Evaluation of novel candidate filtration markers from a global metabolomic discovery for glomerular filtration rate estimation.

Creatinine and cystatin-C are recommended for estimating glomerular filtration rate (eGFR) but accuracy is suboptimal. Here, using untargeted metabolomics data, we sought to identify candidate filtration markers for a new targeted assay using a novel approach based on their maximal joint association with measured GFR (mGFR) and with flexibility to consider their biological properties. We analyzed metabolites measured in seven diverse studies encompasing 2,851 participants on the Metabolon H4 platform that had Pearson correlations with log mGFR and used a stepwise approach to develop models to < -0.5 estimate mGFR with and without inclusion of creatinine that enabled selection of candidate markers. In total, 456 identified metabolites were present in all studies, and 36 had correlations with mGFR < -0.5. A total of 2,225 models were developed that included these metabolites; all with lower root mean square errors and smaller coefficients for demographic variables compared to estimates using untargeted creatinine. Seventeen metabolites were chosen, including 12 new candidate filtration markers. The selected metabolites had strong associations with mGFR and little dependence on demographic factors. Candidate metabolites were identified with maximal joint association with mGFR and minimal dependence on demographic variables across many varied clinical settings. These metabolites are excreted in urine and represent diverse metabolic pathways and tubular handling. Thus, our data can be used to select metabolites for a multi-analyte eGFR determination assay using mass spectrometry that potentially offers better accuracy and is less prone to non-GFR determinants than the current eGFR biomarkers.

Glomerular Filtration Rate Estimation Using ß2-Microglobulin and ß-Trace Protein in Adults With Solid Tumors: A Prospective Cross-Sectional Study.

RATIONALE & OBJECTIVE: ß2-Microglobulin (B2M) and ß-trace protein (BTP) are novel endogenous filtration markers that may improve the accuracy of estimated glomerular filtration rate (eGFR) beyond creatinine and cystatin C (eGFRcr-cys), but they have not been assessed in patients with cancer. STUDY DESIGN: Cross-sectional analysis. SETTING & PARTICIPANTS: Prospective cohort of 1,200 patients with active solid tumors recruited between April 2015 and September 2017. EXPOSURE: CKD-EPI equations without race combining B2M and/or BTP with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR). OUTCOME: Performance of equations compared with eGFRcr-cys and non-GFR determinants of serum B2M and BTP (SB2M, and SBTP, respectively). Measured GFR (mGFR) was determined using the plasma clearance of chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA). ANALYTICAL APPROACH: Bias was defined as the median of the differences between mGFR and eGFR, and 1-P30 was defined as the percentage of estimates that differed by more than 30% from the mGFR (1-P30). Linear regression was used to assess association of clinical and laboratory variables with SB2M, and SBTP after adjustment for mGFR. RESULTS: Mean age and mGFR were 58.8±13.2 SD years and 78.4±21.7 SD mL/min/1.73m2, respectively. Performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys (lesser bias and 1-P30). Performance of 2-marker panel equations was as good as eGFRcr-cys (lesser bias and similar 1-P30). SB2M and SBTP were not strongly influenced by cancer site. LIMITATIONS: Participants may have had better clinical performance status than the general population of patients with solid tumors. CONCLUSIONS: B2M and BTP can improve the accuracy of eGFR and may be useful as confirmatory tests in patients with solid tumors, either by inclusion in a multimarker panel equation with creatinine and cystatin C, or by substituting for cystatin C in combination with creatinine. PLAIN-LANGUAGE SUMMARY: The most accurate method to assess estimate kidney function is estimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFRcr-cys). We studied whether using ß2-microglobulin (B2M) and/or ß-trace protein (BTP) with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR) might be useful in patients with active solid tumors. The performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys. Performance of 2-marker panel equations was as good as eGFRcr-cys. We conclude that B2M and BTP can improve the accuracy of eGFR and may be useful as a confirmatory test in patients with solid tumors either by inclusion in multimarker panel equation with creatinine and cystatin C or by substituting for cystatin C in combination with creatinine.

Clinical and molecular characterization of limb-girdle muscular dystrophy 2G/R7 in a large cohort of Brazilian patients.

Limb-girdle muscular dystrophy type 2G/R7 (LGMD2G/R7) is an ultra-rare condition initially identified within the Brazilian population. We aimed to expand clinical and genetic information about this disease, including its worldwide distribution. A multicenter historical cohort study was performed at 13 centers in Brazil in which data from index cases and their affected relatives from consecutive families with LGMD2G/R7 were reviewed from July 2017 to August 2023. Additionally, a systematic literature review was conducted to identify case reports and series of the disease worldwide. Forty-one LGMD2G/R7 cases were described in the Brazilian cohort, being all subjects homozygous for the c.157C>T/(p.Gln53*) variant in TCAP. Survival curves showed that the median disease duration before individuals required walking aids was 21 years. Notably, women exhibited a slower disease progression, requiring walking aids 13 years later than men. LGMD2G/R7 was frequently reported not only in Brazil but also in China and Bulgaria, with 119 cases identified globally, with possible founder effects in the Brazilian, Eastern European, and Asian populations. These findings are pivotal in raising awareness of LGMD2G/R7, understanding its progression, and identifying potential modifiers. This can significantly contribute to the development of future natural history studies and clinical trials for this disease.

Assessing the trophic ecology and migration on the exposure of cape petrels and Wilson's storm petrels from Antarctica to perfluoroalkylated substances, trace and major elements.

Chemical pollution is a global concern as contaminants are transported and reach even the remote regions of Antarctica. Seabirds serve as important sentinels of pollution due to their high trophic position and wide distribution. This study examines the influence of migration and trophic ecology on the exposure of two Antarctic seabirds, Wilson's storm petrel (Oceanites oceanicus - Ooc), and Cape petrel (Daption capense - Dca), to chemical elements and perfluoroalkyl substances (PFAS). Our methodology involved assessing the concentration of these pollutants in feather samples obtained from carcasses, offering a practical means for monitoring contamination. Trace and major element concentrations were comparable in both species, suggesting that migratory patterns have a minimal impact on exposure levels. However, Ooc had higher concentration of PFAS compared to Dca (mean, ng g-1dry weight, PFOA: Ooc:0.710, Dca:0.170; PFTrDA: Ooc:0.550, Dca:0.360, and PFTeDA: Ooc:1.01, Dca:0.190), indicating that migration to the more polluted Northern Hemisphere significantly affects PFAS exposure. Furthermore, while no strong associations were found between either trace elements or PFAS and the three stable isotopes (δ13C, δ15N, and δ34S), a negative association was observed between PFUnDA and δ15N, hinting at potential biodilution. The research concludes that the migratory patterns of these seabird species affect their PFAS exposure, underscoring the critical need for further exploration and understanding of these relationships to better inform conservation strategies.

The rs2018736 fibulin-5 polymorphism as a determinant for pelvic organ prolapse: a case-control study.

OBJECTIVE: Fibulin-5 is a connective tissue component and may play a role in pelvic organ prolapse (POP) pathogenesis. This study aimed to verify the association of the rs2018736 polymorphism of the fibulin-5 gene with POP in postmenopausal Brazilian women, and to determine the risk factors for POP. METHOD: This observational, cross-sectional, case-control study assessed postmenopausal women with advanced POP (stages III and IV) and control women (stages 0 and I) by examination and peripheral blood sample collection. DNA sequences were analyzed by real-time reverse-transcriptase polymerase chain reaction. A logistic regression model was used with p < 0.05 for significance. RESULTS: A total of 565 participants were evaluated (325 POP and 240 control). The homozygous C allele of rs2018736 (CC) was protective against POP (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26-0.91). Age (OR 1.09, 95% CI 1.05-1.13), number of pregnancies (OR 1.14, 95% CI 1.01-1.28), vaginal delivery (OR 5.32, 95% CI 2.58-11.01), forceps delivery (OR 3.34, 95% CI 1.72-6.47), weight of newborn (OR 1.0007, 95% CI 1.0002-1.0011), family history of POP (OR 2.35, 95% CI 1.24-4.44), hypertension (OR 1.74, 95% CI 1.01-3.00) and diabetes (OR 2.19, 95% CI 1.07-4.48)] were independent predictors for POP; cesarean (OR 0.02, 95% CI 0.005-0.09) was protective. CONCLUSION: The rs2018736-CC genotype of the fibulin-5 gene has a protective role against POP.

Prevalence of urinary incontinence in Brazilian para athletes.

OBJECTIVE: To describe the prevalence of urinary incontinence (UI) in para athletes in Brazil. METHODS: This is a cross-sectional study with Brazilian para athletes with physical impairments from all para sports. The data from 86 participants of both sexes (60 males and 26 females) were collected through an online survey that gathered sociodemographic data and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form, from March to July 2023. RESULTS: The prevalence of UI was 45.3% (n=39), with the average impact on quality of life scored at 6.1±3.5 on a scale of 0-10. Most para athletes reported moderate (43.5%) or severe (38.4%) symptoms. The most common type was mixed UI (46.1%), with an average of 3±1.9 episodes of urinary loss per athlete in the last 4 weeks. Adjusted Poisson regression (controlling for sex, age and level of competition) revealed that para athletes with orthopaedic impairments had a 58% lower prevalence of UI (prevalence ratio=0.42; 95% CI 0.24, 0.83) compared with those with neurological impairments. Furthermore, ordinal regression indicated that para athletes with neurological impairments were 147% more likely to experience a progression from 'severe' to 'very severe' UI (OR=2.47; 95% CI 1.59, 3.93). CONCLUSIONS: UI is highly prevalent among para athletes, particularly those with neurological impairments, underscoring the need for specialised genitourinary healthcare and the need for further treatment and monitoring of the condition. There is a critical need to raise awareness among coaches, healthcare providers and the athletes themselves about UI and its impact to foster the comprehensive well-being of these athletes.

Intra and Inter-Device Reliabilities of the Instrumented Timed-Up and Go Test Using Smartphones in Young Adult Population.

The Timed-Up and Go (TUG) test is widely utilized by healthcare professionals for assessing fall risk and mobility due to its practicality. Currently, test results are based solely on execution time, but integrating technological devices into the test can provide additional information to enhance result accuracy. This study aimed to assess the reliability of smartphone-based instrumented TUG (iTUG) parameters. We conducted evaluations of intra- and inter-device reliabilities, hypothesizing that iTUG parameters would be replicable across all experiments. A total of 30 individuals participated in Experiment A to assess intra-device reliability, while Experiment B involved 15 individuals to evaluate inter-device reliability. The smartphone was securely attached to participants' bodies at the lumbar spine level between the L3 and L5 vertebrae. In Experiment A, subjects performed the TUG test three times using the same device, with a 5 min interval between each trial. Experiment B required participants to perform three trials using different devices, with the same time interval between trials. Comparing stopwatch and smartphone measurements in Experiment A, no significant differences in test duration were found between the two devices. A perfect correlation and Bland-Altman analysis indicated good agreement between devices. Intra-device reliability analysis in Experiment A revealed significant reliability in nine out of eleven variables, with four variables showing excellent reliability and five showing moderate to high reliability. In Experiment B, inter-device reliability was observed among different smartphone devices, with nine out of eleven variables demonstrating significant reliability. Notable differences were found in angular velocity peak at the first and second turns between specific devices, emphasizing the importance of considering device variations in inertial measurements. Hence, smartphone inertial sensors present a valid, applicable, and feasible alternative for TUG assessment.

Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis.

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

Feeding reduced levels of trace minerals in proteinate form and selenium-yeast to transition cows: Performance, trace minerals, and antioxidant status, peripheral neutrophil activity, and oocyte quality.

An experiment was conducted to evaluate the effects of inorganic trace minerals (TM) and reduced levels of TM by using proteinate forms of Co, Zn, Mn, and Cu, and Se-yeast in diets of transition cows on performance, TM concentrations in colostrum, plasma, and liver, blood metabolites, antioxidant status, peripheral neutrophil activity, and oocyte quality. Thirty-two Holstein cows (22 multiparous and 10 primiparous cows) were enrolled in this study from 30 d before the expected calving date to 56 DIM. Cows were blocked according to body condition score, parity, and previous milk yield and randomly assigned to one of the following treatments: control (CON), with TM (Zn, Cu, Mn, and Co) supplied in form of sulfate and Se as sodium selenite to meet or exceed requirement estimates of the National Research Council; and proteinate trace minerals (PTM), with TM supplied bound with AA and peptides at 50% of CON levels and inorganic Se replaced with Se-yeast at 100% of CON level. Treatments were supplied until 56 DIM. Eight cows were removed from the study because of early calving (n = 3) or health issues (n = 5); thus, data of 24 cows (16 multiparous and 8 primiparous cows) were used in the statistical analysis. No differences between treatments were detected on nutrient intake or digestibility. Total excretion of purine derivatives was decreased when feeding PTM during the prepartum period. Feeding reduced levels of TM in proteinate form resulted in greater yield of milk (27.7 and 30.9 kg/d for CON and PTM, respectively) and protein (0.890 and 0.976 kg/d) between wk 5 and 8 of lactation. No treatment differences were detected for feed efficiency, milk somatic cell count, and milk urea nitrogen. Cows fed PTM had lower milk fat concentration during the 56 d of evaluation (4.08 and 3.74% for CON and PTM, respectively). Selenium concentration was greater in colostrum of cows fed PTM compared with CON (48.5 and 71.3 µg/L for CON and PTM, respectively), whereas Zn, Cu, and Mn concentrations were not different. Cows fed PTM showed lower liver Cu concentration compared with CON (51.4 and 73.8, respectively). Plasma concentrations of Mn and Zn were lower, but plasma Se concentration tended to be higher with PTM treatment. Feeding PTM resulted in greater blood concentrations of urea-N (16.6 and 18.2 mg/dL for CON and PTM, respectively) and ß-hydroxybutyrate (0.739 and 0.940 mmol/L). Counts of lymphocytes were higher with PTM but counts of monocytes were lower in complete blood cell count. No differences were observed in serum concentrations of superoxide dismutase and glutathione peroxidase. No differences were detected in phagocytosis and oxidative burst potential of neutrophils after incubation with bacteria. Cows fed PTM had fewer viable oocytes per ovum pick-up in comparison with CON (8.00 and 11.6). Feeding PTM to transition cows may sustain performance without altering neutrophil activity despite some alterations in blood TM concentrations. More studies should be performed to evaluate production and fertility measurements when reducing TM dietary levels by using proteinate forms and Se-yeast with larger number of animals.

ConectAR: Collaborative network of patients with asthma and carers actively involved in health research: a protocol for patient and public involvement.

Summary: Background. Patients and Public Involvement in every stage of the patient-centered health research cycle is the key to the development of innovative solutions with an impact on patients' care. Methods. This protocol describes the development of ConectAR, a network to promote the involvement of patients with asthma and their carers in the health research cycle. Results. This protocol comprehends 4 tasks: 1) define the mission, vision, governance and activities of the network through focus groups; 2) establish the communication strategy and tools; 3) test the feasibility of the network in a Delphi study on the research priorities for asthma in Portugal; 4) coordination and dissemination activities. Conclusions. This network will improve research by ensuring that patients and carers have an active role in the co-creation of impactful solutions for asthma.

BRAF, TERT and HLA-G Status in the Papillary Thyroid Carcinoma: A Clinicopathological Association Study.

As BRAF, TERT, HLA-G, and microRNAs have been individually associated with papillary thyroid carcinoma (PTC), we aimed to evaluate the individual and collaborative role of these markers in PTC in the same patient cohort. HLA-G and BRAF tumor expression was evaluated by immunohistochemistry. Using molecular methods, BRAFV600E and TERT promoter mutations were evaluated in thyroid fine needle aspirates. MicroRNA tumor profiling was investigated using massively parallel sequencing. We observed strong HLA-G (67.96%) while BRAF (62.43%) staining was observed in PTC specimens. BRAF overexpression was associated with poor response to therapy. The BRAFV600E (52.9%) and TERTC228T (13%) mutations were associated with extrathyroidal extension, advanced-age, and advanced-stage cancer. The TERT rs2853669 CC+TC genotypes (38%) were overrepresented in metastatic tumors. Nine modulated microRNAs targeting the BRAF, TERT, and/or HLA-G genes were observed in PTC and involved with cancer-related signaling pathways. The markers were individually associated with PTC features, emphasizing the synergistic effect of BRAFV600E and TERTC228T; however, their collaborative role on PTC outcome was not fully demonstrated. The differentially expressed miRNAs targeting the BRAF and/or HLA-G genes may explain their increased expression in the tumor milieu.

Spatial-temporal analysis of hospitalizations with death caused by oral cancer in Brazil and its correlation with the expansion of healthcare coverage.

BACKGROUND: Oral cancer (OC) is a growing public health problem worldwide. In Brazil, the National Oral Health Policy, implemented in 2004, expanded access to oral health services and prioritized OC care. However, it is not known whether this expansion resulted in a reduction in hospital admissions with death. This study aimed to analyze the proportion of hospital admissions who progressed to death due to OC in Brazil from 2007 to 2019 and its correlation with the coverage of health services. MATERIAL AND METHODS: This study is an ecological, longitudinal, and analytical study of hospital admissions with death due to OC recorded in the Brazilian Hospital Information System. The following analyses were performed: descriptive, spatial (choropleth maps and Moran index), and negative binomial regression, with a hierarchical approach, estimating crude and adjusted regression coefficients (ß) and respective 95% confidence intervals (95% CI) (alpha=5%). RESULTS: In 2019, Moran's index (I) of spatial autocorrelation showed a negative association between hospital admissions with death and dentist surgeon/inhabitant rate (I=-0.176), physician/inhabitant rate (I=-0.157), family health strategy (FHS) coverage (I=-0.080), oral health team (OHT) coverage (I= -0.129), dental specialty centers (DSC)/inhabitant rate (I= -0.200), and oncology bed/inhabitant rate (I= -0.101). In the adjusted regression analysis, the proportion of hospitalizations with deaths caused by OC was higher in Brazilian states with a lower medical ̸inhabitant ratio (ß= -0.014; p=0.040), a lower dentists/inhabitant ratio (ß= -0.720; p=0.045), a lower number of DSC (ß= -0.004; p<0.000), a lower amount paid per hospitalization (ß= -10.350; p<0.001), and a lower number of biopsies (ß= -0.00008; p=0.010). The proportion of hospitalizations that progressed to death showed a positive association with the number of days of hospitalization (ß= 0.00002; p=0.002). CONCLUSIONS: Increased health care coverage has decreased serious hospital admissions with deaths caused by OC in Brazil.

Effect of shading on the physiological and reproductive parameters in Nelore cows.

This study aimed to evaluate the physiological and reproductive parameters of Nelore cows under various microclimatic conditions. The experiment was performed in Central Brazil, which has a tropical climate with dry winters and rainy summers. The experimental groups were divided into an area with shading (5.8 trees/ha; n = 42) and an area with little shading (0.4 trees/ha; n = 42). The physiological (heart rate, respiratory rate, rectal temperature, surface body temperature, and vaginal temperature) and reproductive (estrus detection, conception rate, and rate of pregnancy loss) parameters were then assessed. The rectal temperature (p = 0.002); surface body temperature on the flanks, forehead, and shoulder (p < 0.001); and vaginal temperature (p < 0.001) of cows in the group with shading were significantly lower than those of cows in the group without shading. Estrus was higher (p = 0.08) in the shaded group; however, no effect was observed on conception and pregnancy loss rates. In conclusion, shading (5.8 trees/ha) provided better thermal comfort for Nelore animals in the tropical climatic region. However, this did not affect their performance after fixed-time artificial insemination.

Czech dysplasia mimicking rheumatoid arthritis: Case series and literature review.

OBJECTIVE: This study reported a family with most members affected by Czech dysplasia. We examined the patients' clinical, laboratory, and imaging characteristics and evaluated their functional capacity using the Stanford Health Assessment Questionnaire-Disability Index. METHODS: The method used was case series description and literature review. RESULTS: This study showed that the pathogenic variant c.823C>T in the COL2A1 gene, which is a characteristic of Czech dysplasia, was found in 12 Brazilian individuals. Half of the patients in this family met the criteria for rheumatoid arthritis (RA) based on the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria. Patients had arthritis in their hand joints, synovitis detected by ultrasound, and alterations in inflammatory tests. The Stanford Health Assessment Questionnaire-Disability Index assessment revealed that all patients exhibited moderate-to-severe functional disability. What distinguish Czech dysplasia from RA are an autosomal dominant inheritance pattern, platyspondyly, sensorineural hearing loss, and shortening of the metatarsal bones. CONCLUSIONS: It is important to consider Czech dysplasia as a potential differential diagnosis for RA. This autosomal dominant skeletal dysplasia is associated with normal height, short metatarsals, platyspondyly, hearing loss, enlarged epiphyses, and precocious osteoarthritis. Inflammatory findings such as arthritis, synovitis, and alteration of inflammatory markers may also be present in individuals with Czech dysplasia.

Extraction, identification and antitumor activity in cell cultures of cubebin isolated from dry seeds Piper cubeba (Piperaceae).

The Pipercubeba, it is one spice, widely consumed in Europe, which has several bioactive molecules, between those a lignan named cubebin. Cubebin has several known biological activities, such as analgesic activity and anti-inflammatory, trypanocidal activity, leishmanicidal and antitumor activity. The objective of this study was to evaluate the antiproliferative activity "in vitro" cubebin in eight different human tumor cell lines. It was fully characterized by IR analysis, NMR, mass spectrometry, DSC, TGA, residual solvent and elemental analysis. The antitumor activity of cubebin was evaluated "in vitro" on eight different human tumor cell lineages. Cubebin showed GI50≤30µg/mL for lineage cell U251 (glioma CNS), 786-0 (kidney), PC-3 (prostate), HT-29 (colon rectum). For K562 cells (leukemia), cubebin presented GI50≤to 4.0mg/mL. For the other lineages cells, MCF-7 (breast) and NCI-H460 to cubebin can be considered inactive because of GI50>250mg/mL. Analyzing the selectivity index for cubebin, it can be observed that high selectivity of cubebin to K562 lineage cells (leukemia). Analyzing the cytotoxic potential of cubebin was observed that probably acts cubebin altering metabolism, inhibiting cell growth - a cytostatic effect, showing no cytocidal effect on any lineage cell.

Biogas production from malt bagasse from craft beer industry: kinetic modeling and process simulation.

In this work, biogas was synthesized from malt enriched-craft beer bagasse with the objective to generate clean energy. Thus, a kinetic model based on thermodynamic parameters was proposed to represent the process with coefficient determination (R2) of 0.82. A bench-top biodigester of 2.0 × 10-3 m3 was built in glass, and equipped with sensors to measure pressure, temperature, and methane concentration. The inoculum selected for the anaerobic digestion was the granular sludge, and malt bagasse was used as substrate. Data were fitted to a pseudo-first-order model for the formation of methane gas using the Arrehnius equation as basis. For the simulations of biogas production, the Aspen Plus™ software was used. Results from 23 factorial design experiments evidenced that equipment was efficient, and the craft beer bagasse showed great biogas production, with nearly 95% of methane yield. The temperature was the variable that showed most influence in the process. Moreover, the system has a potential for the generation of 10.1 kWh of clean energy. Kinetic constant rate for methane production was 5.42 × 10-7 s-1 and activation energy 8.25 kJ mol-1. A statistical analysis using a math software was performed and evidenced that the temperature played a major role in the biomethane conversion. Supplementary Information: The online version contains supplementary material available at 10.1007/s10163-023-01715-7.

A prospective cross-sectional study estimated glomerular filtration rate from creatinine and cystatin C in adults with solid tumors.

Current guidelines recommend estimating glomerular filtration rate (eGFR) using creatinine (eGFRcr) with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation as the first test for GFR evaluation, but the Cockcroft-Gault (CG) equation is still commonly used in oncology practice and clinical trials despite increasing evidence of its inaccuracy compared to measured GFR (mGFR). Guidelines recommend eGFR using cystatin C (eGFRcys) or both markers (eGFRcr-cys) as a confirmatory test, but neither was carefully evaluated in cancer patients. Therefore, we compared performance of the CKD-EPI equations and others to the CG equation in adults with a variety of solid tumors. The mGFR was determined by plasma clearance of 51Cr-EDTA. Bias was defined as the median of the differences between mGFR and eGFR while accuracy was defined as the percentage of estimates that differed by more than 30% from the measured GFR (1-P30). We prospectively recruited 1,200 patients between April 2015 and September 2017 with a mean age and mGFR of 58.8 years and 78.4 ml/min/1.73m2, respectively. Bias among eGFRcr equations varied from -8.1 to +6.1 ml/min/1.73 m2. CG was the least accurate, 1-P30 (95% confidence interval) was 24.9 (22.4- 27.3)%; CKD-EPI had 1-P30 of 19.1 (16.8-21.2)% while eGFRcr-cys had the best performance: bias -2.0 (-2.6 to -1.1) ml/min/1.73m2 and 1-P30 7.8 (6.3-9.4)%. Thus, the CG equation should not be preferred over CKD-EPI equation, and eGFRcr-cys can be used as a confirmatory test in adults with solid tumors. Hence, a major policy implication would be to adopt general practice guideline-recommended methods for GFR evaluation in oncology practice and clinical trials.

The association of physical illness and low-grade inflammatory markers with depressive symptoms in a large NHANES community sample: Dissecting mediating and moderating effects.

BACKGROUND: Both low-grade elevation in peripheral inflammatory markers (e.g., white blood count (WBC) and C-reactive protein (CRP)) and physical illness (both chronic and acute) have been associated with depressive symptomology. However, it is unclear if low-grade elevation in inflammatory markers mediates relationships between physical illness and depression or if physical illness positively moderates relationships between inflammatory markers and depression. METHODS: In a well-powered, racially diverse cohort (n = 21,525) from NHANES datasets, we examined if inflammatory markers (CRP and WBC) and physical illnesses (acute and chronic) were independently associated with depression severity. We also examined if associations between physical illness and depression severity were mediated by inflammatory markers and if physical illness moderated associations between inflammatory markers and depression. RESULTS: We found that both inflammatory markers and physical illness were associated with depression severity, even after considering a wide range of potential confounders (e.g., age, gender, body mass index). Inflammatory markers mediated a marginal portion (<5%; p < 0.001) of potential effects of physical illness on depression severity. In moderation analyses, associations between inflammatory markers and depression severity were significantly stronger in participants with chronic physical illness than those without. This moderating effect was not present for acute physical illness. CONCLUSIONS: Inflammatory markers and physical illness appear independently linked to depression severity and, in individuals with chronic physical illness, inflammatory markers are more tightly connected to depressive symptomology. Such findings could help guide future individualized treatment research for depression based on both inflammatory marker level and physical illness burden.

The rs2165241 polymorphism of the Loxl1 gene in postmenopausal women with pelvic organ prolapse.

OBJECTIVE: This study aimed to verify the presence of polymorphism rs2165241 of the lysyl oxidase-like 1 (Loxl1) gene and its association with pelvic organ prolapse (POP) in Brazilian women and determine risk factors for POP development. METHODS: The study was previously approved by the local research and ethics board. Postmenopausal women were included and divided into POP (stages III and IV) and control (stages 0 and I) groups. Peripheral blood samples were collected, and the DNA sequence of interest was analyzed by real-time reverse-transcriptase polymerase chain reaction. We used logistic regression and considered a recessive model of inheritance for the analysis, with p < 0.05 for significance. RESULTS: A total of 836 women were assessed: 426 POP cases and 410 controls. The frequencies of CC, CT and TT genotypes were similar in both groups. Age (odds ratio [OR] = 1.1, 95% confidence interval [CI] = 1.07; 1.14), number of vaginal births (OR = 17.06, 95% CI = 5.94; 48.97), family history (OR = 2.87, 95% CI = 1.57; 5.22) and weight of largest newborn (OR = 1.001, 95% CI = 1.0003; 1.001) were independent risk factors for POP, while multiple cesarean sections (two or more) was protective (OR = 0.17, 95% CI = 0.07; 0.42). CONCLUSION: No association was detected between rs2165241 of the Loxl1 gene and POP.

Severe cutaneous adverse drug reactions: diagnostic approach and genetic study in a Brazilian case series.

Summary: Background. Severe cutaneous adverse reactions (SCAR) are potentially fatal reactions. Genetic predisposition is involved in their pathogenesis related to drugs and ethnicities, however in a mixed population these relationships are still unknown. The aim of this study was to describe phenotypes, suspect drugs and HLA-alleles related to SCAR, identified by a systematized approach in a Brazilian case series. Methods. Patients who were diagnosed with SCAR between March 2011 and July 2019 at our university hospital were included. European Network for Drug Allergy (ENDA) questionnaire was used to collect clinical and laboratory data and algorithms for assessment of drug causality were applied. Socio-demographic variables included age, gender and skin color/ethnicity. Drug patch tests (DPT) and HLA-A, -B, -DRB1 typing were carried out. Results. A total of 74 patients were included: 36 (48.64%) with SJS/TEN, 32 (43.24%) DRESS/DIHS, 3 (4.05%) AGEP, 2 (2.70%) overlap(DRESS/SJS and DRESS/AGEP) and 1 (1.35%) GBFDE. The median age was31.5 years (IQR = 14-52.25), most were female (n = 44/59.46%) and brown (n = 38/51.35%). Anticonvulsants (n = 32/43.24%) were the largest group involved and antibiotics (n = 26/35.13%) were the second most common. Two patients with DRESS died during the acute phase. Positive DPT were shown only in anticonvulsant associated DRESS. HLA related to abacavir, allopurinol and carbamazepine were identified. Conclusions. A systematized approach allowed the phenotypic characterization of SCAR. The HLA-A*31:01, B*57:01 and B*58:01 alleles were identified, reinforcing the causality in SCAR by CBZ, ABC and ALLO in the Brazilian population.