Fuzzy and spatial analysis of cutaneous leishmaniasis in Pará State, Brazilian Amazon: an ecological and exploratory study.

INTRODUCTION: This study sought to analyze the relationships between cutaneous leishmaniasis and its epidemiological, environmental and socioeconomic conditions, in the 22 microregions of Pará state, Brazil, for the period from 2017 to 2022. METHODOLOGY: In this ecological and exploratory study, the microregions were used as spatial units because they are formed by contiguous municipalities with similar characteristics. The epidemiological, environmental, socioeconomic, and public health policy data employed were obtained from the official information systems at the Ministry of Health, National Institute for Space Research, and Brazilian Institute of Geography and Statistics. A fuzzy system was developed to identify risk factors for the disease, using Python programming language. The results were analyzed with the bivariate Global Moran spatial analysis technique. RESULTS: It was observed that the Altamira microregion had the highest risk percentage for the disease, while Breves had the lowest, with significant differences in the relevance of its conditioning factors, mainly related to land use and cover patterns, in addition to demography and living conditions index, education and public health policies. CONCLUSIONS: The fuzzy system associated with the geostatistical technique was satisfactory for identifying areas with health vulnerability gradients related to deforestation, pasture, poverty, illiteracy, and health services coverage, as its conditioning variables. Thus, it was demonstrated that deforestation was the main risk factor for the disease. The system can also be used in environmental and epidemiological surveillance.

Assessment of space changes in the lower dental arch after the premature unit loss of a primary molar: A randomized clinical trial.

BACKGROUND: Premature loss of primary teeth presents a significant challenge in oral health, with conflicting views on using space maintainers. AIM: To assess mandibular arch space changes associated with premature lower primary molar (PM) loss with or without a space maintainer. DESIGN: A randomized clinical trial with children (6-9 years old) with premature loss of a lower PM divided into two groups: control group (CG), without a space maintainer, and intervention group (IG), with a space maintainer. Dental casts were measured at baseline, 3 months, and 6 months. Linear distance; intercanine width and length; and arch width, length, and perimeter were measured. ANOVA and t-test were applied (p = .05). RESULTS: Twenty-six patients (mean: 7.3 years; standard deviation [SD]: 0.92) were included: 14 in CG and 12 in IG. CG had a greater space loss (-0.9 mm; SD: 0.45) than IG (-0.4 mm; SD: 0.61) at 3 months (p < .05). No difference between the groups was observed after 6 months (p = .610). CG decreases space at 6 months, especially with the first permanent molars without intercuspation (-2 mm; SD: 0.71; p = .007). CONCLUSION: Premature lower PM loss resulted in reduced arch space loss after 6 months, regardless of a space maintainer use. CG showed more loss of space when the first permanent molars lacked intercuspal relationship.

A Contribution towards Sustainable Development in the Amazon Based on a Socioeconomic and Environmental Analysis of Visceral Leishmaniasis in the State of Pará, Brazil.

Human Visceral Leishmaniasis is an endemic public health problem in the Amazon. This article analyzed the spatial distribution of this disease and its relationship with socioeconomic, environmental and public health policy variables in four mesoregions of the state of Pará, from 2011 to 2022. This ecological study used secondary data obtained from official Brazilian agencies. Spatial analysis was performed using the Flow, Kernel and Global Moran bivariate techniques expressed in thematic maps. In the mesoregions studied, 2685 cases of the disease were confirmed, with the highest number of cases in Southeast Pará state. The epidemiological profile followed the national pattern of occurrence of the disease, with a higher number of cases in children below school age. Spatial dependence was observed between the prevalence of the disease and socio-economic indicators. The most intense movement of patients was towards the Belém Metropolitan mesoregion. The disease showed an inhomogeneous pattern of distribution of cases, with a direct relationship between areas with cases and deforestation associated with different anthropic activities. There is a socio-environmental production of the disease that goes beyond the border limits of the mesoregions, and its establishment is related to the unsustainable development model implemented in the region.

Distribution of pharmacogene allele and phenotype frequencies in Brazilian psychiatric patients.

Purpose: This work was designed to identify the pharmacogenetic profile of Brazilian psychiatric patients receiving psychoactive drug treatment according to ethnicity. Methods: Based on the GnTech® database, this cross-sectional study analyzed data from self-reported sociodemographic and genetic results from the next-generation sequencing panel composed of 26 pharmacogenes from 359 psychotropic drug users. Results: Variant frequencies of multiple pharmacogenes presented differences between ethnicities (CYP3A5, CYP2D6, CYP1A2, CYP2B6, CYP3A4, UGT1A4, UGT2B15, ABCB1 rs1045642, ADRA2A rs1800544, COMT rs4680, GRIK4 rs1954787, GSK3B rs334558, GSK3B rs6438552, HTR1A rs6295, HTR2A rs7997012, HTR2C rs1414334, MTHFR rs1801131, OPRM1 rs1799971 and 5-HTTLPR), endorsing the necessity of individual-level analyses in drug treatment. Conclusion: A discussion of pharmacogenomic test implementation in psychiatric clinical practice is needed to improve treatment choices, especially in Brazil, a multiethnic country.

The Impact in Intestines and Microbiota in BALB/c Mice Through Consumption of Milk Fermented by Potentially Probiotic Lacticaseibacillus casei SJRP38 and Limosilactobacillus fermentum SJRP43.

The present study aimed to evaluate the effect of consumption of milk fermented by Lacticaseibacillus (Lc.) casei SJRP38 and Limosilactobacillus (Lm.) fermentum SJRP43 on bacterial translocation, stool analysis, and intestinal morphology of healthy BALB/c mice. Potentially probiotic lactic acid bacteria, Lc. casei SJRP38, and Lm. fermentum SJRP43 were evaluated and analyzed for translocation, fecal analysis, and intestinal morphology of four groups of mice: water control (WC), milk control (MC), milk fermented by Lc. casei SJRP38 (FMLC), and milk fermented by Lm. fermentum SJRP43 (FMLF), in co-culture with Streptococcus thermophilus ST080. The results of the animal assay indicate that the population of Lactobacilli and Bidobacterium sp. in the gastrointestinal tract of BALB/c mice was greater than 6.0 log10 CFU/g, and there was no evidence of bacteremia due to the low incidence of bacterial translocation. Ingesting fermented milk containing Lc. casei SJRP38 and Lm. fermentum SJRP43 was found to promote a healthier microbiota, as it led to a reduction in Clostridium sp. and an increase in Lactobacilli and Bifidobacterium sp. in feces. Furthermore, the dairy treatments (MC, FMLC, and FMLF) resulted in taller intestinal villi and an increase in the frequency of goblet cells in the intestines. Overall, the consumption of fermented milk containing Lc. casei SJRP38 and Lm. fermentum SJRP43 strains was deemed safe and demonstrated beneficial effects on the intestines of BALB/c mice.

Pediatric oncohematological exercise program in hospital: clinical trial study protocol.

Leukemias are the most common types of hematological cancers in children, and negatively impact functional capacity. There is evidence in the literature that therapeutic exercises can have a positive impact on functions. The aim of this study is to evaluate functional capacity, muscle strength, fatigue and quality of life through the application of a protocol of therapeutic exercises during pediatric leukemia hospitalization. Children will be allocated into two groups: one will carry out a protocol of therapeutic exercises, while the other will undergo conventional respiratory physiotherapy. The protocol is approved by the ethics and research committee of the host institution (No. 5.439.594). Results will be disseminated through peer-reviewed journal articles and conferences. Clinical trial registration: RBR-8sxnfyd (https://ensaiosclinicos.gov.br).

Medium composition and aeration to high (R,R)-2,3-butanediol and acetoin production by Paenibacillus polymyxa in fed-batch mode.

Concerning the potential application of the optically active isomer (R,R)-2,3-butanediol, and its production by a non-pathogenic bacterium Paenibacillus polymyxa ATCC 842, the present study evaluated the use of a commercial crude yeast extract Nucel®, as an organic nitrogen and vitamin source, at different medium composition and two airflows (0.2 or 0.5 vvm). The medium formulated (M4) with crude yeast extract carried out with the airflow of 0.2 vvm (experiment R6) allowed for a reduction in the cultivation time and kept the dissolved oxygen values at low levels until the total glucose consumption. Thus, the experiment R6 led to a fermentation yield of 41% superior when compared to the standard medium (experiment R1), which was conducted at airflow of 0.5 vvm. The maximum specific growth rate at R6 (0.42 h-1) was lower than R1 (0.60 h-1), however, the final cell concentration was not affected. Moreover, this condition (medium formulated-M4 and low airflow-0.2 vvm) was a great alternative to produce (R,R)-2,3-BD at fed-batch mode, resulting in 30 g.L-1 of the isomer at 24 h of cultivation, representing the main product in the broth (77%) and with a fermentation yield of 80%. These results showed that both medium composition and oxygen supply have an important role to produce 2,3-BD by P. polymyxa.

Prospecting and engineering yeasts for ethanol production under inhibitory conditions: an experimental design analysis.

The recently discovered wild yeast Wickerhamomyces sp. UFFS-CE-3.1.2 was analyzed through a high-throughput experimental design to improve ethanol yields in synthetic media with glucose, xylose, and cellobiose as carbon sources and acetic acid, furfural, formic acid, and NaCl as fermentation inhibitors. After Plackett-Burman (PB) and central composite design (CCD), the optimized condition was used in a fermentation kinetic analysis to compare this yeast's performance with an industrial Saccharomyces cerevisiae strain (JDY-01) genetically engineered to achieve a higher xylose fermentation capacity and fermentation inhibitors tolerance by overexpressing the genes XYL1, XYL2, XKS1, and TAL1. Our results show that furfural and NaCl had no significant effect on sugar consumption by UFFS-CE-3.1.2. Surprisingly, acetic acid negatively affected glucose but not xylose and cellobiose consumption. In contrast, the pH positively affected all the analyzed responses, indicating a cell's preference for alkaline environments. In the CCD, sugar concentration negatively affected the yields of ethanol, xylitol, and cellular biomass. Therefore, fermentation kinetics were carried out with the average concentrations of sugars and fermentation inhibitors and the highest tested pH value (8.0). Although UFFS-CE-3.1.2 fermented glucose efficiently, xylose and cellobiose were mainly used for cellular growth. Interestingly, the genetically engineered strain JDY-01 consumed ~ 30% more xylose and produced ~ 20% more ethanol. Also, while UFFS-CE-3.1.2 only consumed 32% of the acetic acid of the medium, JDY-01 consumed > 60% of it, reducing its toxic effects. Thus, the overexpressed genes played an essential role in the inhibitors' tolerance, and the applied engineering strategy may help improve 2G ethanol production.

Visceral Leishmaniasis and Land Use and Cover in the Carajás Integration Region, Eastern Amazon, Brazil.

Human visceral leishmaniasis is a major public health problem in the Amazon. Thus, we analyzed the spatial distribution of this disease and its relationship with epidemiological, socioeconomic, and environmental variables in the Carajás Integration Region, Pará state, from 2011 to 2020. Epidemiological data for this ecological study were obtained from the State Public Health Secretariat, environmental data were obtained from the National Space Research Institute, and socioeconomic data were obtained from the Brazilian Geography and Statistics Institute. ArcGIS 10.5.1 software was used for classifying land use and cover and for the Kernel and Moran spatial analyses. It was observed in 685 confirmed cases that the epidemiological profile followed the national pattern of the disease occurrence, with a high prevalence in children who were not school-aged. The disease had a non-homogeneous distribution with clusters related to different human activities, such as urbanization, ranching, and mining. A spatial dependence between the disease prevalence and socioeconomic indicators was observed. The municipalities presented gradients of case densities associated with a direct relationship between areas with cases and deforestation. The disease is developing due to risk factors such as establishment and maintenance related to the non-sustainable development model implemented in the region, pointing to the need for its revision.

Applicability of the drainage effectiveness of Blake drains and Tenckhoff catheters in the peritoneal dialysis of healthy rabbits (Oryctolagus cuniculus).

OBJECTIVE: To compare the efficacy of dialysate drainage between Tenckhoff (TC) catheter and Blake (BL) in peritoneal dialysis (PD) in healthy rabbits. DESIGN: Prospective experimental study. SETTING: University Teaching Hospital and University research laboratory. ANIMALS: Twenty healthy, male, New Zealand rabbits. INTERVENTIONS: PD via the TC catheter and the BL abdominal drain was compared during 3 consecutive days of dialysis delivery. MEASUREMENTS AND MAIN RESULTS: One session of PD was performed per day for 3 consecutive days (S1: first session, S2: second session, S3: third session) and each session included 4 cycles of infusion, dwell of dialysate in the abdomen, and drainage. Data collection included daily urea, creatinine, alanine aminotransferase, albumin, and potassium, in addition to hematological parameters (eg, RBC, HCT, hemoglobin, WBC, and platelet count). Statistical analysis using a mixed linear model with multiple comparisons was performed. The BL drain resulted in an increase in volume drained (ml/kg) when compared to TC catheter on S2 (third and fourth cycles) and S3 (first and second cycles). CONCLUSIONS: The BL drain proved to be superior to the TC catheter, being capable of draining a larger volume of dialysate during the drainage processes in the peritoneal PD of healthy rabbits. The TC catheter had major complications with regard to fluid retention in the abdomen, representing reduced drainage efficiency, while the BL drain showed a greater tendency for the peritoneal fluid to leak.

Uroterapia y mindfulness en el tratamiento de niños con disfunción vesical e intestinal: protocolo para un ensayo clínico.

OBJETIVO: Presentar un protocolo para ensayo clínico controlado y aleatorizado que estudie los resultados de la asociación entre técnicas de uroterapia estándar y mindfulness en la adhesión al programa y reducción de síntomas de disfunción vesical e intestinal en escolares. MÉTODO: Presentación descriptiva del protocolo. RESULTADOS: El grupo de control deberá recibir orientaciones de medidas comportamentales gradualmente en visitas semanales, durante cuatro semanas. Tales medidas deberán contemplar: control de la ingesta de agua, intervalo de evacuación, ingestión de potenciales irritantes de la vejiga, y entrenamiento muscular del fondo pélvico. El grupo experimental deberá ser sometido al mismo protocolo, además de las técnicas de atención plena (mindfulness), previamente al inicio de cada consulta de uroterapia. CONCLUSIÓN: Se espera estimular la aplicación de este protocolo en diferentes escenarios y así evaluar la contribución de la práctica de atención plena en la adhesión al tratamiento y en la reducción de síntomas.

Assessment of the psychological impact of the COVID-19 pandemic on pregnant women.

Purpose: This is a cross-sectional observational study that aims to evaluate the impact of the COVID-19 pandemic in pregnant women.Method: A form containing the validated Impact of Event Scale - Revised questionnaire was sent to the participants.Results: From the 106 participants, 13 had been contaminated by the Sars-Cov2 virus during the pregnancy. More than half of the women (51.89%) presented some degree of psychological impact, 20 participants were classified as having a mild impact, 6 with moderated impact and 29 with severe impact. The psychological impact was more prominent in women in their third gestational trimester, 36.07% of these women presented a severe impact, 4.92% a moderated impact and 14.75% a mild impact. The IES-R questionnaire had a mean score of 35.62 in the group of contaminated patients, indicating a higher psychological impact in comparison with the mean score of 26.76 in the group of patients who were not contaminated by the vírus.Conclusion: It can be inferred that the pregnant women who were not contaminated by the Sars-Cov2 presented a lower psychological impact than those who were contaminated. In addition, patients with lower psychological impact did not miss their ultrasound exams. Furthermore, more than half of the women who participated in the study, whether they were contaminated or not, presented some degree of psychological impact.

Increased biofilm formation by Staphylococcus aureus clinical isolates on surfaces covered with plasma proteins.

Introduction. Biofilm formation is a major virulence factor associated with Staphylococcus aureus infections. However, the influence of plasma proteins on biofilm formation of clinical isolates in vitro remains unclear.Hypotheses. We hypothesized that coating surfaces with plasma proteins might induce biofilm formation by S. aureus of different clonal lineages.Aim. To evaluate biofilm production by clinical S. aureus isolates of different clonal lineages isolated in Rio de Janeiro hospitals and investigated the presence of biofilm-associated genes.Methodology. This study assessed biofilm production of 60 S. aureus isolates in polystyrene microtitre plates with and without fibrinogen or fibronectin. The biochemical composition of the biofilm matrices was determined and the biofilm formation on fibrinogen-coated surfaces was also evaluated by confocal laser scanning microscopy. The presence of biofilm-related genes was detected by PCR, and the typing and functionality of agr operon was also evaluated.Results. Most of the isolates (45 %) were weak biofilm producers or non-producers. However, most of them presented a significant increase in biofilm production on plates covered with plasma proteins. There was no significant difference in biofilm formation between methicillin-resistant and -susceptible S. aureus isolates, or between different clonal lineages, except for ST30-IV (weak producers) and ST239-III (strong producers). The fnbB gene was associated with higher biofilm production.Conclusion. An increase in biofilm production in the presence of plasma proteins highlights the importance of investigating biofilm formation by S. aureus clinical isolates under different conditions since this virulence factor contributes to persistent infections and increased resistance to antimicrobials.

HIV treatment non-adherence is associated with ICU mortality in HIV-positive critically ill patients.

INTRODUCTION: Combined antiretroviral therapy has led to significant decreases in morbidity and mortality in acquired immunodeficiency syndrome patients. Survival among these patients admitted to intensive care units has also improved in the last years. However, the prognostic predictors of human immunodeficiency vírus patients in intensive care units have not been adequately studied. The main objective of this study was to evaluate if non-adherence to antiretroviral therapy is a predictor of hospital mortality. METHODS: A unicentric, retrospective, cohort study composed of patients admitted to a 59-bed mixed intensive care unit including all patients with human immunodeficiency vírus infection. Patients were excluded if exclusive palliative care was established before completing 48 h of intensive care unit admission. Clinical and treatment data were obtained, including demographic records, underlying diseases, Simplified Acute Physiology III score at the time of intensive care unit admission, CD4 lymphocyte count, antiretroviral therapy adherence, admission diagnosis, human immunodeficiency vírus-related diseases, sepsis and use of mechanical ventilation and hemodialysis. The outcome analyzed was hospital mortality. RESULTS: Overall, 167 patients were included in the study, and intensive care unit mortality was 34.7%. Multivariate analysis indicated that antiretroviral therapy adherence and the Simplified Acute Physiology 3 score were independently related to hospital mortality. antiretroviral therapy adherence was a protective factor (OR 0.2; 95% CI 0.05-0.71; P = 0.01), and Simplified Acute Physiology 3 (OR 1.04; 95% CI 1.01-1.08; P < 0.01) was associated with increased hospital mortality. CONCLUSION: Non-adherence to antiretroviral therapy is associated with hospital mortality in this population. Highly active antiretroviral therapy non-adherence may be associated with other comorbidities that may be associated with a worst prognosis in this scenario.

Effect of Combined Therapy of Virtual Reality and Transcranial Direct Current Stimulation in Children and Adolescents With Cerebral Palsy: A Study Protocol for a Triple-Blinded Randomized Controlled Crossover Trial.

Background: Transcranial direct current stimulation (tDCS) and therapy-based virtual reality (VR) have been investigated separately. They have shown promise as efficient and engaging new tools in the neurological rehabilitation of individuals with cerebral palsy (CP). However, the recent literature encourages investigation of the combination of therapy tools in order to potentiate clinic effects and its mechanisms. Methods: A triple-blinded randomised sham-controlled crossover trial will be performed. Thirty-six individuals with gross motor function of levels I to IV (aged 4-14 years old) will be recruited. Individuals will be randomly assigned to Group A (active first) or S (sham first): Group A will start with ten sessions of active tDSC combined with VR tasks. After a 1-month washout, this group will be reallocated to another ten sessions with sham tDCS combined with VR tasks. In contrast, Group S will carry out the opposite protocol, starting with sham tDCS. For the active tDCS the protocol will use low frequency tDCS [intensity of 1 milliampere (mA)] over the primary cortex (M1) area on the dominant side of the brain. Clinical evaluations (reaction times and coincident timing through VR, functional scales: Abilhand-Kids, ACTIVLIM-CP, Paediatric Evaluation of Disability Inventory-PEDI- and heart rate variability-HRV) will be performed at baseline, during, and after active and sham tDCS. Conclusion: tDCS has produced positive results in treating individuals with CP; thus, its combination with new technologies shows promise as a potential mechanism for improving neurological functioning. The results of this study may provide new insights into motor rehabilitation, thereby contributing to the better use of combined tDCS and VR in people with CP. Trial Registration: ClinicalTrials.gov, NCT04044677. Registered on 05 August 2019.

Imaging and immunometabolic phenotyping uncover changes in the hepatic immune response in the early phases of NAFLD.

BACKGROUND & AIMS: The precise determination of non-alcoholic fatty liver disease (NAFLD) onset is challenging. Thus, the initial hepatic responses to fat accumulation, which may be fundamental to our understanding of NAFLD evolution and clinical outcomes, are largely unknown. Herein, we chronologically mapped the immunologic and metabolic changes in the liver during the early stages of fatty liver disease in mice and compared this with human NAFLD samples. METHODS: Liver biopsies from patients with NAFLD (NAFLD activity score [NAS] 2-3) were collected for gene expression profiling. Mice received a high-fat diet for short periods to mimic initial steatosis and the hepatic immune response was investigated using a combination of confocal intravital imaging, gene expression, cell isolation, flow cytometry and bone marrow transplantation assays. RESULTS: We observed major immunologic changes in patients with NAS 2-3 and in mice in the initial stages of NAFLD. In mice, these changes significantly increased mortality rates upon drug-induced liver injury, as well as predisposing mice to bacterial infections. Moreover, deletion of Toll-like receptor 4 in liver cells dampened tolerogenesis, particularly in Kupffer cells, in the initial stages of dietary insult. CONCLUSION: The hepatic immune system acts as a sentinel for early and minor changes in hepatic lipid content, mounting a biphasic response upon dietary insult. Priming of liver immune cells by gut-derived Toll-like receptor 4 ligands plays an important role in liver tolerance in initial phases, but continuous exposure to insults may lead to damage and reduced ability to control infections. LAY SUMMARY: Fatty liver is a very common form of hepatic disease, leading to millions of cases of cirrhosis every year. Patients are often asymptomatic until becoming very sick. Therefore, it is important that we expand our knowledge of the early stages of disease pathogenesis, to enable early diagnosis. Herein, we show that even in the early stages of fatty liver disease, there are significant alterations in genes involved in the inflammatory response, suggesting that the hepatic immune system is disturbed even following minor and undetectable changes in liver fat content. This could have implications for the diagnosis and clinical management of fatty liver disease.

Caffeine Consumption plus Physical Exercise Improves Behavioral Impairments and Stimulates Neuroplasticity in Spontaneously Hypertensive Rats (SHR): an Animal Model of Attention Deficit Hyperactivity Disorder.

Attention deficit hyperactivity disorder (ADHD) is a prevalent and disabling disorder, mainly characterized by hyperactivity, inattention, and impulsivity, but also by olfactory and memory impairments that frequently persist throughout lifetime. The pathophysiology of ADHD is complex, involving several brain regions and neural pathways including alterations in adenosine neuromodulation. The administration of caffeine (a non-selective adenosine receptor antagonist) and physical exercise have been independently pointed as effective approaches for the management of ADHD symptoms. Here, we evaluated the effects of caffeine consumption (0.3 mg/mL in drinking water) plus physical exercise in running wheels during 6 weeks-starting during either adolescence (30 days old) or adulthood (4-5 months old)-on behavioral performance (including olfactory discrimination, open field, object recognition, and water maze tests) on the brain levels of monoamines (by high-performance liquid chromatography), on proteins related to synaptic plasticity and on brain-derived neurotrophic factor signaling (by Western blot analysis) in spontaneously hypertensive rats (SHRs), a validated animal model of ADHD. SHRs displayed persistent impairments of olfactory and short-term recognition memory from adolescence to adulthood, which were accompanied by lower levels of synaptosomal-associated protein 25 (SNAP-25) in the prefrontal cortex and hippocampus. The association of caffeine plus physical exercise during adolescence or adulthood restored the olfactory discrimination ability and, in an independent manner, improved short-term recognition memory of SHRs. These benefits were not associated to alterations in locomotor activity or in the hypertensive phenotype. The association of caffeine consumption plus physical exercise during adolescence increased the levels of SNAP-25, syntaxin, and serotonin in the hippocampus and prefrontal cortex, and striatal dopamine levels in SHRs. These results provide new evidence of the potential of caffeine and physical exercise, starting at adolescence or adult life, to improve behavioral impairments and stimulate neuroplasticity in ADHD.

Correction to: High lactobionic acid production by immobilized Zymomonas mobilis cells: a great step for large-scale process.

In the original publication, table captions were incorrectly published. The correct captions are given here.

High lactobionic acid production by immobilized Zymomonas mobilis cells: a great step for large-scale process.

Lactobionic acid and sorbitol are produced from lactose and fructose in reactions catalyzed by glucose-fructose oxidoreductase and glucono-δ-lactonase, periplasmic enzymes present in Zymomonas mobilis cells. Considering the previously established laboratory-scale process parameters, the bioproduction of lactobionic acid was explored to enable the transfer of this technology to the productive sector. Aspects such as pH, temperature, reuse and storage conditions of Ca-alginate immobilized Z. mobilis cells, and large-scale bioconversion were assessed. Greatest catalyst performance was observed between pH range of 6.4 and 6.8 and from 39 to 43 °C. The immobilized biocatalyst was reused for twenty three 24-h batches preserving the enzymatic activity. The activity was maintained during biocatalyst storage for up to 120 days. Statistically similar results, approximately 510 mmol/L of lactobionic acid, were attained in bioconversion of 0.2 and 3.0 L, indicating the potential of this technique of lactobionic acid production to be scaled up to the industrial level.

Temporal development of behavioral impairments in rats following locus coeruleus lesion induced by 6-hydroxydopamine: Involvement of ß3-adrenergic receptors.

Noradrenergic degeneration in the locus coeruleus (LC) seems a convergent neuropathological marker of different neurodegenerative diseases. Herein, we investigated the temporal development of apoptotic signaling activation in the LC, noradrenergic dysfunction and behavioral impairments in rats following the noradrenergic lesion of the LC. For this purpose, the dopamine reuptake inhibitor nomifensine was administered 1 h before the stereotaxic bilateral injections of 6-hydroxydopamine (6-OHDA; 5, 10 or 20 µg/hem) into the LC. The behavioral and neurochemical analyses were performed at 7, 21 and 42 days after 6-OHDA injections. All doses of 6-OHDA induced neuronal death in LC, but only the highest dose (20 µg/hem) disrupted the motor function. 6-OHDA (5 µg/hem) injection induced short-term memory deficits in all periods, olfactory discrimination and long-term memory impairments at 7 days, and depressive-like behaviors at 21 and 42 days after injection. Moreover, 6-OHDA infusion increased Bax/Bcl2 ratio and caspase 3 levels, and decreased the dopamine ß-hydroxylase immunocontent in the LC. Noradrenergic neurotransmission dysfunction was observed in the LC, olfactory bulb, prefrontal cortex, hippocampus and striatum. The intranasal (i.n.) noradrenaline (NA) infusion restored the impairments in the olfactory discrimination, short-term memory and depressive-like behavior of 6-OHDA-lesioned rats. In addition, these effects were blocked by the prior i.n. infusion of the ß3-adrenergic receptor antagonist SR59230A. These findings indicate that the 6-OHDA injection into the LC induced the apoptosis signaling activation, noradrenergic neurotransmission dysfunction and behavioral impairments that were restored via ß3-adrenergic receptors activation mediated by the i.n. NA administration.