Antimicrobial efficiency of chlorine dioxide and its potential use as anti-SARS-CoV-2 agent: mechanisms of action and interactions with gut microbiota.

Chlorine dioxide (ClO2) is a disinfectant gas with strong antifungal, antibacterial, and antiviral activities. Applied on hard, non-porous surfaces as an aqueous solution or gas, the ClO2 exerts antimicrobial activity through its interaction and destabilization of cell membrane proteins, as well as through DNA/RNA oxidation, triggering cell death. As for viruses, the ClO2 promotes protein denaturalization mechanisms, preventing the union between the human cells and the viral envelope. Currently, ClO2 has been pointed out as a potential anti-SARS-CoV-2 clinical treatment for use in humans with the ability to oxidize the cysteine residues in the spike protein of SARS-CoV-2, inhibiting the subsequent binding with the Angiotensin-converting enzyme type 2 receptor, located in the alveolar cells. Orally administered ClO2 reaches the gut tract and exacerbates the symptoms of COVID-19, generating a dysbiosis with gut inflammation and diarrhea as side effects, and once absorbed, produces toxic effects including methemoglobinemia and hemoglobinuria, which can trigger respiratory diseases. These effects are dose-dependent and may not be entirely consistent between individuals since the gut microbiota composition is highly heterogeneous. However, to support the use of ClO2 as an anti-SARS-CoV-2 agent, further studies focused on its effectiveness and safety both in healthy and immunocompromised individuals, are needed.

Active Compounds in Zingiber officinale as Possible Redox Inhibitors of 5-Lipoxygenase Using an In Silico Approach.

5-Lipoxygenase (5-LOX) converts arachidonic acid to lipidic inflammatory mediators such as leukotrienes (LTs). In diseases such as asthma, LTs contribute to a physiopathology that could be reverted by blocking 5-LOX. Natural products with anti-inflammatory potential such as ginger have been used as nutraceuticals since ancient times. 6-Gingerol and 6-shogaol are the most abundant compounds in the ginger rhizome; they possess anti-inflammatory, antioxidant, and chemopreventive properties. In the present study, 6-gingerol and 6-shogaol structures were analyzed and compared with two commercial 5-LOX inhibitors (zileuton and atreleuton) and with other inhibitor candidates (3f, NDGA, CP 209, caffeic acid, and caffeic acid phenethyl ester (CAPE)). The pharmacokinetics and toxicological properties of 6-gingerol, 6-shogaol, and the other compounds were evaluated. Targeted molecular coupling was performed to identify the optimal catalytic pocket for 5-LOX inhibition. The results showed that 6-gingerol and 6-shogaol follow all of the recommended pharmacokinetic parameters. These compounds could be inhibitors of 5-LOX because they present specific interactions with the residues involved in molecular inhibition. The current study demonstrated the potential of 6-gingerol and 6-shogaol as anti-inflammatory agents that inhibit 5-LOX, as they present a high level of performance in the toxicological analysis and could be catabolized by the cytochrome p450 enzymatic complex; however, 6-gingerol was superior in safety compared to 6-shogaol.

Effective microencapsulation of Enterococcus faecium in biopolymeric matrices using spray drying.

The objective of this work was to evaluate the potential of whey protein concentrate (WPC), native agave fructans (NAF), and their mixture (WPC-NAF, 1:1 w/w) as wall materials and evaluate the physicochemical properties and stability of encapsulated Enterococcus faecium during the spray drying, storage, and passage through the simulated gastrointestinal tests. The encapsulated microorganisms with WPC-NAF by spray drying showed greater viability (9.26 log CFU/g) and a higher microencapsulation yield (88.43%). They also had a smaller reduction in the cell count (0.61 log cycles), while the microcapsules produced with NAF had the greatest reduction in viability during the simulated gastrointestinal tests. Similarly, probiotics encapsulated with WPC-NAF revealed a higher survival rate (> 8 log CFU/g) when stored at a water activity of 0.328. The thermal analysis showed that the addition of NAF to the WPC produced a slight shift in the Tg towards temperatures higher than that shown by NAF. Therefore, this study provides evidence that the spray drying process was appropriate to encapsulate the probiotic strain Enterococcus faecium and that the mixture WPC-NAF protected it from adverse drying conditions and improved the viability of Enterococcus faecium during storage and simulated gastrointestinal tests, demonstrating that the combination of NAF and WPC as encapsulating material is adequate in the production of more stable microcapsules with potential application in various foods.Key Points• E. faecium was successfully encapsulated in WPC and NAF.• WPC-NAF offered protection to E. faecium in the gastrointestinal tests and during storage.• Aw around 0.328 positively influenced the viability of the microorganism during storage. Graphical abstract.

Identification of a nursery area for the critically endangered hammerhead shark (Sphyrna lewini) amid intense fisheries in the southern Gulf of Mexico.

Since the 1980s, there has been growing concern in the Mexican Atlantic regarding high catches of neonate and juvenile sharks in small-scale fisheries. Fishery-dependent data from 1993 to 1994 and 2007 to 2017 and fishers' ecological knowledge from 2017 were used to identify nursery areas for scalloped hammerhead, Sphyrna lewini, in the southern Gulf of Mexico. Catch records and fishing areas of neonates, YOYs, juveniles and adults of S. lewini (N = 1885) were obtained from calcareous and terrigenous regions in the western Yucatan Peninsula. The results suggest that a nursery for scalloped hammerhead is found in the terrigenous region, characterized by relatively shallow and turbid waters due to rivers' discharges. Neonates and YOYs (96% and 86% of their total records, respectively) were commonly found there over the years in May-August in multiple fishing areas identified by fishers, although mainly between isobaths 10-30 m. The enforcement of management measures is necessary because the nursery is located in a region with intense fishing effort.

Age and gender influence on foveal avascular zone in healthy eyes.

The foveal avascular zone (FAZ) is the capillary-free area in the central macula with high photoreceptor density and metabolic activity. In the present study we measured the superficial and deep macular foveal avascular zone (sFAZ, dFAZ) in the eyes of healthy adults of both sexes of various ages ranging from 10 to 69 years using optical coherence tomography angiography (OCT-A) in order to evaluate the influence of gender and age on FAZ size. A cross-sectional study was carried out in 240 eyes of 120 healthy subjects, OCT-A was performed by means of a Topcon swept source OCT. sFAZ and dFAZ areas were measured using the IMAGEnet6 software package. Subjects were grouped by age (six groups) and gender. The mean ±â€¯sd age of the subjects was 39.2 ±â€¯17.4 years (50% women, 50% men), ranging from 10 to 69 years. The overall mean sFAZ size in women (0.297 ±â€¯0.110 mm2) was significantly larger (p = 0.002) than in men (0.254 ±â€¯0.098 mm2). Similarly, the overall mean dFAZ in women (0.322 ±â€¯0.111 mm2) was significantly larger (p < 0.001) than in men (0.273 ±â€¯0.099). However, when analyzed by age group, these gender differences appeared only in groups younger than 20 years old and older than 50 years old. Men did not show differences among the six age groups. In women, for both sFAZ and dFAZ, the 20-29 year old group had a smaller FAZ size than the 50-59 year old group. In conclusion for both sFAZ and dFAZ, women have larger areas than men, but this occurs only in the young and old age groups. In men, age does not seem to influence the size of the FAZ, but in women, both sFAZ and dFAZ were significantly smaller in younger than in older ages. These results suggest that retinal changes in retinal structure caused by aging may be different in woman than in men, probably reflecting the more hormonal variations known to exist with age in women.

Microencapsulation of cocoa liquor nanoemulsion with whey protein using spray drying to protection of volatile compounds and antioxidant capacity.

The aim of this study was microencapsulated a nanoemulsion of cocoa liquor with whey protein by spray drying, and evaluate the effect of different inlet drying temperatures on the properties of microcapsules. The nanoemulsion showed a particle size of 202.13 nm, PdI of 0.424, and ζ-potential of -25.20 mV. The inlet drying temperature showed differences in physicochemical properties of microcapsules. Microcapsules presented good thermal stability and protection against the melting of cocoa liquor. Microcapsules obtained showed excellent yields of polyphenolic compounds (78-93%), and high retention of volatile compounds, especially of pyrazines. Greater microencapsulation yield of bioactive compounds and retention of volatile compounds was obtained at higher drying temperature (180 °C). Excellent stability of polyphenols content, antioxidant capacity, and volatile compounds of cocoa liquor were observed during storage of the microcapsules at different temperature conditions, indicating the feasibility of this powder for its incorporation into functional foods.

Reproductive characteristics and reproductive tract anatomy of the California butterfly ray Gymnura marmorata (Myliobatiformes: Gymnuridae).

The California butterfly ray Gymnura marmorata is frequently caught by artisanal fisheries in north-western Mexico (Baja California Sur; BCS). The aim of this study was to estimate reproductive characteristics and describe the micro and macroscopic reproductive structures of female and male G. marmorata. Sampling was carried out at two fisheries landing sites located on the west coast BCS, from 2008 to 2012. The largest disc width (WD ) ever recorded for this species was 131.0 cm and females were larger than males. The male sample was composed exclusively of adult specimens, with a median size at 50% maturity (WD50 ) estimated at 44.9 cm WD . For females, size at onset of maturity was estimated at 63.0 cm WD ; WD50 , at 64.7 cm WD ; and size at pregnancy at 80.1 cm WD . Gonadal asymmetry was observed for the first time in this species. Indeed, in males only the left testis was functional (testicular asymmetry), while in females, only the left ovary was functional (ovarian asymmetry).

ULTRASONOGRAPHIC FINDINGS IN THE VITREOUS OF PATIENTS WITH AGE-RELATED MACULAR DEGENERATION TREATED WITH INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS.

PURPOSE: We aimed to assess the relationship of repeated intravitreal injection of anti-vascular endothelial growth factor, the main treatment for exudative age-related macular degeneration, with changes in vitreous ultrasonographic findings in patients with age-related macular degeneration. METHODS: We retrospectively collected data from 41 patients (41 age-related macular degeneration eyes, 41 control eyes) on age, sex, number of injections, and type of anti-vascular endothelial growth factor (ranibizumab, aflibercept). Ocular ultrasonography was performed with open eyelids, under topical anesthesia, and using carbomers as ultrasonographic gel. Topographic, quantitative, and kinetic ultrasonography was performed in all eye quadrants using a 10-MHz posterior pole probe, and vitreous reflectivity was assessed. RESULTS: The mean age of patients was 79 (range: 59-94) years, with a mean of five intravitreal anti-vascular endothelial growth factor injections (range: 1-13). No significant ultrasonographic differences were found relative to the incidence of partial or complete posterior vitreous detachment. Vitreous hyperechogenicity increased in the treated eye (P < 0.001), and the vitreous reflectivity range increased with the number of injections (P = 0.041, R = 0.214). However, the type of anti-vascular endothelial growth factor used and the time elapsed since the last intravitreal injection was not significant (P > 0.05). CONCLUSION: These preliminary results indicate a proportional increase in ultrasonographic reflectivity of vitreous gel with the number of injections.

[Growth and photochemical efficiency of photosystem ii in seedlings of two varieties of Capsicum annuum L. inoculated with rhizobacteria and arbuscular mycorrhizal fungi]. / Crecimiento y eficiencia fotoquímica del fotosistema ii en plántulas de 2 variedades de Capsicum annuum L. inoculadas con rizobacterias u hongos micorrícicos arbusculares.

Plant growth promoting rhizobacteria (PGPR) and arbuscular mycorrhizal fungi (AMF) are a biological alternative for the sustainable management of Capsicum annuum L. This research work evaluated the effects of both PGPR and AMF on bell pepper and jalapeno pepper plants. Five bacterial strains isolated from several locations in Estado de Mexico were used: [P61 (Pseudomonas tolaasii), A46 (P. tolaasii), R44 (Bacillus pumilus), BSP1.1 (Paenibacillus sp.), and OLs-Sf5 (Pseudomonas sp.)], and three treatments with AMF [H1 (consortium isolated from pepper crops in the State of Puebla), H2 (Rhizophagus intraradices), and H3 (consortium isolated from the rhizosphere of lemon trees, State of Tabasco)]. In addition, a fertilized treatment (Steiner nutrient solution at 25%) and an unfertilized control were included. Seedlings of "Caloro" jalapeno pepper and "California Wonder" bell pepper were inoculated with AMF at seed sowing, and PGPR were inoculated after 15 days of seedling emergence; seedlings were grown under plant growth chamber conditions. P61 bacterium and H1 AMF consortia were the most effective microorganisms for jalapeno pepper whereas R44 bacterium and AMF H3 and H1 were the most effective for bell peppers, when compared to the unfertilized control. Furthermore, P61 and R44 bacteria showed beneficial effects on PSII efficiency.

A calmodulin-like protein (LCALA) is a new Leishmania amazonensis candidate for telomere end-binding protein.

BACKGROUND: Leishmania spp. telomeres are composed of 5'-TTAGGG-3' repeats associated with proteins. We have previously identified LaRbp38 and LaRPA-1 as proteins that bind the G-rich telomeric strand. At that time, we had also partially characterized a protein: DNA complex, named LaGT1, but we could not identify its protein component. METHODS AND RESULTS: Using protein-DNA interaction and competition assays, we confirmed that LaGT1 is highly specific to the G-rich telomeric single-stranded DNA. Three protein bands, with LaGT1 activity, were isolated from affinity-purified protein extracts in-gel digested, and sequenced de novo using mass spectrometry analysis. In silico analysis of the digested peptide identified them as a putative calmodulin with sequences identical to the T. cruzi calmodulin. In the Leishmania genome, the calmodulin ortholog is present in three identical copies. We cloned and sequenced one of the gene copies, named it LCalA, and obtained the recombinant protein. Multiple sequence alignment and molecular modeling showed that LCalA shares homology to most eukaryotes calmodulin. In addition, we demonstrated that LCalA is nuclear, partially co-localizes with telomeres and binds in vivo the G-rich telomeric strand. Recombinant LCalA can bind specifically and with relative affinity to the G-rich telomeric single-strand and to a 3'G-overhang, and DNA binding is calcium dependent. CONCLUSIONS: We have described a novel candidate component of Leishmania telomeres, LCalA, a nuclear calmodulin that binds the G-rich telomeric strand with high specificity and relative affinity, in a calcium-dependent manner. GENERAL SIGNIFICANCE: LCalA is the first reported calmodulin that binds in vivo telomeric DNA.

Study of prevalence of Personality Disorders in inmate men sample with Substance Use Disorders using of PDQ-4+ Self-Report.

INTRODUCTION: The study focused on examining the prevalence of Personality Disorders (PD) in 51 male inmates diagnosed with Substance Use Disorders (SUDs) lifetime within a specialized unit at a prison. METHODS: The instruments administered included the Structured Clinical Interview for DSM-IV Axis I and the Personality Diagnostic Questionnaire-4+. RESULTS: The type of crime most frequently committed by the incarcerated was the robbery (76.5%), including robbery with violence. 45.1% of the patients screened positive for Antisocial PD, followed by 35.3% for Paranoid and 23.5% for Obsessive Compulsive PD. The results reflect a male inmate sample exhibiting a clinical profile characterized by SUDs and PD, with almost half of the total sample presenting Antisocial PD. CONCLUSIONS: The presence of Antisocial and Paranoid PD with SUD suggests a more complex personality profile, with a tendency to carry out more aggressive crimes, including robbery with violence. A more comprehensive PD assessment should be carried out in prison settings in order to identify dangerous individuals who are at risk of recidivism.

Nutraceutical potential, and antioxidant and antibacterial properties of Quararibea funebris flowers.

The flowers of Quararibea funebris tree are an important component of tejate, a traditional Mexican beverage. The flowers exhibited a high concentration of total polyphenolic compounds, total carotenoids, and vitamin C. UPLC analysis revealed the presence of salicylic acid, kaemferol-3-O-glucoside, trans-cinnamic acid, rutin, scopoletin, l-phenylalanine, 4-coumaric acid and quercetin-3-glucoside, among others metabolites. The flowers exhibited volatile compounds as isolongifolene, α-cedrene, 2,5,5-trimethyl-2,3,4,5,6,7-hexahydro-1H-2,4a-ethanonaphthalene, while that linoleic acid, palmitic acid, and linolenic acid were the major fatty acids present in the oil extract. Magnesium, potassium, and calcium were the minerals most abundant in the flowers. In addition the methanolic extract of the flowers exhibited antimicrobial properties against the tested pathogenic microbial strains. In conclusion, these results showed that the Q. funebris flowers not only have an aromatic and flavoring power for the Tejate beverage, but also contains compounds with antioxidant, antimicrobial, and nutraceutical potential, which helps to explain its therapeutic uses.

Lauroylated, Acetylated, and Succinylated Agave tequilana Fructans Fractions: Structural Characterization, Prebiotic, Antibacterial Activity and Their Effect on Lactobacillus paracasei under Gastrointestinal Conditions.

The effect of chemical modification of fractions of native agave fructans (NAF), high performance (HPAF), and a high degree of polymerization (HDPAF) by lauroylation, acetylation, and succinylation reactions on their prebiotic activity, antibacterial properties were evaluated and survival of L. paracasei in a simulated gastrointestinal system. The characterization of the reactions was confirmed by NMR and FTIR. The lauroylated and succinylated fructan fractions showed higher antibacterial activity against pathogenic bacteria such as Escherichia coli, Enterococcus faecalis and Staphylococcus aureus than the unmodified ones. Analyses with L. paracasei showed that the acetylated fructan fractions had a greater prebiotic effect, and simulated gastrointestinal tests demonstrated that the acetylated and succinylated fractions favored the survival of L. paracasei during the gastrointestinal phase. The effect of modifying the agave fructans fractions on the evaluated properties depended on the structure, size, and polarity of each incorporated functional group, as well as the degree of polymerization and substitution of each fraction. These results show that the chemical modification of the fructan fractions analyzed improves their functional properties, offering an alternative in the food and pharmaceutical industry.

Profilin cross-reactive panallergen causes latex sensitization in the pediatric population allergic to pollen.

BACKGROUND: Component-resolved diagnostics (CRD) has been demonstrated to be an excellent new tool for improving the current diagnosis of allergies, and it allows differentiation between polysensitization and cross-reactivity. OBJECTIVE: To demonstrate the role of cross-reactive pollen allergens in pediatric patients living in areas with large amounts of airborne grass pollen grains who are sensitive to grass pollen and latex. METHODS: Serum samples were obtained from 106 children between 3 and 14 years of age diagnosed with allergies to pollen based on clinical history, skin prick tests, and specific immunoglobulin E (IgE). None of them had allergy symptoms to latex or fruits. From these 106 children, 56 patients revealed positive results to Phleum-specific major allergens but not to cross-reactive allergens. The other 50 patients who showed positive specific IgE to Phleum-specific major allergens and to cross-reactive pollen allergens also showed positive results to latex allergens. CRD was carried out by specific IgE quantification using a fluoro-enzyme immunoassay (ImmunoCAPT System). RESULTS: Results demonstrated a positive significant relationship between the specific IgE to Hev b 8 and Phl p 12 and also between the specific IgE to Hev b 8 and latex extract in the group of patients sensitized to species-specific and cross-reactive Phleum allergens. Positive significant relationships were also found between profilin and avocado or peach sensitizations. No other latex allergens gave positive results. CONCLUSION: The apparent sensitization to latex in pediatric patients allergic to grass pollen is caused by the cross-reactive profilin panallergen; however, it is appears not to be clinically relevant.

Characteristics of COPD smokers and effectiveness and safety of smoking cessation medications.

INTRODUCTION: Smoking is the main cause of chronic obstructive pulmonary disease (COPD), and smoking cessation is the only treatment shown to be effective in arresting the progression of COPD. Different epidemiological and population-based studies have shown smokers with COPD to have specific smoking characteristics that differentiate them from the rest of smokers and which complicate smoking cessation. The main objective of this study is to analyze the effectiveness and safety of drug treatments for smoking cessation in smokers with severe or very severe COPD. METHODS: Smokers with severe or very severe COPD (Global Initiative for Chronic Obstructive Lung Disease stages III and IV) received treatment for smoking cessation. The treatment program consisted of a combination of behavioral therapy and drug treatment. Patients were followed up at 1, 2, 4, 6, 8, 10, 12, 18, and 24 weeks after the quit date. RESULTS: Four hundred seventy-two patients were seen, 65% were male, and their mean age was 58.3 (9.8). They smoked an average of 29.7 (13.4) cigarettes/day, and their mean Fagerström test for nicotine dependence score was 7.4 (2.1). Continuous abstinence rate from 9 to 24 weeks (CAR 9-24) was 48.5%. According to type of treatment used, CAR 9-24 for nicotine replacement therapy (NRT), bupropion, and varenicline were 38.2%, 55.6%, and 58.3%, respectively. Varenicline was more effective than nicotine patches: 61% versus 44.1% (odds ratio: 1.98; 95% CI: 1.25-3.12; p = .003). NRT was the treatment producing the fewest adverse effects. The onset of psychiatric symptoms due to medication was rare and evenly distributed across groups. CONCLUSIONS: This study shows that smokers with severe or very severe COPD are predominantly males with a high degree of physical dependence upon nicotine. CAR 9-24 was 48.5%. Varenicline and bupropion yielded higher abstinence rates than NRT. Varenicline was more effective than nicotine patches: all types of treatments were safe.

Dietary encapsulated Bifidobacterium animalis and Agave fructans improve growth performance, health parameters, and immune response in broiler chickens.

OBJECTIVE: The present study was conducted to evaluate the effects of dietary supplementation with Bifidobacterium animalis, Agave fructans, and symbiotic of both encapsulated on growth performance, feed efficiency, blood parameters, and immune status in broiler chickens, and to compare these with diets including antibiotic growth promoters and without additives. METHODS: A comparative experimental study was carried out with 135 male Ross 308 broiler chickens. Each trial was divided into 5 equal groups. Control group (CON) received a standard diet without growth promoter; GPA, a standard diet with colistin sulfate and zinc bacitracin (0.25 g/kg of feed); PRE, a standard diet with 1% Agave fructans; PRO, a standard diet with Bifidobacterium animalis (11.14±0.70 log CFU/g); SYM, a standard diet with B. animalis and Agave fructans. RESULTS: A significant decrease in food consumption was found for the GPA, PRE, and SYM, compared to the CON group. The results show a better feed conversion index in PRE and GPA with respect to the CON group with the highest conversion index. Interestingly, the weight of the gastrointestinal tract shows a statistically significant difference between GPA and PRE groups. Moreover, the length of the gastrointestinal tract of the GPA group was less than the PRE group. In the total leukocyte count, there was a statistically significant increase in the GPA group compared to the CON, PRE, and PRO groups, and the heterophiles-lymphocytes index was lower in PRO. Regarding the cytokines, interleukin 10 (IL-10) decreased in PRO compared to CON and PRE, while IL-1ß increased in the SYM group. CONCLUSION: Alternative treatments were shown to achieve similar productive results as growth-promoting antibiotics and showed improvement over diet without additives; however, they have immunomodulatory properties and improved the development of the gastrointestinal tract compared to the treatment of growth-promoting antibiotics.

Cocoa Nanoparticles to Improve the Physicochemical and Functional Properties of Whey Protein-Based Films to Extend the Shelf Life of Muffins.

A novel nanocomposite whey protein-based film with nanoemulsified cocoa liquor (CL) was prepared using one-stage microfluidization to evaluate the emulsion properties and the effect of CL on the film properties by response surface methodology (RSM). The results indicated that the number of cycles by microfluidization had a significant effect (p < 0.05) on the particle size and polydispersity of the nanoemulsion, with a polyphenol retention of approximately 83%. CL decreased the solubility (<21.87%) and water vapor permeability (WVP) (<1.57 g mm h-1 m-2 kPa-1) of the film. FTIR analysis indicated that CL modified the secondary protein structure of the whey protein and decreased the mechanical properties of the film. These results demonstrate that applying the film as a coating is feasible and effective to improve the shelf life of bakery products with a high moisture content. This nanocomposite film is easy to produce and has potential applications in the food industry.

Predictors of Changes in Alcohol Craving Levels during a Virtual Reality Cue Exposure Treatment among Patients with Alcohol Use Disorder.

BACKGROUND/OBJECTIVE: Determining the predictive variables associated with levels of alcohol craving can ease the identification of patients who can benefit from treatments. This study aimed to describe changes (improvement or no change/deterioration) in alcohol craving levels and explore the predictors of these changes from admission to discharge in outpatients with alcohol use disorder (AUD) undergoing treatment-as-usual (TAU), or treatment-as-usual supplemented with virtual reality cue-exposure therapy (TAU + VR-CET). METHOD: A prospective cohort study was conducted amongst 42 outpatients with AUD (n = 15 TAU + VR-CET and n = 27 TAU) from a clinical setting. Changes in the levels of alcohol craving between admission and discharge were assessed with the Multidimensional Alcohol Craving Scale. Sociodemographic characteristics (age, gender, education, and socioeconomic and civil status), cognitive-affective behavioral patterns (AUD severity, abstinence duration, psychiatric comorbidity, state anxiety, attentional bias, and substance use), and type of treatment (TAU + VR-CET and only TAU) were also evaluated. RESULTS: The TAU + VR-CET group showed greater changes of improvement in the levels of alcohol craving than the TAU group (χ2 = 10.996; p = 0.001). Intragroup changes in alcohol craving from pre to post-treatment were significant in the TAU + VR-CET group (χ2 = 13.818; p = 0.003) but not within the TAU group (χ2 = 2.349; p = 0.503). The odds of an improvement in any of the craving levels between pre- and post-test was 18.18 (1/0.055) times higher in the TAU + VR-CET group with respect to the TAU group. The use of illicit drugs in the month prior to the test increased the odds of having a positive change by 18.18 (1/0.055) with respect to not having consumed. CONCLUSIONS: Including VR-CET in TAU programs may provide benefits in the treatment of AUDs mainly among patients with intense alcohol craving and individuals having used illicit substances prior to treatment.

A 1-year retrospective review of ranibizumab for naive nonsubfoveal choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: To assess efficacy and safety in the treatment of nonsubfoveal choroidal neovascularization secondary to age-related macular degeneration with intravitreal ranibizumab. METHODS: Retrospective, multicentric, noncomparative, interventional case series. We included patients with naïve extrafoveal and juxtafoveal choroidal neovascularization treated with intravitreal ranibizumab and a follow-up of 1 year. Patients were evaluated using visual acuity testing with Snellen charts, fluorescein angiography, and optical coherence tomography scans. RESULTS: There were 15 patients with a mean age of 72.4 years (SD, 7.2). There were 11 juxtafoveal lesions (73.3%) and 4 extrafoveal lesions (26.6%). Eight lesions were predominantly classic (53.3%), 6 lesions were occult (40%), and 1 lesion was minimally classic (6.6%). The mean visual acuity improved from 20/60 (mean logarithm of the minimum angle of resolution = 0.47) at baseline to 20/40 (mean logarithm of the minimum angle of resolution = 0.34) at the 1-year follow-up visit (P = 0.03). The mean foveal thickness improved from 312 microm to 262 microm (P = 0.01), and the mean lesion size (disk areas) improved from 1.9 to 1.1 (P = 0.01). No cases progressed to a subfoveal location. The mean number of injections was 3.8. As complications, we had an endophthalmitis and a macular hole. CONCLUSION: In our study, intravitreal ranibizumab showed efficacy for the treatment of nonsubfoveal choroidal neovascularization secondary to age-related macular degeneration mainly in terms of preventing subfoveal progression.

Strategy-Driven Exploration for Rule-Based Models of Biochemical Systems with PORGY.

This chapter presents PORGY-an interactive visual environment for rule-based modelling of biochemical systems. We model molecules and molecule interactions as port graphs and port graph rewrite rules, respectively. We use rewriting strategies to control which rules to apply, and where and when to apply them. Our main contributions to rule-based modelling of biochemical systems lie in the strategy language and the associated visual and interactive features offered by PORGY. These features facilitate an exploratory approach to test different ways of applying the rules while recording the model evolution, and tracking and plotting parameters. We illustrate PORGY's features with a study of the role of a scaffold protein in RAF/MEK/ERK signalling.