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1.
Cureus ; 16(5): e59794, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38846179

RESUMO

BACKGROUND: Root canal treatment (RCT) is a vital dental procedure aimed at preserving tooth function and minimizing infection. Access to accurate and comprehensive information about RCT is crucial for informed decision-making. With the increasing reliance on the Internet for health-related information, it is essential to evaluate the quality and readability of web-based RCT content, particularly in Arabic-speaking regions. METHODS: This study conducted an extensive web search using three major search engines (Google, Yahoo, and Bing) to identify Arabic-language websites providing information on RCT. Inclusion criteria required websites in Arabic with comprehensive RCT content. Quality assessment employed the DISCERN instrument, JAMA benchmarks, and Health on the Net (HON) assessment tools, while readability was assessed using Flesch Kincaid Grade Level (FKGL), Simple Measure of Gobbledygook (SMOG), and Flesch Reading Ease (FRE) metrics. RESULTS: Out of 152 websites included, the majority were affiliated with university/medical centers (56.58%) and non-profit organizations (28.29%). Quality assessment revealed that the mean DISCERN score was 2.82, indicating moderate quality. Only one website achieved a high DISCERN score. JAMA benchmarks showed limited compliance, with only two websites meeting all criteria. The HON code was found on only five websites. Readability analysis indicated that most websites were reasonably easy to read by the general population. CONCLUSION: This study highlights the significant gap in the quality and reliability of web-based health information related to RCT in Arabic. While the majority of websites examined in this study did not meet established quality standards, there is a clear need for improvements in the accuracy and comprehensiveness of online resources. Patients seeking information on RCT should exercise caution and consider consulting healthcare professionals for trustworthy guidance. Further research should explore strategies to enhance the quality of web-based health information and expand the scope of evaluation to ensure that individuals have access to reliable resources for making informed decisions about their dental health.

2.
Nat Commun ; 15(1): 5266, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902237

RESUMO

Functionally characterizing the genetic alterations that drive pancreatic cancer is a prerequisite for precision medicine. Here, we perform somatic CRISPR/Cas9 mutagenesis screens to assess the transforming potential of 125 recurrently mutated pancreatic cancer genes, which revealed USP15 and SCAF1 as pancreatic tumor suppressors. Mechanistically, we find that USP15 functions in a haploinsufficient manner and that loss of USP15 or SCAF1 leads to reduced inflammatory TNFα, TGF-ß and IL6 responses and increased sensitivity to PARP inhibition and Gemcitabine. Furthermore, we find that loss of SCAF1 leads to the formation of a truncated, inactive USP15 isoform at the expense of full-length USP15, functionally coupling SCAF1 and USP15. Notably, USP15 and SCAF1 alterations are observed in 31% of pancreatic cancer patients. Our results highlight the utility of in vivo CRISPR screens to integrate human cancer genomics and mouse modeling for the discovery of cancer driver genes with potential prognostic and therapeutic implications.


Assuntos
Sistemas CRISPR-Cas , Neoplasias Pancreáticas , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Gencitabina , Regulação Neoplásica da Expressão Gênica , Mutação , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo
3.
Cureus ; 16(5): e60561, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38887354

RESUMO

Introduction In recent years, the increased use of smartphones has adversely affected students, leading to issues like musculoskeletal pain. Therefore, our objective was to assess the correlation between smartphone addiction and neck and lower back pain. Methodology An observational cross-sectional study was conducted at Al-Baha University, Al-Baha, Saudi Arabia. The Smartphone Addiction Scale Short Version (SAS-SV) was used to measure the level of smartphone addiction while the Nordic Musculoskeletal Questionnaire (NMQ) was utilized to evaluate musculoskeletal pain. Results Smartphone addiction was prevalent in 72% of the participants (n = 293). Significantly, lower back pain was associated with smartphone addiction (p-value = 0.004). However, none of the demographic characteristics were associated with neck or lower back pain (p-value > 0.05). Students in clinical years had a higher risk of neck pain than those in an internship (p-value = 0.048). Conclusion Almost two-thirds of the students were addicted to smartphones, with a significant association with lower back pain. Students addicted to their smartphones had a higher risk of developing lower back pain, while clinical-year students had a higher risk of developing neck pain. It's important to raise awareness about the health and safety dangers linked to smartphones and other devices.

4.
J Dent ; 146: 105058, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38729286

RESUMO

OBJECTIVES: This review aimed to map taxonomy frameworks, descriptions, and applications of immersive technologies in the dental literature. DATA: The Preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) guidelines was followed, and the protocol was registered at open science framework platform (https://doi.org/10.17605/OSF.IO/H6N8M). SOURCES: Systematic search was conducted in MEDLINE (via PubMed), Scopus, and Cochrane Library databases, and complemented by manual search. STUDY SELECTION: A total of 84 articles were included, with 81 % between 2019 and 2023. Most studies were experimental (62 %), including education (25 %), protocol feasibility (20 %), in vitro (11 %), and cadaver (6 %). Other study types included clinical report/technique article (24 %), clinical study (9 %), technical note/tip to reader (4 %), and randomized controlled trial (1 %). Three-quarters of the included studies were published in oral and maxillofacial surgery (38 %), dental education (26 %), and implant (12 %) disciplines. Methods of display included head mounted display device (HMD) (55 %), see through screen (32 %), 2D screen display (11 %), and projector display (2 %). Descriptions of immersive realities were fragmented and inconsistent with lack of clear taxonomy framework for the umbrella and the subset terms including virtual reality (VR), augmented reality (AR), mixed reality (MR), augmented virtuality (AV), extended reality, and X reality. CONCLUSIONS: Immersive reality applications in dentistry are gaining popularity with a notable surge in the number of publications in the last 5 years. Ambiguities are apparent in the descriptions of immersive realities. A taxonomy framework based on method of display (full or partial) and reality class (VR, AR, or MR) is proposed. CLINICAL SIGNIFICANCE: Understanding different reality classes can be perplexing due to their blurred boundaries and conceptual overlapping. Immersive technologies offer novel educational and clinical applications. This domain is fast developing. With the current fragmented and inconsistent terminologies, a comprehensive taxonomy framework is necessary.


Assuntos
Odontologia , Humanos , Classificação , Educação em Odontologia , Realidade Virtual , Realidade Aumentada
5.
PLoS One ; 19(5): e0303308, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38781283

RESUMO

BACKGROUND: This study assesses the quality and readability of Arabic online information about orthodontic pain. With the increasing reliance on the internet for health information, especially among Arabic speakers, it's critical to ensure the accuracy and comprehensiveness of available content. Our methodology involved a systematic search using the Arabic term for (Orthodontic Pain) in Google, Bing, and Yahoo. This search yielded 193,856 results, from which 74 websites were selected based on predefined criteria, excluding duplicates, scientific papers, and non-Arabic content. MATERIALS AND METHODS: For quality assessment, we used the DISCERN instrument, the Journal of the American Medical Association (JAMA) benchmarks, and the Health on the Net (HON) code. Readability was evaluated using the Simplified Measure of Gobbledygook (SMOG), Flesch Reading Ease Score (FRES), and Flesch-Kincaid Grade Level (FKGL) scores. RESULTS: Results indicated that none of the websites received the HONcode seal. The DISCERN assessment showed median total scores of 14.96 (± 5.65), with low overall quality ratings. In JAMA benchmarks, currency was the most achieved aspect, observed in 45 websites (60.81%), but none met all four criteria simultaneously. Readability scores suggested that the content was generally understandable, with a median FKGL score of 6.98 and a median SMOG score of 3.98, indicating middle school-level readability. CONCLUSION: This study reveals a significant gap in the quality of Arabic online resources on orthodontic pain, highlighting the need for improved standards and reliability. Most websites failed to meet established quality criteria, underscoring the necessity for more accurate and trustworthy health information for Arabic-speaking patients.


Assuntos
Compreensão , Internet , Humanos , Informação de Saúde ao Consumidor/normas , Idioma , Dor , Árabes , Leitura
6.
Mol Syst Biol ; 20(6): 719-740, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38580884

RESUMO

Tumor suppressor p53 (TP53) is frequently mutated in cancer, often resulting not only in loss of its tumor-suppressive function but also acquisition of dominant-negative and even oncogenic gain-of-function traits. While wild-type p53 levels are tightly regulated, mutants are typically stabilized in tumors, which is crucial for their oncogenic properties. Here, we systematically profiled the factors that regulate protein stability of wild-type and mutant p53 using marker-based genome-wide CRISPR screens. Most regulators of wild-type p53 also regulate p53 mutants, except for p53 R337H regulators, which are largely private to this mutant. Mechanistically, FBXO42 emerged as a positive regulator for a subset of p53 mutants, working with CCDC6 to control USP28-mediated mutant p53 stabilization. Additionally, C16orf72/HAPSTR1 negatively regulates both wild-type p53 and all tested mutants. C16orf72/HAPSTR1 is commonly amplified in breast cancer, and its overexpression reduces p53 levels in mouse mammary epithelium leading to accelerated breast cancer. This study offers a network perspective on p53 stability regulation, potentially guiding strategies to reinforce wild-type p53 or target mutant p53 in cancer.


Assuntos
Mutação , Estabilidade Proteica , Proteína Supressora de Tumor p53 , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Animais , Humanos , Camundongos , Feminino , Sistemas CRISPR-Cas , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Regulação Neoplásica da Expressão Gênica , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas
7.
J Pharm Bioallied Sci ; 16(Suppl 1): S459-S462, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38595626

RESUMO

This study aims to highlight the challenges that undergraduates face when traveling a significant distance from home to study. These challenges are psychological, financial, and nutritional. The study was descriptive and based on a survey conducted to investigate the challenges faced by university students while studying away from their hometown. A questionnaire was used to collect data from 214 undergraduates between February and April 2021. The collected data were analyzed using the computer program SPSS version 24. Pearson's Chi-square and Fisher's exact tests were applied to observe associations between qualitative variables. A total of 214 undergraduates participated in the study, with a median age of 22 years. The study found significant relationships between weight change and housing (P < 0.001), weight change and distance (P < 0.001), level of homesickness and housing (P < 0.001), level of homesickness and college distance (P < 0.001), and financial status with housing (P = 0.025). The study revealed that a significant number of undergraduate participants face psychological, financial, and nutritional challenges. These challenges include psychosocial issues, such as homesickness financial difficulties, such as money issues, and nutritional concerns, such as weight changes.

8.
Cureus ; 16(3): e55405, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38562346

RESUMO

Meningitis caused by Salmonella enterica can be a fatal condition that is more common in low- and middle-income countries and uncommon in infants. This case of a 2-month-old male infant reported Salmonella meningitis symptoms, such as fever, irritability, altered sensorium, and diarrhoea. Clinical examination revealed bulging anterior fontanelles, dehydration, and sunken eyes. Screening for normal hearing, cranial ultrasound, and magnetic resonance imaging (MRI) revealed no brain abnormalities. A cerebrospinal fluid (CSF) culture revealed gram-negative Salmonella enterica bacilli. Treatment with meropenem and ampicillin was initiated after antibiotic susceptibility testing showed sensitivity. The patient's cerebrospinal fluid parameters and bacterial growth improved after antibiotic therapy. Two weeks later, the baby was neurologically healthy and discharged. Paediatricians should be aware that Salmonella enterica can cause meningitis in children with non-specific symptoms.

9.
J Prosthet Dent ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38480014

RESUMO

STATEMENT OF PROBLEM: With the increasing interest in using robots in dentistry and the widespread dissemination of information on this topic and its applications, a comprehensive review of robot applications in prosthodontics is needed. PURPOSE: The purpose of this scoping review was to assess the current status of prosthodontic robotic applications, their achievements to date, and the barriers hindering their broader adoption and further advancement. MATERIAL AND METHODS: The checklist for Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) was used to conduct this review. A comprehensive search methodology was developed to identify relevant studies on the use of robots in prosthodontic procedures in the PubMed, Scopus, Web of Science, and Google Scholar databases. The inclusion criteria were studies that specifically outlined the application of robots in the field of prosthodontics. RESULTS: Eighteen relevant studies were found. Of these, 10 studies focused on assessing the effectiveness of robotic systems through in vitro testing using phantom models for tooth preparation. These studies specifically explored the processes involved in creating complete crowns and veneers. The remaining 8 studies investigated the use of robotics in tooth alignment, with a specific focus on complete dentures. CONCLUSIONS: Robots have the potential to improve precision and accuracy in prosthetic dentistry. However, clinical studies are needed to confirm the widespread use of robots in prosthodontics, as their clinical application is still in its early stages.

10.
Cancer Immunol Immunother ; 73(5): 90, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554147

RESUMO

Clinically approved head and neck squamous cell carcinoma (HNSCC) immunotherapies manipulate the immune checkpoint blockade (ICB) axis but have had limited success outside of recurrent/metastatic disease. Interleukin-7 (IL7) has been shown to be essential for effector T-cell survival, activation, and proliferation. Here, we show that IL7 in combination with radiotherapy (RT) is effective in activating CD8 + T-cells for reducing tumor growth. Our studies were conducted using both human papillomavirus related and unrelated orthotopic HNSCC murine models. Immune populations from the tumor, draining lymph nodes, and blood were compared between treatment groups and controls using flow cytometry, proteomics, immunofluorescence staining, and RNA sequencing. Treatment with RT and IL7 (RT + IL7) resulted in significant tumor growth reduction, high CD8 T-cell tumor infiltration, and increased proliferation of T-cell progenitors in the bone marrow. IL7 also expanded a memory-like subpopulation of CD8 T-cells. These results indicate that IL7 in combination with RT can serve as an effective immunotherapy strategy outside of the conventional ICB axis to drive the antitumor activity of CD8 T-cells.


Assuntos
Neoplasias de Cabeça e Pescoço , Interleucina-7 , Humanos , Camundongos , Animais , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Células T de Memória , Linfócitos T CD8-Positivos , Neoplasias de Cabeça e Pescoço/radioterapia , Microambiente Tumoral
11.
Cureus ; 16(1): e52085, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38344597

RESUMO

As Saudi Arabia advances in medical education and patient care, assessing its contribution to cleft lip and palate (CLP) research is vital. This bibliometric analysis aims to map the trends, collaborations, and impact of Saudi research in CLP. Utilizing the Web of Science database, this study conducted a comprehensive bibliometric analysis of CLP research related to Saudi Arabian publications. The analysis included data extraction and assessment of publications, citations, H-index, and international collaborations using advanced bibliometric tools and software. A total of 89 CLP-related articles in Saudi Arabia were retrieved. The findings indicated a steady increase in publications and citations over the years, reflecting growing interest and recognition of CLP's challenges in the Saudi healthcare context. King Abdulaziz University and King Saud University emerged as leading contributors. International collaboration was evident, with significant partnerships with countries like the USA, Canada, the UK, and others. The Cleft Palate-Craniofacial Journal and the Saudi Dental Journal were identified as the most influential journals in disseminating Saudi CLP research. The study highlights a positive growth trajectory in Saudi CLP research, marked by increased publications, citations, and international collaborations. It underscores the importance of continuous research and the need for enhanced efforts to further the understanding and treatment of CLP. Future studies should consider including a broader range of databases to provide a more comprehensive global view of CLP research trends.

12.
Med ; 5(3): 254-270.e8, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38423011

RESUMO

BACKGROUND: Perineural invasion (PNI) and nerve density within the tumor microenvironment (TME) have long been associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). This prompted an investigation into how nerves within the tumor microenvironment affect the adaptive immune system and tumor growth. METHODS: We used RNA sequencing analysis of human tumor tissue from a recent HNSCC clinical trial, proteomics of human nerves from HNSCC patients, and syngeneic orthotopic murine models of HPV-unrelated HNSCC to investigate how sensory nerves modulate the adaptive immune system. FINDINGS: Calcitonin gene-related peptide (CGRP) directly inhibited CD8 T cell activity in vitro, and blocking sensory nerve function surgically, pharmacologically, or genetically increased CD8 and CD4 T cell activity in vivo. CONCLUSIONS: Our data support sensory nerves playing a role in accelerating tumor growth by directly acting on the adaptive immune system to decrease Th1 CD4 T cells and activated CD8 T cells in the TME. These data support further investigation into the role of sensory nerves in the TME of HNSCC and points toward the possible treatment efficacy of blocking sensory nerve function or specifically inhibiting CGRP release or activity within the TME to improve outcomes. FUNDING: 1R01DE028282-01, 1R01DE028529-01, 1P50CA261605-01 (to S.D.K.), 1R01CA284651-01 (to S.D.K.), and F31 DE029997 (to L.B.D.).


Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Neoplasias de Cabeça e Pescoço , Animais , Humanos , Camundongos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Microambiente Tumoral
13.
Clin Cancer Res ; 30(9): 1916-1933, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38363297

RESUMO

PURPOSE: Head and neck cancer (HNC) improvements are stagnant, even with advances in immunotherapy. Our previous clinical trial data show that altered fatty acid (FA) metabolism correlates with outcome. We hypothesized that pharmacologic and dietary modulation of FA catabolism will affect therapeutic efficacy. EXPERIMENTAL DESIGN: We performed in vivo and in vitro experiments using PPARα agonism with fenofibrate (FF) or high oleic acid diets (OAD) with radiotherapy, generating metabolomic, proteomic, stable isotope tracing, extracellular flux analysis, and flow-cytometric data to investigate these alterations. RESULTS: FF improved antitumor efficacy of high dose per fraction radiotherapy in HNC murine models, whereas the OAD reversed this effect. FF-treated mice on the control diet had evidence of increased FA catabolism. Stable isotope tracing showed less glycolytic utilization by ex vivo CD8+ T cells. Improved efficacy correlated with intratumoral alterations in eicosanoid metabolism and downregulated mTOR and CD36. CONCLUSIONS: Metabolic intervention with increased FA catabolism improves the efficacy of HNC therapy and enhances antitumoral immune response.


Assuntos
Neoplasias de Cabeça e Pescoço , Ácido Oleico , PPAR alfa , Animais , PPAR alfa/agonistas , Camundongos , Ácido Oleico/farmacologia , Humanos , Neoplasias de Cabeça e Pescoço/imunologia , Fenofibrato/farmacologia , Linhagem Celular Tumoral , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Ácidos Graxos/metabolismo , Modelos Animais de Doenças
14.
BMJ Paediatr Open ; 8(1)2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216310

RESUMO

OBJECTIVE: To determine the role of heated humidified high flow therapy (HHHFT) as primary respiratory support in spontaneously breathing moderate-late, very and extreme preterm neonates with respiratory distress syndrome (RDS) at a tertiary care hospital from a developing country. DESIGN: Retrospective cohort study. SETTING: Neonatal intensive care unit of Indus Hospital and Health Network, Karachi, Pakistan. PATIENTS: All preterm neonates with RDS and who received HHHFT as primary respiratory support were included retrospectively, while neonates with orofacial anomalies, congenital heart and lung diseases other than RDS, abdominal wall defects, encephalopathy, congenital pneumonia and received continuous positive airway pressure or invasive ventilation were excluded. INTERVENTIONS: HHHFT as primary respiratory support for RDS. MAIN OUTCOME MEASURES: Effectiveness, duration, failure rate and complications of HHHFT as a primary respiratory support in moderate-late, very and extremely preterm neonates were evaluated. RESULTS: The cohort included 138 neonates during a period of 12 months. The median gestational age was 32 weeks, and the median birth weight was 1607 g. Grade 1-2 RDS was seen in 97%, surfactant instillation was done in 10.8% and HHHFT was provided in all the neonates as primary respiratory support. The total duration of HHHFT support was <1 week in 94% of neonates. Bronchopulmonary dysplasia and pneumothorax until discharge or death were observed in one neonate, haemodynamically significant Patent Ductus Artriosus (HsPDA) in two neonates and intraventricular haemorrhage Grade ≥2 in five neonates, while only one neonate died. CONCLUSION: This study appears to show that HHHFT is a simple, safe, efficient and cheap mode of primary respiratory support that can be given to spontaneously breathing moderate-late, very and extremely preterm neonates with RDS, especially in low- or middle-income countries.


Assuntos
Lactente Extremamente Prematuro , Síndrome do Desconforto Respiratório do Recém-Nascido , Recém-Nascido , Humanos , Lactente , Estudos Retrospectivos , Paquistão , Atenção Terciária à Saúde , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia
15.
Cureus ; 15(11): e49038, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38116365

RESUMO

BACKGROUND: Preeclampsia is associated with the incidence of common fetal problems including intra-uterine growth restriction (IUGR), premature delivery oligohydramnios, placental abruption, fetal discomfort, and intrauterine fetal death. Pregnant women are not well-informed about preeclampsia, including its symptoms, risk factors, and consequences. The aim of the current study is to evaluate the awareness of preeclampsia and its associated factors among women in the Al Baha region, Saudi Arabia. METHODOLOGY: An observational cross-sectional design was employed to assess the awareness of preeclampsia and its associated factors among women in the Al Baha region of Saudi Arabia. Data was collected from April 2023 to September 2023. A questionnaire was designed to gather information on participants' sociodemographic characteristics (such as age, educational level, and residency) and their awareness of preeclampsia, including knowledge about signs/symptoms, risk factors, and complications. RESULTS: In the current study, we included 485 pregnant women. The majority of participants were aged 40 years or older (37.5%), followed by those aged 35-39 (20.4%). Among the participants, 70.9% confirmed that they had heard about pre-eclampsia before. The most common signs and symptoms were high blood pressure (47.4%), increased protein in urine (40.2%), continuous headache (39.2%), and vomiting/nausea (40.0%). Participants demonstrated awareness of obesity (29.7%), diabetes mellitus (35.5%), chronic hypertension (47.0%), and chronic kidney disease (31.3%) as major risk factors. Participants were aware of potential risks such as kidney disorders (34.6%), heart disorders (23.7%), and preterm delivery (50.9%). The analysis reveals that younger participants below 20 years old (3.3%) and lower educational levels (5.6%) had lower awareness of preeclampsia compared to older age groups. CONCLUSION: The findings of this study highlight a reasonable level of preeclampsia awareness and knowledge among Saudi Arabian women residing in the Al Baha region. While the majority of participants were familiar with preeclampsia, there were significant knowledge gaps regarding the precise symptoms, risk factors, and consequences of the condition.

16.
Sci Adv ; 9(44): eadh3083, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37922356

RESUMO

Mutational signatures represent a genomic footprint of endogenous and exogenous mutational processes through tumor evolution. However, their functional impact on the proteome remains incompletely understood. We analyzed the protein-coding impact of single-base substitution (SBS) signatures in 12,341 cancer genomes from 18 cancer types. Stop-gain mutations (SGMs) (i.e., nonsense mutations) were strongly enriched in SBS signatures of tobacco smoking, APOBEC cytidine deaminases, and reactive oxygen species. These mutational processes alter specific trinucleotide contexts and thereby substitute serines and glutamic acids with stop codons. SGMs frequently affect cancer hallmark pathways and tumor suppressors such as TP53, FAT1, and APC. Tobacco-driven SGMs in lung cancer correlate with smoking history and highlight a preventable determinant of these harmful mutations. APOBEC-driven SGMs are enriched in YTCA motifs and associate with APOBEC3A expression. Our study exposes SGM expansion as a genetic mechanism by which endogenous and carcinogenic mutational processes directly contribute to protein loss of function, oncogenesis, and tumor heterogeneity.


Assuntos
Neoplasias , Humanos , Mutação , Neoplasias/genética , Neoplasias/patologia , Citidina Desaminase/genética , Desaminases APOBEC/genética , Desaminases APOBEC/metabolismo , Fumar Tabaco
17.
Cureus ; 15(10): e46708, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38021713

RESUMO

Introduction Acute poisoning, arising from exposure to toxic substances, is a critical healthcare challenge. In the United States, it's one of the primary causes of morbidity and mortality. European institutions report that about 1% of all emergency department admissions relate to poisoning, a statistic that becomes alarming given the life-threatening implications. While there's an underreporting of these cases, the actual figure could be much higher. Acute poisoning has resulted in over a million morbidity cases with a 20% mortality rate. Most concerning is the World Health Organization's data indicating that over 90% of accidental poisoning deaths occur in low to middle-income countries. Methods This was a cross-sectional study conducted over a 12-month period in three major hospitals in Saudi Arabia. The study population comprised of 1470 patients who presented to emergency departments with suspected acute poisoning. Medical records were retrospectively reviewed, capturing data on patient demographics, nature and type of poisoning, initial management, and outcomes. Data were analyzed using SPSS software version 28.0 (IBM Corp., Armok, NY). Descriptive statistics were used to summarize the data, while Chi-square tests were employed to determine associations between demographic factors and the nature of poisoning. Furthermore, the Pearson correlation was used to evaluate the link between referrals to specialized centers and patient outcomes. Results Out of the 1470 participants, a significant majority were males, constituting 77.1%. The dominant age group was between 18-24 years, representing 71.4% of the sample. A substantial 88.6% had visited the emergency room due to medical complications stemming from poisoning. When queried about their understanding of acute poisoning, 60.0% were able to correctly define the term. However, a concerning 54.3% reported they had never received any formal training or been part of awareness programs regarding poisoning. There was a marked association (p < 0.001) between demographics and the nature of toxin exposure. Delving deeper into the specifics of poisoning incidents, medications were identified as the primary culprits in 8.6% of the cases, followed by household chemicals at 5.7%. Crucially, a vast majority, 82.9%, were of the opinion that with the right education and precautions in place, the incidence of poisoning cases could be substantially reduced. Conclusion Acute poisoning is a pressing concern in Saudi Arabia, with a significant proportion of the population unaware or inadequately trained to handle such emergencies. This study underscores the importance of awareness campaigns, formal education, and specialized training to prevent and effectively manage poisoning cases in emergency settings. Moreover, the strong association between certain demographics and toxin exposures suggests that targeted interventions might be necessary for specific groups.

18.
Cureus ; 15(10): e47122, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38022272

RESUMO

INTRODUCTION: Saudi Arabia is witnessing a demographic shift characterized by a rising elderly population. Cases of fall in this demographic have emerged as a significant health concern, especially in emergency room (ER) settings. Despite this, there is limited research on the causes and outcomes of such incidents. This study intends to bridge the gap in understanding the factors leading to falls in elderly patients presenting to ERs and the subsequent outcomes. Such understanding is pivotal for the formulation of effective prevention strategies and enhanced healthcare services for the elderly. METHODS: To achieve the study's objectives, we employed SPSS software for Windows, version 28.0 (IBM Corp., Armonk, NY) for data analysis. We collected demographic information, including age, gender, education, employment status, and location, to measure patient satisfaction with the quality and responsiveness of emergency care, using Likert scale responses via electronic survey conducted as a cross-sectional study from January 2023 to August 2023, summarizing it using descriptive statistics. We analyzed categorical variables by frequencies and percentages. Chi-square tests were utilized to examine differences in distribution across categories for fall factors, and a p-value below 0.05 was deemed significant. Through logistic regression, we pinpointed the predictors of falls among older adults, showcasing the strength and direction of these relationships. Adjusted odds ratios with 95% confidence intervals were documented. A perception survey was also conducted to evaluate ER patient satisfaction. RESULTS: Our results shed light on various aspects of fall prevention and emergency care. There was a pronounced representation in age groups of 18-24 and 25-34 years, indicating the need for interventions tailored to different age groups. Patterns were identified where subjects engaged in limited physical activity and consumed alcohol infrequently. Mobility and balance problems were commonly found, stressing the need to address these issues. Chronic conditions such as hypertension and diabetes correlated with fall incidents. Additionally, sociodemographic factors like gender, education, and employment status played a role in influencing the risk of falls. Although age and location seemed to have a less pronounced effect, there exists an opportunity to enhance communication and patient participation in emergency care for improved experiences. CONCLUSION: The findings from our study provide crucial insights into the prevention of falls and enhancement of emergency care for Saudi Arabia's elderly population. By revealing the intricate relationships between sociodemographic attributes, health indicators, chronic ailments, and incidents of falls, we emphasize the need for well-rounded interventions. There is a pressing requirement for comprehensive fall prevention initiatives tailored to specific risk groups. Additionally, improving ER services is integral to ensuring the safety and well-being of older adults. This research can serve as a foundational resource for healthcare professionals and policymakers to devise robust strategies to reduce fall-related injuries and elevate the quality of emergency care outcomes.

19.
Cureus ; 15(10): e46879, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37841990

RESUMO

BACKGROUND: Orthodontic treatments aim to enhance dental aesthetics, functionality, and long-term oral health. Clear aligners have gained popularity as an aesthetic and convenient option for patients seeking orthodontic correction. However, the quality and readability of online Arabic patient-centered information regarding clear aligners has not been studied yet. The aim of our study is to investigate the quality and readability of Arabic patient-centered information about clear aligners. METHODS: We conducted an extensive evaluation of Arabic web-based content pertaining to clear aligners using three prominent search engines. Eligible websites were categorized based on specialization, organizational affiliation, material type, and presentation style. We assessed website quality and reliability using the DISCERN instrument, Journal of American Medical Association (JAMA) benchmarks, and Health on the Net (HON) code. In addition, we measured readability using the Flesch Reading Ease Score (FRES), Simplified Measure of Gobbledygook (SMOG), and Flesch-Kincaid Grade Level (FKGL). RESULTS: Out of 600 search results, 195 websites met the inclusion criteria. None of the websites were HON-code accredited. DISCERN assessments revealed low content quality, with none of the websites achieving high-quality status. The JAMA benchmarks showed limited compliance with the four items, with currency being the most frequently achieved. Readability assessments indicated generally high readability, with FKGL scores suggesting easy comprehension for the average readers. CONCLUSION: While Arabic web-based information on clear aligners is highly readable, its credibility and quality require significant improvement. Websites should adhere to medical information standards, subject content to rigorous assessments, and seek accreditation to ensure reliability. Enhancing the accessibility and comprehensibility of health-related content will empower individuals to make informed health decisions. Addressing limitations, such as social media and video content evaluation, and conducting comparisons with English websites in future research will provide a more comprehensive understanding of the landscape of online orthodontic information.

20.
Cell Rep ; 42(10): 113256, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37847590

RESUMO

It is widely assumed that all normal somatic cells can equally perform homologous recombination (HR) and non-homologous end joining in the DNA damage response (DDR). Here, we show that the DDR in normal mammary gland inherently depends on the epithelial cell lineage identity. Bioinformatics, post-irradiation DNA damage repair kinetics, and clonogenic assays demonstrated luminal lineage exhibiting a more pronounced DDR and HR repair compared to the basal lineage. Consequently, basal progenitors were far more sensitive to poly(ADP-ribose) polymerase inhibitors (PARPis) in both mouse and human mammary epithelium. Furthermore, PARPi sensitivity of murine and human breast cancer cell lines as well as patient-derived xenografts correlated with their molecular resemblance to the mammary progenitor lineages. Thus, mammary epithelial cells are intrinsically divergent in their DNA damage repair capacity and PARPi vulnerability, potentially influencing the clinical utility of this targeted therapy.


Assuntos
Antineoplásicos , Inibidores de Poli(ADP-Ribose) Polimerases , Humanos , Animais , Camundongos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Antineoplásicos/farmacologia , Reparo do DNA , Recombinação Homóloga , Dano ao DNA
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