Cura por vacío (VAC), a propósito de un caso en Atención Primaria / Vacuum assisted closure (VAC), about a case in primary care

El síndrome compartimental agudo requiere de la descompresión quirúrgica, mediante fasciotomía, esta técnica debe ser urgente y será clave para evitar la instauración de graves secuelas. El posterior abordaje de estas heridas de difícil y lenta cicatrización suponen un reto para los profesionales de la salud y un problema para la salud pública debido a los altos costes y elevada morbilidad. La terapia de presión negativa (TPN) o cura por vacío (VAC, "vacuum assisted closure") es un tratamiento no invasivo que consigue la curación de las heridas favoreciendo la vascularización, la aparición del tejido de granulación y eliminación del exceso de exudado[AU]

Acute compartment syndrome requires surgical decompression by fasciotomy, this technique must be urgent and will be key to avoid the establishment of serious sequels. The subsequent approach to these wounds, which are difficult and slow to heal, is a challenge for health professionals and a problem for public health due to high costs and high morbidity. Negative pressure therapy (NPWT) or vacuum assisted closure (VAC) is a non-invasive treatment that achieves wound healing by promoting vascularization, the appearance of granulation tissue and elimination of excess exudate[AU]

A síndrome compartimental aguda requer descompressão cirúrgica, por fasciotomia, esta técnica deve ser urgente e será fundamental para evitar o estabelecimento de sequelas graves. O tratamento subsequente destas feridas difíceis e de cicatrização lenta é um desafio para os profissionais de saúde e um problema desaúde pública devido aos elevados custos e à elevada morbilidade. A terapia por pressão negativa (NPWT) ou o encerramento assistido por vácuo (VAC) é um tratamento não invasivo que permite a cicatrização de feridas através da promoção da vascularização, do aparecimento de tecido de granulação e da remoção do excesso de exsudado[AU]

Early Readmission and Revision After Total Joint Arthroplasty: An Analysis of Cause and Cost.

Background: Bundled payments for total joint arthroplasty (TJA) were instituted by the Centers for Medicare and Medicaid Services (CMS) to reimburse providers a lump sum for operative and 90-day postoperative costs. Gaining a better understanding of which TJA patients are at risk for early return to the operating room (OR) is critical in preoperative optimization of those with modifiable risks, which could improve bundled-payment performance. Purpose: We sought to identify the most common reason for readmissions, as well as patient characteristics and costs, associated with early return to the OR among TJA patients. Methods: This was a retrospective cohort study of Medicare patients who had undergone primary total hip or knee arthroplasty (THA or TKA) between 2013 and 2018 at a tertiary care hospital. We used the CMS research identifiable files database to identify the most common reasons for readmissions and revisions within 90 days of surgery. Total billing claims were used to determine the cost of early readmissions and revisions. Multivariate regression analysis was used to determine the characteristics associated with early readmission or revision. Results: Out of 20 166 primary TJA patients identified, we found 1349 readmissions (5.6%) and 163 (0.8%) revisions within 90 days of surgery. Dislocation was the most common indication for readmission, and periprosthetic joint infection was the most common indication for revision. Early return to the OR was associated with a mean $105,988 (standard deviation [SD] = $76,865) in CMS claims for the inpatient stay. Factors associated with a higher risk of early reoperation were female sex, THA, longer length of stay, and discharge to long-term care facility. Conclusions: This retrospective cohort study found that early return to the OR after TJA increased overall 90-day costs by 260%, suggesting that early reoperation might have a significant impact on bundled payments. Further study is warranted.

Melanoma Breslow Thickness Classification using Ensemble-based Knowledge Distillation with Semi-supervised Convolutional Neural Networks.

Melanoma is considered a global public health challenge and is responsible for more than 90% deaths related to skin cancer. Although the diagnosis of early melanoma is the main goal of dermoscopy, the discrimination between dermoscopic images of in situ and invasive melanomas can be a difficult task even for experienced dermatologists. Recent advances in artificial intelligence in the field of medical image analysis show that its application to dermoscopy with the aim of supporting and providing a second opinion to the medical expert could be of great interest. In this work, four datasets from different sources were used to train and evaluate deep learning models on in situ versus invasive melanoma classification and on Breslow thickness prediction. Supervised learning and semi-supervised learning using a multi-teacher ensemble knowledge distillation approach were considered and evaluated using a stratified 5-fold cross-validation scheme. The best models achieved AUCs of 0.6186 ±0.0410 and of 0.7501 ±0.0674 on the former and latter classification tasks, respectively. The best results were obtained using semi-supervised learning, with the best model achieving 0.7751 and 0.8164 AUC, respectively. The results obtained show that semi-supervised learning could improve the performance of trained models in different melanoma classification tasks compared to supervised learning. Automatic deep learning-based diagnosis systems could support medical professionals in their decision, serving as a second opinion or as a triage tool for medical centers.

Non-melanoma skin cancer burden in Spain: a nationwide analysis of incidence trends (1990-2019).

Non-melanoma skin cancer (NMSC) is the most -common skin cancer in Spain, yet national data on its incidence trends are limited. To analyse the trends in NMSC incidence in Spain from 1990 to 2019, examining variations by sex, age, period, and birth cohort. Data on NMSC incidence was sourced from the Global Health Data Exchange. Age-standardized incidence rates (ASIRs) were calculated using the direct method. Trends and average annual percentage changes were identified using Joinpoint regression analysis. Age-period-cohort analysis was applied to assess age-specific, period-specific, and cohort-specific relative risks. From 1990 to 2019, Spain reported 2,302,399 NMSC cases. ASIRs significantly declined post-2005, with men exhibiting slightly higher rates than women. Joinpoint analysis revealed distinct trends between genders, with men experiencing an initial rise followed by a decline, while women exhibited periods of increase interspersed with decline. APC analysis showed a net decrease in age-adjusted NMSC rates for both sexes. Local drift analysis showed a downward trend in most age groups, indicating a broad decrease at the population level. However, no decrease was observed in young men (20-24 years). Both sexes showed an increased risk of NMSC between 1990 and 2002, followed by a decrease. In particular, those born at the beginning of the 21st century showed a significant decrease in NMSC risk compared with earlier cohorts, suggesting a possible cohort effect. A comprehensive analysis of NMSC trends in Spain highlights the need for ongoing research and interventions to address the evolving burden.

ICAM1 (CD54) Contributes to the Metastatic Capacity of Gastric Cancer Stem Cells.

Gastric cancer is the fourth leading cause of cancer deaths worldwide. The presence of chemoresistant cells has been used to explain this high mortality rate. These higher tumorigenic and chemoresistant cells involve cancer stem cells (CSCs), which have the potential for self-renewal, a cell differentiation capacity, and a greater tumorigenic capacity. Our research group identified gastric cancer stem cells (GCSCs) with the CD24+CD44+CD326+ICAM1+ immunophenotype isolated from gastric cancer patients. Interestingly, this GCSC immunophenotype was absent in cells isolated from healthy people, who presented a cell population with a CD24+CD44+CD326+ immunophenotype, lacking ICAM1. We aimed to explore the role of ICAM1 in these GCSCs; for this purpose, we isolated GCSCs from the AGS cell line and generated a GCSC line knockout for ICAM1 using CRISPR/iCas9, which we named GCSC-ICAM1KO. To assess the role of ICAM1 in the GCSCs, we analyzed the migration, invasion, and chemoresistance capabilities of the GCSCs using in vitro assays and evaluated the migratory, invasive, and tumorigenic properties in a zebrafish model. The in vitro analysis showed that ICAM1 regulated STAT3 activation (pSTAT3-ser727) in the GCSCs, which could contribute to the ability of GCSCs to migrate, invade, and metastasize. Interestingly, we demonstrated that the GCSC-ICAM1KO cells lost their capacity to migrate, invade, and metastasize, but they exhibited an increased resistance to a cisplatin treatment compared to their parental GCSCs; the GCSC-ICAM1KO cells also exhibited an increased tumorigenic capability in vivo.

Circulating Gastric Cancer Stem Cells as Blood Screening and Prognosis Factor in Gastric Cancer.

Gastric cancer (GC) is the fourth leading cause of cancer-related death, associated with late diagnosis and treatment resistance. Currently, screening tests for GC are not cost-effective or have low accuracy. Previously, we described an extended phenotype of gastric cancer stem cells (GCSCs; CD24+CD44+CD54+EpCAM+) that is associated with metastasis and tumor stage in GC patients. The goal of the current research is to evaluate the presence of these GCSCs in the peripheral blood of GC patients and healthy volunteers. A total of 73 blood samples were collected from 32 GC patients and 41 healthy volunteers. After peripheral blood mononuclear cell (PBMC) extraction, multiparametric flow cytometry was performed looking for GCSCs. Using clustering data through artificial intelligence (AI), we defined high/low levels of circulating GCSCs (cGCSCs) and proceeded to evaluate its association with clinical and prognostic variables. Finally, a diagnostic test analysis was performed evaluating patients and healthy volunteers. We found that cGCSCs are present in most GC patients with a mean concentration of 0.48%. The AI clustering showed two groups with different cGCSC levels and clinical characteristics. Through statistical analysis, we confirmed the association between cGCSC levels and lymph node metastasis, distant metastasis, and overall survival. The diagnostic test analysis showed sensibility, specificity, and area under the curve (AUC) of 83%, 95%, and 0.911, respectively. Our results suggest that the assessment of cGCSCs CD24+CD44+CD54+EpCAM+ could be a potential noninvasive test, with prognostic value, as well as highly sensitive and specific for screening or diagnosis of GC; however, a larger scale study will be necessary to confirm this.

Clinical Impact of the Use of Ologen in Filtering Surgery Performed in Uncontrolled Glaucoma.

Introduction: To compare the efficacy and safety of trabeculectomy with a collagen matrix implant (Ologen®) versus trabeculectomy with mitomycin C (MMC) versus trabeculectomy with both Ologen® and MMC (OLO + MMC). Methods: This non-randomized study included 119 eyes of 101 patients with uncontrolled open-angle glaucoma who underwent trabeculectomy, either alone or combined with phacoemulsification. The data were initially recorded following a standard surgical protocol, using an electronic database with structured fields. The patients were divided into three groups: 44 received trabeculectomy with adjunctive MMC (MMC group), 34 received surgery with Ologen® (OLO group), and 41 received surgery with both Ologen® and MMC (OLO + MMC group). The main outcome measures were the change in intraocular pressure (IOP), change in number of medications needed, complete success rate (defined as IOP ≤ 20 mmHg and at least 20% IOP reduction without hypotensive medications), rate of complications, and rate of postoperative interventions. The follow-up period was 36 months. Results: IOPs significantly decreased (p = 0.01) in all groups across all study visits, decreasing from 19.8 ± 4.6 mmHg to 12.7 ± 4.2 mmHg in the MMC group, from 20.5 ± 4.7 mmHg to 13.9 ± 3.5 mmHg in the OLO group, and from 23.5 ± 6.1 mmHg to 13.1 ± 3.5 mmHg in the OLO + MMC group. After correcting for the baseline IOP, only the first two postoperative visits (first week and first month) showed a significantly greater IOP reduction in the OLO + MMC group. The number of hypotensive medications was significantly reduced from 3.1 ± 0.6 to 0.56 ± 1.1 in the MMC group, from 2.9 ± 0.4 to 0.83 ± 1.1 in the OLO group, and from 3.0 ± 0.6 to 0.45 ± 0.95 in OLO + MMC group, with no statistically significant differences among the groups (p = 0.57). The complete success rates were 63.6% in the MMC group, 67.6% in the OLO group, and 80.5% in the OLO +MMC group, with no statistically significant differences between the groups (p = 0.21). Suture release was significantly more frequent in the MMC group (86.1%) than in the OLO group (62.1%) and in the OLO + MMC group (45.9%; p = 0.02). Bleb needling, with (33.3%; p = 0.005) or without (66.7%; p = 0.0001) 5-fluorouracil injection (5-FU), was significantly more common in the MMC group. The highest complete success rate (61%) was observed in the OLO + MMC group. Conclusions: The use of Ologen® and mitomycin C provided similar surgical IOP reduction in glaucoma surgery compared with either MMC or Ologen® alone, but significantly reduced the need for postoperative interventions.

Peripherical Blood hsa-miR-335-5p Quantification as a Prognostic, but Not Diagnostic, Marker of Gastric Cancer.

Gastric cancer (GC) is a leading cause of death, and this pathology often receives a diagnosis in an advanced stage. The development of a less invasive and cost-effective test for detection is essential for decreasing the mortality rate and increasing the life expectancy of GC patients. We evaluated the potential targeting of CD54/ICAM1, a marker of gastric cancer stem cells, with miRNAs to detect GC in blood samples. The analyses included 79 blood samples, 38 from GC patients and 41 from healthy donors, who attended INCan, México City. The total RNA was obtained from the blood plasma, and RT-PCR and qPCR were performed to obtain the relative expression of each miRNA. Hsa-miR-335-5p was detected in the plasma of GC patients and healthy donors at the same levels. The ROC curve analyses indicated that this miRNA was not a candidate for the molecular diagnosis of GC. We did not observe a correlation between the expression of hsa-miR-335-5p and clinical variables; however, the Kaplan-Meier analyses indicated that, in patients who survived more than 12 months, a lower expression of hsa-miR-335-5p was correlated with a better prognosis. It would be convenient to evaluate a larger panel of miRNAs, including miRNAs expressed in a limited number of cell types or with a low number targets, to obtain more specific candidates for developing a robust test for the diagnosis/prognosis of GC.

Tongue Tuberculosis as a Complication of Pott's Disease in a Patient on Systemic Steroid Therapy without Pulmonary Tuberculosis.

A 78-year-old man with a previous diagnosis of rheumatoid arthritis on prolonged treatment with corticosteroids presented with intense and progressive pain at the cervical level that prevented him from resting his head and walking, in addition to an ulcerative lesion covering 80% of the lingual area that was previously treated as oral candidiasis without improvement. On arrival, with no clinical or serological data of rheumatoid arthritis, immunosuppressive treatment was suspended, and a biopsy of the oral cavity was requested, confirming the diagnosis of lingual tuberculosis, an extremely rare disease, occurring in less than 1% of extrapulmonary cases. MRI of the cervical spine showed a crush fracture of the C6 and C7 bodies associated with spondylitis of probably infectious etiology that required surgical treatment, and histopathological studies confirmed Pott's disease. The patient displayed no evidence of pulmonary tuberculosis from arrival until the end of the follow-up.

Cancer Stem Cell markers: Symphonic masters of chemoresistance and immune evasion.

Cancer Stem Cells (CSCs) are highly tumorigenic, chemoresistant, and immune evasive. They emerge as a central driver that gives rise to the bulk of tumoral mass, modifies the tumor microenvironment (TME), and exploits it, leading to poor clinical outcomes for patients with cancer. The existence of CSCs thus accounts for the failure of conventional therapies and immune surveillance. Identifying CSCs in solid tumors remains a significant challenge in modern oncology, with the use of cell surface markers being the primary strategy for studying, isolating, and enriching these cells. In this review, we explore CSC markers, focusing on the underlying signaling pathways that drive CSC self-renewal, which simultaneously makes them intrinsically chemoresistant and immune system evaders. We comprehensively discuss the autonomous and non-autonomous functions of CSCs, with particular emphasis on their interactions with the tumor microenvironment, especially immune cells. This reciprocal network enhances CSCs malignancy while compromising the surrounding niche, ultimately defining therapeutic vulnerabilities associated with each CSC marker. The most common CSCs surface markers addressed in this review-CD44, CD133, ICAM1/CD54, and LGR5-provide insights into the interplay between chemoresistance and immune evasion, two critically important phenomena in disease eradication. This new perspective on the state-of-the-art of CSCs will undoubtedly open new avenues for therapy.

Oronasal Fistula Closure and Defect Reconstruction: Two Case Reports Using Periodontal Plastic Surgery Principles.

OBJECTIVES: Oronasal fistulas are common sequelae following cleft lip and palate surgery and can significantly impact a patient's quality of life. They result from various factors, including surgical techniques, tissue management, and patient-specific factors. This case report explores the modern approach to oronasal fistula closure using periodontal plastic surgery principles. MATERIALS AND METHODS: The report presents two cases of patients with oronasal fistulas due to previous maxillofacial surgical intervention. These patients underwent microsurgical procedures that involved partial flap thickness preparation of the fistula areas, the use of connective tissue grafts from the palate, and meticulous suturing techniques to ensure graft integrity. The procedures were performed in stages, and postoperative care was provided. RESULTS: Both cases demonstrated successful fistula closure and graft survival. The patients reported improvements in breathing, speech, aesthetics, and quality of life. The second case also included guided bone regeneration and implant placement. CONCLUSIONS: Oronasal fistulas resulting from maxillofacial surgery can be effectively treated using periodontal plastic surgery techniques, significantly improving patients' quality of life and aesthetic outcomes. This approach represents a valuable addition to the existing repertoire of oronasal fistula closure methods.

Analysis of the loss of phosphatase and tensin homolog expression in thyroid tissue for the diagnosis of Cowden syndrome.

BACKGROUND: Cowden syndrome is an autosomal-dominant disorder caused by a germline phosphatase and tensin homolog mutation, giving rise to several tumors with an aggressive clinical course. In the thyroid, there are certain histologic criteria that could be related to this syndrome that could be useful for its early detection. We sought to analyze the loss of phosphatase and tensin homolog in thyroid histologic pieces with certain histologic criteria and to determine the percentage of patients diagnosed with Cowden syndrome with this methodology. METHODS: Five hundred thirty-five thyroid specimens collected were retrospectively analyzed (2017-2020). Those samples that presented certain histologic criteria were studied for loss of phosphatase and tensin homolog expression. Patients with loss of expression underwent a clinical study to rule out dermatologic or other lesions compatible with Cowden syndrome. Patients with positive clinical study were referred for genetic study. RESULTS: The phosphatase and tensin homolog study was performed in 6.7% (n = 36) of the thyroidectomy samples, showing loss of expression in 22% (n = 8); the most frequent histologic finding was the presence of multiple monomorphous adenomatous nodules. The samples with loss of expression showed more diffuse oncocytic changes. Of the 8 patients with loss of expression, 5 showed dermatologic lesions that could be associated with Cowden syndrome and 1 had a history of macrocephaly. These patients were referred for genetic study, being positive for Cowden syndromein in one quarter of the cases (n = 2). CONCLUSION: The immunohistochemical study of phosphatase and tensin homolog in pieces of thyroidectomies with histologic criteria suggestive of Cowden syndrome can help in its early diagnosis.

Altered RNA export by SF3B1 mutants confers sensitivity to nuclear export inhibition.

SF3B1 mutations frequently occur in cancer yet lack targeted therapies. Clinical trials of XPO1 inhibitors, selinexor and eltanexor, in high-risk myelodysplastic neoplasms (MDS) revealed responders were enriched with SF3B1 mutations. Given that XPO1 (Exportin-1) is a nuclear exporter responsible for the export of proteins and multiple RNA species, this led to the hypothesis that SF3B1-mutant cells are sensitive to XPO1 inhibition, potentially due to altered splicing. Subsequent RNA sequencing after XPO1 inhibition in SF3B1 wildtype and mutant cells showed increased nuclear retention of RNA transcripts and increased alternative splicing in the SF3B1 mutant cells particularly of genes that impact apoptotic pathways. To identify novel drug combinations that synergize with XPO1 inhibition, a forward genetic screen was performed with eltanexor treatment implicating anti-apoptotic targets BCL2 and BCLXL, which were validated by functional testing in vitro and in vivo. These targets were tested in vivo using Sf3b1K700E conditional knock-in mice, which showed that the combination of eltanexor and venetoclax (BCL2 inhibitor) had a preferential sensitivity for SF3B1 mutant cells without excessive toxicity. In this study, we unveil the mechanisms underlying sensitization to XPO1 inhibition in SF3B1-mutant MDS and preclinically rationalize the combination of eltanexor and venetoclax for high-risk MDS.

KRAS Exon 2 Mutations in Patients with Sporadic Colorectal Cancer: Prevalence Variations in Mexican and Latin American Populations.

We searched for the prevalence of actionable somatic mutations in exon 2 of the KRAS gene in western Mexican patients with CRC. Tumor tissue DNA samples from 150 patients with sporadic CRC recruited at the Civil Hospital of Guadalajara were analyzed. Mutations in exon 2 of the KRAS gene were identified using Sanger sequencing, and the data were analyzed considering clinical-pathological characteristics. Variants in codon 12 (rs121913529 G>A, G>C, and G>T) and codon 13 (rs112445441 G>A) were detected in 26 patients (with a prevalence of 17%). No significant associations were found between these variants and clinical-pathological characteristics (p > 0.05). Furthermore, a comprehensive search was carried out in PubMed/NCBI and Google for the prevalence of KRAS exon 2 mutations in Latin American populations. The 17 studies included 12,604 CRC patients, with an overall prevalence of 30% (95% CI = 0.26-0.35), although the prevalence ranged from 13 to 43% across the different data sources. Determining the variation and frequency of KRAS alleles in CRC patients will enhance their potential to receive targeted treatments and contribute to the understanding of the genomic profile of CRC.

Update on ocular manifestations of the main monogenic and polygenic autoinflammatory diseases.

Autoinflammatory diseases include disorders with a genetic cause and also complex syndromes associated to polygenic or multifactorial factors. Eye involvement is present in many of them, with different extent and severity. The present review covers ophthalmological lesions in the most prevalent monogenic autoinflammatory diseases, including FMF (familial Mediterranean fever), TRAPS (TNF receptor-associated periodic syndrome), CAPS (cryopyrin-associated periodic syndromes), Blau syndrome, DADA2 (deficiency of adenosine deaminase 2), DITRA (deficiency of the interleukin-36 receptor antagonist), other monogenic disorders, including several ubiquitinopathies, interferonopathies, and the recently described ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome, and VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Among polygenic autoinflammatory diseases, ocular manifestations have been reviewed in Behçet's disease, PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) syndrome, Still's disease and autoinflammatory bone diseases, which encompass CRMO (chronic recurrent multifocal osteomyelitis) and SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome.

Pyrin-associated autoinflammation with neutrophilic dermatosis: A case report.

Pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND) is a rare, monogenic, autoinflammatory disorder caused by mutations in exon 2 of the MEFV gene. Characterized by neutrophilic dermatosis, recurrent fever, and arthralgia, this syndrome presents a diagnostic challenge due to its low prevalence and varied clinical manifestations. Here, we present the case of a 49-year-old Spanish male with severe hidradenitis suppurativa and pyoderma gangrenosum with a heterozygous variant (p.E244K) in the MEFV gene, consistent with PAAND syndrome. This variant has only been documented in one other case with notable similarities. Both patients share Spanish ancestry and present a severe form of hidradenitis suppurativa. Treatment of the disorder presents challenges due to its variable response to standard therapies. Anti-interleukin-1 agents, such as anakinra or anti-tumor necrosis factor (TNF)-α are the therapeutic approaches supported by the most substantial evidence. Our findings highlight the importance of genetic evaluation of MEFV mutations in individuals with neutrophilic dermatosis and systemic symptoms.

Essential Oil of Fractionated Oregano as Motility Inhibitor of Bacteria Associated with Urinary Tract Infections.

In this research, several analyses were carried out on concentrated fractions of Mexican oregano essential oil (Poliomintha longiflora Gray) in order to determine its ability to inhibit the growth and the motility of Escherichia coli (swimming), Pseudomonas aeruginosa (swimming), and Proteus vulgaris (swarming); these Gram-negative bacteria associated with urinary tract infections are motile due to the presence of flagella, which is considered an important virulence factor that favors their motility when trying to reach the target organ and cause an infection. Also, the resistance pattern to antibiotics of each strain was determined. The results showed resistance pattern (8 out of 12 antibiotics tested) for P. aureginosa, while E. coli and P. vulgaris were resistant to 4 antibiotics out of the 12 tested. On the other hand, fractionated oregano caused an inhibition of growth and a reduction in motility, varying between fractions and among bacteria. Fraction 4 showed major growth reduction, with MBC values ranging from 0.002 to 23.7 mg/mL. Treatment with fractionated oregano (F1, F2, F3, F4) reduced the motility by 92-81% for P. vulgaris, 90-83% for E. coli, and 100-8.9% for P. aeruginosa. These results demonstrated a higher performance with a lower application dose due to its high content of Carvacrol and Thymol; unlike other concentrated fractions, this synergy of oxygenated monoterpenes may cause greater antimicrobial activity.

Evidence for widespread translation of 5' untranslated regions.

Ribosome profiling experiments support the translation of a range of novel human open reading frames. By contrast, most peptides from large-scale proteomics experiments derive from just one source, 5' untranslated regions. Across the human genome we find evidence for 192 translated upstream regions, most of which would produce protein isoforms with extended N-terminal ends. Almost all of these N-terminal extensions are from highly abundant genes, which suggests that the novel regions we detect are just the tip of the iceberg. These upstream regions have characteristics that are not typical of coding exons. Their GC-content is remarkably high, even higher than 5' regions in other genes, and a large majority have non-canonical start codons. Although some novel upstream regions have cross-species conservation - five have orthologues in invertebrates for example - the reading frames of two thirds are not conserved beyond simians. These non-conserved regions also have no evidence of purifying selection, which suggests that much of this translation is not functional. In addition, non-conserved upstream regions have significantly more peptides in cancer cell lines than would be expected, a strong indication that an aberrant or noisy translation initiation process may play an important role in translation from upstream regions.

Differences between Patients with Sporadic and Familial Pheochromocytoma-Is It Possible to Avoid Genetic Testing in Certain Patients?

BACKGROUND: Pheochromocytoma (PHEO) is a rare neuroendocrine tumour with a strong genetic link, which therefore may modify its clinical behaviour and prognosis. The aim of the study is to evaluate the epidemiological and clinical differences between patients with sporadic and familial PHEO, as well as the specific differences in the index cases. METHODS: A retrospective analysis of 136 patients in a tertiary hospital (1984-2021). Epidemiological, clinical, and histological variables were analysed. STATISTICS: SPSS 28.0 software was used. Univariate and multivariate logistic regression analyses were performed. p < 0.05 was considered statistically significant. RESULTS: 64.71% of the cases (n = 88) presented a genetic mutation (familial cases). Additionally, 32.39% (n = 23) corresponded to index cases and the rest to screening cases. The main differences between patients with familial and sporadic PHEO were age (OR = 0.93 (0.89-0.97)), blood pressure-related symptoms (OR = 0.22 (0.06-0.89)), bilaterality (OR = 15.49 (3.76-63.84)), and size (OR = 0.70 (0.54-0.92)). Among patients with sporadic PHEO and index cases, only bilaterality was significant (OR = 13.53 (1.24-144.34)). CONCLUSIONS: Patients with familial PHEO diagnosed by screening differ from sporadic cases in terms of age, clinical features, and size. However, patients with sporadic PHEO only differ from index cases by a lower presence of bilaterality, which reaffirms the importance of genetic screening of patients with PHEO and their relatives.

Performance Projection of Vacuum Gate Dielectric Doping-Free Carbon Nanoribbon/Nanotube Field-Effect Transistors for Radiation-Immune Nanoelectronics.

This paper investigates the performance of vacuum gate dielectric doping-free carbon nanotube/nanoribbon field-effect transistors (VGD-DL CNT/GNRFETs) via computational analysis employing a quantum simulation approach. The methodology integrates the self-consistent solution of the Poisson solver with the mode space non-equilibrium Green's function (NEGF) in the ballistic limit. Adopting the vacuum gate dielectric (VGD) paradigm ensures radiation-hardened functionality while avoiding radiation-induced trapped charge mechanisms, while the doping-free paradigm facilitates fabrication flexibility by avoiding the realization of a sharp doping gradient in the nanoscale regime. Electrostatic doping of the nanodevices is achieved via source and drain doping gates. The simulations encompass MOSFET and tunnel FET (TFET) modes. The numerical investigation comprehensively examines potential distribution, transfer characteristics, subthreshold swing, leakage current, on-state current, current ratio, and scaling capability. Results demonstrate the robustness of vacuum nanodevices for high-performance, radiation-hardened switching applications. Furthermore, a proposal for extrinsic enhancement via doping gate voltage adjustment to optimize band diagrams and improve switching performance at ultra-scaled regimes is successfully presented. These findings underscore the potential of vacuum gate dielectric carbon-based nanotransistors for ultrascaled, high-performance, energy-efficient, and radiation-immune nanoelectronics.