Gene variants for the WNT pathway are associated with severity in periodontal disease.

OBJECTIVE: Studies of Wnt variants-related to bone resorption in periodontitis are limited. The aim of this study was to establish the genotype and allele frequency of gene variants associated with the Wnt pathway in systemically healthy individuals with and without periodontitis (PD). MATERIALS AND METHODS: One hundred fifty-seven systemically healthy individuals were evaluated, 90 with PD and 67 without PD. Periodontal clinical indexes, serological and clinical indices of inflammation, and the following variants associated with the Wnt pathway: DKK, SOST, LRP5, and KREMEN were analyzed by high resolution melting and confirmed by Sanger sequencing. RESULTS: In the PD-free group, 67.2% of the individuals presented the variant for DKKrs1896367 (p = 0.008) and 82.6% had the variant for KREMEN rs132274 (p = 0.016). The heterozygous variant for the DKK rs1896367 polymorphism was associated with the absence of PD and lower severity OR: 0.33 (CI95% 0.15-0.70) and OR: 0.24 (CI95% 0.11-0.53), respectively. Similarly, KREMEN rs132274 was the homozygous variant associated with the absence of PD (OR: 0.33 (CI95% 0.13-0.88)). On the contrary, 85.6% of individuals with PD presented a variant for DKK rs1896368 (p = 0.042), all suffering severe forms of periodontitis. CONCLUSION: The presence of DKKrs1896367 and KREMENrs132274 variants in individuals without PD suggests that these single nucleotide polymorphisms could be protective factors for bone loss in PD. A very interesting finding is that the DKKrs1896368 variant was found in a high percentage of severe cases, suggesting that the presence of this variant may be related to the severe bone loss observed in PD.

Physicochemical Characterization, Antioxidant, and Proliferative Activity of Colombian Propolis Extracts: A Comparative Study.

Propolis extracts have been widely studied due to their popularity in traditional medicine, presenting incredible biodiversity. This study aimed to analyze propolis extracts' phytochemical, physicochemical, and biological activities from four different biogeographic zones of the Huila region (Colombia). The raw material samples were collected by the scraping method and the ethanolic extracts (EEPs) were obtained by cold maceration with ethanol (96%). The physicochemical and sensory characterization was carried out according to the protocols recommended by the Brazilian Ministry of Agriculture and the main components of the EEPs were identified by LC-HRMS analysis. The determination of total phenols and flavonoids was carried out using colorimetric techniques. The antioxidant activity, cytotoxicity, and cell cycle regulation analyses in L929 and HGnF cells were evaluated using DPPH, Alamar Blue, and 7-amino actinomycin D (7-AAD) assays. The propolis samples presented an average yield of 33.1%, humidity between 1.6 and 2.8%, melting point between 54 and 62 °C, ashes between 1.40 and 2.19%, and waxes of 6.6-17.9%, respectively. The sensory characteristics of all samples were heterogeneous, complying with the quality specifications established by international standards. The polyphenolic and total flavonoid content was representative in the samples from Quebradon (255.9 ± 9.2 mg GAE/g, 543.1 ± 8.4 mg QE/g) and Arcadia (543.1 ± 8.4 mg GAE/g, 32.5 ± 1.18 g QE/g) (p < 0.05) that correlated with high antioxidant activity (Quebradon: 37.2 ± 1.2 µmol/g, Arcadia: 38.19 ± 0.7 µmol/g). In the chemical composition analysis, 19 compounds were characterized as phenolic acids and flavonoids, the most representative being chrysoeriol-O-methyl-ether, ellagic acid, and 3,4-O-dimethylcaffeic acid. Regarding biological activity, Quebradon and Arcadia propolis presented low toxicity with IC50 of 2.83 ± 2.3 mg/mL and 4.28 ± 1.4 mg/mL in HGnF cells, respectively, and an arrest of the cell cycle in the G2/M phase of 71.6% and 50.8% compared to the control (11.9%) (p < 0.05). In general, the results of this study contribute to the identification of valid quality criteria to evaluate Colombian propolis, contributing to its study and chemical and biological characterization as a source of raw material for industrial and pharmaceutical use. In addition, Quebradon and Arcadia propolis can be important sources of bioactive molecules for the development of new drugs.

Aspirin 15cH has Different Effects on Morphology and Function of Lipopolysaccharide-Challenged RAW 264.7 Macrophages In Vitro Compared to a Pharmacological Dose of Aspirin.

INTRODUCTION: Aspirin is one of the most commonly used drugs worldwide. It is known to present antipyretic, anti-inflammatory and anti-thrombotic actions, making it extremely useful in a wide range of clinical contexts. Interestingly, homeopathically prepared Aspirin 15cH has been found to have a pro-thrombotic effect in rats, raising the hypothesis that Aspirin 15cH could also modulate the activity of inflammatory cells in different pathological processes. OBJECTIVE: Our objective was to assess what effect Aspirin 15cH has on RAW 264.7 macrophages in vitro. METHODS: The effects of Aspirin 15cH on biochemical and morphological activities of lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages were evaluated. These effects were compared with unchallenged macrophages (negative control), untreated LPS-stimulated macrophages, macrophages treated with succussed water (vehicle control), or aspirin 200 µg/mL (pharmacological inhibitor of LPS activity). Cell morphology (adhered cell area and cytoskeleton arrangements), cell viability, toll-like receptor-4 (TLR-4) expression, and the production of nitric oxide, cytokines and intracellular reactive oxygen species were assessed. RESULTS: Aspirin 15cH reduced the number of cells expressing TLR-4 on the surface (p = 0.03) and induced a "columnar" morphology of macrophage pseudopods, indicating changes in cytoskeleton arrangement. When cells were treated with both Aspirin 15cH and LPS, cell morphology became heterogeneous, suggesting that sub-populations of cells had differing sensitivities to LPS or Aspirin 15cH. Exposure of the cells to LPS alone, succussed water or aspirin 200 µg/mL produced effects consistent with the literature. CONCLUSION: Aspirin 15cH, aspirin 200 µg/mL, LPS and succussed water appear to act as independent stimuli able to induce different patterns of macrophage response. Aspirin 15cH induced changes suggestive of M2 polarization of the macrophages (i.e., toward a wound healing or tissue repair, rather than inflammatory, phenotype). These preliminary findings need to be confirmed in further specific studies.

Chemopreventive and Anti-tumor Potential of Natural Products in Oral Cancer.

Oral cancer (OC) is a multifactorial disease caused by isolated or combined risk factors related to tobacco, alcohol consumption, and human papillomavirus infection. It is an aggressive pathology with a low five-year survival rate after surgery, chemotherapy, and/or radiotherapy, frequently associated with severe side effects. Drugs with the highest anti-tumor effect are obtained from natural products with diverse biological and molecular activities and potential chemopreventive and anticancer properties. This review summarizes the natural products reported to have the chemopreventive and anti-tumor potential for OC treatment, showing that several of these compounds are promising candidates as chemopreventive agents, and those with the highest anti-tumor potential induce apoptosis and inhibit proliferation and metastasis-related processes. For this reason, natural products have the potential to be important preventive and therapeutic options for OC in the future.

Modelling the Reduction in Cancer Incidence After Variations in the Prevalence of Tobacco Consumption in Colombia in the Period 2016-2050.

OBJECTIVE: To evaluate the potential impact of tobacco reduction on future cancer incidence in Colombia. INTRODUCTION: Colombia has implemented multiple actions that led to reducing smoking prevalence in recent years. However, the numbers of cancer cases and deaths associated with smoking exposure remain high highlighting the importance of maintaining efforts to reduce and keep smoking prevalence low. METHODS: We performed a theoretical modeling exercise, projecting expected changes in the incidence of four cancers between 2016 and 2050 under two simulated scenarios of smoking reduction. RESULTS: A cumulative decline of 10% in the prevalence of smoking, a percentage in line with current cigarette taxation policies, will decrease cancer incidence in 2050 by 3.2%, .5%, .2% and .2% of lung, liver, cervical and colorectal cancer incidence, respectively. Complete elimination of tobacco consumption will reduce these by 39.1%, 6.1%, 2.2% and 2.3% respectively, by 2050. CONCLUSION: These results highlight the importance of continuity and reinforcement of current tobacco control programs, including increasing taxation, to further reduce the prevalence of tobacco smoking and reduce cancer cases and deaths in the coming decades.

AR-V7 as a Biomarker for Resistance to Treatment with Abiraterone/Enzalutamide in Three Latin American Countries: A Hypothetical Cost-Saving Analysis.

BACKGROUND: Prostate cancer is the most incident and one of the deadliest male cancers in Latin America. Treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) includes androgen receptor signaling inhibitors such as abiraterone and enzalutamide, for which androgen receptor splice variant 7 (AR-V7) has emerged as a biomarker for primary resistance. Our study sought to analyze the potential economic impact of the use of AR-V7 detection as a treatment indicator in patients with mCRPC in three Latin American countries. MATERIALS AND METHODS: A hypothetical cost prediction model for the use of noninvasive circulating tumor cell-based AR-V7 testing as a treatment indicator for patients eligible for treatment with abiraterone/enzalutamide was conducted using available information on treatment and testing costs from Mexico, Argentina, and Colombia. RESULTS: At an estimated prevalence of AR-V7 positivity of 20%, the use of upfront AR-V7 genetic testing resulted in annual net savings of $9,801,669.97, $6,390,055.75, and $3,096,780.91 in Mexico, Argentina, and Colombia, respectively. A direct relationship between AR-V7 positivity prevalence and net savings was found. CONCLUSION: The use of a noninvasive AR-V7 detection assay as a treatment indicator tool in patients eligible for treatment with abiraterone or enzalutamide in Latin America could be a cost-effective approach for the management of these patients. Additional efforts are needed to accurately determine the incidence of castration-resistant prostate cancer cases and the prevalence of AR-V7 positivity in Latin America in order to predict the potential economic benefit of its clinical use. IMPLICATIONS FOR PRACTICE: In Latin America, prostate cancer is the most frequently diagnosed cancer in men, and the burden of this disease is expected to double in this region by 2030. Noninvasive detection of androgen receptor splice variant 7 (AR-V7) is being currently validated as a predictive biomarker for benefit with androgen receptor signaling inhibitor therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). This hypothetical cost-saving analysis shows that AR-V7 testing in peripheral blood of patients with CRPC eligible for treatment with abiraterone or enzalutamide might represent a cost-effective strategy to select patients who will benefit from AR-axis-directed treatment in three Latin American countries.

Association of Dickkopf-1 Polymorphisms With Radiological Damage and Periodontal Disease in Patients With Early Rheumatoid Arthritis: A Cross-Sectional Study.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease that increased bone resorption. Periodontal disease (PD) is an associated risk factor of RA. Studies suggest an association between bone markers such as the dickkopf-related protein 1 (DKK-1) and progression of radiological damage. We aimed to evaluate the marker DKK-1, its polymorphisms in patients with early rheumatoid arthritis (eRA), and its association with rheumatic, radiological, and periodontal variables. METHODS: This is a cross-sectional study. Samples were obtained from 63 patients with eRA. Radiographs of hands and feet were evaluated by Sharp-van der Heijde score (SHS) and Simple Erosion Narrowing Score (SENS). Serum DKK-1 levels and high-resolution fusion analysis was used for polymorphisms (rs1896368, rs1896367, rs1528873). Bivariate analyses were performed. RESULTS: Individuals heterozygous for rs1896367 had more frequent erosions (p = 0.026) and joint space narrowing (p = 0.005) in the feet, higher SHS (p = 0.016), and higher SENS (p ≤ 0.001). Patients homozygous for rs1896368 had less frequent joint space narrowing in hands and feet as assessed by SHS and less presence of erosions by SENS (odds ratio, 0.04; 95% confidence interval, 0.00-0.93; p < 0.05). The presence of PD was associated with the homozygous of rs1896367 (p = 0.009) and the heterozygous of rs1896368 (p = 0.033). CONCLUSIONS: Polymorphism rs1896367 seems to be associated with greater radiological compromise; rs1896368 confers protection against bone damage in Colombian eRA patients.

Laminin 332 functionalized surface improve implant roughness and oral keratinocyte bioactivity.

Objective: The biological seal (BS) at the implant-tissue interface is essential for the success of dental implants (DIs), and the absence of a proper BS can lead to peri-implantitis. The basement membrane (BM) and junctional epithelium are critical for sealing the peri-implant mucosa, and laminin 332 is an important protein in binding the epithelium to the implant surface. The aim of this study was to evaluate the response of oral keratinocytes to titanium dental implant surfaces biofunctionalized with laminin 332. Design: The dental implant surface was treated with a piranha solution to create hydroxyl (OH) groups, facilitating biofunctionalization with laminin 332. The modified surface underwent scanning electron microscopy, surface roughness evaluation, and chemical composition analysis. Human keratinocytes from the Cal-27 line were then cultured on the modified implants for 24 and 48 h to assess viability, morphology, cytokine secretion, and mRNA expression of tissue repair-associated genes. Results: The results showed that laminin 332 biofunctionalization of the implant surface resulted in lower values of Ra, Rq and positive surface roughness parameters Rsk, Rku and Rv. The elemental composition showed an increase in nitrogen and carbon content corresponding to protein binding. The biofunctionalized surfaces did not affect cell viability and promoted cytokine secretion (IL-1a and IL-8) and a significant increase (p < 0.05) in MCP-1, EGF, FGF, TGF and VEGF gene expression compared to the control. Conclusion: In conclusion, laminin 332 coating Ti implants was shown to be effective in promoting keratinocyte adhesion, spreading, and viability. This approach could be an alternative way to improve biocompatibility.

Down-regulation of human papillomavirus E6 oncogene and antiproliferative effect of Schisandra chinensis and Pueraria lobata natural extracts on Hela cell line.

ETHNOPHARMACOLOGICAL RELEVANCE: Cervical cancer is one of the most common malignancies in women that continues to be a public health problem worldwide. Human papillomavirus (HPV) infection is closely related as the causative agent of almost all cases of cervical cancer. Currently, there is no effective treatment for the persistence of HPV. Although vaccines have shown promising results in recent years, they are still a costly strategy for developing countries and have no therapeutic effect on existing infections, which is why the need arises to search for new strategies that can be used in treatment, suppressing oncogenic HPV and disease progression. Extracts of Schisandra Chinensis and Pueraria lobata have been used in traditional medicine, and it has been shown in recent years that some of their bioactive compounds have pharmacological, antioxidant, antitumor, apoptotic, and proliferation effects in HPV-positive cells. However, its mechanism of action has yet to be fully explored. AIM OF THE STUDY: The following study aimed to determine the chemical composition, antioxidant activity, and potential antiproliferative and viral oncogene effects of natural extracts of S. chinensis and P. lobata on HPV-18 positive cervical cancer cells. MATERIALS AND METHODS: The HPV-18-positive HeLa cells were treated for 24 and 48 h with the ethanolic extracts of S chinensis and P. lobata. Subsequently, cell viability was evaluated using the resazurin method, the effect on the cell cycle of the extracts (1.0, 10, and 100 µg/mL) was measured by flow cytometry, the gene of expression of the E6/E7, P53, BCL-2, and E2F-1 were determined by RT-PCR and the protein expression of p53, Ki-67, x|and Bcl-2 by immunohistochemistry. Additionally, the chemical characterization of the two extracts was carried out using LC-MS, and the total phenolics content (TPC), Total flavonoid content (TFC), and DPPH radical scavenging capacity were determined. Data were analyzed using the Mann-Whitney and Kruskal Wallis U test with GraphPad Prism 6 software. RESULTS: The natural extracts of Schisandra chinensis and Pueraria lobata induced down-regulation of E6 HPV oncogene (p<0.05) and a strong up-regulation of P53 (p<0.05), E2F-1 (p<0.05), and Bcl-2 (p<0.05) gene expression. Simultaneously, the natural extracts tend to increase the p53 protein levels and arrest the cell cycle of HeLa in the G1/S phase (p<0.05). Investigated extracts were characterized by the occurrence of bioactive lignans and isoflavones in S. chinensis and P. lobata, respectively. CONCLUSION: The extracts of S. chinensis and P. lobata within their chemical characterization mainly present lignan and isoflavone-type compounds, which are probably responsible for inhibiting the expression of the HPV E6 oncogene and inducing an increase in the expression of p53, Bcl -2 and E2F-1 producing cell cycle detection in S phase in HeLa cells. Therefore, these extracts are good candidates to continue studying their antiviral and antiproliferative potential in cells transformed by HPV.

Mutational spectrum of breast cancer by shallow whole-genome sequencing of cfDNA and tumor gene panel analysis.

Breast cancer (BC) has different molecular subgroups related to different risks and treatments. Tumor biopsies for BC detection are invasive and may not reflect tumor heterogeneity. Liquid biopsies have become relevant because they might overcome these limitations. We rationalize that liquid cfDNA biopsies through shallow whole genome sequencing (sWGS) could improve the detection of tumor alterations, complementing the genomic profiling. We evaluated the feasibility to detect somatic copy number alterations (SCNAs) in BC using shallow whole genome sequencing (sWGS) in cfDNA from archived samples from National Cancer Institute of Colombia patients. We sequenced tumor tissues from 38 BC patients with different molecular subtypes using a gene panel of 176 genes significantly mutated in cancer, and by liquid biopsies using sWGS on 20 paired samples to detect SCNAs and compare with the tumor samples. We identified an extensive intertumoral heterogeneity between the molecular subtypes of BC, with a mean tumor load of 602 mutations in the gene panel of tumor tissues. There was a 12.3% of concordance in deletions in the cfDNA-tumor pairs considering only the genes covered by the panel encompassing seven genes: BRCA1, CDK12, NF1, MAP2K4, NCOR1, TP53, and KEAP1 in three patients. This study shows the feasibility to complement the genomic analysis of tumor tissue biopsies to detect SCNA in BC using sWGS in cfDNA, providing a wider identification of potential therapeutic targets.

TIROSEC: Molecular, Clinical and Histopathological Profile of Papillary Thyroid Carcinoma in a Colombian Cohort.

INTRODUCTION: In Colombia, thyroid cancer ranks among the highest incidences, yet our population lacks studies on its molecular profile. This study aims to characterize clinical, histopathologic and molecular data in a Colombian cohort with papillary thyroid carcinoma (PTC). METHODS: A retrospective review of clinical history, clinicopathologic characteristics, treatment and 5-10-year follow-up for all patients was done. DNA and RNA were extracted from formalin-fixed paraffin-embedded (FFPE) tissue using the Quick-DNA & RNA FFPE Min iPrep kit (Zymo Research). Next-generation sequencing (NGS) analysis was performed with SOPHiA Solid Tumor Solutions kit (SOPHiA GENETICS). Tumor mutation genomic analysis used SOPHiA DDM™ platform, with descriptive analysis reporting frequencies, means and associations via chi-square analysis. RESULTS: Among 231 sequenced patients, mean age at diagnosis was 46 (± 12.35) years, with higher frequency in women (81.82%). Two cases were reclassified as non-invasive follicular thyroid neoplasm (NIFT-P); an NRAS mutation was found in one of them. Predominant histologic subtype was classic PTC (57.64%) followed by tall cell (28.82%). Of the 229 sequenced carcinomas, mutations were identified in 186 cases, including BRAF, IDH1, RAS and PIK3CA. Notable copy number variations (CNVs) were PDGFRA, CDK4 and KIT, with RET being the most frequent gene fusion, including CCDC6-RET in two classic subtype cases. CONCLUSION: This is the first study in Colombia (TIROSEC) to our knowledge that integrates molecular and histopathologic profiles enriching our local comprehension and knowledge of PTC. The identification of target mutations such as BRAF, RET and NTRK fusions holds the potential to guide targeted therapies for tumor recurrence and predict aggressive behavior.

Methylation marks in blood DNA reveal breast cancer risk in patients fulfilling hereditary disease criteria.

Less than 15-20% of patients who meet the criteria for hereditary breast and ovarian cancer (HBOC) carry pathogenic coding genetic mutations, implying that other molecular mechanisms may contribute to the increased risk of this condition. DNA methylation in peripheral blood has been suggested as a potential epigenetic marker for the risk of breast cancer (BC). We aimed to discover methylation marks in peripheral blood associated with BC in 231 pre-treatment BC patients meeting HBOC criteria, testing negative for coding pathogenic variants, and 156 healthy controls, through methylation analysis by targeted bisulfite sequencing on 18 tumor suppressor gene promoters (330 CpG sites). We found i) hypermethylation in EPCAM (17 CpG sites; p = 0.017) and RAD51C (27 CpG sites; p = 0.048); ii) hypermethylation in 36 CpG-specific sites (FDR q < 0.05) in the BC patients; iii) four specific CpG sites were associated with a higher risk of BC (FDR q < 0.01, Bonferroni p < 0.001): cg89786999-FANCI (OR = 1.65; 95% CI:1.2-2.2), cg23652916-PALB2 (OR = 2.83; 95% CI:1.7-4.7), cg47630224-MSH2 (OR = 4.17; 95% CI:2.1-8.5), and cg47596828-EPCAM (OR = 1.84; 95% CI:1.5-2.3). Validation of cg47630224-MSH2 methylation in one Australian cohort showed an association with 3-fold increased BC risk (AUC: 0.929; 95% CI: 0.904-0.955). Our findings suggest that four DNA methylation CpG sites may be associated with a higher risk of BC, potentially serving as biomarkers in patients without detectable coding mutations.

The Complexity of Tobacco Smoke-Induced Mutagenesis in Head and Neck Cancer.

Tobacco smoke, alone or combined with alcohol, is the predominant cause of head and neck cancer (HNC). Here, we further explore how tobacco exposure contributes to cancer development by mutational signature analysis of 265 whole-genome sequenced HNC from eight countries. Six tobacco-associated mutational signatures were detected, including some not previously reported. Differences in HNC incidence between countries corresponded with differences in mutation burdens of tobacco-associated signatures, consistent with the dominant role of tobacco in HNC causation. Differences were found in the burden of tobacco-associated signatures between anatomical subsites, suggesting that tissue-specific factors modulate mutagenesis. We identified an association between tobacco smoking and three additional alcohol-related signatures indicating synergism between the two exposures. Tobacco smoking was associated with differences in the mutational spectra and repertoire of driver mutations in cancer genes, and in patterns of copy number change. Together, the results demonstrate the multiple pathways by which tobacco smoke can influence the evolution of cancer cell clones.

The Mutographs biorepository: A unique genomic resource to study cancer around the world.

Large-scale biorepositories and databases are essential to generate equitable, effective, and sustainable advances in cancer prevention, early detection, cancer therapy, cancer care, and surveillance. The Mutographs project has created a large genomic dataset and biorepository of over 7,800 cancer cases from 30 countries across five continents with extensive demographic, lifestyle, environmental, and clinical information. Whole-genome sequencing is being finalized for over 4,000 cases, with the primary goal of understanding the causes of cancer at eight anatomic sites. Genomic, exposure, and clinical data will be publicly available through the International Cancer Genome Consortium Accelerating Research in Genomic Oncology platform. The Mutographs sample and metadata biorepository constitutes a legacy resource for new projects and collaborations aiming to increase our current research efforts in cancer genomic epidemiology globally.

Expression of oxysterols in human lenses: Implications of the sterol pathway in age-related cataracts.

Lanosterol, an oxysterol molecule, has been proposed to help maintain lens transparency by inhibiting the formation of protein aggregates. This sterol is produced by the enzyme lanosterol synthase and is part of a metabolic pathway that forms cholesterol as a final step. Abnormalities in lanosterol synthase are responsible for congenital cataracts. The αA-crystallin protein, which acts as a molecular chaperone to lanosterol synthase, has been reported to have anti-protein aggregation, anti-inflammatory and anti-apoptotic properties. In this work, we evaluated the correlation of lanosterol synthase and αA-crystallin in human cataractous lenses with the grade of opacity, as well as the expression of lanosterol synthase, farnesyl DPP, geranyl synthase and squalene epoxidase genes. Lanosterol synthase and αA-crystallin were overexpressed in cataractous lenses as well as farnesyl-DP synthase, squalene epoxidase, lanosterol synthase and geranyl synthase genes in cataratous lenses in comparison with normal lenses. Our data confirm that lanosterol synthase and the sterol pathway are upregulated in cataractous lenses. This argues for a functional role of the oxysterol pathway and its products as an important mediator in the pathogenesis of human cataracts.

Superscan on 68Ga PSMA PET/CT in patients with metastatic prostate carcinoma: A case series.

Prostate cancer is the second most common malignancy in men worldwide, with a good prognosis when is detected and treated in early stages, but, when it presents progression to castration-resistant metastatic prostate cancer, most of the cases will have bone metastasis, decreasing the quality of life and life expectancy. For the evaluation of the disease in the routinary clinical practice, 68Ga-PSMA PET/CT, among others is a valuable tool for the evaluation of the disease extension. 68Ga-PSMA PET/CT detects the presence of PSMA receptor in the tumoral tissue, but also has physiologic uptake in certain organs, such as liver, spleen, intestine, kidneys, lacrimal and salivary glands. Total or partial absence of uptake in those organs is rare and may be due to a high metastatic tumor burden, a phenomenon originally described in bone scintigraphy as super scan. We describe a case series of seven patients with prostate cancer from the National Institute of Cancerology in Colombia, in which a super scan pattern was found in the evaluation with 68Ga-PSMA PET/CT, proposing the suppression of uptake in the intestine, liver, spleen, lacrimal and salivary glands as the main criteria for its definition, and showing that renal uptake persists in most cases, considering that, unlike the super scan in conventional bone scintigraphy, this is not a criterion necessary for its definition in the study with 68Ga-PSMA.

Posttranslational modifications in psoriatic arthritis: A systematic literature review.

BACKGROUND AND AIMS: Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The aim of this systematic review was to collect all published evidence regarding posttranslational modifications in PsA, and the main outcome was to evaluate an association between disease outcomes and specific posttranslational modifications in PsA. METHODS: A systematic electronic search was performed in Medline, PubMed, Cochrane, Virtual Health Library, and Embase databases. A total of 587 articles were identified; 59 were evaluated after removing duplicates and scanning, of which 47 were included. A descriptive analysis was conducted, with results grouped according to the type of posttranslational modification evaluated. The protocol was registered at the PROSPERO database. RESULTS: Seven posttranslational modifications were identified: citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress. Anti-citrullinated peptide and anti-carbamylated protein have been evaluated in rheumatoid arthritis. There is now information suggesting that these antibodies may be helpful in improving the diagnosis of PsA and that they may demonstrate a correlation with worse disease progression (erosions, polyarticular involvement, and poor treatment response). Glycosylation was associated with increased inflammation and phosphorylation products related to the expression of SIRT2 and pSTAT3 or the presence of Th17 and cytokine interleukin-22, suggesting a possible therapeutic target. CONCLUSIONS: Posttranslational modifications often play a key role in modulating protein function in PsA and correlate with disease outcomes. Citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress were identified as associated with diagnosis and prognosis.

Evaluation of genetic alterations in hereditary cancer susceptibility genes in the Ashkenazi Jewish women community of Mexico.

Background: Individuals of Ashkenazi Jewish ancestry have been identified as having higher prevalence of specific pathogenic variants associated with susceptibility to specific rare and chronic diseases. In Mexico, the prevalence and composition of rare cancer predisposing germline variants in Ashkenazi Jewish individuals has not been evaluated. Aim and methods: We aimed to evaluate the prevalence of pathogenic variants by massive parallel sequencing in a panel of 143 cancer-predisposing genes in 341 women from the Ashkenazi Jewish community of Mexico, who were contacted and invited to participate in the study through the ALMA Foundation for Cancer Reconstruction. Pre- and posttest genetic counseling was given and a questionnaire on personal, gyneco-obstetric, demographic and lifestyle variables was conducted. From peripheral blood DNA, the complete coding region, and splicing sites of a panel of 143 cancer susceptibility genes, including 21 clinically relevant genes, were sequenced. The Mexican founder mutation BRCA1 ex9-12del [NC_000017.10(NM_007294):c. (825+1-826-1)_(4,589+1-4,590-1)del] was also evaluated. Results: Among study participants (mean age ±standard deviation: 47 ± 14) 15% reported a personal history of cancer (50/341). Fourteen percent of participants (48/341) were carriers of pathogenic and likely pathogenic variants distributed among seven high-risk genes (APC, CHEK2, MSH2, BMPR1A, MEN1, MLH1, and MSH6), whereas 18.2% (62/341) had variants of uncertain clinical significance in genes associated with breast and ovarian cancer susceptibility (list of genes with VUS). Pathogenic and likely pathogenic variants in 16 susceptibility genes with ambiguous or non-well-established risk association for cancer were detected in 17.6% (60/341) of participants. Sixty four percent of participants reported current alcohol consumption compared with the 39 percent prevalence of alcohol consumption in Mexican women. None of the participants carried the recurrent Ashkenazi and Mexican founder mutations in BRCA1 or BRCA2, but 2% (7/341) had pathogenic Ashkenazi Jewish founder variants in BLM. Conclusion: Our findings show a diverse pathogenic variant composition among the recruited individuals of Ashkenazi Jewish ancestry in Mexico consistent with being a high-risk population for genetic diseases, which warrants further investigation to adequately assess the burden of hereditary breast cancer in this group and implement appropriate preventative programs.

Comparative analysis of two biomaterials mixed with autogenous bone graft for vertical ridge augmentation: A histomorphometric study in humans.

BACKGROUND: The vertical increase of the alveolar ridge dimension using allograft or xenograft mixed with autogenous bone graft and covered by a nonabsorbable high-density polytetrafluoroethylene (d-PTFE) membrane is well documented in the literature. PURPOSE: The aim of this study was to assess vital mineralized tissue formation in vertical ridge augmentation (VRA) procedures using autogenous bone chips mixed either with an allograft or a xenograft. METHODS: This prospective clinical trial recruited 16 partially edentulous patients to undergo vertical ridge augmentation in one or more sites, making up a total of 24 samples for histological evaluation. Patients were sequentially stratified into Group A (treated with a freeze-dried bone allograft [FDBA] mixed with autogenous bone) or to Group B (treated with a bovine xenograft mixed with autogenous bone). Histological samples were analyzed according to the biomaterial used for VRA. Histological samples were obtained on the same day of membrane removal and implant placement. RESULTS: Thirty-three implants were placed in 16 sites of regenerated bone via VRA, 13 patients with ridge augmentation in the posterior mandible, and 3 patients with VRA in the anterior maxilla. Group A (FDBA + autogenous) and Group B (xenograft + autogenous) showed a percent vital mineralized tissue (VMT) area of 67.64 ± 16.84 and 60.93 ± 18.25, respectively. A significant difference between the two biomaterials was not observed. CONCLUSION: When mixed with autogenous bone, either allografts or xenografts may provide a successful augmentation. Either mixture could serve as reliable alternative in VRA for obtaining a high percentage of VMT.