Pelvic lymph node involvement and risk of recurrence in HPV-associated endocervical adenocarcinoma stage IA2-IB1 according to Silva's system in two Colombian cancer centers.

OBJECTIVE: To compare the pelvic lymph node involvement and risk of recurrence in patients with human papillomavirus (HPV)-associated endocervical adenocarcinoma stage IA2-IB1 undergoing hysterectomy and/or trachelectomy plus lymphadenectomy, according to Silva's classification system. METHODS: A retrospective cohort study was performed in two Colombian cancer centers. The cases were classified according to the Silva classification system. Clinical, surgical, and histopathological variables were evaluated. Recurrence risk was analyzed by patterns A, B, or C. A logistic regression model was performed for tumor recurrence. The Kaplan-Meier method was used to estimate overall survival and disease-free survival (DFS). A weighted kappa was performed to determine the degree of concordance between pathologists. RESULTS: A total of 100 patients were identified, 33% pattern A, 29% pattern B, and 38% pattern C. The median follow-up time was 42.5 months. No evidence of lymph node involvement was found in patients classified as A and B, while in the C pattern was observed in 15.8% (n = 6) of cases (P < 0.01). There were 7% of cases with recurrent disease, of which 71.5% corresponded to type C pattern. Patients with Silva pattern B and C had 1.22- and 4.46-fold increased risk of relapse, respectively, compared with pattern A. The 5-year DFS values by group were 100%, 96.1%, and 80.3% for patterns A, B, and C, respectively. CONCLUSION: For patients with early-stage HPV-associated endocervical adenocarcinoma, the type C pattern presented more lymph node involvement and risk of recurrence compared to the A and B patterns. The concordance in diagnosis of different Silva's patterns by independents pathologists were good.

Reduced C-reactive protein levels after root canal treatment in clinically healthy young apical periodontitis individuals at cardiovascular risk. A prospective study.

AIM: To determine the systemic inflammatory burden, including hsCRP and its monomeric forms, in patients with apical lesions of endodontic origin treated with root canal treatment (RCT). METHODOLOGY: Prospective pre-/post-study. Apical periodontitis (AP) individuals aged 16-40 were included (N = 29). Individuals received RCT and were followed at 1 and 6 months. Fasting blood samples were obtained. Apical lesions of endodontic origin (ALEO) diameter (mm), and periapical index (PAI), were recorded. The serum concentrations of total hsCRP were determined by turbidimetry. Tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, IL-1ß, and soluble (s) E-selectin were assessed by Multiplex assay. Additionally, mCRP forms were determined in the serum of AP patients with a baseline moderate to high cardiovascular risk based on hsCRP stratification (hsCRP ≥1 mg/L) by immunowestern blot (n = 15). Also, CRP isoforms were explored in ALEOs from AP individuals (n = 4). Data were analysed with StataV16. RESULTS: Periapical index and ALEO sizes were reduced at both follow-up visits after RCT (p < .05). Serum levels of TNF-α, IL-6, IL-10, IL-1ß, and sE-selectin did not show significant differences. CRP was borderline reduced at 1 month (p = .04); however, in AP individuals at cardiovascular risk (hsCRP ≥ 1 mg/L), hsCRP and its monomeric isoform significantly decreased at 1 and 6 months (p < .05). CONCLUSIONS: High-sensitivity CRP and mCRP are reduced after RCT in AP individuals at cardiovascular risk.

Generation of a human induced pluripotent stem cell line (OGIi001) from peripheral blood mononuclear cells of a healthy male donor.

We have successfully derived a novel human induced pluripotent stem cell (hiPSC) line using non-integrative Sendai virus. This hiPSC line was generated from a healthy male adult donor, aged 55, and subjected to thorough characterization and extensive quality control. The analysis confirmed the expression of undifferentiated stem cell markers, demonstrated the ability to differentiate into the three germ layers, and revealed the absence of any chromosomal abnormalities.

Association of Periodontitis and Atopic Dermatitis with the Levels of IL-13, IL-31, and TSLP in the Gingival Crevicular Fluid.

Emerging epidemiological evidence links atopic dermatitis (AD) and periodontitis, although the mechanisms remain unclear. Th2-derived cytokines are key in the development of both diseases, and different gingival crevicular fluid (GCF) profiles among healthy and diseased subjects have been previously reported. This case-control study examined the GCF levels of interleukins (IL)-13, IL-31, and thymic stromal lymphopoietin (TSLP) in 29 subjects with moderate-to-severe AD and 33 controls. All subjects underwent comprehensive clinical and oral evaluations, followed by GCF collection. GCF levels of IL-13, IL-31, and TSLP were assessed using a multiplex-bead immunoassay. Demographic and periodontal parameters were similar among groups (p > 0.05). The GCF levels of IL-31 and TSLP were higher in AD subjects compared to controls (p < 0.05), whereas no significant differences in the GCF levels of IL-13 were noticed (p = 0.377). Moderate-to-severe AD was positively associated with the GCF levels of IL-31 and TSLP, whereas severe periodontitis was negatively associated with IL-31 (p < 0.05). The GCF levels of IL-13 showed no significant associations with either condition (p = 0.689). There was no significant interaction between AD and periodontitis for IL-31 (p < 0.869). These results suggest that AD and periodontitis independently influence the GCF levels of IL-31 in opposing ways, whereas AD alone influences the levels of TSLP.

Inhibition of pepper huasteco yellow veins virus by foliar application of ZnO nanoparticles in Capsicum annuum L.

The Pepper huasteco yellow vein virus (PHYVV) is an endemic geminivirus in Mexico causing partial or total losses in the pepper crop since the damage caused by the virus has not been fully controlled. In this work, we evaluated the effect of ZnO NPs (0, 50, 100, 150, and 200 mM) as a preventive (72 h before) and curative (72 h after) treatment of PHYVV infection in two jalapeño pepper varieties. In this study, we observed a decrease in symptoms, and it could be caused by an induction of the defense system in pepper plants and a direct action on PHYVV by foliar application of ZnO NPs. Our findings suggest that ZnO NP application significantly decreased the viral titer for both varieties at 200 mM by 15.11-fold. However, this effect was different depending on the timing of application and the variety of pepper. The greatest decrease in the viral titer in the preventive treatment in both varieties was at the concentration of 200 mM (1781.17 and 274.5 times, respectively). For curative treatment in cv. Don Pancho at the concentration of 200 mM (333.33 times) and cv. Don Benito at 100 mM (43.10 folds). compared to control. Furthermore, virus mobility was generally restricted for both varieties at 100 mM (15.13-fold) compared to the control. The results possibly delineated that ZnO NPs increased plant resistance possibly by increasing POD (2.08 and 0.25 times) and SOD (0.998 and 1.38) in cv. Don Pancho and cv. Don Benito, respectively. On the other hand, in cv. Don Pancho and cv. Don Benito presented a decrease in CAT (0.61 and 0.058) and PAL (0.78 and 0.77), respectively. Taken together, we provide the first evidence to demonstrate the effect of ZnO NPs on viral symptoms depending on the plan-virus-ZnO NP interaction.

Sperm morphology and comparison morphometry measurements of two species of bats, Molossus molossus and Molossops temminckii (Chiroptera: Molossidae).

Sperm morphology is considered a species-specific character and has been used as a tool in the classification of numerous mammalian taxa. Neotropical bats have been poorly studied, and important aspects on sperm morphology have not been elucidated. The aim of the present study was to describe and compare the sperm morphology and morphometry of Molossus molossus and Molossops temminckii. A total of 14 adults specimens were analyzed from the Colección Mamíferos Lillo, Universidad Nacional de Tucumán: five M. molossus and nine M. temminckii. The epididymis were extracted and macerated in Farmer's solution, followed by a coloration with different stains. To carry out the description and morphometric analysis, microphotographs were taken under an optical, epifluorescence, and scanning electron microscope (SEM). A total of 50 sperm from each individual were measured for morphometric analysis. The length and width of the head, midpiece and tail were taken as variables. Sperm from M. molossus and M. temminckii were practically identical, both morphologically and morphometrically. In both species, a distal bulge was observed at the end of the intermediate piece in a percentage greater than 85%. The main characteristics shared between the species were: presence of acrosomal blebs in the upper half of the head of the spermatozoa; cephalic equatorial segment with filiform ornamentations; intermembrane space of head apex wedge-shaped; helical middle piece and annulus at the end of middle piece. In the present study, SEM allowed us to visualize structures, such as acrosomal vesicles, that were not detected with other types of microscopy. RESEARCH HIGHLIGHTS: The similarities in the sperm morphology between M. molossus and M. temminckii were observed with three types of microscopy: optical, epifluorescence and scanning electron, and supported by morphometric and statistical analyses.

Biomethane is produced by acetate cleavage, not direct interspecies electron transfer: genome-centric view and carbon isotope.

Understanding the source of methane (CH4) is of great significance for improving the anaerobic fermentation efficiency in bioengineering, and for mitigating the emission potential of natural ecosystems. Microbes involved in the process named direct interspecies electron transfer coupling with CO2 reduction, i.e., electrons released from electroactive bacteria to reduce CO2 into CH4, have attracted considerable attention for wastewater treatment in the past decade. However, how the synergistic effect of microbiota contributes to this anaerobic carbon metabolism accompanied by CH4 production still remains poorly understood, especial for wastewater with antibiotic exposure. Results show that enhancing lower-abundant acetoclastic methanogens and acetogenic bacteria, rather than electroactive bacteria, contributed to CH4 production, based on a metagenome-assembled genomes network analysis. Natural and artificial isotope tracing of CH4 further confirmed that CH4 mainly originated from acetoclastic methanogenesis. These findings reveal the contribution of direct acetate cleavage (acetoclastic methanogenesis) and provide insightsfor further regulation of methanogenic strategies.

Granuloma piogénico oral de comportamiento agresivo: Reporte de un caso

El granuloma piogénico es una lesión vascular reactiva benigna del tejido blando que surge en respuesta a irritantes crónicos de bajo grado. Rara vez crece más de 2 cm de diámetro y por lo general, no provoca cambios en el hueso alveolar. Presentamos un caso inusual de granuloma piógeno en una mujer de 19 años, de extenso tamaño y comportamiento agresivo, asociado a resorción ósea severa, movilidad dentaria, hemorragia, anemia ferropénica y recurrencias.

Pyogenic granuloma is a benign reactive vascular lesion of the soft tissue that arises in response to chronic low-grade irritants. It rarely grows more than 2 cm in diameter and usually does not cause changes in the alveolar bone. We present the case of a 19-year-old woman with an unusual pyogenic granuloma of extensive size and aggressive behavior, associated with severe bone resorption, tooth mobility, hemorrhage, iron deficiency anemia and recurrences.

Transitional dendritic cells are distinct from conventional DC2 precursors and mediate proinflammatory antiviral responses.

High-dimensional approaches have revealed heterogeneity amongst dendritic cells (DCs), including a population of transitional DCs (tDCs) in mice and humans. However, the origin and relationship of tDCs to other DC subsets has been unclear. Here we show that tDCs are distinct from other well-characterized DCs and conventional DC precursors (pre-cDCs). We demonstrate that tDCs originate from bone marrow progenitors shared with plasmacytoid DCs (pDCs). In the periphery, tDCs contribute to the pool of ESAM+ type 2 DCs (DC2s), and these DC2s have pDC-related developmental features. Different from pre-cDCs, tDCs have less turnover, capture antigen, respond to stimuli and activate antigen-specific naïve T cells, all characteristics of differentiated DCs. Different from pDCs, viral sensing by tDCs results in IL-1ß secretion and fatal immune pathology in a murine coronavirus model. Our findings suggest that tDCs are a distinct pDC-related subset with a DC2 differentiation potential and unique proinflammatory function during viral infections.

Lipopolysaccharides from Porphyromonas endodontalis and Porphyromonas gingivalis promote angiogenesis via Toll-like-receptors 2 and 4 pathways in vitro.

AIM: Angiogenesis contributes to the development of apical periodontitis, periodontitis, and other oral pathologies; however, it remains unclear how this process is triggered. The aim was to evaluate whether lipopolysaccharide (LPS) from Porphyromonas endodontalis and Porphyromonas gingivalis induced angiogenesis-related effects in vitro via TLR2 and TLR4. METHODOLOGY: Porphyromonas endodontalis LPS (ATCC 35406 and clinical isolate) was purified with TRIzol, whereas P. gingivalis LPS was obtained commercially. The effects of the different LPS (24 h) in endothelial cell migration were analysed by Transwell assays, following quantification in an optical microscope (40×). The effects of LPS on FAK Y397 phosphorylation were assessed by Western blotting. Angiogenesis in vitro was determined in an endothelial tube formation assay (14 h) in Matrigel in the absence or presence of either LPS. IL-6 and VEGF-A levels were determined in cell supernatants, following 24 h treatment with LPS, and measured in multiplex bead immunoassay. The involvement of TLR2 and TLR4 was assessed with blocking antibodies. The statistical analysis was performed using STATA 12® (StataCorp LP). RESULTS: The results revealed that P. endodontalis LPS, but not P. gingivalis LPS, stimulated endothelial cell migration. Pre-treatment with anti-TLR2 and anti-TLR4 antibodies prevented P. endodontalis LPS-induced cell migration. P. endodontalis LPS promoted FAK phosphorylation on Y397, as observed by an increased p-FAK/FAK ratio. Both P. gingivalis and P. endodontalis LPS (ATCC 35406) induced endothelial tube formation in a TLR-2 and -4-dependent manner, as shown by using blocking antibodies, however, only TLR2 blocking decreased tube formation induced by P. endodontalis (clinical isolate). Moreover, all LPS induced IL-6 and VEGF-A synthesis in endothelial cells. TLR2 and TLR4 were required for IL-6 induction by P. endodontalis LPS (ATCC 35406), while only TLR4 was involved in IL-6 secretion by the other LPS. Finally, VEGF-A synthesis did not require TLR signalling. CONCLUSION: Porphyromonas endodontalis and P. gingivalis LPS induced angiogenesis via TLR2 and TLR4. Collectively, these data contribute to understanding the role of LPS from Porphyromonas spp. in angiogenesis and TLR involvement.

Obesity is related to maternal periodontitis severity in pregnancy: a cross-sectional study.

OBJECTIVES: To evaluate the relationship between obesity and periodontitis staging compared with periodontal healthy or gingivitis in pregnant women. MATERIALS AND METHODS: An analytical cross-sectional study was conducted on pregnant women between 11 and 14 weeks of pregnancy. Sociodemographic, clinical, obstetric, and periodontal variables were studied. The exposure variable was obesity (body mass index [BMI] ≥ 30), and the primary outcome was periodontitis staging versus periodontal healthy/gingivitis. Data were analysed and estimated by multinomial logistic regression models. RESULTS: The present study screened 1086 pregnancies and analysed 972 women with a median age of 29 years; 36.8% were diagnosed as obese. 26.9% of patients were diagnosed as periodontal healthy or gingivitis, 5.5% with stage I periodontitis, 38.6% with stage II periodontitis, 24% with stage III periodontitis, and 5.1% with stage IV periodontitis. After identifying and adjusting for confounding variables (educational level and plaque index), obesity had a relative risk ratio (RRR) of 1.66 (95% CI: 1.05-2.64; p = 0.03) and 1.57 (95% CI: 1.09-2.27; p = 0.015) for stage III periodontitis compared to periodontal healthy/gingivitis and stage II periodontitis, respectively. CONCLUSION: Besides the already known risk indicators for periodontitis (age, smoking, and educational level), our study suggests a relationship between obesity and periodontitis staging in pregnancy. CLINICAL RELEVANCE: Obesity can alter host immune responses, leading to increased susceptibility to infections and overactive host immunity, which could influence the prevalence and severity of maternal periodontitis in pregnancy.

Identification of diverse antibiotic resistant bacteria in agricultural soil with H218O stable isotope probing combined with high-throughput sequencing.

BACKGROUND: We aimed to identify bacteria able to grow in the presence of several antibiotics including the ultra-broad-spectrum antibiotic meropenem in a British agricultural soil by combining DNA stable isotope probing (SIP) with high throughput sequencing. Soil was incubated with cefotaxime, meropenem, ciprofloxacin and trimethoprim in 18O-water. Metagenomes and the V4 region of the 16S rRNA gene from the labelled "heavy" and the unlabelled "light" SIP fractions were sequenced. RESULTS: An increase of the 16S rRNA copy numbers in the "heavy" fractions of the treatments with 18O-water compared with their controls was detected. The treatments resulted in differences in the community composition of bacteria. Members of the phyla Acidobacteriota (formally Acidobacteria) were highly abundant after two days of incubation with antibiotics. Pseudomonadota (formally Proteobacteria) including Stenotrophomonas were prominent after four days of incubation. Furthermore, a metagenome-assembled genome (MAG-1) from the genus Stenotrophomonas (90.7% complete) was retrieved from the heavy fraction. Finally, 11 antimicrobial resistance genes (ARGs) were identified in the unbinned-assembled heavy fractions, and 10 ARGs were identified in MAG-1. In comparison, only two ARGs from the unbinned-assembled light fractions were identified. CONCLUSIONS: The results indicate that both non-pathogenic soil-dwelling bacteria as well as potential clinical pathogens are present in this agricultural soil and several ARGs were identified from the labelled communities, but it is still unclear if horizontal gene transfer between these groups can occur.

Thrive or survive: prokaryotic life in hypersaline soils.

BACKGROUND: Soil services are central to life on the planet, with microorganisms as their main drivers. Thus, the evaluation of soil quality requires an understanding of the principles and factors governing microbial dynamics within it. High salt content is a constraint for life affecting more than 900 million hectares of land, a number predicted to rise at an alarming rate due to changing climate. Nevertheless, little is known about how microbial life unfolds in these habitats. In this study, DNA stable-isotope probing (DNA-SIP) with 18O-water was used to determine for the first time the taxa able to grow in hypersaline soil samples (ECe = 97.02 dS/m). We further evaluated the role of light on prokaryotes growth in this habitat. RESULTS: We detected growth of both archaea and bacteria, with taxon-specific growth patterns providing insights into the drivers of success in saline soils. Phylotypes related to extreme halophiles, including haloarchaea and Salinibacter, which share an energetically efficient mechanism for salt adaptation (salt-in strategy), dominated the active community. Bacteria related to moderately halophilic and halotolerant taxa, such as Staphylococcus, Aliifodinibius, Bradymonadales or Chitinophagales also grew during the incubations, but they incorporated less heavy isotope. Light did not stimulate prokaryotic photosynthesis but instead restricted the growth of most bacteria and reduced the diversity of archaea that grew. CONCLUSIONS: The results of this study suggest that life in saline soils is energetically expensive and that soil heterogeneity and traits such as exopolysaccharide production or predation may support growth in hypersaline soils. The contribution of phototrophy to supporting the heterotrophic community in saline soils remains unclear. This study paves the way toward a more comprehensive understanding of the functioning of these environments, which is fundamental to their management. Furthermore, it illustrates the potential of further research in saline soils to deepen our understanding of the effect of salinity on microbial communities.

Diversity and assembly of active bacteria and their potential function along soil aggregates in a paddy field.

Numerous studies have found that soil microbiomes differ at the aggregate level indicating they provide spatially heterogeneous habitats for microbial communities to develop. However, an understanding of the assembly processes and the functional profile of microbes at the aggregate level remain largely rudimentary, particularly for those active members in soil aggregates. In this study, we investigated the diversity, co-occurrence network, assembly process and predictive functional profile of active bacteria in aggregates of different sizes using H218O-based DNA stable isotope probing (SIP) and 16S rRNA gene sequencing. Most of the bacterial reads were active with 91 % of total reads incorporating labelled water during the incubation. The active microbial community belonged mostly of Proteobacteria and Actinobacteria, with a relative abundance of 55.32 % and 28.12 %, respectively. Assembly processes of the active bacteria were more stochastic than total bacteria, while the assembly processes of total bacteria were more influenced by deterministic processes. Furthermore, many functional profiles such as environmental information processing increased in active bacteria (19.39 %) compared to total bacteria (11.22 %). After incubation, the diversity and relative abundance of active bacteria of certain phyla increased, such as Proteobacteria (50.70 % to 59.95 %), Gemmatimonadetes (2.63 % to 4.11 %), and Bacteroidetes (1.50 % to 2.84 %). In small macroaggregates (SMA: 0.25-2 mm), the active bacterial community and its assembly processes differed from that of other soil aggregates (MA: microaggregates, <0.25 mm; LMA: large macroaggregates, 2-4 mm). For functional profiles, the relative abundance of important functions, such as amino acid metabolism, signal transduction and cell motility, increased with incubation days and/or in SMA compared to other aggregates. This study provides robust evidence that the community of active bacteria and its assembly processes in soil aggregates differed from total bacteria, and suggests the importance of dominant active bacteria (such as Proteobacteria) for the predicted functional profiles in the soil ecosystem.

A Pathogenic Variant Reclassified to the Pseudogene PMS2P1 in a Patient with Suspected Hereditary Cancer.

The PMS2 gene is involved in DNA repair by the mismatch repair pathway. Deficiencies in this mechanism have been associated with Lynch Syndrome (LS), which is characterized by a high risk for colorectal, endometrial, ovarian, breast, and other cancers. Germinal pathogenic variants of PMS2 are associated with up to 5% of all cases of LS. The prevalence is overestimated for the existence of multiple homologous pseudogenes. We report the case of a 44-year-old woman diagnosed with breast cancer at 34 years without a relevant cancer family history. The presence of pathogenic variant NM_000535.7:c.1A > T, (p.Met1Leu) in PMS2 was determined by next-generation sequencing analysis with a panel of 322 cancer-associated genes and confirmed by capillary sequencing in the patient. The variant was determined in six family members (brothers, sisters, and a son) and seven non-cancerous unrelated individuals. Analysis of the amplified region showed high homology of PMS2 with five of its pseudogenes. We determined that the variant is associated with the PMS2P1 pseudogene following sequence alignment analysis. We propose considering the variant c.1A > T, (p.Met1Leu) in PMS2 for reclassification as not hereditary cancer-related, given the impact on the diagnosis and treatment of cancer patients and families carrying this variant.

Distinct responses of soil methanotrophy in hummocks and hollows to simulated glacier meltwater and temperature rise in Tibetan glacier foreland.

Glacier foreland soils are known to be essential methane (CH4) consumers. However, global warming and increased glacier meltwater have turned some foreland meadows into swamp meadows. The potential impact of this change on the function of foreland soils in methane consumption remains unclear. Therefore, we collected Tibetan glacier foreland soils in the non-melting season from typical microtopography in swamp meadows (hummock and hollow). Three soil moisture conditions (moist, saturated, and submerged) were set by adding glacier runoff water. Soil samples were then incubated in the laboratory for two weeks at 10 °C and 20 °C. About 5 % of 13CH4/12CH4 was added to the incubation bottles, and daily methane concentrations were measured. DNA stable isotope probing (DNA-SIP) and high-throughput sequencing were combined to target the active methanotroph populations. The results showed that type Ia methanotrophs, including Crenothrix, Methylobacter, and an unclassified Methylomonadaceae cluster, actively oxidized methane at 10 °C and 20 °C. There were distinct responses of methanotrophs to soil moisture rises in hummock and hollow soils, resulting in different methane oxidation potentials. In both hummock and hollow soils, the methane oxidation potential was positively correlated with temperature. Furthermore, saturated hummock soils exhibited the highest methane oxidation potential and methanotroph populations, while submerged hollow soils had the lowest. This suggests that the in-situ hummock soils, generally saturated with water, are more essential than in-situ hollows, typically submerged in water, for alleviating the global warming potential of swamp meadows in the Tibetan glacier foreland during the growing season.

A Previously Unrecognized Molecular Landscape of Lynch Syndrome in the Mexican Population.

Lynch syndrome (LS) is the main hereditary colorectal cancer syndrome. There have been few reports regarding the clinical and molecular characteristics of LS patients in Latin America; this is particularly true in the Mexican population, where no information is available. The present study aims to describe the clinical and molecular spectrum of variants in a cohort of patients diagnosed with LS in Mexico. We present a retrospective analysis of 412 patients with suspected LS, whose main site of cancer diagnosis was the colon (58.25%), followed by the endometrium (18.93%). Next-generation sequencing analysis, with an extensive multigene panel, showed that 27.1% (112/414) had a variant in one of the genes of the mismatch repair pathway (MMR); 30.4% (126/414) had a variant in non-MMR genes such as CHEK2, APC, MUTYH, BRCA1, and BRCA2; and 42.5% (176/414) had no genetic variants. Most of the variants were found in MLH1. Pathogenic variants (PVs) in MMR genes were identified in 65.7% (96/146) of the total PVs, and 34.24% (45/146) were in non-MMR genes. Molecular and clinical characterization of patients with LS in specific populations allowed personalized follow-up, with the option for targeted treatment with immune checkpoint inhibitors and the development of public health policies. Moreover, such characterization allows for family cascade testing and consequent prevention strategies.