COVID-19 inpatient mortality in Brazil from 2020 to 2022: a cross-sectional overview study based on secondary data.

BACKGROUND: In Brazil, the COVID-19 pandemic found the universal and public Unified Health System (SUS) with problems accumulated over time, due, among other reasons, to low investments, and disparities in resource distribution. The preparedness and response of the healthcare system, involving the SUS and a private sector, was affected by large socioeconomic and healthcare access inequities. This work was aimed at offering an overview of COVID-19 inpatient mortality during the pandemic in Brazil, exploring factors associated with its variations and, specifically, differences across public, private (for-profit) and philanthropic (private non-profit) inpatient healthcare units, providers, and non-providers of services to the SUS. METHODS: This cross-sectional study used public secondary data. The main data source was the SIVEP-Gripe, which comprises data on severe acute respiratory illness records prospectively collected. We also employed the National Record of Health Establishments, the SUS' Hospitalization Information System and municipalities' data from IBGE. We considered adult COVID-19 hospitalizations registered in SIVEP-Gripe from February 2020 to December 2022 in inpatient healthcare units with a minimum of 100 cases in the period. Data analyses explored the occurrence of inpatient mortality, employing general linear mixed models to identify the effects of patients', health care processes', healthcare units' and municipalities' characteristics on it. RESULTS: About 70% of the COVID-19 hospitalizations in Brazil were covered by the SUS, which attended the more vulnerable population groups and had worse inpatient mortality. In general, non-SUS private and philanthropic hospitals, mostly reimbursed by healthcare insurance plans accessible for more privileged socioeconomic classes, presented the best outcomes. Southern Brazil had the best performance among the macro-regions. Black and indigenous individuals, residents of lower HDI municipalities, and those hospitalized out of their residence city presented higher odds of inpatient mortality. Moreover, adjusted inpatient mortality rates were higher in the pandemic peak moments and were significantly reduced after COVID-19 vaccination reaching a reasonable coverage, from July 2021. CONCLUSIONS: COVID-19 exposed socioeconomic and healthcare inequalities and the importance and weaknesses of SUS in Brazil. This work indicates the need to revert the disinvestment in the universal public system, a fundamental policy for reduction of inequities in the country.

Cross-cultural adaptation and validation of the Hospital Survey on Patient Safety Culture 2.0 - Brazilian version.

BACKGROUND: Patient safety culture concerns the values, beliefs and standards shared by an organisation's health staff and other personnel which influence their care provision actions and conduct. Several countries have made a priority of strengthening patient safety culture to improve the quality and safety of health care. In this direction, measuring the patient safety culture through validated instruments is a strategy applied worldwide. The purpose of this study was to adapt transculturally and validate the HSOPSC 2.0 to Brazilian Portuguese and the hospital context in Brazil. METHODS: Of the various validated scales for measuring safety culture, the instrument most used internationally is the Hospital Survey on Patient Safety Culture (HSOPSC) developed by the United States Agency for Healthcare Research and Quality in 2004 and revised in 2019, when version 2.0 was released. Adaptation was conducted on a universalist approach and the adapted instrument was then applied to a sample of 2,702 respondents (56% response rate) comprising staff of a large general hospital in the city of São Paulo. Construct validity was investigated by Exploratory Structural Equation Modelling-within-Confirmatory Factor Analysis (ESEM-within-CFA) and reliability was measured in each dimension by means of Cronbach alpha coefficients. RESULTS: ESEM fit indexes showed good data fit with the proposed model: χ2 = 634.425 df = 221 χ2/df ratio = 2.9 p-value < 0.0000; RMSEA = 0.045 (90% C.I. = 0.041-0.050) and probability RMSEA < = .05 = 0.963; CFI = 0.986; TLI = 0.968. However, ten items had loads lower than 0.4. Cronbach alpha values were 0.6 or more for all dimensions, except Handoffs and information exchange ([Formula: see text]= 0.50) and Staffing and work pace ([Formula: see text] = 0.41). CONCLUSION: The psychometric properties of the Brazilian version were found to be satisfactory, demonstrating good internal consistency and construct validity as expressed by estimates of reliability and indexes of model fit. However, given factor loadings smaller than 0.4 observed in ten items and considering that the scale translated and adapted to Portuguese was tested on a single sample during the Covid-19 pandemic, the authors recognize the need for it to be tested on other samples in Brazil to investigate its validity.

In Vitro Anthelminthic Activity and Ultrastructural Analysis of Barbatic Acid against Schistosomulae and Juvenile Worms of Schistosoma mansoni.

Schistosomiasis affects about 260 million people worldwide and the search for new schistosomicidal compounds is urgent. In this study we evaluated the in vitro effect of barbatic acid against schistosomulae and young worms of Schistosoma mansoni. The barbatic acid was evaluated through the bioassay of motility and mortality, cellular viability and ultrastructural analysis of juvenile stages through Scanning Electron Microscopy. Barbatic acid showed a schistosomicidal effect against schistosomulae and young worms of S. mansoni after 3 h of exposure. At the end of 24 h, barbatic acid showed 100 %, 89.5 %, 52 % and 28.5 % of lethality for schistosomulae at the concentrations of 200, 100, 50 and 25 µM, respectively. For young worms, barbatic acid showed 100 % and 31.7 % of lethality at the concentrations of 200 and 100 µM, respectively. Motility changes were observed at all sublethal concentrations. There was a significant reduction in the viability of young worms after exposure to barbatic acid at 50, 100 and 200 µM. Extensive damage to the schistosomulae and young worm's tegument, was observed from 50 µM. This report provides data showing the schistosomicidal effect of barbatic acid on schistosomulae and young worms of S. mansoni, causing death, motility changes and ultrastructural damage to worms.

Skeletal-dental features in 33 bull terrier dogs.

BACKGROUND: The Bull terrier breed has been reported in the veterinary literature to suffer frequent dental and skeletal malocclusions. In this retrospective case series, we report skeletal-dental anomalies in a group of 33 Bull terriers presented for a dental consultation. RESULTS: Out of 33 dogs examined, 24 cases had full mouth radiography or Cone-beam computed tomography performed. Eruption and development abnormalities observed were as follows: hypodontia in 54.1% (13/24), eruption changes in 29.2% (7/24), and tooth shape abnormalities in 33.3% (8/24). All dogs presented with some type of dental or skeletal malocclusion: neutroclusion was the most common (66.7% of the animals), followed by mandibular mesioclusion (18.8%), maxillo-mandibular asymmetry (9.4%), and mandibular distoclusion (6.3%). Dental abnormalities noted included rotation of mandibular and maxillary premolar teeth, distal displacement of the incisor teeth, lingual displacement of the mandibular canine teeth, and absence of mandibular premolar and molar teeth. Lingual displacement of mandibular canine teeth was associated with malocclusion causing trauma (odds ratio 7.1, 95% confidence interval [1.4 to 36.1], p = 0.024). CONCLUSIONS: Malocclusions and tooth shape abnormalities were found to be the most frequent finding in this group of Bull terriers. Although these findings cannot be generalized to the global population further studies are needed to observe the true expression of these anomalies in the general breed population.

Patterns of hospital utilization in the Unified Health System in six Brazilian capitals: comparison between the year before and the first six first months of the COVID-19 pandemic.

OBJECTIVE: To analyze the temporal evolution of the pattern of hospital use in the context of the COVID-19 pandemic in Brazil. METHODS: This retrospective observational study compared hospital use and mortality in the Brazilian Unified Health System (SUS) in the first six months of the COVID-19 pandemic with the year before the onset of the pandemic in six Brazilian capitals (São Paulo, Rio de Janeiro, Manaus, Fortaleza, Recife, and Brasilia). It was based on secondary administrative data from the SUS Hospital Information System (SIH), focusing on the number of hospitalizations per fortnight, age, and gender of patients, hospital length of stay, and the proportions of surgical, elective, with the use of ICU, and resulting in death hospitalizations. It also compared the number of hospitalizations and mortality related to frequent diagnostic groups. RESULTS: A significant drop was identified in the number of hospitalizations as of March 2020, with the first peak of COVID-19 hospitalizations in five capitals recorded in May 2020. In the six capitals, we observed significant reductions in the mean number of hospitalizations per fortnight from the beginning of the pandemic. We also identified an increase in the mean age of the patients and the proportion of male patients. The proportion of surgical and elective hospitalizations dropped significantly in all capitals, while the proportion of hospitalizations with ICU use increased significantly. Significant increases in-hospital mortality were also recorded in the six capitals with the pandemic, including or excluding COVID-19 hospitalizations from the comparison. CONCLUSION: The pandemic caused changes in the pattern of use and hospital indicators in the first six months in the cities considered, evidencing the need for attention to diseases with a hospital production altered by the COVID-19 course and health system performance problems in the face of challenges.

Cladonia verticillaris (lichen) indicates negative impacts derived from the combustion of biodiesel blends: an alert for the environmental management for biofuels use.

The use of biodiesel blends with petroleum diesel in vehicular engines demands the evaluation of the possible impacts and effects of the gases emitted from their combustion on the environment. Among studies on these questions, biomonitoring using lichens is a viable alternative, given their interactions with the elements dispersed in the atmosphere, as well as its sensitivity and capacity to retain contaminants. In this study, we analyzed the effects of gas emissions from the combustion of biodiesel mixture with petroleum diesel on Cladonia verticillaris thalli. Samples of the lichen (10 g) were exposed to the gases emitted by the exhaust of the generator engine during the combustion process of biodiesel mixtures to petroleum diesel (7% (B7), 10% (B10), 40% (B40), 50% (B50), and 70% (B70)). At 90 days after exposure, samples were analyzed for n-alkane profiles, thallus morphology, photosynthetic pigment contents, and secondary lichen metabolites (protocetraric and fumarprotocetraric acids). Sets B7 and B10 showed better resistance of the lichen to pollutants. Set B40 showed a high stress evidenced by the chain elongation of n-alkanes structure and high chlorophyll production, presenting high morphological damages when compared to the control sets, B7 and B10. The results showed significant reductions of n-alkanes profiles for mixtures with high concentrations of biodiesel (B50 and B70), as well as decreases in the chlorophyll content. These groups showed an increase in the synthesis of secondary metabolites, corroborating the hypothesis that high concentrations of biodiesel in the mixture with petroleum diesel have greater impacts on the lichen. Schematic model for demonstration of using the lichen Cladonia verticillaris as biomonitor of effects from gas emissions from the combustion of biodiesel blends with petroleum diesel by a stationary engine.

Enhanced Light-Driven Hydrogen Production by Self-Photosensitized Biohybrid Systems.

Storage of solar energy as hydrogen provides a platform towards decarbonizing our economy. One emerging strategy for the production of solar fuels is to use photocatalytic biohybrid systems that combine the high catalytic activity of non-photosynthetic microorganisms with the high light-harvesting efficiency of metal semiconductor nanoparticles. However, few such systems have been tested for H2 production. We investigated light-driven H2 production by three novel organisms, Desulfovibrio desulfuricans, Citrobacter freundii, and Shewanella oneidensis, self-photosensitized with cadmium sulfide nanoparticles, and compared their performance to Escherichia coli. All biohybrid systems produced H2 from light, with D. desulfuricans-CdS demonstrating the best activity overall and outperforming the other microbial systems even in the absence of a mediator. With this system, H2 was continuously produced for more than 10 days with a specific rate of 36 µmol gdcw-1 h-1 . High apparent quantum yields of 23 % and 4 % were obtained, with and without methyl viologen, respectively, exceeding values previously reported.

Citrus carotenoid isomerase gene characterization by complementation of the "Micro-Tom" tangerine mutant.

KEY MESSAGE: Complementation of the "Micro-Tom" tomato tangerine mutant with a Citrus CRTISO allele restores the wild-type fruit carotenoid profile, indicating that the Citrus allele encodes an authentic functional carotenoid isomerase. Citrus fruits are rich in carotenoids; the genus offers a large diversity in composition, yet to be fully explored to improve fruit nutritional quality. As perennial tree species, Citrus lack the resources for functional genetic studies, requiring the use of model plant systems. Here, we used the "Micro-Tom" (MT) tomato carrying the tangerine mutation (t), deficient for the carotenoid isomerase (CRTISO) gene, to functionally characterize the homologous C. sinensis genes. We identified four putative loci in the C. sinensis genome, named CsCRTISO, CsCRTISO-Like 1, CsCRTISO-Like 2, and CsCRTISO-Like 2B, with the latter as a presumed duplication of CRTISO-Like 2. In general, all the Citrus paralogs showed less expression specialization than the tomato ones, with CsCRTISO being the most expressed gene in all tissues analyzed. MT-t plants were successfully complemented with the CsCRTISO, and fruits showed a carotenoid profile similar to the control, indicating that the Citrus allele indeed encodes an authentic functional carotenoid isomerase and that the signal peptide is functional in tomato. MT was silenced using an inverted repeat of a fragment from the Citrus CRTISO resulting in a stronger phenotype than MT-t. MT-t and MT silenced for CRTISO presented an overall decrease in transcript accumulation of all genes from the biosynthesis pathway. The expression of the Citrus CRTISO gene is able to restore the biosynthesis of carotenoids with the appropriate regulation in MT-t. The decrease in transcript accumulation in MT-t and MT-CRTISO-suppressed lines reinforces previous suggestions that transcriptional regulation of the carotenoid biosynthesis involves regulatory loops by intermediate products.

Performance and Profitability of Fungicides for Managing Soybean White Mold: A 10-Year Summary of Cooperative Trials.

White mold, caused by Sclerotinia sclerotiorum, is a yield-limiting disease of soybean in Brazil. Uniform fungicide trials have been conducted annually since 2009. Data from 74 cooperative field trials conducted over a 10-year period were assembled. We selected five fungicides applied two times around flowering: dimoxystrobin plus boscalid (DIMO+BOSC), carbendazim plus procymidone (CARB+PROC), fluazinam (FLUZ), fluopyram (FLUO), and procymidone (PROC). For comparison, thiophanate-methyl (TMET) applied four times was also included as a low-cost treatment. Network models were fitted to the log of white mold incidence (percentages) and log of sclerotia mass data (grams/hectare) and to the nontransformed yield data (kilograms/hectare) for each treatment, including the untreated check. Back-transformation of the meta-analytic estimates indicated that the lowest and highest mean (95% confidence interval [CI]) percent reductions in incidence and sclerotia mass were 54.2 (49.3 to 58.7) and 51.6% (43.7 to 58.3) for TMET and 83.8 (79.1 to 87.5) and 87% (81.9 to 91.6) for CARB+PROC, respectively. The overall mean (95% CI) yield responses ranged from 323 kg/ha (247.4 to 400.3) for TMET to 626 kg/ha (521.7 to 731.7) for DIMO+BOSC, but the variance was significantly reduced by a binary variable (30% threshold) describing disease incidence in the untreated check. On average, an increment of 352 kg/ha was estimated for trials where the incidence was >30% compared with the low-disease scenario. Hence, the probability of breaking even on fungicide costs for the high-disease scenario was >65% for the more effective, but more expensive fungicide (FLUZ) than TMET. For the low-disease scenario, profitability was less likely and depended more on variations in fungicide cost and soybean price.

Usnic Acid Potassium Salt: Evaluation of the Acute Toxicity and Antinociceptive Effect in Murine Model.

To obtain usnic acid potassium salt (PS-UA), the usnic acid (UA) was extracted and purified from the lichen Cladonia substellata, and modified to produce PS-UA. The structure was determined by 1H-NMR, IR and elemental analysis, ratified through computational models, as well as identification the site of K+ insertion in the molecule. Antinociceptive activity was detected through contortions in mice induced by acetic acid and formalin (phases I and II) after treatments with 10 and 20 mg/kg of PS-UA, indicating interference in both non-inflammatory and inflammatory pain. After oral administration at doses of 500, 1000 and 2000 mg/kg, no deaths of mice with treatments below 2000 mg/kg were observed. Except for body weight gain, food and water consumption decreased with treatments of 1000 and 2000 mg/kg, and the number of segmented leukocytes was higher for both treatments. Regarding serum levels, cholesterol and triglycerides decreased, however, there was an increase in hepatic transaminases with both treatments. Liver and kidney histological changes were detected in treatments of 2000 mg/kg, while the spleen was preserved. The PS-UA demonstrated antinociceptive activity while the acute toxicity at the concentration of 2000 mg/kg was the only dose that presented morphological changes in the liver and kidney.

Challenges to the improvement of obstetric care in maternity hospitals of a large Brazilian city: an exploratory qualitative approach on contextual issues.

BACKGROUND: Maternal morbidity and mortality are still serious public health concerns in Brazil, and access to quality obstetric care is one critical point of this problem. Despite efforts, obstetric care quality problems and sub-optimal/poor outcomes persist. The study aimed to identify contextual elements that would potentially affect the implementation of an obstetric care quality improvement intervention. METHODS: A qualitative study was conducted in three public maternity hospitals of a large Brazilian city, with high annual volume of births and buy-in from high-level managers. Individual interviews with doctors and nurses were conducted from July to October 2015. Semi-structured interviews sought to explore teamwork, coordination and communication, and leadership, being open to capture other contextual elements that could emerge. Interviews were recorded and transcribed, and the categories of analysis were identified and updated based on the constant comparative method. RESULTS: Twenty-seven interviews were carried out. Extra-organizational context concerning the dependence of the maternity hospitals on primary care units, responsible for antenatal care, and on other healthcare organizations' services emerged from interviews, but the main findings of the study centered on intra-organizational context with potential to affect healthcare quality and actions for its improvement, including material resources, work organization design, teamwork, coordination and communication, professional responsibility vis-à-vis the patient, and leadership. A major issue was the divergence of physicians' and nurses' perspectives on care quality, which in turn negatively affected their capacity to work together. CONCLUSION: Overall, the findings suggest that care on the maternity hospitals was fragmented and lacked continuity, putting at risk the quality. Redesigning work organization, promoting conditions for multi-professional teamwork, better communication and coordination, improving more systemic accountability/lines of authority, and investing in team members' technical competence, and fitness of organizational structures and processes are all imbricated actions that may contribute to obstetric care quality improvement.

The application of Iberoamerican study of adverse events (IBEAS) methodology in Brazilian hospitals.

OBJECTIVE: To assess the prevalence of adverse events (AE) and to investigate its association with factors related to the patient and to hospital admission. DESIGN: Cross-sectional study. SETTING: Four general hospitals located in the southeastern region of Brazil. PARTICIPANTS: All patients admitted to the participating hospitals at the time of the study were surveyed. INTERVENTION: The methodology was based on the Iberoamerican study of adverse events, a two-stage medical record review. MAIN OUTCOME MEASURE: Medical records were screened for AE only in the day (24-h) immediately before the review process, independently of the admission date. RESULTS: A total of 695 admissions were examined. Prevalence was 12.8%. Almost 43% of AE were preventable. More than 60% of patients with an event prolonged hospital stay. In final regression model, urgent admission (OR: 2.68; Confidence Interval (CI) 95%: 1.53-4.69), submission to a procedure (odds ratio (OR): 2.41; CI 95%: 1.33-4.39), presence of central venous catheter (OR: 2.25; CI 95%: 1.14-4.41) and immunosuppressive therapy (OR: 3.41; CI 95%: 1.57-7.40) were statistically associated with AE. CONCLUSIONS: Our results indicate that around 1.3 AE happen in each 10 hospital admissions in Brazil. As patient safety continues to be a Public Health concern worldwide and mainly in developing countries, this would indicate the potential use of prevalence measures for monitoring patient safety in Brazilian context.

Meta-Analytic Modeling of the Decline in Performance of Fungicides for Managing Soybean Rust after a Decade of Use in Brazil.

An apparent decline of fungicide performance for the control of soybean rust in Brazil has been reported but the rate at which it has occurred has not been formally quantified. Control efficacy and yield response to three fungicides applied as single active ingredients (a.i.)-azoxystrobin (AZOX), cyproconazole (CYPR), and tebuconazole (TEBU)-and four applied as mixtures-AZOX+CYPR, picoxystrobin + CYPR, pyraclostrobin + epoxiconazole, and trifloxystrobin + prothioconazole (TRIF+PROT)-were summarized using network meta-analytic models fitted to mean severity and yield data from 250 trials (10-year period). The effect of year was tested on both variables in a meta-regression model. Overall control efficacy ranged from 56 to 84%; the three single-a.i. fungicides performed the poorest (56 to 62%). Yield increase for single-a.i. fungicides was as low as 30% but ranged from 47 to 65% for the premixes. Significant declines in both variables were detected for all fungicides except TRIF+PROT. For TEBU, control efficacy (yield response) declined the most: 78% (18%) to 54% (8%) from 2004-05 to 2013-14. The recent surge of resistant populations of Phakopsora pachyrhizi to both demethylation inhibitor and quinone outside inhibitor fungicides is likely the driving force behind a significant decline after 4 years of fungicide use.

Barbatic Acid Offers a New Possibility for Control of Biomphalaria Glabrata and Schistosomiasis.

This study evaluated the biological activity of an ether extract and barbatic acid (BAR) from Cladia aggregata on embryos and adult mollusks of Biomphalaria glabrata, cercariae of Schistosoma mansoni and the microcrustacean Artemia salina. The ether extract and BAR were obtained by successive extractions with diethyl ether. The obtained extracts were analyzed using thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), proton nuclear magnetic resonance (¹H-NMR) and infrared (IR) spectroscopy. The results demonstrated that the ether extract exerted embryotoxic effects at 50 and 100 µg/mL and molluscicidal effects at 20 and 25 µg/mL. BAR exhibited no embryotoxicity, and its molluscicidal concentration was equal to that of the ether extract. However, after 60 min of exposure, 1 µg/mL BAR presented cercaricidal activity against the parasite S. mansoni at the second larval stage. Neither substance induced toxicity against A. salina. These results indicate the potential molluscicidal activities of the ether extract and BAR against B. glabrata and S. mansoni cercariae. In addition to these effects, there was a lack of toxicity against the aquatic environment and no damage to the biota, indicating the potential of these products for large-scale control and/or eradication of schistosomiasis.

Bioenergetic adaptations of the human liver in the ALPPS procedure - how liver regeneration correlates with mitochondrial energy status.

BACKGROUND: The Associating Liver Partition and Portal Ligation for Staged Hepatectomy (ALPPS) depends on a significant inter-stages kinetic growth rate (KGR). Liver regeneration is highly energy-dependent. The metabolic adaptations in ALPPS are unknown. AIMS: i) Assess bioenergetics in both stages of ALPPS (T1 and T2) and compare them with control patients undergoing minor (miHp) and major hepatectomy (MaHp), respectively; ii) Correlate findings in ALPPS with volumetric data; iii) Investigate expression of genes involved in liver regeneration and energy metabolism. METHODS: Five patients undergoing ALPPS, five controls undergoing miHp and five undergoing MaHp. Assessment of remnant liver bioenergetics in T1, T2 and controls. Analysis of gene expression and protein content in ALPPS. RESULTS: Mitochondrial function was worsened in T1 versus miHp; and in T2 versus MaHp (p < 0.05); but improved from T1 to T2 (p < 0.05). Liver bioenergetics in T1 strongly correlated with KGR (p < 0.01). An increased expression of genes associated with liver regeneration (STAT3, ALR) and energy metabolism (PGC-1α, COX, Nampt) was found in T2 (p < 0.05). CONCLUSION: Metabolic capacity in ALPPS is worse than in controls, improves between stages and correlates with volumetric growth. Bioenergetic adaptations in ALPPS could serve as surrogate markers of liver reserve and as target for energetic conditioning.

Mitochondrial bioenergetics and posthepatectomy liver dysfunction.

BACKGROUND: Liver regeneration requires an enormous energy supply. Experimental evidence suggests that mitochondrial function is of paramount importance for liver regeneration. However, this has not been investigated in the clinical setting. We aimed to: (i) evaluate changes in mitochondrial function during hepatectomy, especially after hepatic pedicle clamping; and (ii) correlate these changes with postoperative hepatocellular function and clinical outcome. MATERIALS AND METHODS: Prospective study of thirty patients undergoing hepatectomy. Measurement of mitochondrial membrane potential, respiration and adenosine triphosphate content in intra-operative liver biopsies performed in nonresected parenchyma. Correlation of findings with duration of hepatic pedicle clamping, postoperative markers of hepatocellular necrosis and function (aminotransferases, arterial lactate, international normalized ratio, bilirubin), and morbidity. RESULTS: Longer hepatic pedicle clamping was associated with worse mitochondrial depolarization (r = -0·519; P = 0·011) and longer lag phase (r = 0·568; P = 0·006). Higher postoperative peak aminotransferases, international normalized ratio and bilirubin correlated with worse mitochondrial function (P < 0·05). After major hepatectomy, mitochondrial respiration correlated with postoperative arterial lactate clearance (r = 0·756; P = 0·049). Mitochondrial bioenergetic parameters were significantly decreased in patients with liver-specific morbidity and postoperative liver failure (P < 0·05). On multivariate analysis, decrease in mitochondrial potential was an independent risk factor for liver-specific morbidity (OR = 13·7; P = 0·043). Worse lag phase was highly predictive of posthepatectomy liver failure (area under the curve: 0·933; P = 0·008). CONCLUSIONS: There is a relationship between mitochondrial function, duration of hepatic pedicle clamping and clinical outcome after hepatectomy. Mitochondrial bioenergetics can potentially translate into clinical practice, assisting in earlier diagnosis of postoperative liver dysfunction, and as a target for future pharmacological therapies.

Electron transfer pathways of formate-driven H2 production in Desulfovibrio.

The potential of sulfate-reducing bacteria (SRB) as biocatalysts for H2 production from formate was recently demonstrated, but the electron transfer pathways involved were not described. In the present work, we analyzed the H2 production capacity of five Desulfovibrio strains: Desulfovibrio vulgaris, Desulfovibrio desulfuricans, Desulfovibrio alaskensis, Desulfovibrio fructosivorans, and Desulfovibrio gigas. D. vulgaris showed the highest H2 productivity (865 mL Lmedium (-1)), and D. gigas the lowest one (374 mL Lmedium (-1) of H2). The electron transfer pathways involved in formate-driven H2 production by these two organisms were further investigated through the study of deletion mutants of hydrogenases (Hases) and formate dehydrogenases (Fdhs). In D. vulgaris, the periplasmic FdhAB is the key enzyme for formate oxidation and two pathways are apparently involved in the production of H2 from formate: a direct one only involving periplasmic enzymes and a second one that involves transmembrane electron transfer and may allow energy conservation. In the presence of selenium, the Hys [NiFeSe] Hase is the main periplasmic enzyme responsible for H2 production, and the cytoplasmic Coo Hase is apparently involved in the ability of D. vulgaris to grow by converting formate to H2, in sparging conditions. Contrary to D. vulgaris, H2 production in D. gigas occurs exclusively by the direct periplasmic route and does not involve the single cytoplasmic Hase, Ech. This is the first report of the metabolic pathways involved in formate metabolism in the absence of sulfate in SRB, revealing that the electron transfer pathways are species-specific.

Desulfovibrio vulgaris Growth Coupled to Formate-Driven H2 Production.

Formate is recognized as a superior substrate for biological H2 production by several bacteria. However, the growth of a single organism coupled to this energetic pathway has not been shown in mesophilic conditions. In the present study, a bioreactor with gas sparging was used, where we observed for the first time that H2 production from formate can be coupled with growth of the model sulfate-reducing bacterium Desulfovibrio vulgaris in the absence of sulfate or a syntrophic partner. In these conditions, D. vulgaris had a maximum growth rate of 0.078 h(-1) and a doubling time of 9 h, and the ΔG of the reaction ranged between -21 and -18 kJ mol(-1). This is the first report of a single mesophilic organism that can grow while catalyzing the oxidation of formate to H2 and bicarbonate. Furthermore, high volumetric and specific H2 production rates (125 mL L(-1) h(-1) and 2500 mL gdcw(-1) h(-1)) were achieved in a new bioreactor designed and optimized for H2 production. This high H2 production demonstrates that the nonconventional H2-producing organism D. vulgaris is a good biocatalyst for converting formate to H2.

Ultrastructural analysis of Leishmania infantum chagasi promastigotes forms treated in vitro with usnic acid.

Leishmaniasis is considered by the World Health Organization as one of the infectious parasitic diseases endemic of great relevance and a global public health problem. Pentavalent antimonials used for treatment of this disease are limited and new phytochemicals emerge as an alternative to existing treatments, due to the low toxicity and cost reduction. Usnic acid is uniquely found in lichens and is especially abundant in genera such as Alectoria, Cladonia, Evernia, Lecanora, Ramalina, and Usnea. Usnic acid has been shown to exhibit antiviral, antiprotozoal, antiproliferative, anti-inflammatory, and analgesic activity. The aim of this study was to evaluate the antileishmanial activity of usnic acid on Leishmania infantum chagasi promastigotes and the occurrence of drug-induced ultrastructural damage in the parasite. Usnic acid was effective against the promastigote forms (IC50=18.30±2.00 µg/mL). Structural and ultrastructural aspects of parasite were analyzed. Morphological alterations were observed as blebs in cell membrane and shapes given off, increasing the number of cytoplasmic vacuoles, and cellular and mitochondrial swelling, with loss of cell polarity. We concluded that the usnic acid presented antileishmanial activity against promastigote forms of Leishmania infantum chagasi and structural and ultrastructural analysis reinforces its cytotoxicity. Further, in vitro studies are warranted to further evaluate this potential.

Expectorant and antioxidant activities of purified fumarprotocetraric acid from Cladonia verticillaris lichen in mice.

UNLABELLED: The lichen Cladonia verticillaris produces bioactive secondary metabolites, such as fumarprotocetraric (FUM) and protocetraric acids. Species of the genus Cladonia demonstrate anti-tumor, anti-inflammatory and antipyretic activities and have been used in folk medicine to treat respiratory diseases (throat irritation, cough, asthma and tuberculosis). The aim of the present study was to evaluate the expectorant and mucolytic activities of fumarprotocetraric acid in albino Swiss mice. FUM was extracted and purified from an acetone extract of C. verticillaris. The phenol red quantification method was used on the bronchoalveolar lavage fluid following the administration of FUM (25, 50 or 100 mg/kg orally or intraduodenally and 12.5, 25 or 50 mg/kg, intraperitoneally) for the evaluation of expectorant activity. Control groups received either saline solution (7.5 mL/kg) or ambroxol (1 mg/kg) through the same administration routes. Antioxidant activity was evaluated using the thiobarbituric acid reactive species assay in mouse lung tissue treated with the FUM at 25, 50 or 100 mg/kg orally, followed by a lipopolysaccharide solution at 1 mg/kg intrapleurally. The same protocol was used for the control groups using either saline solution (7.5 mL/kg, orally) or N-acetylcysteine (20 mg/kg, orally). RESULTS: Orally administered FUM at doses of 25 and 50 mg/kg promoted significantly greater dose-dependent phenol red activity in the bronchoalveolar lavage and expectorant activity in comparison to the controls (p < 0.05). Lipid peroxidation (malondialdehyde equivalent) was reduced by 50% in the lung tissue. CONCLUSION: The results confirm the expectorant and antioxidant properties of fumarprotocetraric acid produced by the lichen C. verticillaris.