The use of social simulation modelling to understand adherence to diabetic retinopathy screening programs.

The success of screening programs depends to a large extent on the adherence of the target population, so it is therefore of fundamental importance to develop computer simulation models that make it possible to understand the factors that correlate with this adherence, as well as to identify population groups with low adherence to define public health strategies that promote behavioral change. Our aim is to demonstrate that it is possible to simulate screening adherence behavior using computer simulations. Three versions of an agent-based model are presented using different methods to determine the agent's individual decision to adhere to screening: (a) logistic regression; (b) fuzzy logic components and (c) a combination of the previous. All versions were based on real data from 271,867 calls for diabetic retinopathy screening. The results obtained are statistically very close to the real ones, which allows us to conclude that despite having a high degree of abstraction from the real data, the simulations are very valid and useful as a tool to support decisions in health planning, while evaluating multiple scenarios and accounting for emergent behavior.

Effect of physical exercise on immune, inflammatory, cardiometabolic biomarkers, and fatty acids of breast cancer survivors: results from the MAMA_MOVE Gaia After Treatment trial.

PURPOSE: Physical exercise has positive effects on clinical outcomes of breast cancer survivors such as quality of life, fatigue, anxiety, depression, body mass index, and physical fitness. We aimed to study its impact on immune, inflammatory, cardiometabolic, and fatty acids (FA) biomarkers. METHODS: An exploratory sub-analysis of the MAMA_MOVE Gaia After Treatment trial (NCT04024280, registered July 18, 2019) was performed. Blood sample collections occurred during the control phase and at eight weeks of the intervention phase. Samples were subjected to complete leukocyte counts, cytokine, and cardiometabolic marker evaluation using flow cytometry, enzyme-linked immunoassays, and gas chromatography. RESULTS: Ninety-three percent of the 15 participants had body mass index ≥ 25 kg/m2. We observed a decrease of the plasmatic saturated FA C20:0 [median difference - 0.08% (p = 0.048); mean difference - 0.1 (95%CI - 0.1, - 0.0)], positively associated with younger ages. A tendency to increase the saturated FA C18:0 and the ratio of unsaturated/saturated FA and a tendency to decrease neutrophils (within the normal range) and interferon-gamma were observed. CONCLUSIONS: Positive trends of physical exercise on circulating immune cells, inflammatory cytokines, and plasmatic FA were observed. Larger studies will further elucidate the implications of physical exercise on metabolism. These exploratory findings may contribute to future hypothesis-driven research and contribute to meta-analyses.

Fruit wings accelerate germination in Anacyclus clavatus.

PREMISE: The lateral membranous expansions of fruits, commonly referred to as wings, have long been theorized to serve only dispersal functions. Alternatively, because winged fruits typically have earlier seed germination than unwinged fruits, we hypothesized that wings could increase the contact surface with water, ultimately triggering earlier germination. METHODS: We investigated this alternative hypothesis by exploring the potential role of fruit wings on germination in the heterocarpic species Anacyclus clavatus (Desf.) Pers. (Asteraceae), which produces both winged and unwinged fruits. First, we measured the speed and degree of water absorption in winged and unwinged fruits. Second, we investigated the effects of wings on germination performance, by either reducing wing size or by preventing water absorption by sealing wings with wax. Next, we tested the influence of water availability on the germination performance of winged and unwinged fruits by reducing the water potential. RESULTS: Winged fruits absorbed more water at a faster rate than unwinged fruits. The sealing of wings delayed germination, whereas germination time was not significantly altered by wing cutting. The restriction of water availability by decreasing water potential significantly delayed seed germination of unwinged fruits, whereas winged fruits remained unaffected. CONCLUSIONS: Altogether, our results support the effect of wings on germination and cast doubt on the unique role of wings in dispersal. Whether or not wings contribute to dispersal, we propose that they also improve seed germination and seedling establishment by facilitating water absorption after the release from their mother plants.

Adaptive changes in the DNA damage response during skeletal muscle cell differentiation.

DNA double-strand breaks (DSBs) trigger specialized cellular mechanisms that collectively form the DNA damage response (DDR). In proliferating cells, the DDR serves the function of mending DNA breaks and satisfying the cell-cycle checkpoints. Distinct goals exist in differentiated cells that are postmitotic and do not face cell-cycle checkpoints. Nonetheless, the distinctive requirements and mechanistic details of the DDR in differentiated cells are still poorly understood. In this study, we set an in vitro differentiation model of human skeletal muscle myoblasts into multinucleated myotubes that allowed monitoring DDR dynamics during cell differentiation. Our results demonstrate that myotubes have a prolonged DDR, which is nonetheless competent to repair DSBs and render them significantly more resistant to cell death than their progenitors. Using live-cell microscopy and single-molecule kinetic measurements of transcriptional activity, we observed that myotubes respond to DNA damage by rapidly and transiently suppressing global gene expression and rewiring the epigenetic landscape of the damaged nucleus. Our findings provide novel insights into the DDR dynamics during cellular differentiation and shed light on the strategy employed by human skeletal muscle to preserve the integrity of the genetic information and sustain long-term organ function after DNA damage.

Hydrocinnamic acid and perillyl alcohol are effective against Escherichia coli biofilms when used alone and combined with antibiotics.

AIMS: The use of phytochemicals to improve the effectiveness of antibiotics is a promising strategy for the development of novel antimicrobials. In this study, the antibiofilm activity of perillyl alcohol and hydrocinnamic acid, both phytochemicals present in several plants, and two antibiotics from different classes (amoxicillin and chloramphenicol) was tested, alone and in combination, against Escherichia coli. METHODS AND RESULTS: Each molecule was tested at the minimum inhibitory concentration (MIC), 5 × MIC, and 10 × MIC, and characterized concerning biomass removal, metabolic inactivation, and cellular culturability. The highest percentages of metabolic inactivation (88.5% for 10 × MIC) and biomass reduction (61.7% for 10 × MIC) were obtained with amoxicillin. Interestingly, for 5 × MIC and 10 × MIC, phytochemicals provided a total reduction of colony-forming units (CFUs). Dual and triple combinations of phytochemicals and antibiotics (at MIC and 5 × MIC) demonstrated high efficacy in metabolic inactivation, moderate efficacy in terms of biomass reduction, and total reduction of cellular culturability for 5 × MIC. CONCLUSIONS: The results demonstrated the antibiofilm potential of phytochemicals, highlighting the advantage of phytochemical/antibiotic combinations for biofilm control.

Small Indels in the Androgen Receptor Gene: Phenotype Implications and Mechanisms of Mutagenesis.

CONTEXT: Despite high abundance of small indels in human genomes, their precise roles and underlying mechanisms of mutagenesis in Mendelian disorders require further investigation. OBJECTIVE: To profile the distribution, functional implications, and mechanisms of small indels in the androgen receptor (AR) gene in individuals with androgen insensitivity syndrome (AIS). METHODS: We conducted a systematic review of previously reported indels within the coding region of the AR gene, including 3 novel indels. Distribution throughout the AR coding region was examined and compared with genomic population data. Additionally, we assessed their impact on the AIS phenotype and investigated potential mechanisms driving their occurrence. RESULTS: A total of 82 indels in AIS were included. Notably, all frameshift indels exhibited complete AIS. The distribution of indels across the AR gene showed a predominance in the N-terminal domain, most leading to frameshift mutations. Small deletions accounted for 59.7%. Most indels occurred in nonrepetitive sequences, with 15.8% situated within triplet regions. Gene burden analysis demonstrated significant enrichment of frameshift indels in AIS compared with controls (P < .00001), and deletions were overrepresented in AIS (P < .00001). CONCLUSION: Our findings underscore a robust genotype-phenotype relationship regarding small indels in the AR gene in AIS, with a vast majority presenting complete AIS. Triplet regions and homopolymeric runs emerged as prone loci for small indels within the AR. Most were frameshift indels, with polymerase slippage potentially explaining half of AR indel occurrences. Complex frameshift indels exhibited association with palindromic runs. These discoveries advance understanding of the genetic basis of AIS and shed light on potential mechanisms underlying pathogenic small indel events.

The value of waist circumference as a preditor of cardiovascular risk in adult patients with classic phenylketonuria.

BACKGROUND AND AIMS: We aimed to evaluate the differences in some cardiovascular risk (CVR) factors between adult patients without and with phenylketonuria (PKU) and to explore the correlation between waist circumference (WC) and body mass index (BMI) with the previous variables. METHODS: This was an observational case-control study that included patients older than 18 years with a diagnosis of classic PKU. The controls were age- and sex-matched individuals. We collected demographic, epidemiological, clinical, and laboratory variables, including WC, BMI, and lipid profile parameters. RESULTS: A total of 72 patients (25 controls and 47 cases) were included with a mean age of 36 years, of which 45 (62%) were women. Adult PKU patients showed lower high-density lipoprotein cholesterol (HDL-c) and higher triglyceride (TG) levels than the control group. We found an association between WC and uric acid (B=0.024, P=0.013, 95%CI: 0.005-0.043), TG (B=0.768, P=0.024, 95%CI: 0.107-1.428), and HDL-c (B=-0.254, P=0.026, 95%CI: -0.477 to (-0.032)) levels in PKU patients. However, we did not find any trend between WC and uric acid, TG and HDL-c levels that reached statistical significance (P<0.05) in patients without PKU. CONCLUSIONS: Waist circumference rather than BMI may better represent the CVR in patients with PKU.

Doxorubicin Dose-Dependent Impact on Physiological Balance-A Holistic Approach in a Rat Model.

Doxorubicin (DOX) is commonly used in several chemotherapies to treat various cancers, but it is known to cause cardiotoxicity and cardiac symptoms. Autonomic dysfunction is thought to contribute to the cardiotoxic effects of DOX, but the specific dose required to disrupt homeostatic processes is still unclear and is influenced by numerous factors. This study aimed to investigate how the DOX dosage affects autonomic function and physiological parameters, to elucidate the neurocardiac mechanisms underlying the observed cardiovascular side effects. Wistar rats were treated with DOX for four weeks and divided into three dosing groups: DOX8 (2 mg/kg/week), DOX16 (4 mg/kg/week), and DOX20 (5 mg/kg/week). A control group received NaCl 0.9% saline (1 mL/kg/week). In an acute experiment, we recorded blood pressure (BP), electrocardiogram, heart rate (HR), and respiratory rate (RF). Baroreflex gain and chemoreflex sensitivity were calculated, and cardiac tissue was analyzed with picrosirius histochemistry to measure collagen content. Our results showed that the LF/HF ratio, indicative of autonomic activity, was altered along with hypotension and bradycardia at a cumulative DOX dose threshold of 16 mg/kg. We observed a positive correlation between DOX dose and BP, HR, urinary norepinephrine, LF/HF ratio, and fibrotic heart area. Lower LF/HF ratios were associated with high DOX doses, reflecting drug-induced impairment of autonomic control of HR. This study provides valuable insights into the dose-dependent effects of DOX on physiological parameters and the development of cardiovascular dysfunction. These findings are critical, which is important for optimizing the management and therapeutic strategies for patients undergoing DOX-based chemotherapy.

Current communication practices for biomarker testing in non-small cell lung cancer: Exploring patient and clinician perspectives.

OBJECTIVES: We qualitatively explored patient and clinician experiences with biomarker testing in one academic health system to identify current communication practices and unmet testing information needs. METHODS: We conducted 1:1 in-depth interviews with 15 clinicians (i.e., nurses, oncologists, pathologists) and 12 patients diagnosed with non-small cell lung cancer between January and May 2022. Participants described experiences with biomarker testing as well as associated communication practices and needs. Interviews were audio-recorded and transcribed. Analysis was informed by the Framework Method. RESULTS: Patients described challenges retaining information early in their patient journey. While patients were generally aware of biomarkers and their effect on treatment options, they expressed limited knowledge of expected time delays between testing and receiving results. Additionally, many did not know their testing results. Clinicians and patients both noted no standard education material on biomarker testing is currently available. They suggested such materials could support patient knowledge and decision-making. CONCLUSIONS: Communication between patients and clinicians about biomarker testing is largely delivered through verbal counseling at a time when patients may be cognitively compromised. All participants supported the idea of delivering standard, tangible education materials on biomarker testing to patients. PRACTICE IMPLICATIONS: Education materials may enhance counseling efforts and patient knowledge.

Ecological niches in the polyploid complex Linum suffruticosum s.l.

Introduction: The high frequency of polyploidy in the evolutionary history of many plant groups occurring in the Mediterranean region is likely a consequence of its dynamic paleogeographic and climatic history. Polyploids frequently have distinct characteristics that allow them to overcome the minority cytotype exclusion. Such traits may enable polyploid individuals to grow in habitats different from their parentals and/or expand to new areas, leading to spatial segregation. Therefore, the successful establishment of polyploid lineages has long been associated with niche divergence or niche partitioning and the ability of polyploids to cope with different, often more stressful, conditions. In this study, we aimed to explore the role of environmental variables associated with the current distribution patterns of cytotypes within the polyploid complex Linum suffruticosum s.l.. Methods: The distribution and environmental niches of the five main cytotypes of Linum suffruticosum s.l. (diploids, tetraploids, hexaploids, octoploids and decaploids) were studied across its distribution range. Realized environmental niche of each cytotype was determined using niche modelling tools, such as maximum entropy modelling and niche equivalency and similarity tests. Results: Differences in the environmental conditions of L. suffruticosum s.l. cytotypes were observed, with polyploids being associated with habitats of increased drought and soil pH, narrower temperature ranges and decreased soil water and cation exchange capacities. Diploids present the widest environmental niche, and polyploids occupy part of the diploid niche. Although some polyploids have equivalent potential ecological niches, cytotypes do not co-occur in nature. Additionally, the ecological niche of this polyploid complex is different between continents, with North African habitats being characterised by differences in soil texture, higher pH, and low cation exchange capacity, precipitation and soil water capacity and higher temperatures than habitats in southwest Europe. Discussion: The different ecological conditions played a role in the distribution of cytotypes, but the mosaic distribution could not be entirely explained by the environmental variables included in this study. Other factors, such as reproductive isolation and competitive interactions among cytotypes, could further explain the current diversity and distribution patterns in white flax. This study provides relevant data on the niche requirements of each cytotype for further competition and reciprocal transplant experiments. further competition and reciprocal transplant experiments.

Plasmatic MicroRNAs and Treatment Outcomes of Patients with Metastatic Castration-Resistant Prostate Cancer: A Hospital-Based Cohort Study and In Silico Analysis.

Prostate cancer (PCa) is one of the most common malignancies among men worldwide. Inevitably, all advanced PCa patients develop metastatic castration-resistant prostate cancer (mCRPC), an aggressive phase of the disease. Treating mCRPC is challenging, and prognostic tools are needed for disease management. MicroRNA (miRNA) deregulation has been reported in PCa, constituting potential non-invasive prognostic biomarkers. As such, this study aimed to evaluate the prognostic potential of nine miRNAs in the liquid biopsies (plasma) of mCRPC patients treated with second-generation androgen receptor axis-targeted (ARAT) agents, abiraterone acetate (AbA) and enzalutamide (ENZ). Low expression levels of miR-16-5p and miR-145-5p in mCRPC patients treated with AbA were significantly associated with lower progression-free survival (PFS). The two miRNAs were the only predictors of the risk of disease progression in AbA-stratified analyses. Low miR-20a-5p levels in mCRPC patients with Gleason scores of <8 were associated with worse overall survival (OS). The transcript seems to predict the risk of death regardless of the ARAT agent. According to the in silico analyses, miR-16-5p, miR-145-5p, and miR-20a-5p seem to be implicated in several processes, namely, cell cycle, proliferation, migration, survival, metabolism, and angiogenesis, suggesting an epigenetic mechanism related to treatment outcome. These miRNAs may represent attractive prognostic tools to be used in mCRPC management, as well as a step further in the identification of new potential therapeutic targets, to use in combination with ARAT for an improved treatment outcome. Despite the promising results, real-world validation is necessary.

Biofilm Production by Critical Antibiotic-Resistant Pathogens from an Equine Wound.

As in human medicine, in veterinary medicine, chronic wounds are often related to polymicrobial infections and the presence of a biofilm, which compromises the effectiveness of therapeutic approaches. In this study, a Lusitano mare presented a 21-day-old chronic wound that was only being treated with an antiseptic. A swab sample was collected, and three isolates of Staphylococcus aureus and one of Pseudomonas aeruginosa were isolated. S. aureus did not show resistance to a panel of antibiotics. However, the P. aeruginosa isolate showed a resistance profile to carbapenems and fluoroquinolones, which may suggest a cross-resistance between antiseptic and antibiotics, given that no antibiotic therapy was applied to the wound or the mare in the previous year. Further experiments were conducted to assess the ability of the isolates to form biofilms, and to ascertain their susceptibility to gentamicin. The results demonstrated that the isolates produced biofilms. Gentamicin at the minimum inhibitory concentration (MIC) and 10× MIC caused biofilm removal between 59.3% and 85.7%, with the highest removal percentage being obtained for the P. aeruginosa isolate (at 10× MIC concentration). This study reveals that an equine wound was colonized by antibiotic resistant bacteria, and that all the wound colonizers could form biofilms, demonstrating the relevance of an adequate diagnosis and treatment when there is a suspicion of a biofilm-infected wound. It also highlights the possibility of resistance transmission between animals, animals and humans, or animals and the environment.

Assessment of Oxidative Stress Markers in Hypertensive Patients under the Use of Renin-Angiotensin-Aldosterone Blockers.

As in other fields, chronotherapy applied to arterial hypertension (AHT) may have implications on oxidative stress. We compared the levels of some redox markers between hypertensive patients with morning and bedtime use of renin-angiotensin-aldosterone system (RAAS) blockers. This was an observational study that included patients older than 18 years with a diagnosis of essential AHT. Blood pressure (BP) figures were measured using twenty-four-hour ambulatory BP monitoring (24-h ABPM). Lipid peroxidation and protein oxidation were assessed using the thiobarbituric acid reactive substances (TBARS) and reduced thiols assays. We recruited 70 patients with a median age of 54 years, of whom 38 (54%) were women. In hypertensive patients with bedtime use of RAAS blockers, reduced thiol levels showed a positive correlation with nocturnal diastolic BP decrease. TBARS levels were associated with bedtime use of RAAS blockers in dipper and non-dipper hypertensive patients. In non-dipper patients, bedtime use of RAAS blockers was also associated with a decrease in nocturnal diastolic BP. Chronotherapy applied to bedtime use of some BP-lowering drugs in hypertensive patients may be linked to a better redox profile.

Drinking-water isolated Delftia acidovorans selectively coaggregates with partner bacteria and facilitates multispecies biofilm development.

Coaggregation plays an important role in the development of multispecies biofilms in different environments, often serving as an active bridge between biofilm members and other organisms that, in their absence, would not integrate the sessile structure. The ability of bacteria to coaggregate has been reported for a limited number of species and strains. In this study, 38 bacterial strains isolated from drinking water (DW) were investigated for their ability to coaggregate, in a total of 115 pairs of combinations. Among these isolates, only Delftia acidovorans (strain 005P) showed coaggregating ability. Coaggregation inhibition studies have shown that the interactions mediating D. acidovorans 005P coaggregation were both polysaccharide-protein and protein-protein, depending on the interacting partner bacteria. Dual-species biofilms of D. acidovorans 005P and other DW bacteria were developed to understand the role of coaggregation on biofilm formation. Biofilm formation by Citrobacter freundii and Pseudomonas putida strains highly benefited from the presence of D. acidovorans 005P, apparently due to the production of extracellular molecules/public goods favouring microbial cooperation. This was the first time that the coaggregation capacity of D. acidovorans was demonstrated, highlighting its role in providing a metabolic opportunity for partner bacteria.

Hydrocinnamic Acid and Perillyl Alcohol Potentiate the Action of Antibiotics against Escherichia coli.

The treatment of bacterial infections has been troubled by the increased resistance to antibiotics, instigating the search for new antimicrobial therapies. Phytochemicals have demonstrated broad-spectrum and effective antibacterial effects as well as antibiotic resistance-modifying activity. In this study, perillyl alcohol and hydrocinnamic acid were characterized for their antimicrobial action against Escherichia coli. Furthermore, dual and triple combinations of these molecules with the antibiotics chloramphenicol and amoxicillin were investigated for the first time. Perillyl alcohol had a minimum inhibitory concentration (MIC) of 256 µg/mL and a minimum bactericidal concentration (MBC) of 512 µg/mL. Hydrocinnamic acid had a MIC of 2048 µg/mL and an MBC > 2048 µg/mL. Checkerboard and time-kill assays demonstrated synergism or additive effects for the dual combinations chloramphenicol/perillyl alcohol, chloramphenicol/hydrocinnamic acid, and amoxicillin/hydrocinnamic acid at low concentrations of both molecules. Combenefit analysis showed synergism for various concentrations of amoxicillin with each phytochemical. Combinations of chloramphenicol with perillyl alcohol and hydrocinnamic acid revealed synergism mainly at low concentrations of antibiotics (up to 2 µg/mL of chloramphenicol with perillyl alcohol; 0.5 µg/mL of chloramphenicol with hydrocinnamic acid). The results highlight the potential of combinatorial therapies for microbial growth control, where phytochemicals can play an important role as potentiators or resistance-modifying agents.

The role of phenylalanine levels in the neuropsychological and neuroanatomical status of adult patients with phenylketonuria: The impact of fluctuations.

We aimed to evaluate the role of plasma phenylalanine (Phe) levels and its fluctuations in some neurocognitive domains and brain magnetic resonance imaging (MRI) findings in adult patients with phenylketonuria (PKU). It was an observational study that included patients older than 18 years with early-treated classical PKU. Plasma Phe levels were measured every other month throughout 2 years and predictor variables were the mean, maximum (max), minimum (min), range (min-max), and plasma Phe levels at the time of cognitive testing. Patients were evaluated for executive function, processing speed, visual attention, and fluid cognitive abilities using the Trail Making Test (TMT) and for the presence of brain MRI abnormalities. In all, 22 patients with a mean age of 34 years were included, of which 18 (81%) were women. Patients with higher range and maximum Phe levels had a poorer time-based performance on TMT form A and form B. Patients with brain MRI abnormalities had higher range, maximum, and mean Phe levels. Range of Phe levels showed a good performance for MRI abnormalities (area under the curve (AUC): 0.881, standard error (SE): 0.095, 95% CI: 0.695-0.999, p = 0.044) and for the poorest time-based performances on TMT form A (AUC: 0.822, SE: 0.092, 95% CI: 0.641-0.999, p = 0.024) and B (AUC: 0.816, SE: 0.094, 95% CI: 0.632-0.999, p = 0.021). Greater Phe variability may have a negative impact on some neurocognitive domains and could be related to the severity of brain structural damage in adult patients with PKU.

The correlation of lipid profile and waist circumference with phenylalanine levels in adult patients with classical phenylketonuria.

INTRODUCTION AND OBJECTIVES: Some studies have pointed to a relationship between Phenyketonuria (PKU) and an increased cardiovascular risk (CVR). This study aimed to evaluate the influence of metabolic control on classical CVR factors in adult patients with PKU. MATERIAL AND METHODS: It was a cross-sectional study conducted in patients older than 18 years with a diagnosis of classical PKU and under strict dietary control. Demographic, epidemiological and laboratory variables related to CVR were collected. The variables of metabolic control were some parameters related to phenylalanine (Phe) plasma levels. RESULTS: A total of 47 patients were included with a mean age of 36±10 years of which 30 (64%) were women. Multivariate analysis revealed that range Phe (B=-2.211, P=0.044, 95%CI: -4.354-(-0.068)) levels were within the model for triglyceride concentrations, while minimum (B=-2.803, P=0.051, 95%CI: -5.612-0.007) and range (B=-1.515, P=0.039, 95%CI: -2.945-(-0.084)) Phe levels were within the model for high-density lipoprotein cholesterol concentrations. Median Phe levels showed a stronger correlation with waist circumference (WC) (B=1.216, P=0.002, 95%CI: 0.462-1.969) than with body mass index (B=0.355, P=0.052, 95%CI: -0.004-0.714). CONCLUSIONS: High Phe levels and wide Phe fluctuations were related to weight gain, increased WC and lipid profile abnormalities. Systematic CVR assessments and comprehensive monitoring of Phe levels may be desirable to prevent or delay cardiovascular disease in PKU patients.

Evidence for a Founder Effect of SDHB Exon 1 Deletion in Brazilian Patients With Paraganglioma.

CONTEXT: Limited information is available concerning the genetic spectrum of pheochromocytoma and paraganglioma (PPGL) patients in South America. Germline SDHB large deletions are very rare worldwide, but most of the individuals harboring the SDHB exon 1 deletion originated from the Iberian Peninsula. OBJECTIVE: Our aim was to investigate the spectrum of SDHB genetic defects in a large cohort of Brazilian patients with PPGLs. METHODS: Genetic investigation of 155 index PPGL patients was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification, and/or target next-generation sequencing panel. Common ancestrality was investigated by microsatellite genotyping with haplotype reconstruction, and analysis of deletion breakpoint. RESULTS: Among 155 index patients, heterozygous germline SDHB pathogenic or likely pathogenic variants were identified in 22 cases (14.2%). The heterozygous SDHB exon 1 complete deletion was the most frequent genetic defect in SDHB, identified in 8 out of 22 (36%) of patients. Haplotype analysis of 5 SDHB flanking microsatellite markers demonstrated a significant difference in haplotype frequencies in a case-control permutation test (P = 0.03). More precisely, 3 closer/informative microsatellites were shared by 6 out of 8 apparently unrelated cases (75%) (SDHB-GATA29A05-D1S2826-D1S2644 | SDHB-186-130-213), which was observed in only 1 chromosome (1/42) without SDHB exon 1 deletion (X2 = 29.43; P < 0.001). Moreover, all cases with SDHB exon 1 deletion had the same gene breakpoint pattern of a 15 678 bp deletion previously described in the Iberian Peninsula, indicating a common origin. CONCLUSION: The germline heterozygous SDHB exon 1 deletion was the most frequent genetic defect in the Brazilian PPGL cohort. Our findings demonstrated a founder effect for the SDHB exon 1 deletion in Brazilian patients with paragangliomas.