Evaluation of Probiotic Properties of Novel Brazilian Lactiplantibacillus plantarum Strains

Probiotics and Antimicrobial Proteins - Beneficial effects of Lactiplantibacillus plantarum strains have been widely reported. Knowing that the effects of probiotic bacteria are strain-dependent,...     

Treatment-resistant depression: definition,prevalence, detection,management, and investigational interventions

Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision-making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision-making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo-resistant (e.g., due to inadequacy of treatment trials or non-adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non-response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co-administered with an antidepressant) are established as efficacious in the management of TRD. Some second-generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA-approved for individuals with TRD, with accelerated theta-burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non-inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual-based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population.     

Evolutionary analysis of the picornavirus family

An exhaustive evolutionary analysis of the picornavirus family has been carried out using the amino acid sequences of several proteins of the viruses including: the capsid proteins (1D, 1B, and 1C) situated at the 5 end of the genome and responsible for the serotype of the viruses, and the viral polymerase (3D), located at the 3 end of the genome. The evolutionary relationships found among the viruses studied support the new classification, recently suggested, in contrast to the classical one, and the existence of a new genus for the picornavirus family. In the new taxonomic organization, five genera form the picornavirus family: (1) aphthoviruses, (2) cardioviruses, (3) hepatoviruses (previously classified as enteroviruses), (4) renteroviruses (which mainly constitute a combination of the previous genera rhinovirus and enterovirus), and (5) a new genus, with a new and unique representative: the echovirus 22. Our analysis also allowed us, for the first time, to propose the most probable sequence of speciation events to have given rise to the current picornavirus family.The bootstrap procedure was used to check the reliability of the phylogenetic trees obtained. The application of the method of the statistical geometry in distance space to internal branches of the tree revealed a high degree of evolutionary noise, which makes the resolution of some internal branching points difficult. Correspondence to: J. Dopazo     

Synthesis of new azino fused benzimidazolium salts. a new family of DNA intercalating agents. I

A series of new pyrido[1,2-a]- and pyridazino[1,6-a]benzimidazolium salts have been synthesized from readily available 1,3-disubstituted 2-alkylbenzimidazolium salts. Their affinity to DNA and in vitro cytotoxicity versus HT-29 have been tested. The initial results show that the title compounds are a new family of intercalating agents.     

Gene expression in normal and virally transformed mouse 3T3B and hamster BHK21 cells

Cell lines 3T3B (mouse), 3T3B-SV40, BHK21 (hamster) and BHK21 polyoma virus (PyY) were labelled with [³⁵S]methionine under conditions in which 500–600 cpm were incorporated per cell during a 20 h incubation period. Two-dimensional gel electrophoresis analysis of the total [³⁵S]methionine-labelled polypeptides from 200–300 cells followed by fluorography revealed about 500 acidic (isoelectric focusing, IEF) and 150 basic polypeptides (non-equilibrium pH gradient electrophoresis, NEPHGE) whose position could be reproducibly assessed. Counting of 33 abundant acidic polypeptides present in both 3T3B and 3T3B-SV40 revealed significant changes in the relative proportion of ten of them. Seven, including the subunit of the 100 Å filaments ‘fibroblast type’ (55K) (1.1% in 3T3B; 0.6% in 3T3B-SV40), three cytoarchitectural proteins and three soluble proteins, corresponded to a decrease of 40% or more in the radioactivity of the spots in transformed cells, and only in three cases was there a significant increase in radioactivity of polypeptides in 3T3B-SV40 cells. Among the polypeptides that show less than 40% variation we have identified total actin (42K) (13% of total label in 3T3B; 10% in 3T3B-SV40), α- and β-tubulin (55K) (1.6% of total label in 3T3B; 2% in 3T3B-SV40), eleven polypeptides present in Triton skeletons, and nine soluble proteins. We have also observed 25 obvious changes in polypeptide intensities (16 acidic and 9 basic) but these were not quantitated. Only three polypeptides were found in transformed cells that were not detected in normal cells. One of these corresponded to the large T antigen and the other two to Triton-soluble proteins of a molecular weight in the range of 52–54K. Similar quantitative studies on the hamster BHK21/BHK21PyY pair confirmed at least the major observations made in 3T3B and 3T3B-SV40.     

Alcohol:NAD oxidoreductase in brain of rats from a colony fed dilute ethanol for many generations.

—Alcohol:NAD oxidoreductase (EC 1.1.1.1) was studied in brain cortex, hypothalamus, cerebellum and midbrain of adult and immature rats, and in the whole encephalon of neonatal rats. The rats used in this study were (i) from a colony which has been given 12% (v/v) aqueous ethanol as the only fluid for 54 generations (‘E.F.’ rats); (ii) rats removed from this colony after the forty-eighth generation and thereafter fed water instead of the alcohol solution (‘E.F./H₂O’ rats); and (iii) normal rats. Enzyme activity in the 20,000 g supernatant of tissue homogenates was measured by the method of Raskin and Sokoloff. Activity was found to be highest in neonatal rat brain and to decrease as the age increased. Activity in the hypothalamus of adult E.F. rats was significantly higher than that found in the same region of adult E.F./H₂O rats. Immature rat cerebellum alcohol:NAD oxidoreductase activity was higher both in ‘E.F.’ and ‘E.F./H₂O’ suggesting a possible genetic change be involved in this CNS region. It may be concluded that, with the exception of neonatal rats, ethanol consumption induces an increase in rat CNS alcohol :NAD oxidoreductase activity.     

Vegetative innervation of the esophagus. II. Intraganglionic laminar endings.

The intraganglionic laminar endings in the esophagus of the cat and the rhesus monkey show absolute equivalence between the results in both species from the morphological standpoint. The different types of apparatus found are described, with their location in the esophagus and their percentage distribution in relation to the different portions of its wall. The osmium tetroxide-zinc iodide technique gives pictures equivalent to those using silver impregnations, with the added advantage that the former brings out the morphological details more clearly, to the point of showing up the peculiar characteristics of the edges with their thorn-like protrusions. The complete independence of these structures within the ganglion is confirmed, and evidence is provided for rejecting the possibility that they might be dendritic prolongations of the neuronal elements composing the intramural ganglia. A possible afferent function is proposed, which, however, must be considered an open question, pending the results of further experimental investigation.