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Abstract Background Human Papillomavirus (HPV) in cervical epithelium has been identified as the main etiological factor in the developing of Cervical Cancer (CC), which has recently become a public health problem in Mexico. This finding has allowed for the development of vaccines that help prevent this infection. In the present study, we aimed to determine the prevalence and HPV type-distribution in Mexican women with CC, high-grade squamous intraepithelial lesion (HSIL), low-grade squamous intraepithelial lesion (LSIL), and Normal cytology (N) to estimate the impact of the HPV vaccines. Methods The PubMed database was used to identify and review all articles that reported data on HPV prevalence in CC, precursor lesions, and normal cytology of Mexican women. Results A total of 8,706 samples of the tissues of Mexican women were stratified according to diagnosis as follows: 499 for CC; 364 for HSIL; 1,425 for LSIL, and 6,418 for N. According to the results, the most prevalent genotypes are the following: HPV16 (63.1%), -18 (8.6%), -58, and −31 (5%) for CC; HPV-16 (28.3%), 58 (12.6%), 18 (7.4%), and 33 (6.5%) for HSIL; HPV-16 (13.1%), 33 (7.4%), 18 (4.2%), and 58 (2.6%) for LSIL, and HPV-16 (3.4%), 33 (2.1%), 18, and 58 (1.2%) for N. Conclusions Taken together, genotypes 58 and 31 (10%) are more common than type 18 (8.6%) in CC. Therefore, the inclusion of these two genotypes in a second-generation vaccine would provide optimal prevention of CC in Mexico.

Abstract Background Association between DNA alterations and clinical parameters as recurrence, survival or prognosis has been found in a variety of tumors. A clear association between Medullary Thyroid Carcinoma (MTC) and RET oncogene mutation has been accepted. Specifically M918T RET mutation represents the main genetic event in most cases of sporadic MTC (SMTC) and limited chromosomal alterations analyses have been performed. Methods In the present work, a comparative genomic hybridization (CGH) study was performed using DNA from a primary tumor in a M918T RET mutation-positive SMTC patient and from its lymph node metastasis to investigate additional genetic alterations. We studied a patient with 15 years of follow-up and persistence of disease, confirmed by periodical elevated serum calcitonin (CT) levels. Results Only 3 chromosomal imbalances were identified in the primary tumor, gain of 18p, and loss of 6p and 16p region, whereas 25 chromosomal imbalances were identified in the metastasis (9 gains and 16 losses). Conclusion The chromosomal changes 6p-, 16p-, 18p + could determine in part the oncogenic phenotype in the primary M918T RET positive tumor and probably related to persistence of high serum CT levels in this patient. The additional chromosomal changes observed could be related to the metastasis phenotype. We suggest that some genes mapped at 6p, 16p and 18p chromosomal regions, could act as genes associated to cancer and could be related to persistent SMTC and good prognosis. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1720753793691097

The diagnosis and identification of melanoma are not always accurate, even for experienced dermatologists. Histopathology continues to be the gold standard, assessing specific parameters such as the Breslow index. However, it remains invasive and may lack effectiveness. Therefore, leveraging mathematical modeling and informatics has been a pursuit of diagnostic methods favoring early detection. Fractality, a mathematical parameter quantifying complexity and irregularity, has proven useful in melanoma diagnosis. Nonetheless, no studies have implemented this metric to feed artificial intelligence algorithms for the automatic classification of dermatological lesions, including melanoma. Hence, this study aimed to determine the combined utility of fractal dimension and unsupervised low-computational-requirements machine learning models in classifying melanoma and non-melanoma lesions. We analyzed 39,270 dermatological lesions obtained from the International Skin Imaging Collaboration. Box-counting fractal dimensions were calculated for these lesions. Fractal values were used to implement classification methods by unsupervised machine learning based on principal component analysis and iterated K-means (100 iterations). A clear separation was observed, using only fractal dimension values, between benign or malignant lesions (sensibility 72.4% and specificity 50.1%) and melanoma or non-melanoma lesions (sensibility 72.8% and specificity 50%) and subsequently, the classification quality based on the machine learning model was ≈80% for both benign and malignant or melanoma and non-melanoma lesions. However, the grouping of metastatic melanoma versus non-metastatic melanoma was less effective, probably due to the small sample size included in MM lesions. Nevertheless, we could suggest a decision algorithm based on fractal dimension for dermatological lesion discrimination. On the other hand, it was also determined that the fractal dimension is sufficient to generate unsupervised artificial intelligence models that allow for a more efficient classification of dermatological lesions.

Background and Objectives : Leukemia, characterized by abnormal leukocyte production, exhibits clonal origin from somatic mutations. Globally, it ranked 15th in cancer incidence in 2020, with higher prevalence in developing countries. In Mexico, it was the ninth most frequent cancer. Regional registries are vital for understanding its epidemiology. This study aims to analyze the prevalence and age-standardized incidence rates of leukemias in a tertiary care hospital in the Mexican Bajio region. Materials and Methods : Leukemia cases from 2008-2018 were analyzed, and 535 medical records were included in this study. The prevalence, distribution, and age-specific incidence rate of different types and subtypes of leukemia were determined according to sex and age groups. Results : Overall, 65.79% consisted of lymphocytic leukemia, 33.64% of myeloid leukemia, and 0.56% of monocytic leukemia. No significant sex-based differences were found, but age-specific patterns were observed. Leukemia distribution by age revealed significant associations. Lymphocytic leukemia dominated in the pediatric population, particularly acute lymphocytic leukemia, while myeloid leukemia shifted towards adulthood. Age-specific incidence patterns showed, first, that lymphocytic leukemia is the most common leukemia in pediatric ages, and second, there is a shift from acute lymphocytic leukemia dominance in pediatric ages to myeloid leukemia incidence in late adulthood, emphasizing nuanced epidemiological dynamics. Conclusions : Acute leukemia cases occurred with high prevalence in our study population, with a high incidence in pediatric and adulthood populations, especially for acute lymphocytic leukemia, showing a (<18 years) 153.8 age-standardized incidence rate in the pediatric group, while in the adult population, the age-standardized rate was 59.84. In the age-specific analysis, we found that the childhood group (5-9 years) were the most affected by acute lymphocytic leukemia in the pediatric population, while in the adult population, the early-adulthood group (15-29 years) were the most affected age group. In contrast, chronic myeloid leukemia affected both adults and the pediatric populations, while chronic lymphocytic leukemia and monocytic leukemia were exclusive to adults. The study underscores the need for tailored diagnostic, treatment, and preventive strategies based on age, contributing valuable insights into the leukemia epidemiology of the Bajio region.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder characterized by the presence of the Philadelphia chromosome, a product of the reciprocal translocation t(9;22)(q34;q11), in the BCR and ABL genes. These rearrangements in both genes lead to the formation of various fusion mRNA products, with preferential expression of b2a2 , b3a2 , and other BCR::ABL1 mRNA variants, combined with additional chromosomal abnormalities. Notably, the distribution and frequency of different mRNA variants vary in different populations. However, studies concerning this in Mexico are limited, and the results have been inconclusive. This study therefore aimed to determine the distribution of BCR::ABL1 mRNA variants in different clinical phases of CML and their effect on hematological parameters and patient survival. This study included 33 patients, whose demographic, clinical, and molecular data on BCR::ABL1 mRNA variants and hematological parameters were collected to identify potential associations. A total of 84.8% (n = 28) of patients had BCR::ABL1 translocation and increased platelet and basophil counts. The most frequent mRNA variant was b3a2 (64.3%), followed by b2a2 (28.6%) and e1a2 (3.6%). Concerning the clinical phases of CML, 75.8% (n = 25), 21.2% (n = 7), and 3% (n = 1) of patients were in the chronic, blast, and accelerated phases, respectively. Moreover, the b3a2 mRNA variant was more commonly identified in patients in the chronic phase. No correlation was observed between mRNA variant expression and patient survival. However, b2a2 was indicative of patients with longer survival as well as those treated with imatinib or nilotinib. Additionally, platelet count could be a marker of BCR::ABL1 translocation.

Chronic myeloid leukemia (CML) is associated with the Philadelphia chromosome and distinct BCR::ABL1 gene transcripts. We assessed the frequencies of these transcripts in Mexico, Latin America, and worldwide. We determined the prevalence of BCR::ABL1 transcripts in CML patients and intercontinental or regional variations using specialized databases and keywords. We analyzed 34 studies from 20 countries, encompassing 5795 patients. Keyword-based searches in specialized databases guided data collection. ANOVA was employed for transcript distribution analysis. The b3a2 transcript was most prevalent globally, followed by b2a2 , with e1a2 being the least frequent. Interestingly, Mexico City exhibited a higher incidence of b2a2 , while b3a2 predominated in the remaining country. Overall, no significant intercontinental or regional variations were observed. b3a2 was the most common BCR::ABL1 transcript worldwide, with b2a2 following closely; e1a2 was infrequent. Notably, this trend remained consistent in Mexico. Evaluating transcript frequencies holds clinical relevance for CML management. Understanding the frequency of transcript informs personalized CML treatments.

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Introduction: The prevalence of the different genotypes of human papillomavirus (HPV) varies depending on lesion severity and geographic region., Objective: To identify multiple HPV infections in low- and high-grade cervical lesions in a group of women from the Mexican Bajío region referred with inconclusive cytology., Methods: Pilot study of women referred from primary care units of Guanajuato, Mexico, with cytology suggestive of cervical lesion. Cervical smears were subjected to DNA extraction and HPV genotyping using microarrays., Results: 100 consecutive cases were collected and 90 were analyzed; HPV positivity was observed in 26% of healthy women, and 62% had some degree of cervical lesion. The most common HPV genotypes were 59, 31, 16 and 51. Multiple infections were found in most samples., Conclusions: HPV heterogeneity was identified in the samples of the study population in contrast to worldwide reports; furthermore, multiple infections are common in precursor lesions and decrease in high-grade lesions. These data could have an impact on current HPV vaccination programs., (Copyright: © 2022 Permanyer.)

Introduction: Transplants and organ donation are greatly aided by future medical professionals having adequate knowledge of this topic. This study aimed to elucidate the level of Mexican medical students' knowledge in the field of transplants and organ donation., Materials and Methods: The evaluation instrument was designed and validated. The design used simple sampling with replacement, selecting a random sample of 5 universities from among the institutional members of the Mexican Association of Departments and Schools of Medicine (Asociación Mexicana de Facultades y Escuelas de Medicina [AMFEM]). The sample was composed of 3214 medical students. Measures of central tendency were determined, and the mean scores obtained across the different universities were compared using a Kruskal-Wallis test. The odds ratio was calculated for the students whose school or department included instruction on transplants and donation within their curriculum. Kendall correlation was used for the students' academic grade level and score. All analyses considered a threshold of P < .05., Results: A questionnaire was administered to a sample of 2563 students to evaluate their knowledge of transplants and organ donation. The average score was 4.02 on a scale of 0 to 10 (standard deviation 0.03), with a 95% confidence interval (3.96-4.08). Students whose school or department taught the subject of transplants and donations within their curriculum obtained an odds ratio of 1.44 (P = .0000822)., Conclusions: The findings of this study suggest that medical students in Mexico do not have sufficient knowledge of transplants and organ donation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: This study presents a prediction of putative miRNA within several Human Papillomavirus (HPV) types by using bioinformatics tools and a strategy based on sequence and structure alignment. Currently, little is known about HPV miRNAs., Methods: Computational methods have been widely applied in the identification of novel miRNAs when analyzing genome sequences. Here, ten whole-genome sequences from HPV-6, -11, -16, -18, -31, -33, -35, -45, -52, and -58 were analyzed. Software based on local contiguous structure-sequence features and support vector machine (SVM), as well as additional bioinformatics tools, were utilized for identification and classification of real and pseudo microRNA precursors., Results: An initial analysis predicted 200 putative pre-miRNAs for all the ten HPV genome variants. To derive a smaller set of pre-miRNAs candidates, stringent validation criteria was conducted by applying <‒10 ΔG value (Gibbs Free Energy). Thus, only pre-miRNAs with total scores above the cut-off points of 90% were considered as putative pre-miRNAs. As a result of this strategy, 19 pre-miRNAs were selected (hpv-pre-miRNAs). These novel pre-miRNAs were located in different clusters within HPV genomes and some of them were positioned at splice regions. Additionally, the 19 identified pre-miRNAs sequences varied between HPV genotypes. Interestingly, the newly identified miRNAs, 297, 27b, 500, 501-5, and 509-3-5p, were closely implicated in carcinogenesis participating in cellular longevity, cell cycle, metastasis, apoptosis evasion, tissue invasion and cellular growth pathways., Conclusions: The novel putative miRNAs candidates could be promising biomarkers of HPV infection and furthermore, could be targeted for potential therapeutic interventions in HPV-induced malignancies., (Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.)

The role of human papillomavirus (HPV) infection in penile carcinoma (PeC) is currently reported and about half of the PeC is associated with HPV16 and 18. We used a PCR-based strategy by using HPV general primers to analyze 86 penile carcinomas paraffin-embedded tissues. Some clinical data, the histological subtype, growth pattern, and differentiation degree were also collected. The amplified fragments were then sequenced to confirm the HPV type and for HPV16/18 variants. DNA samples were also subjected to relative real time PCR for hTERC gene copy number. Some clinical data were also collected. Global HPV frequency was 77.9%. Relative contributions was for HPV16 (85%), 31 (4.4%), 11 (4.4%), 58, 33, 18, and 59 (1.4% each one). Sequence analysis of HPV16 identified European variants and Asian-American (AAb-c) variants in 92% and in 8% of the samples, respectively. Furthermore hTERC gene amplification was observed in only 17% of the cases. Our results suggest that some members of HPV A9 group (represented by HPV16, 58, and 31) are the most frequent among PeC patients studied with an important contribution from HPV16 European variant. The hTERC gene amplification could be poorly related to penile epithelial tissue.

Introduction: Non-medical staff members in hospitals are highly credible at population level, and are a source of opinion even though they do not have sufficient medical training., Objectives: To analyse the attitudes of non-medical professionals of Spanish and Latin American hospitals towards organ donation and identify the factors that influence these attitudes., Material and Method: Through the "Proyecto Colaborativo Internacional Donante" (International Collaborative Donor Project), a stratified random sample was selected from non-medical services of eleven hospitals: 3 Spanish (n=277), 5 Mexican (n=632), 2 Cuban (n=42) and 1 Costa Rican (n=101)., Results: Of the 1052 professionals surveyed, 72% (n=754) were in favour of donating an organ after death. By country, 98% of Cubans, 80% of Mexicans, 66% of Costa Ricans and 52% of Spanish were in favour (P<.001). The most influential variables were: 1) country, with results being more positive in Mexico (odds ratio [OR]=2.197), 2) believing in the possibility that they will require a transplant (OR=2.202), 3) having discussed the issue with their family (OR=3.23), 4) the positive attitude of their partner towards donation (OR=3.322), 5) not being concerned about possible mutilation of their body after donation (OR=3.378), 6) preferring options other than burial (OR=2.525), 7) accepting an autopsy (OR=2.958)., Conclusions: The attitude of non-medical staff members of hospitals towards the donation of their own organs varies greatly depending on the country of the respondent. Psychosocial factors that influence these attitudes are similar to those described at the population level.

The transplant of organs is one of the greatest therapeutic achievements of the twentieth century. In organ transplantation, the adaptive immunity is considered the main response exerted to the transplanted tissue, since the principal target of the immune response is the MHC (major histocompatibility complex) molecules expressed on the surface of donor cells. However, we should not forget that the innate and adaptive immunities are closely interrelated and should be viewed as complementary and cooperating. When a human transplant is performed, HLA (human leukocyte antigens) molecules from a donor are recognized by the recipient's immune system triggering an alloimmune response Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. This paper will present MHC, the innate and adaptive immunities, and clinical HLA testing.

We developed a procedure to detect the 7 point mutations at Cys634 of the proto-oncogene RET, which is responsible for medullary thyroid carcinoma (MTC). Genomic DNA was prepared from blood samples obtained from normal and MTC-affected individuals belonging to a family with a history of the disease. The RET genotype for each individual was first established by performing restriction and sequencing analyses. Single-stranded target DNA was prepared by asymmetric polymerase chain reaction (PCR) amplification of a 93-bp fragment containing Cys634. The target was annealed with pairs of prelabeled stacking oligonucleotides designed to create appropriate 7-nucleotide gaps, which served as the sites of subsequent hybridization with glass-immobilized 7-mer probes. The target-stacking oligonucleotide duplexes were hybridized with DNA chips containing a set of eight 7-mer probes designed to detect the wild-type sequence and the seven point mutations described. We tested two sets of immobilized probes containing internal or 5'-terminal codon-634 single-base variations. Both groups of probes were able to discriminatively identify the mutations. The hybridization patterns indicated that the disease in this family was due to the C634Y mutation, in accord with the original sequence analysis. The hybridization-based mutation assignment was additionally supported by determination of the control homozygous and heterozygous hybridization patterns produced with synthetic targets having the normal or codon 634 mutant sequences. The effects of mismatch type and nearest-neighbor sequences on the occurrence of false-positive (mismatched) hybridizations are discussed.

Multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are characterized by development of medullary thyroid carcinoma (MTC) and caused by germline RET mutations. Patients with MEN 2A also develop pheochromocytoma and/or hyperparathyroidism (HPT). However, MEN 2A-affected individuals could display the FMTC phenotype at first clinical manifestation. To establish the correct phenotype and improve clinical management of patients affected by hereditary MTC, clinical screening, RET mutational analysis, penetrance of MTC, and genotype-phenotype correlation were performed in a large, suspected FMTC kindred of 86 individuals. Germline C634Y RET mutation was confirmed in 22 individuals, 15 of whom were thyroidectomized when high serum calcitonin levels were detected. MTC was confirmed in 12 individuals and C-cell hyperplasia in 3. HPT was detected in two patients. High penetrance of MTC at young age (79% at 30 yr of age) was found. This family was considered to be affected by FMTC for several years because MTC was the sole clinical manifestation. However, our results allowed reclassifying the family as MEN 2A, thereby improving clinical management of family members. Our findings regarding penetrance and genotype-phenotype correlation suggest that patients considered to have FMTC may in fact have MEN 2A in some kindreds.