Genome-based analyses to learn from and about Paenibacillus sonchi genomovar Riograndensis SBR5T.

Paenibacillus sonchi genomovar Riograndensis SBR5T is a plant growth-promoting rhizobacterium (PGPR) isolated in the Brazilian state of Rio Grande do Sul from the rhizosphere of Triticum aestivum. It fixes nitrogen, produces siderophores as well as the phytohormone indole-3-acetic acid, solubilizes phosphate and displays antagonist activity against Listeria monocytogenes and Pectobacterium carotovorum. Comprehensive omics analysis and the development of genetic tools are key to characterizing and engineering such non-model microorganisms. Therefore, the complete genome of SBR5T was sequenced, and shown to encode 6,705 proteins, 87 tRNAs, and 27 rRNAs and it enabled a landscape transcriptome analysis that unveiled conserved transcriptional and translational patterns and characterized operon structures and riboswitches. The pangenome of P. sonchi species is open with a stable core pangenome. At the same time, the analysis of genes coding for nitrogenases revealed that the trait of nitrogen fixation is sparse within the Paenibacillaceae family and the presence of Fe-only nitrogenase in the P. sonchi group was exclusive to SBR5T. The development of genetic tools for SBR5T enabled genetic transformation, plasmid construction for constitutive and inducible gene expression, and gene repression using the CRISPRi system. Altogether, the work with P. sonchi can guide the study of non-model bacteria with economic potential.

Factors associated with diet quality among Brazilian individuals with cardiovascular diseases.

BACKGROUND: An individual's dietary pattern contributes in different ways to the prevention and control of recurrent cardiovascular events. However, the quality of the diet is influenced by several factors. The present study aimed to evaluate the quality of the diet of individuals with cardiovascular diseases and determine whether there is an association between sociodemographic and lifestyle factors. METHODS: This is a cross-sectional study carried out with individuals with atherosclerosis (coronary artery disease, cerebrovascular disease or peripheral arterial disease) recruited from 35 reference centres for the treatment of cardiovascular disease in Brazil. Diet quality was assessed according to the Modified Alternative Healthy Eating Index (mAHEI) and stratified into tertiles. For comparing two groups, the Mann-Whitney or Pearson's chi-squared tests were used. However, for comparing three or more groups, analysis of variance or Kruskal-Wallis was used. For the confounding analysis, a multinomial regression model was used. p < 0.05 was considered statistically significant. RESULTS: In total, 2360 individuals were evaluated: 58.5% male and 64.2% elderly. The median (interquartile range [IQR]) of the mAHEI was 24.0 (20.0-30.0), ranging from 0.4 to 56.0 points. When comparing the odds ratios (ORs) for the low (first tertile) and medium (second tertile) diet quality groups with the high-quality group (third tertile), it was observed that there was an association between diet quality with a family income of 1.885 (95% confidence intervals [CI] = 1.302-2.729) and 1.566 (95% CI = 1.097-2.235), as well as physical activity of 1.391 (95% CI = 1.107-1.749) and 1.346 (95% CI = 1.086-1.667), respectively. In addition, associations were observed between diet quality and region of residence. CONCLUSIONS: A low-quality diet was associated with family income, sedentarism and geographical area. These data are extremely relevant to assist in coping with cardiovascular disease because they enable an assessment of the distribution of these factors in different regions of the country.

Reflections on research ethics in a public health emergency: Experiences of Brazilian women affected by Zika.

In Brazil, the epicenter of the Zika crisis, brown, black, and indigenous poor women living in municipalities with scarce resources were disproportionally affected. The gendered consequences of the epidemic exposed how intersectional lenses are central to understand the impact of public health emergencies in the lives of women and girls. The demand for Zika-affected children and women to be research participants is relevant for an ethical analysis of participant protection procedures during a crisis. We investigated how women experienced research participation by analyzing their narratives. Two-year-long longitudinal qualitative study in Brazilian sites located in the epidemic's epicenter was performed using mixed methods: ethnography with women from two distinct states and individual semi-structured interviews with five women in different Zika-affected states, four of which were community leaders. All women in the study were mothers or grandmothers of Zika-affected children. Thematic analysis was used for data evaluation. Women perceived being pressured to participate in research and a lack of benefit sharing. Structural determinants of gender inequality, such as its effect on power distribution, were found to impact research participant protection. Formal procedures for research protocols approvals were insufficient in protecting participants because these instruments were unable to account for structural aspects. Communitarian mobilization, through WhatsApp groups, was found to be an important mechanism to create conditions to challenge oppressive structures. Strengthening public health, effective community-based participation in research planning and implantation of ethical strategies that promotes gender equality can have transformative effect on unequal power structures and promote participant protection.

Immunological profile of periapical endodontic infection in patients undergoing haematopoietic transplantation.

OBJECTIVES: To evaluate the mRNA expression levels of cytokines interferon-γ, tumour necrosis factor-α, interleukin IL-1ß, IL-10, and the chemokine CCL2/MCP-1, CCL4, and CXCR4 in the periapical interstitial fluid from root canal infections before and after bacterial load reduction in patients undergoing haematopoietic stem cell transplantation (HSCT). MATERIALS AND METHODS: The case group was composed of 10 patients undergoing HSCT, and our control group included 10 healthy patients. Clinical samples were taken from teeth with pulp necrosis. Three paper points were placed in the RCS and maintained for 2 min for microbial evaluation before cleaning and shaping procedures. After cleaning and drying the canal, three paper points were introduced into the root canal, passing passively through the root apex (2 mm) into the periapical tissues for 1 min. Samples were collected immediately after root canal cleaning and 7 days later (restrained root canal bacterial load) to characterize gene expression using real-time PCR. RESULTS: The results showed significantly reduction in the microbial load on day 7. An increased expression level of TNF-α and IFN-γ on day 7 in control and case groups was observed (p < 0.05). The mRNA levels of IL-1ß and IL-10 in the pre-HSCT group increased in the samples from day 7 (p < 0.05). The chemokine CCL-2/MCP-1 was not detected in pre-HSCT group. Chemokine receptor CXCR4 levels increased in samples obtained from the day 7 in the control group (p < 0.05). CONCLUSIONS: Individuals undergoing HSTC presented similar cytokine and chemokine mRNA expression compared with healthy individuals. However, it was observed the total absence of mRNA MCP-1/CCL2 expression in those individuals undergoing HSCT. CLINICAL RELEVANCE: Patients undergoing HSCT are at higher risk of infection. No study has analysed the periapical immune responses to root canal infections in HSCT individuals.

Selenium intracanal dressing: effects on the periapical immune response.

OBJECTIVES: To evaluate the selenium (Se) behavior when used as an endodontic dressing in teeth with pulp necrosis. Additionally, its effects was also compared with the calcium hydroxide (C.H.), which is used globally as a root canal dressing, and the combination of the C.H. with Se (C.H. + Se). MATERIALS AND METHODS: The sample consisted of 60 patients requiring endodontic treatment who were divided into groups, i.e., without intracanal medication (empty) and with medications as follows: selenium (Se), calcium hydroxide (C.H.), and calcium hydroxide + selenium (C.H. + Se) (n = 15). After the coronary opening, three absorbent paper points were placed in the RCS and maintained for 2 min for microbial evaluation. Following the cleaning and shaping procedures, new paper points were introduced into the root canal system, passing passively through the root apex (2 mm) into the periapical tissues for 2 min, for immune evaluation. The collections were performed again 15 days later. Real-time PCR quantified the expression of the prokaryotic 16S ribosomal RNA. The 16S mRNA was evaluated before the cleaning and shaping procedures and 15 days later in the groups treated with or without medication. RESULTS: A significant reduction in the microbial load was observed only in the groups that received endodontic dressing (p < 0.05). The cytokines IFN-γ, TNF-α, IL-1α, IL-17A, IL-10, IL-6 and MCP-1, were also quantified by real-time PCR. There was an increase in the gene expression level of the cytokines (T15) TNF-α and IL-10 in the C.H. group compared to the other groups (p < 0.05). The IFN-γ mRNA expression was reduced in the groups treated with the medications (Se, C.H., and C.H. + Se). CONCLUSIONS: The findings of the present study indicate that in the case of treatment over multiple sessions, the use of root canal dressing is essential to avoid the root canal system (RCS) microbial recolonization. Selenium potentiated the effects of calcium hydroxide inducing an anti-inflammatory response in periapical tissues. CLINICAL RELEVANCE: Se is a mineral essential for the formation of the amino acid selenocysteine, which is directly involved in the maintenance of the immune response. Selenium has been widely used in the medical field in the treatment of cancer, as an activator of bone metabolism, and as a stimulator of the immune system. In this study, it was shown that the incorporation of Se, whether as intracanal medication alone or in conjunction with other medications, may potentiate periapical tissue repair after RCS cleaning and shaping procedures.

Does Interrupting Prolonged Sitting With 10- or 20-Min Standing Attenuate Postprandial Glycemia and Blood Pressure in Middle-Aged and Older Adults With Type 2 Diabetes?

We carried out three types of 2-hr experimental sessions with middle-aged and older adults with Type 2 diabetes in order to examine the acute effect of interrupting prolonged sitting with varying periods of standing on postprandial glycemia and blood pressure (BP): (a) prolonged sitting after breakfast; (b) standing for 10 min, 30 min after breakfast; and (c) standing for 20 min, 30 min after breakfast. Glucose and BP were assessed before and after breakfast. A generalized linear model revealed no significant differences for the incremental area under the curve of glucose between standing for 10 min, 30 min after breakfast, versus prolonged sitting after breakfast (ß = -4.5 mg/dl/2 hr, 95% CI [-17.3, 8.4]) and standing for 20 min, 30 min after breakfast, versus prolonged sitting after breakfast (ß = 0.9 mg/dl/2 hr, 95% CI [-11.9, 13.7]). There was no difference in area under the curve of systolic and diastolic BP among the sessions. Interrupting prolonged sitting time with 10 or 20 min of standing 30 min after breakfast does not attenuate postprandial glycemia or BP in middle-aged and older adults with Type 2 diabetes.

CRISPR interference-based gene repression in the plant growth promoter Paenibacillus sonchi genomovar Riograndensis SBR5.

Gene repression using the endonucleolytically deactivated dCas9 protein and sgRNAs (CRISPR interference or CRISPRi) is a useful approach to study gene functions. Here, we established CRISPRi in Paenibacillus sonchi genomovar Riograndensis SBR5, a plant growth promoting bacterium. CRISPRi system with sgRNAs targeting SBR5 endogenous genes spo0A, yaaT and ydjJ and plasmid-borne gfpUV was constructed and analyzed. Flow cytometry analysis revealed a significant decrease of reporter protein GFPUV signal in P. sonchi strains expressing gfpUV sgRNA in comparison with non-targeting controls. CRISPRi-based repression of chromosomal genes for regulation of sporulation spo0A and yaaT decreased sporulation and increased biofilm formation in SBR5. Repression of the sorbitol catabolic gene ydjJ revealed decreased specific activity of YdjJ in crude cell extracts and reduced biomass formation from sorbitol in growth experiments. Our work on CRISPRi-based gene repression serves as basis for gene function studies of the plant growth promoter P. sonchi SBR5. To our knowledge, the present study presents the first tool for gene repression established in Paenibacillus species.Key points• CRISPRi toward gene repression was applied for the first time in Paenibacillus.• CRISPRi of spo0A and yaaT depleted spores and increased biofilms in SBR5.• CRISPRi-based ydjJ repression decreased specific activity of sorbitol dehydrogenase.

Impact of CRISPR interference on strain development in biotechnology.

Genetic perturbation systems are of great interest to redirect metabolic fluxes for value-added production, as well as genetic screening for the development of new drugs, or to identify new targets for biotechnological applications. Here, we review CRISPR interference (CRISPRi), a method for gene expression using a catalytically inactive version of the CRISPR-associated protein 9 (dCas9) of the widely applied CRISPR-Cas9 genome editing system. In combination with the appropriate sgRNA, dCas9 binds to specific DNA sequences without causing double-stranded DNA breakage but interfering with transcription initiation or elongation. Besides manifold uses to interrogate the physiology of a bacterial cell, CRISPRi is used in applications for metabolic engineering and strain development in industrial biotechnology. Albeit in its infancy, CRISPRi has already delivered the first success stories; however, we also analyze limitations of the CRISPRi system and give future perspectives.

Understanding sexual and reproductive health needs of young women living in Zika affected regions: a qualitative study in northeastern Brazil.

BACKGROUND: In 2016, the World Health Organization declared a Public Health Emergency of International Concern due to Zika's association with microcephaly and other neurological disorders. Brazil was the epicenter of this epidemic and the most affected region has the lowest Human Development Index and the highest rates of adolescent pregnancy. Despite the end of the epidemic, Brazil continues to be the epicenter of Zika illness. This study examined the barriers faced by young women who seek sexual and reproductive health (SRH) care services living in affected areas and their attitudes towards SRH needs and the available services. METHODS: Individual semi-structured interviews were conducted with 22 young women, aged 14-24 years in three Zika affected municipalities in the Brazilian Northeast. This qualitative research used thematic analysis for data analysis. RESULTS: Almost half (n = 10) of the participants had their first pregnancy during adolescence (from 12 to 19), all of which were unintended. Lack of information and barriers to access family planning were found to contribute to the unmet need for contraception. Participants reported knowledge gaps about contraception. Zika was not considered a health concern and participants were unaware of the possibility of Zika's sexual transmission. CONCLUSIONS: The young women's knowledge and attitudes towards their SRH needs highlight the barriers to access care. It also implies that comprehensive, biopsychosocial and political, understanding is necessary in order to adequately provide SRH to this population and meet their needs. The government should place women at the center of any public health response to an emergency affecting women of reproductive age and focus on improving access to information and family planning services in a culturally and age appropriate manner.

Clinical endodontic procedures modulate periapical cytokine and chemokine gene expressions.

OBJECTIVES: To identify the gene expression of the cytokines IL-9, TNF-α, IL-1, INF-γ, IL-17A, and IL-10 and the chemokines CCL-2/MCP-1 and CCR-6 in the periapical fluid of human root canal infections. MATERIALS AND METHODS: Twenty samples were collected immediately and 7 days after the cleaning and shaping procedures (after reducing the intracanal microbial load) in an attempt to characterize the expression of these genes. The endogenous expression levels of cytokines and chemokines were analyzed by real-time polymerase chain reaction. The Shapiro-Wilk and the Wilcoxon tests analyzed data. RESULTS: Significantly higher levels of the IL-9, INF-γ, TNF-α, IL-1, and IL-10 markers on day 7 were observed compared with day 0 (p < 0.05). However, IL-17A and the chemokines CCL-2/MCP-1 and CCR-6 did not show a significant difference in mRNA expression when comparing both timepoints (p > 0.05). CONCLUSIONS: The clinical variation of the periapical immune status after endodontic therapy suggests that the cytokine and chemokine-mediated pro-inflammatory response appears to be modulated in an IL-10/IL-9-dependent manner. CLINICAL RELEVANCE: Few studies have investigated the role of Th9 cells in periapical lesions. IL-9 presents exciting plasticity, performing immunosuppressive actions, and it is also capable of changing their phenotype in the presence of IL-17. Hence, it is relevant to investigate its role in the context of the known mediators involved the periapical immune process.

Methanol-Essential Growth of Corynebacterium glutamicum: Adaptive Laboratory Evolution Overcomes Limitation due to Methanethiol Assimilation Pathway.

Methanol is a sustainable substrate for biotechnology. In addition to natural methylotrophs, metabolic engineering has gained attention for transfer of methylotrophy. Here, we engineered Corynebacterium glutamicum for methanol-dependent growth with a sugar co-substrate. Heterologous expression of genes for methanol dehydrogenase from Bacillus methanolicus and of ribulose monophosphate pathway genes for hexulose phosphate synthase and isomerase from Bacillus subtilis enabled methanol-dependent growth of mutants carrying one of two independent metabolic cut-offs, i.e., either lacking ribose-5-phosphate isomerase or ribulose-5-phosphate epimerase. Whole genome sequencing of strains selected by adaptive laboratory evolution (ALE) for faster methanol-dependent growth was performed. Subsequently, three mutations were identified that caused improved methanol-dependent growth by (1) increased plasmid copy numbers, (2) enhanced riboflavin supply and (3) reduced formation of the methionine-analogue O-methyl-homoserine in the methanethiol pathway. Our findings serve as a foundation for the engineering of C. glutamicum to unleash the full potential of methanol as a carbon source in biotechnological processes.

Establishment and application of CRISPR interference to affect sporulation, hydrogen peroxide detoxification, and mannitol catabolism in the methylotrophic thermophile Bacillus methanolicus.

Bacillus methanolicus is a thermophilic, Gram-positive, rod-shaped bacterium. It is a facultative methylotroph which can use carbon and energy sources including mannitol and the one-carbon (C1) and non-food substrate methanol for growth and overproduction of amino acids, which makes it a promising candidate for biotechnological applications. Despite a growing tool box for gene cloning and expression, tools for targeted chromosomal gene knockouts and gene repression are still missing for this organism. Here, the CRISPRi-dCas9 technique for gene repression was established in B. methanolicus MGA3. Significantly reduced spore formation on the one hand and increased biofilm formation on the other hand could be demonstrated when the stage zero sporulation protein A gene spo0A was targeted. Furthermore, when the mannitol-1-phosphate 5-dehydrogenase gene mtlD was targeted by CRISPRi, mtlD RNA levels, and MtlD specific activities in crude extracts were decreased to about 50 % which resulted in reduced biomass formation from mannitol. As a third target, the catalase gene katA was chosen. Upon targeting katA by CRISPRi, catalase activity was decreased to about 25 % as shown in H2O2 drop assays and by determination of specific catalase activity in crude extracts. Our results support the predicted functions of Spo0A in sporulation and biofilm formation, of MtlD for mannitol catabolism, and of catalase in hydrogen peroxide dismutation. Thus, CRISPR interference as developed here serves as basis for the functional characterization of B. methanolicus physiology as well as for its application in biotechnology.

Resolvin E1 Reverses Experimental Periodontitis and Dysbiosis.

Periodontitis is a biofilm-induced inflammatory disease characterized by dysbiosis of the commensal periodontal microbiota. It is unclear how natural regulation of inflammation affects the periodontal biofilm. Promoters of active resolution of inflammation, including resolvin E1 (RvE1), effectively treat inflammatory periodontitis in animal models. The goals of this study were 1) to compare periodontal tissue gene expression in different clinical conditions, 2) to determine the impact of local inflammation on the composition of subgingival bacteria, and 3) to understand how inflammation impacts these changes. Two clinically relevant experiments were performed in rats: prevention and treatment of ligature-induced periodontitis with RvE1 topical treatment. The gingival transcriptome was evaluated by RNA sequencing of mRNA. The composition of the subgingival microbiota was characterized by 16S rDNA sequencing. Periodontitis was assessed by bone morphometric measurements and histomorphometry of block sections. H&E and tartrate-resistant acid phosphatase staining were used to characterize and quantify inflammatory changes. RvE1 treatment prevented bone loss in ligature-induced periodontitis. Osteoclast density and inflammatory cell infiltration in the RvE1 groups were lower than those in the placebo group. RvE1 treatment reduced expression of inflammation-related genes, returning the expression profile to one more similar to health. Treatment of established periodontitis with RvE1 reversed bone loss, reversed inflammatory gene expression, and reduced osteoclast density. Assessment of the rat subgingival microbiota after RvE1 treatment revealed marked changes in both prevention and treatment experiments. The data suggest that modulation of local inflammation has a major role in shaping the composition of the subgingival microbiota.

Detailed transcriptome analysis of the plant growth promoting Paenibacillus riograndensis SBR5 by using RNA-seq technology.

BACKGROUND: The plant growth promoting rhizobacterium Paenibacillus riograndensis SBR5 is a promising candidate to serve as crop inoculant. Despite its potential in providing environmental and economic benefits, the species P. riograndensis is poorly characterized. Here, we performed for the first time a detailed transcriptome analysis of P. riograndensis SBR5 using RNA-seq technology. RESULTS: RNA was isolated from P. riograndensis SBR5 cultivated under 15 different growth conditions and combined together in order to analyze an RNA pool representing a large set of expressed genes. The resultant total RNA was used to generate 2 different libraries, one enriched in 5'-ends of the primary transcripts and the other representing the whole transcriptome. Both libraries were sequenced and analyzed to identify the conserved sequences of ribosome biding sites and translation start motifs, and to elucidate operon structures present in the transcriptome of P. riograndensis. Sequence analysis of the library enriched in 5'-ends of the primary transcripts was used to identify 1082 transcription start sites (TSS) belonging to novel transcripts and allowed us to determine a promoter consensus sequence and regulatory sequences in 5' untranslated regions including riboswitches. A putative thiamine pyrophosphate dependent riboswitch upstream of the thiamine biosynthesis gene thiC was characterized by translational fusion to a fluorescent reporter gene and shown to function in P. riograndensis SBR5. CONCLUSIONS: Our RNA-seq analysis provides insight into the P. riograndensis SBR5 transcriptome at the systems level and will be a valuable basis for differential RNA-seq analysis of this bacterium.

Magnesium aminoclay-based transformation of Paenibacillus riograndensis and Paenibacillus polymyxa and development of tools for gene expression.

Members of the genus Paenibacillus are widespread facultative anaerobic, endospore-forming bacteria. Some species such as Paenibacillus riograndensis or Paenibacillus polymyxa fix nitrogen and may play an important role in agriculture to reduce mineral nitrogen fertilization in particular for non-legume plants. The genetic manipulation of Paenibacillus is an imperative for the functional characterization, e.g., of its plant growth-promoting activities and metabolism. This study showed that P. riograndensis and P. polymyxa can be readily transformed using physical permeation by magnesium aminoclays. By means of the fluorescent reporter genes gfpUV, mcherry, and crimson, a two-plasmid system consisting of a theta-replicating plasmid and a rolling circle-replicating plasmid was shown to operate in both species. Xylose-inducible and mannitol-inducible fluorescent reporter gene expression was demonstrated in the compatible two-plasmid system by fluorescence-activated cell scanning. As a metabolic engineering application, the biotin requiring P. riograndensis was converted to a biotin-prototrophic strain based on mannitol-inducible expression of the biotin biosynthesis operon bioWAFDBI from Bacillus subtilis.

Increased expression of ACTH (MC2R) and androgen (AR) receptors in giant bilateral myelolipomas from patients with congenital adrenal hyperplasia.

BACKGROUND: Although chronic adrenocorticotropic hormone (ACTH) and androgen hyperstimulation are assumed to be involved in the pathogenesis of adrenal myelolipomas associated with poor-compliance patients with congenital adrenal hyperplasia (CAH), the expression of their receptors has not yet been demonstrated in these tumors so far. METHODS: We analyzed Melanocortin 2 receptor (MC2R), Androgen Receptor (AR), Leptin (LEP), and Steroidogenic factor 1 (SF1) expression using real-time qRT-PCR in two giant bilateral adrenal myelolipomas from two untreated simple virilizing CAH cases and in two sporadic adrenal myelolipomas. In addition, the X-chromosome inactivation pattern and CAG repeat numbers in AR exon 1 gene were evaluated in the 4 cases. RESULTS: The MC2R gene was overexpressed in myelolipomas from 3 out of 4 patients. AR overexpression was detected in 2 tumors: a giant bilateral myelolipoma in a CAH patient and a sporadic case. Simultaneous overexpression of AR and MC2R genes was found in two of the cases. Interestingly, the bilateral giant myelolipoma associated with CAH that had high androgen and ACTH levels but lacked MC2R and AR overexpression presented a significantly shorter AR allele compared with other tumors. In addition, X-chromosome inactivation pattern analysis showed a polyclonal origin in all tumors, suggesting a stimulatory effect as the trigger for tumor development. CONCLUSION: These findings are the first evidence for MC2R or AR overexpression in giant bilateral myelolipomas from poor-compliance CAH patients.

Riboflavin overproduction from diverse feedstocks with engineered Corynebacterium glutamicum.

Riboflavin overproduction by Corynebacterium glutamicum was achieved by screening synthetic operons, enabling fine-tuned expression of the riboflavin biosynthetic genes ribGCAH. The synthetic operons were designed by means of predicted translational initiation rates of each open reading frame, with the best-performing selection enabling riboflavin overproduction without negatively affecting cell growth. Overexpression of the fructose-1,6-bisphosphatase (fbp) and 5-phosphoribosyl 1-pyrophosphate aminotransferase (purF) encoding genes was then done to redirect the metabolic flux towards the riboflavin precursors. The resulting strain produced 8.3 g/L of riboflavin in glucose-based fed-batch fermentations, which is the highest reported riboflavin titer with C. glutamicum. Further genetic engineering enabled both xylose and mannitol utilization by C. glutamicum, and we demonstrated riboflavin overproduction with the xylose-rich feedstocks rice husk hydrolysate and spent sulfite liquor, and the mannitol-rich feedstock brown seaweed hydrolysate. Remarkably, rice husk hydrolysate provided 30% higher riboflavin yields compared to glucose in the bioreactors. .

Hospitalizations for mental and behavioral disorders due to alcohol and other psychoactive substance use among adolescents in Brazil, 2017-2022.

OBJECTIVE: To assess the epidemiological profile and trend in hospitalizations for mental and behavioral disorders due to alcohol and other psychoactive substance use among Brazilian adolescents, between 2017 and 2022. METHODS: This was a time-series study using data from the Hospital Information System of the Brazilian National Health System; the trend analysis was performed by estimating the annual percentage change (APC) of hospitalization rates per 100,000 inhabitants and respective confidence intervals (95%CI), using the Prais-Winsten method. RESULTS: A total of 29,991 hospitalizations were recorded in the study period, with a decreasing trend observed, from 16.18/100,000 inhabitants in 2017 to 13.72/100,000 inhab. in 2022 (percent change of -2.65%; 95%CI -4.47;-0.80), a greater decline was found in males (-3.48%; 95%CI -5.20;-1.72), in the age group of 15 to 19 years (-2.79%; 95%CI -4.49;-1.06), in the South (-3.29%; 95%CI -5.37;-1.16) and Midwest (-3.64%; 95%CI -5.75;-1.49) regions of the country. CONCLUSION: Hospitalizations showed a decreasing trend in the study period, with sociodemographic disparities.

Antitumor effects of electrochemical treatment.

Electrochemical treatment is an alternative modality for tumor treatment based on the application of a low intensity direct electric current to the tumor tissue through two or more platinum electrodes placed within the tumor zone or in the surrounding areas. This treatment is noted for its great effectiveness, minimal invasiveness and local effect. Several studies have been conducted worldwide to evaluate the antitumoral effect of this therapy. In all these studies a variety of biochemical and physiological responses of tumors to the applied treatment have been obtained. By this reason, researchers have suggested various mechanisms to explain how direct electric current destroys tumor cells. Although, it is generally accepted this treatment induces electrolysis, electroosmosis and electroporation in tumoral tissues. However, action mechanism of this alternative modality on the tumor tissue is not well understood. Although the principle of Electrochemical treatment is simple, a standardized method is not yet available. The mechanism by which Electrochemical treatment affects tumor growth and survival may represent more complex process. The present work analyzes the latest and most important research done on the electrochemical treatment of tumors. We conclude with our point of view about the destruction mechanism features of this alternative therapy. Also, we suggest some mechanisms and strategies from the thermodynamic point of view for this therapy. In the area of Electrochemical treatment of cancer this tool has been exploited very little and much work remains to be done. Electrochemical treatment constitutes a good therapeutic option for patients that have failed the conventional oncology methods.