a specific scenario, and this, in turn, may eventually improve early ASD detection procedures.     

Detection of Anatoxin-a and Three Analogs in Anabaena spp. Cultures: New Fluorescence Polarization Assay and Toxin Profile by LC-MS/MS

Anatoxin-a (ATX) is a potent neurotoxin produced by several species of Anabaena spp. Cyanobacteria blooms around the world have been increasing in recent years; therefore, it is urgent to develop sensitive techniques that unequivocally confirm the presence of these toxins in fresh water and cyanobacterial samples. In addition, the identification of different ATX analogues is essential to later determine its toxicity. In this paper we designed a fluorescent polarization (FP) method to detect ATXs in water samples. A nicotinic acetylcholine receptor (nAChR) labeled with a fluorescein derivative was used to develop this assay. Data showed a direct relationship between the amount of toxin in a sample and the changes in the polarization degree of the emitted light by the labeled nAChR, indicating an interaction between the two molecules. This method was used to measure the amount of ATX in three Anabaena spp. cultures. Results indicate that it is a good method to show ATXs presence in algal samples. In order to check the toxin profile of Anabaena cultures a LC-MS/MS method was also developed. Within this new method, ATX-a, retention time (RT) 5 min, and three other molecules with a mass m/z 180.1 eluting at 4.14 min, 5.90 min and 7.14 min with MS/MS spectra characteristic of ATX toxin group not previously identified were detected in the Anabaena spp. cultures. These ATX analogues may have an important role in the toxicity of the sample.