Recurrence of fusocellular subtype GIST with SDHB mutation: A case of SDHB-loss and therapeutic challenges.

Gastrointestinal stromal tumors (GISTs) are sarcomas affecting the stomach and small intestine, with a rare subtype characterized by succinate dehydrogenase B (SDHB)-loss posing significant diagnostic and therapeutic challenges. A 62-year-old man with weight loss and abdominal pain was diagnosed with a gastric GIST showing SDHB-loss. Initial treatment with Imatinib reduced the tumor size, but surgery revealed no residual tumor. Despite adjuvant Imatinib, recurrence occurred, necessitating further surgical intervention. While GISTs typically benefit from surgery and tyrosine kinase inhibitors (TKIs), those with SDHB-loss are resistant to TKIs, requiring a different management approach. This case emphasizes the importance of surgical intervention for SDHB-deficient GISTs and the need for ongoing research into effective treatments for this subtype.

Serological evidence of exposition to Toxoplasma gondii in Saimiri spp. kept in a research institution as biomodels in Rio de Janeiro.

Anti-Toxoplasma gondii antibodies were investigated in 125 Saimiri spp. kept at a research institute. A total of 12% of primates tested positive, all of which were Saimiri sciureus. These results highlight the need to minimize the possibility of this protozoan's circulation, which can lead to fulminant infection in these animals.

Efficiency and safety of single anastomosis sleeve ileal (SASI) bypass in the treatment of obesity and associated comorbidities: a systematic review and meta-analysis.

INTRODUCTION: The Single Anastomosis Sleeve Ileal (SASI) bypass is a new bariatric surgery corresponding to an adaptation of the Santoro approach, consisting of a sleeve gastrectomy (SG) followed by loop gastroileostomy. Therefore, we aimed to systematically assess all the current literature on SASI bypass in terms of safety, weight loss, improvement in associated comorbidities, and complications. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) recommendations, we conducted a systematic review and meta-analysis by searching three databases (PubMed, Scopus, and Web of Science). We performed a meta-analysis of risk ratios and mean differences to compare surgical approaches for excessive weight loss, improvement/remission in type 2 diabetes mellitus (T2DM), hypertension (HT), dyslipidemia (DL), obstructive sleep apnea (OSA), and complications. Heterogeneity was assessed using the I2 statistic. RESULTS: Eighteen studies were included in the qualitative analysis and four in the quantitative analysis, comparing SASI bypass with SG and One-Anastomosis Gastric Bypass (OAGB). A comparison between Roux-en-Y Gastric Bypass (RYGB) and SASI bypass could not be performed. Compared to SG, the SASI bypass was associated with improved weight loss (MD = 11.32; 95% confidence interval (95%CI) [7.89;14.76]; p < 0.0001), and improvement or remission in T2DM (RR = 1.35; 95%CI [1.07;1.69]; p = 0.011), DL (RR = 1.41; 95%CI [1.00;1.99]; p = 0.048) and OSA (RR = 1.50; 95%CI [1.01;2.22]; p = 0.042). No statistically significant differences in any of the assessed outcomes were observed when compared with OAGB. When compared to both SG and OAGB, the complication rate of SASI was similar. CONCLUSION: Although studies with longer follow-up periods are needed, this systematic review and meta-analysis showed that SASI bypass has a significant effect on weight loss and metabolic variables. Variations in outcomes between studies reinforce the need for standardization.

Nano copper in the diet of laying quails: productive performance, metabolism, and tissue concentration.

The study evaluated the use of nano copper in semi-purified diets for laying quails and its effect on performance, metabolic state, and bioavailability. A total of 160 (180-days-old) quails were distributed in a completely randomized design, in a 3x3+1 factorial. The copper sources used were copper sulfate, copper oxide, and nano copper oxide, at levels of 200, 400, and 800 ppm each, totaling nine treatments plus a negative control (with no copper inclusion). The following variables were determined: weight gain, feed intake, egg production, egg weight, hemoglobin, hematocrit, Cu in the tissues and Cu bioavailability. Data were subjected to analysis of variance at 5% probability. The effect of sources and levels, as well as the interaction between the factors were evaluated. When interaction was observed, the effect of sources was evaluated separately by the Tukey's test and the effect of levels by regression, both at 5% probability. Copper nano oxide can be used at up to 800 ppm in the diet of laying quails without altering the productive performance, and with higher bioavailability than conventional copper oxide. Hemoglobin increases with the inclusion of 200 and 400 ppm of nano copper oxide and the hematocrit with 400 ppm.

High- and low-carb diet and fasting state modify alternative maximal accumulated oxygen deficit.

This investigation aimed to assess if alternative method to estimate the maximal accumulated oxygen deficit (MAODalt) can detect changes in energy system contribution in different substrate availabilities. Following a graded exercise test to determine maximal oxygen uptake intensity (iVO2max), 26 recreational runners performed a time to exhaustion effort (TTE) as baseline at 110% iVO2max. The same TTE was performed in fasting state, then, a muscle glycogen depletion protocol was executed. Subsequently, participants received low-carbohydrate diet and beverage containing high (H-CHO, 10.8±2.1g·kg-1), moderate (M-CHO, 5.6±1.1g·kg-1), or zero (Z-CHO, 0.24±0.05g·kg-1) carbohydrate. Another TTE was performed 24h later. Each energy system contribution was assessed. Generalized linear mixed models were used for statistical analysis (p<0.05). H-CHO increased relative anaerobic capacity (slope effect [baseline-intervention]x[H-CHO-M-CHO]) due to the relative lactic contribution maintenance (slope effect [baseline-intervention]x[H-CHO-Z-CHO] or [H-CHO-M-CHO]) and increase in relative alactic contribution (6.3±3.5kJ·min-1). The aerobic contribution was lower (-8.7±4.0kJ·min-1), decreasing performance (-34±16s) for H-CHO. M-CHO and Z-CHO maintained anaerobic capacity due to increase in alactic contribution (slope effect [fasting-intervention]x[M-CHO-H-CHO]; and Z-CHO was 7.3±3.4kJ·min-1 higher than baseline). Fasting increased relative alactic (2.9±1.7kJ·min-1) but decreased aerobic contribution (-3.3±2.3kJ·min-1), impairing performance (-17±12s). In conclusion, MAODalt can detect changes in energy system supply in different nutritional states. Therefore, participant's nutritional state must be considered prior to conducting the test.

Unveiling foliar secreting sites and secretion composition in the legume tree Swartzia flaemingii Raddi.

Secretory structures in plants play a crucial role in producing bioactive compounds. Despite the potential of the Swartzia genus, comprehensive studies in this context are still scarce. Swartzia is a legume tree (Fabaceae) that occurs in the Brazilian Atlantic Forest, a biodiversity hotspot, and includes species such as Swartzia flaemingii. Therefore, we aim to achieve: (1) identify and characterize the key secretory sites responsible for saponin production in S. flaemingii leaflets; (2) confirm the presence of saponins in S. flaemingii leaves by comparing them with known chemical profiles of other Swartzia species; (3) assess the potential hemolytic and cytotoxic effects of crude leaf extracts. Our investigation unveils the presence of phenolic idioblasts, mucilage cells, and articulate laticifers, which play pivotal roles in defense and adaptation. Notably, we report the first-ever ultrastructural details of laticifers in a legume species. Additionally, oleanane-type saponins were identified in the leaves, giving insights into the chemotaxonomic profile of Swartzia. The crude extracts show low cytotoxicity levels, showcasing as a promising alternative source of saponins. This investigation reinforces the importance of conserving plants in threatened regions like the Atlantic Forest, a global biodiversity hotspot facing substantial anthropogenic pressures.

Caregivers' concerns through health professionals' eyes.

OBJECTIVES: Advancements in medicine and science have enabled more and more people to live longer with a chronic medical condition, namely cancer. Nevertheless, the palliative care (PC) approach continues to be introduced and incorporated later in the lives of patients and families dealing with such conditions. Thus, the need for individuals to care for this population in our society is increasing, giving rise to the so-called "informal caregivers." The present study intends to examine the main obstacles faced by informal caregivers taking care of a cancer patient receiving PC based on what health professionals working in these settings perceive and write down. To achieve this goal, the written files of 2 Portuguese palliative care institutions were analyzed. METHODS: An inductive thematic analysis was conducted, focusing on the contact between health professionals and family caregivers and based on the notes taken by health professionals. RESULTS: Three main overarching themes were identified: (1) burden, (2) intra-family impact of the illness, and (3) network vulnerabilities. Included in this are the emphasis on the role of the family and social support, the high levels of psychological morbidity and caregiver burden present over this period, and a great need for information about the illness. SIGNIFICANCE OF RESULTS: This study provided a broader awareness regarding the daily struggle experienced by family caregivers, particularly those who juggle between "roles." It is vital to understand the scope of the obstacles experienced by caregivers during the terminal phase of their loved one's illness, given how important it is to address the family's needs. Future studies and practitioners should consider these observations and topics when considering new approaches for this population, as they ought to be quite focused and short in time in order to meet people's needs.

Insights into the role of the cobalt(III)-thiosemicarbazone complex as a potential inhibitor of the Chikungunya virus nsP4.

Chikungunya virus (CHIKV) is the causative agent of chikungunya fever, a disease that can result in disability. Until now, there is no antiviral treatment against CHIKV, demonstrating that there is a need for development of new drugs. Studies have shown that thiosemicarbazones and their metal complexes possess biological activities, and their synthesis is simple, clean, versatile, and results in high yields. Here, we evaluated the mechanism of action (MOA) of a cobalt(III) thiosemicarbazone complex named [CoIII(L1)2]Cl based on its in vitro potent antiviral activity against CHIKV previously evaluated (80% of inhibition on replication). Furthermore, the complex has no toxicity in healthy cells, as confirmed by infecting BHK-21 cells with CHIKV-nanoluciferase in the presence of the compound, showing that [CoIII(L1)2]Cl inhibited CHIKV infection with the selective index of 3.26. [CoIII(L1)2]Cl presented a post-entry effect on viral replication, emphasized by the strong interaction of [CoIII(L1)2]Cl with CHIKV non-structural protein 4 (nsP4) in the microscale thermophoresis assay, suggesting a potential mode of action of this compound against CHIKV. Moreover, in silico analyses by molecular docking demonstrated potential interaction of [CoIII(L1)2]Cl with nsP4 through hydrogen bonds, hydrophobic and electrostatic interactions. The evaluation of ADME-Tox properties showed that [CoIII(L1)2]Cl presents appropriate lipophilicity, good human intestinal absorption, and has no toxicological effect as irritant, mutagenic, reproductive, and tumorigenic side effects.

Spread of Mycobacterium tuberculosis in Southern Brazilian persons deprived of liberty: a molecular epidemiology study.

To evaluate the genetic diversity and clustering rates of M. tuberculosis strains to better understand transmission among persons deprived of liberty (PDL) in Rio Grande do Sul (RS), southern Brazil. This is a cross-sectional study, including strains of M. tuberculosis isolated from PDL, stored at the Central Laboratory of RS, in the period from 2013 to 2018. The molecular characterization was performed using the MIRU-VNTR 15 loci method. A total of 598 M. tuberculosis strains were genotyped, and 37.5% were grouped into 53 clusters. Cluster sizes ranged from 2 to 34 strains. The largest cluster of the study had strains from 34 PDL, and 58.8% of the PDL of this cluster were in P01. Among the clusters formed, in 60.3%, there was at least one strain from P01. The most common strains in RS were LAM (53.2%) and Haarlem (31.1%). The LAM strain was the most likely to form clusters, and Haarlem was associated with anti-TB drug resistance. This was translational research, and the results can collaborate with the TB control programs, leading to improved strategies that allow the reduction of the TB burden in prisons.

Antimicrobial activity of cleansers on the cobalt-chromium surface of removable partial denture: a systematic review.

This study aimed to review systematically the literature about the antimicrobial action of evaluated cleansers on the Co-Cr alloy of RPD. The search was conducted in MEDLINE/PubMed, Scopus, Lilacs, Embase and Science Direct May, 2022. The review was performed based on PRISMA guidelines and recorded in Open Science Framework. Independent reviewers performed the search, selection, extraction, and analysis of the data. The risk of bias of the in vitro and clinical trials studies was analyzed by the Joanna Briggs Institute tool. A total of 187 articles were found and 9 were included. The cleansers that showed antimicrobial action were 2% and 5.25% sodium hypochlorite, 0.12% chlorhexidine and NitrAdine effervescent tablet. Polident, Corega Tabs effervescent tablets and 5 mg/mL chitosan solution showed intermediate effects. Propolis and green tea toothpaste were not effective. Three articles presented a high risk of bias and 6, low risk. The cleansers that showed the highest antimicrobial efficacy on Co-Cr alloy were 0.12% chlorhexidine digluconate and NitrAdine and can be safely used on RPD framework.

CO2 laser irradiation combined with fluoridated dentifrice improved its protective effect on caries lesion progression regardless of the acidulated phosphate fluoride gel application: An in situ study.

OBJECTIVE: This in situ study aimed to investigate the efficacy of CO2 laser at a 10.6-µm wavelength combined with 1.23% acidulated phosphate fluoride (APF) and fluoridated dentifrice with 1100 µg F/g (FD) to control enamel caries progression. MATERIALS AND METHODS: Sixteen volunteers wore palatal appliances containing eight demineralized enamel specimens for four 14-day phases under sucrose exposure. These specimens were submitted to CO2 laser irradiation and APF alone or combined with FD. Treatment groups were non-fluoridated dentifrice-NFD, NFD + CO2 laser, NFD + APF, NFD + CO2 laser + APF, FD, FD + CO2 laser, FD + APF, and FD + CO2 laser + APF. Mineral loss, calcium fluoride (CaF2), fluorapatite (FAp), and fluoride in the biofilm were analyzed by analysis of variance followed by the Student-Newman-Keuls test, p < 0.05. RESULTS: The highest mineral loss inhibition was noted when FD and CO2 laser irradiation were combined, which did not significantly differ from the FD + CO2 laser + APF group. The CaF2, FAp, and F in the biofilm were more pronounced when the FD and APF were combined. The CO2 laser irradiation promoted a slightly higher concentration of CaF2 in the enamel and F in the biofilm. CONCLUSION: Although APF promotes the high formation of CaF2 and FAp, the combined use of FD with CO2 laser overcomes the APF effect in inhibiting the progression of artificial caries-like lesions in situ. CLINICAL SIGNIFICANCE: Under the in situ design of this study, remineralization of white spot lesions was achieved through CO2 laser irradiation and daily use of fluoridated dentifrice. Future clinical trials are encouraged to substantiate this finding.

What is the value of faster acting prandial insulin? Focus on ultra rapid lispro.

Rapid-acting insulins (RAIs) have been instrumental in the management of diabetes because of their improved postprandial glucose (PPG) control compared with regular human insulin. However, their absorption rate and time action following subcutaneous administration still falls short of the normal physiological response to meal consumption, increasing the risk of early postmeal hyperglycaemia and late postmeal hypoglycaemia. Increased demand for faster acting insulins, which can quickly control PPG excursions without increasing the risk of late hypoglycaemia, led to the development of ultra-rapid-acting insulins, including ultra-rapid lispro (URLi). URLi is a novel formulation of insulin lispro with accelerated absorption driven by two excipients: treprostinil, which increases local vasodilation, and citrate, which increases local vascular permeability. Clinical pharmacology studies consistently showed an earlier onset and shorter duration of action with URLi compared with Lispro. In a head-to-head study with Faster aspart, Aspart and Lispro, URLi was absorbed faster, provided earlier insulin action, and more closely matched physiological glucose response than the other insulins tested. URLi's unique pharmacokinetic properties increase its potential for improved PPG control beyond that achieved with RAIs. Indeed, in pivotal phase 3 trials, URLi was superior to Lispro for PPG control both at 1 and 2 hours after a meal in type 1 and type 2 diabetes with multiple daily injections, and in type 1 diabetes with continuous subcutaneous insulin infusion. This was achieved without increasing the risk of hypoglycaemia. In this review, we focus on the clinical and pharmacological evidence for URLi in the treatment of diabetes and discuss the potential benefits and considerations with URLi compared with RAIs.

Variability in detection of SARS-CoV-2-specific antibody responses following mild infection: a prospective multicentre cross-sectional study, London, United Kingdom, 17 April to 17 July 2020.

IntroductionImmunoassays targeting different SARS-CoV-2-specific antibodies are employed for seroprevalence studies. The degree of variability between immunoassays targeting anti-nucleocapsid (anti-NP; the majority) vs the potentially neutralising anti-spike antibodies (including anti-receptor-binding domain; anti-RBD), particularly in mild or asymptomatic disease, remains unclear.AimsWe aimed to explore variability in anti-NP and anti-RBD antibody detectability following mild symptomatic or asymptomatic SARS-CoV-2 infection and analyse antibody response for correlation with symptomatology.MethodsA multicentre prospective cross-sectional study was undertaken (April-July 2020). Paired serum samples were tested for anti-NP and anti-RBD IgG antibodies and reactivity expressed as binding ratios (BR). Multivariate linear regression was performed analysing age, sex, time since onset, symptomatology, anti-NP and anti-RBD antibody BR.ResultsWe included 906 adults. Antibody results (793/906; 87.5%; 95% confidence interval: 85.2-89.6) and BR strongly correlated (ρ = 0.75). PCR-confirmed cases were more frequently identified by anti-RBD (129/130) than anti-NP (123/130). Anti-RBD testing identified 83 of 325 (25.5%) cases otherwise reported as negative for anti-NP. Anti-NP presence (+1.75/unit increase; p < 0.001), fever (≥ 38°C; +1.81; p < 0.001) or anosmia (+1.91; p < 0.001) were significantly associated with increased anti-RBD BR. Age (p = 0.85), sex (p = 0.28) and cough (p = 0.35) were not. When time since symptom onset was considered, we did not observe a significant change in anti-RBD BR (p = 0.95) but did note decreasing anti-NP BR (p < 0.001).ConclusionSARS-CoV-2 anti-RBD IgG showed significant correlation with anti-NP IgG for absolute seroconversion and BR. Higher BR were seen in symptomatic individuals, particularly those with fever. Inter-assay variability (12.5%) was evident and raises considerations for optimising seroprevalence testing strategies/studies.

MG-Pe: A Novel Galectin-3 Ligand with Antimelanoma Properties and Adjuvant Effects to Dacarbazine.

Melanoma is a highly metastatic and rapidly progressing cancer, a leading cause of mortality among skin cancers. The melanoma microenvironment, formed from the activity of malignant cells on the extracellular matrix and the recruitment of immune cells, plays an active role in the development of drug resistance and tumor recurrence, which are clinical challenges in cancer treatment. These tumoral metabolic processes are affected by proteins, including Galectin-3 (Gal-3), which is extensively involved in cancer development. Previously, we characterized a partially methylated mannogalactan (MG-Pe) with antimelanoma activities. In vivo models of melanoma were used to observe MG-Pe effects in survival, spontaneous, and experimental metastases and in tissue oxidative stress. Analytical assays for the molecular interaction of MG-Pe and Gal-3 were performed using a quartz crystal microbalance, atomic force microscopy, and contact angle tensiometer. MG-Pe exhibits an additive effect when administered together with the chemotherapeutic agent dacarbazine, leading to increased survival of treated mice, metastases reduction, and the modulation of oxidative stress. MG-Pe binds to galectin-3. Furthermore, MG-Pe antitumor effects were substantially reduced in Gal-3/KO mice. Our results showed that the novel Gal-3 ligand, MG-Pe, has both antitumor and antimetastatic effects, alone or in combination with chemotherapy.

Debonding of orthodontic appliance changes salivary physicochemical properties and favors regression of active caries lesions: A 13-week follow-up study.

AIM: This prospective cohort study aimed to investigate whether orthodontic appliance removal (OAR) combined with caries-preventive strategies and fluoride varnish treatments alters salivary physicochemical properties, changes the activity of carbonic anhydrase VI (CA VIACT ) and α-amylase (α-AMLACT ), and favors the regression of active caries lesions (ACL). DESIGN: Twenty-two individuals aged between 13 and 24 years were assessed for the presence of visible biofilm, daily sugar exposure, caries activity, salivary flow rate (SFR), pH, buffering capacity (BC), and CA VIACT and α-AMLACT activity at baseline, and 1, 5, and 13 weeks after OAR. Variables were assessed using repeated-measures analysis of variance, Cochran's Q and McNemar's test, and Pearson's correlation. RESULTS: We observed a significant decrease in the number of ACL at the 5-week (29% reduction) and 13-week follow-ups (58% reduction). At the 5- and 13-week follow-ups, the percentage of visible biofilm and sugar exposure decreased, whereas the salivary pH and α-AMLACT activity significantly increased. BC and CA VIACT remained unchanged throughout the follow-up. CONCLUSION: OAR combined with caries-preventive strategies and fluoride varnish treatments favored the regression of ACL and increased salivary pH and α-AMLACT activity, whereas BC and CA VIACT remained stable.

Caring for people who take care: What is already done?

OBJECTIVE: The growing prevalence and impact of cancer on the family system calls for a palliative care approach with the family as the unit of care. This study aimed at providing an overview of the intervention programs that have been developed to offer support to the family caregivers of oncologic patients receiving palliative care. METHOD: Sixteen articles were included in the final review, encompassing (i) studies focused on intervention programs with family caregivers of cancer patients in palliative care, (ii) studies including a pre- and post-test evaluation of the intervention program, (iii) and studies whose cancer patients were at least 18 years old. RESULTS: A great heterogeneity was verified with respect to care settings, number of sessions, outcome measures, or timing of assessment within the reviewed programs. These findings mirrored the complexity of the palliative care approach, which is difficult to standardize. Nonetheless, some interventions with different features accomplished good and sometimes similar results. The studies' main outcomes were clustered in five categories: psychological symptomatology, general quality of life, caregiving role, family relational variables, and bereavement/grief. Moreover, 44% of the main outcomes were psychological symptomatology of family caregivers, with an emphasis toward anxiety and depression. Also shown was a growing emergence of technology use among these interventions. SIGNIFICANCE OF RESULTS: Results revealed a scarcity of family-oriented programs and lack of certified mental health professionals as interventionists. Future studies and interventions should focus on the positive outcomes of the caregiving experience and must acknowledge the cultural differences when trying to replicate programs. Considering that there is no precise formula for dealing with terminal illness and grief, we submit that family-centered and systemic lenses are excellent approaches for support during this adjustment process. In conclusion, the present study advocates for increased investment in the field, underscoring the importance of family caregivers' mental health.

Fasting and postprandial plasma glucose contribution to glycated haemoglobin and time in range in people with type 2 diabetes on basal and bolus insulin therapy: Results from a pooled analysis of insulin lispro clinical trials.

AIMS: To investigate the interrelations between glycaemic metrics of fasting plasma glucose (FPG), postprandial glucose (PPG), glycated haemoglobin (HbA1c), and percentage of time in target range 3.9 to 10.0 mmol/L (%TIR) in patients on insulin therapy. MATERIALS AND METHODS: A pooled analysis was conducted using datasets extracted from an integrated database of insulin lispro clinical trials (Eli Lilly and Company). Studies in patients with type 2 diabetes on basal-bolus or basal-plus insulin therapy, and with ≥7-point self-monitored blood glucose profiles were included in the analysis. A multivariate regression model was used to quantify the contribution of FPG and PPG change to the change in HbA1c and %TIR. In addition, a linear regression model was used to describe the relationship between %TIR and HbA1c. RESULTS: Five studies encompassing 1572 patients met the criteria for inclusion. On average, a 1-mmol/L change in FPG was associated with 2.7 mmol/mol (0.25%) change in HbA1c (range 2.0 to 2.8 mmol/mol [0.18%-0.26%]; all P <0.0001), and a 1-mmol/L change in PPG with 1.8 mmol/mol (0.16%) change in HbA1c (range 1.2 to 2.1 mmol/mol [0.11%-0.19%]; all P <0.01). Furthermore, a 1-mmol/L reduction in FPG and PPG was associated with an increase in TIR of 6.5% (range 5.8%-9.2%) and 5.3% (range 4.1%-8.7%), respectively, all P <0.0001. A decrease in HbA1c of 10.9 mmol/mol (1%) corresponded with an increase in TIR of 8.3%, on average. CONCLUSIONS: In patients with type 2 diabetes on basal-bolus or basal-plus insulin therapy, management of both FPG and PPG is important for achievement of HbA1c and TIR goals.

Duration of antibiotic treatment using procalcitonin-guided treatment algorithms in older patients: a patient-level meta-analysis from randomized controlled trials.

BACKGROUND: Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients. OBJECTIVE AND DESIGN: We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome. SUBJECTS AND METHODS: We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (<75 years [n = 7,079], 75-80 years [n = 1,034], 81-85 years [n = 803] and >85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay. RESULTS: Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of -1.99 (95% confidence interval [CI] -2.36 to -1.62), -1.98 (95% CI -2.94 to -1.02), -2.20 (95% CI -3.15 to -1.25) and - 2.10 (95% CI -3.29 to -0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05). CONCLUSIONS: This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.

Relationship between cocaine and cocaethylene blood concentration with the severity of clinical manifestations.

BACKGROUND: Poisonings resulting from the abuse of drugs currently represent a serious problem for public health. Among the main agents involved, cocaine stands out. It became one of the most abused drugs around the world, and one of the main reasons for visits to the emergency department due to the use of illicit substances. The use of cocaine is primarily in combination with alcoholic beverages. There are few studies that correlate cocaine blood concentration and the severity of clinical manifestations in patients evaluated at Emergency Department. The aim of the present study was to verify the possible relationship between the blood concentration of cocaine and cocaethylene (product of the interaction of cocaine with ethanol) with the severity of the clinical manifestations presented by patients with cocaine intoxication. METHODS: Blood levels were measured by high-performance liquid chromatography (HPLC) and the severity of clinical manifestations was assessed using the Stimulant Intoxication Score (SIS). To establish this relationship, Pearson's chi-square statistical test (x2) was used for categorical variables and Student's t for continuous variables, with statistical significance of 5% (p < 0.05). RESULTS: Of the 81 patients included in the study, 77.8% were men with a mean age of 32.5 years ± 8.5 and mean of SIS 3.4 ± 2.5. Considering the toxicological analysis results, 24.7% of the blood samples were positive. The mean of cocaine and cocaethylene concentrations were 0.34 µg/mL ± 0.45 and 0.38 µg/mL ± 0.34, respectively. The blood concentration of cocaine and cocaethylene has not been shown to be useful information for the treatment and prognosis of patients, but blood levels of these substances at the time of treatment, regardless of their concentration, may be an indicator of severity, showing that any concentrations of these substances should be considered as potentially toxic. CONCLUSION: The application of the SIS score proved to be an important alternative capable of predicting the severity of the patients due to cocaine intoxication in a fast and simplified way.

Bloodwood: the composition and secreting-site of the characteristic red exudate that gives the name to the Swartzia species (Fabaceae).

The Swartzia species are commonly known as bloodwood due to the red exudate released from the stem after injury. This exudate has aroused great interest, and an integrative study is essential to describe it in detail. Thus, this work aimed to identify the red exudate's secreting-site in S. flaemingii and S. langsdorffii, and determine if it is a latex or a resin. Samples of the stem bark and the secondary xylem were prepared for histological analysis. Fresh exudates were dissolved in deuterated methanol and analyzed by 1H-NMR; other samples were resuspended in MeOH:H2O (9:1), partitioned with organic solvents and analyzed by direct infusion mass spectrometry. Total phenolic and total flavonoid contents were determined spectrophotometrically, and antioxidant capacity was determined using ferric reducing antioxidant power assay. The results showed that the exudate is a red latex produced by articulated laticifers located among the phloem cells. The latex is composed of sucrose, catechin glucosides, chlorophyll derivatives, and hederagenin-type saponins. Both samples of S. flaemingii and S. langsdorffii presented high amounts of phenolics and flavonoids, as well as a strong antioxidant capacity. The anatomical study showed that the secreting-site of the Swartzia red exudates were laticifers. This finding allows us to exclude other substances such as resin or oleoresin, generally produced by secretory cavities or ducts. Furthermore, since laticifers are rare in Fabaceae, this finding is significant, and represents an essential taxonomic feature. The showy red color is due to the large amounts of flavonoids. This latex probably has a protective role against microorganisms and photodamage. The bioactive potential of this exudate inspires further studies, which may boost the economic importance of Swartzia.