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1.
Biochem Mol Biol Educ ; 52(2): 136-144, 2024.
Article in English | MEDLINE | ID: mdl-37850840

ABSTRACT

Online case-based learning (CBL) is a method used by King Abdulaziz University to teach medical students in their preclinical years. The use of CBL in basic sciences is important for enabling medical students to correlate basic sciences with future clinical practice. This study implemented online CBL for biochemistry teaching as part of the medical genetic module for 3rd-year preclinical students. Teaching during the study was completely online because of restricted precautions caused by the COVID-19 pandemic, except for practical sessions that were held on campus. The case was presented to the students involved in prenatal screening and diagnosis. Students were guided to learn and discuss the biochemical tests used for prenatal screening and diagnosis and their clinical importance. They were divided into two groups: the control group was given an online lecture and the intervention group was given an online CBL session before the lecture. The online lecture was given to both groups simultaneously by the same instructor, and then 10 MCQs tests were distributed to both groups after the lecture, and their test scores were compared. A 10-question survey was administered to the intervention group to assess their perception of the online CBL session after the test. A significant difference was found between the intervention and control groups regarding test scores (p < 0.001), and most students found the online CBL session enjoyable and motivating.


Subject(s)
COVID-19 , Students, Medical , Humans , Pandemics , Universities , COVID-19/epidemiology , Learning
2.
NPJ Breast Cancer ; 9(1): 91, 2023 Nov 08.
Article in English | MEDLINE | ID: mdl-37940649

ABSTRACT

Breast cancer prognosis and management for both men and women are reliant upon estrogen receptor alpha (ERα) and progesterone receptor (PR) expression to inform therapy. Previous studies have shown that there are sex-specific binding characteristics of ERα and PR in breast cancer and, counterintuitively, ERα expression is more common in male than female breast cancer. We hypothesized that these differences could have morphological manifestations that are undetectable to human observers but could be elucidated computationally. To investigate this, we trained attention-based multiple instance learning prediction models for ERα and PR using H&E-stained images of female breast cancer from the Cancer Genome Atlas (TCGA) (n = 1085) and deployed them on external female (n = 192) and male breast cancer images (n = 245). Both targets were predicted in the internal (AUROC for ERα prediction: 0.86 ± 0.02, p < 0.001; AUROC for PR prediction = 0.76 ± 0.03, p < 0.001) and external female cohorts (AUROC for ERα prediction: 0.78 ± 0.03, p < 0.001; AUROC for PR prediction = 0.80 ± 0.04, p < 0.001) but not the male cohort (AUROC for ERα prediction: 0.66 ± 0.14, p = 0.43; AUROC for PR prediction = 0.63 ± 0.04, p = 0.05). This suggests that subtle morphological differences invisible upon visual inspection may exist between the sexes, supporting previous immunohistochemical, genomic, and transcriptomic analyses.

3.
PLoS One ; 18(11): e0293633, 2023.
Article in English | MEDLINE | ID: mdl-37922281

ABSTRACT

UK medical and dental school curricula limit opportunities for students to gain experience in research. This parallels a decline in the number of clinical academics. To address this at grass roots level, we organised and arranged a residential summer taster week; INSPIRE (Introducing New Skills to Promote Inspirational Research Experience)-Aberdeen). The purpose was to give first and second year medical and dental students who wished to explore a potential clinical academic career a taste of wet laboratory research and to gain experience in basic research skills. Seventeen students from eight different UK medical and dental schools attended this free residential course and were exposed to various laboratory techniques with clinical translation and application in diagnostic and therapeutic medicine. Students were given access to relevant online learning tools of the techniques being used beforehand and seminar style presentations were used to emphasise their clinical application. Students met daily with clinical academics from different specialities to give them a flavour of potential clinical academic career pathways and options. All students felt that the summer school helped them consider academic medicine as a career thus achieving our aim to inspire clinical academics of the future.


Subject(s)
Education, Medical, Undergraduate , Medicine , Students, Medical , Humans , Students, Dental , Education, Medical, Undergraduate/methods , Curriculum , Schools , Career Choice
4.
Vet World ; 16(5): 888-894, 2023 May.
Article in English | MEDLINE | ID: mdl-37576758

ABSTRACT

Background and Aims: Bovine mastitis is a disease that affects dairy cows and impacts the global dairy industry. Bacillus spp. can infect the mammary gland during lactation, intramammary treatment, or dry cow therapy. This study aimed to isolate and identify Bacillus spp. in raw milk samples from cows with subclinical mastitis from dairy farms in Beheira, Giza, Alexandria, and Menoufia Governorate, Egypt. We also investigated their antibiotic sensitivity and detected the enterotoxigenic and antibiotic resistance genes. Materials and Methods: A total of 262 milk samples (15-20 ml each) were examined microscopically, biochemically, and phenotypically. A polymerase chain reaction was used for genotypic identification and detecting antibiotic-resistance and enterotoxigenic genes. Antibiotic sensitivity was tested using the agar well diffusion test. Results: Bacillus cereus was identified in 47.7% of samples. Nhe and hblD enterotoxin genes were found in 93.64% (103/110) and 91.82% (101/110) of the samples, respectively. Tetracycline and ß-lactam antibiotic-resistance genes were present in 0% (0/110) and 98.18% (108/110), respectively, of the samples. All isolates were resistant to cefepime, cefixime, and oxacillin, while they were susceptible to amoxicillin-clavulanic, chloramphenicol, ampicillin/sulbactam, and levofloxacin. Conclusion: These results highlight the need to promote awareness regarding B. cereus, the most common pathogen causing mastitis in Egyptian dairy cows. We also emphasized that antibiotic misuse during mastitis is a potential public health threat.

5.
Spec Care Dentist ; 43(6): 869-882, 2023.
Article in English | MEDLINE | ID: mdl-37186085

ABSTRACT

INTRODUCTION: There has been a global increase in patients with special needs. Undergraduate dental curricula need to adjust to meet the needs of these patients. This study aimed to identify how confident final year dental students felt about treating patients with special needs upon graduation and evaluate the influence that the curriculum had on their preparedness based on competencies outlined by the International Association for Disability and Oral Health (iADH). METHODS: A questionnaire was administered to final year dental students at two different Universities in Scotland and in Spain to: (1) evaluate how prepared students felt when treating patients with special needs and (2) assess the competencies outlined by iADH. RESULTS: The response rate was 18.4% (30/163 students). Overall, 83.3% of the students (n = 25) perceived they would benefit from more practical sessions with patients with learning and physical disabilities to improve their clinical management of these patients. 53.3% (n = 16) didn't feel that had the knowledge to properly treat all special care dentistry (SCD) patients upon graduation (scored 5 or 6 on the IADH competency framework). 83.3% of the students (n = 25) felt that the mode of teaching should be problem-based complemented with small group seminars. CONCLUSION: Students from both Universities agreed that more clinical practice might be required for them to further their skills to treat special needs patients upon graduation, which correlates with the need to have more practical sessions to consolidate competency 4 (communication skills with SCD) and competency 6 (clinical management of patients requiring SCD).


Subject(s)
Curriculum , Students, Dental , Humans , Education, Dental , Surveys and Questionnaires , Oral Health , Clinical Competence
6.
Cancers (Basel) ; 15(6)2023 Mar 10.
Article in English | MEDLINE | ID: mdl-36980582

ABSTRACT

Background: Head and neck cancer (HNC) has a high mortality rate, with late diagnosis remaining the most important factor affecting patient survival. Therefore, it is imperative to identify markers that aid in early detection and prediction of disease progression. HNCs evade the immune system by different mechanisms, including immune checkpoints. Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) is an immune checkpoint receptor that downregulates anti-tumour immune responses, with evidence of involvement in HNC. The less studied, alternatively spliced, soluble isoform (sCTLA-4) also plays an immunosuppressive role that contributes to immune escape. We quantified sCTLA-4 in normal, potentially malignant, and malignant oral and oropharyngeal tissues to elucidate any role in tumourigenesis and identify its potential as a biomarker for diagnosis and patient stratification. Methods: Normal, low- and high-grade epithelial dysplasia, and squamous cell carcinoma oral and oropharyngeal biopsies were selectively stained for sCTLA-4 and quantified using the image analysis software QuPath. Results: Distinct sCTLA-4 staining patterns were observed, in which normal epithelial sCTLA-4 expression correlated with keratinocyte differentiation, while disrupted expression, both in intensity and localisation, was observed in dysplastic and neoplastic tissues. Conclusions: Our data indicate an additional, previously unknown role for sCTLA-4 in epithelial cell differentiation and proliferation. Furthermore, our findings suggest the potential of sCTLA-4 as a biomarker for predicting disease progression and patient stratification for targeted HNC therapies.

7.
Cancers (Basel) ; 15(5)2023 Feb 28.
Article in English | MEDLINE | ID: mdl-36900301

ABSTRACT

The incidence of oral squamous cell carcinoma (OSCC), and its precursor, oral epithelial dysplasia (OED), is on the rise, especially in South Asia. OSCC is the leading cancer in males in Sri Lanka, with >80% diagnosed at advanced clinical stages. Early detection is paramount to improve patient outcome, and saliva testing is a promising non-invasive tool. The aim of this study was to assess salivary interleukins (lL1ß, IL6, and IL8) in OSCC, OED and disease-free controls in a Sri Lankan study cohort. A case-control study with OSCC (n = 37), OED (n = 30) patients and disease-free controls (n = 30) was conducted. Salivary lL1ß, IL6, and IL8 were quantified using enzyme-linked immuno-sorbent assay. Comparisons between different diagnostic groups and potential correlations to risk factors were assessed. Salivary levels for the three tested interleukins increased from disease-free controls through OED, and were highest in OSCC samples. Furthermore, the levels of IL1ß, IL6, and IL8 increased progressively with OED grade. The discrimination between patients (OSCC and OED) and controls, as assessed by AUC of receiver operating characteristic curves, was 0.9 for IL8 (p = 0.0001) and 0.8 for IL6 (p = 0.0001), while IL1ß differentiated OSCC from controls (AUC 0.7, p = 0.006). No significant associations were found between salivary interleukin levels and smoking, alcohol, and betel quid risk factors. Our findings suggest that salivary IL1ß, IL6, and IL8 are associated with disease severity of OED, and are potential biomarkers for predicting disease progression in OED, and the screening of OSCC.

8.
Brain Behav ; 13(4): e2955, 2023 04.
Article in English | MEDLINE | ID: mdl-36924079

ABSTRACT

BACKGROUND: Several studies have shown that autoimmune diseases are associated with psychiatric diseases like depression and psychosis. Genetic evidence supports this association. The aim of this study was to investigate if genetic variants predisposing to autoimmune diseases and psychiatric disorders are genetically linked, constructing the common haplotypes. METHODS: All registered single nucleotide polymorphisms (SNPs) in the Genome-wide association studies ("GWAS catalog") having been associated with autoimmune rheumatic and endocrine diseases were investigated for being in linkage disequilibrium with any psychiatric disorders' associated SNPs. Analysis was performed by the LDtrait and LDhap bioinformatics tools. RESULTS: Multiple chromosomal regions have been detected containing rheumatic/endocrine diseases' predisposing SNPs and psychiatric disorders' predisposing SNPs. The genetic haplotypes have been constructed for some of these genetic regions. Six of the autoimmune rheumatic and endocrine diseases examined here share a common haplotype with psychiatric diseases at the HLA locus 6p21-22. CONCLUSION: Our study shows that autoimmune diseases and psychiatric diseases are genetically linked. Genetic haplotypes have been constructed, showing in detail this genetic linkage.


Subject(s)
Autoimmune Diseases , Endocrine System Diseases , Mental Disorders , Humans , Haplotypes , Genome-Wide Association Study , Genetic Predisposition to Disease/genetics , Linkage Disequilibrium , Mental Disorders/genetics , Autoimmune Diseases/genetics , Polymorphism, Single Nucleotide
9.
Lancet Oncol ; 24(2): e74-e85, 2023 02.
Article in English | MEDLINE | ID: mdl-36725152

ABSTRACT

Although similar phenotypically, there is evidence that male and female breast cancer differ in their molecular landscapes. In this systematic review, we consolidated all existing prognostic biomarker data in male breast cancer spanning genetics, transcriptomics, proteomics, and epigenetics, and phenotypic features of prognostic value from articles published over a 29-year period (March 16, 1992, to May 1, 2021). We identified knowledge gaps in the existing literature, discussed limitations of the included studies, and outlined potential approaches for translational biomarker discovery and validation in male breast cancer. We also recognised STC2, DDX3, and DACH1 as underexploited markers of male-specific prognostic value in breast cancer. Finally, beyond describing the cumulative knowledge on the extensively researched markers oestrogen receptor-α, progesterone receptor, HER2, androgen receptor, and BRCA2, we highlighted ATM, CCND1, FGFR2, GATA3, HIF1-α, MDM2, TP53, and c-Myc as well studied predictors of poor survival that also aligned with several hallmarks of cancer.


Subject(s)
Breast Neoplasms, Male , Breast Neoplasms , Male , Humans , Female , Prognosis , Breast Neoplasms, Male/genetics , Breast Neoplasms/genetics , Transcriptome , Proteomics , Biomarkers, Tumor/genetics , Genomics , Epigenesis, Genetic
10.
Oral Dis ; 29(8): 3136-3151, 2023 Nov.
Article in English | MEDLINE | ID: mdl-36404123

ABSTRACT

Several scoring systems have been developed to evaluate disease severity in mucosal lichen planus, but only a few have been validated to ensure reproducible and accurate assessment of disease severity. The current systematic review was undertaken to identify clinical severity scoring systems in mucosal lichen planus that have undergone validity or reliability testing and to describe their operating characteristics. We performed a bibliographic search in five databases from their inception to October 2022 for severity scoring systems in mucosal lichen planus that have undergone validity or reliability tests. Quality assessment was conducted using the Joanna Briggs Institute Critical Appraisal tools. We have included 118 studies and identified 11 clinical severity scoring systems for oral lichen planus that have undergone validity or reliability testing. Of these, the most reported were the Thongprasom score, the Oral Disease Severity Score (ODSS) and the REU (Reticular/hyperkeratotic, Erosive/erythematous, Ulcerative) scoring systems. We did not identify clinical scoring systems for extraoral mucosal lichen planus that have undergone validity or reliability testing. The ODSS and REU scoring systems have undergone the highest number of validation attempts and reliability assessments for oral lichen planus respectively. However, we have identified numerous factors that have hampered the universal adoption of a standardised scoring system. There is a need for the development and validation of scoring systems for extraoral mucosal lichen planus.


Subject(s)
Lichen Planus, Oral , Lichen Planus , Humans , Lichen Planus, Oral/diagnosis , Reproducibility of Results , Severity of Illness Index , Patient Acuity
11.
Vet World ; 15(4): 890-897, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35698499

ABSTRACT

Background and Aim: Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae have become a serious public health hazard worldwide. This importance is derived from the increase of new variants, particularly blaTEM, blaSHV, and blaCTX-M genes. This study aimed to examine ESBL-producing Escherichia coli isolated from different governorates in Egypt from dairy cows infected with subclinical and clinical mastitis. Materials and Methods: This study examined 207 milk samples for the resistance of isolates against 14 different antibiotics and ran serological identification of ESBL-producing E. coli isolates with complete antibiotic resistance. Genotypic and sequencing analyses of several resistance genes were conducted using a polymerase chain reaction. Results: E. coli was identified in cases with subclinical mastitis (80.5%) and clinical mastitis (85.7%). ESBL-producing E. coli was isolated from 38.2% of subclinical mastitic milk compared to 39.3% in clinical cases, where O26:k60, O125:k70, and O25:k11 were the serotypes with complete resistance to antibiotics. ESBL-producing E. coli isolates were resistant to cefotaxime, amoxicillin, cloxacillin, oxacillin, rifampicin, and penicillin in 100% but susceptible to amoxicillin and clavulanic acid in 82.5% of the cases. Results also revealed that 51.25%, 52.5%, 66.25%, 77.5% and 60% of ESBL-producing E. coli isolates were responsive to ciprofloxacin, ofloxacin, norfloxacin, levofloxacin, and gentamycin, respectively. The detected genes were registered in GenBank as MW345819.1 and MW345820.1 for the E. coli blaTEM gene and MW295407 for the E. coli blaSHV gene. Conclusion: This study found ESBL-producing E. coli in mastitic milk samples from Egyptian dairy farms and confirmed the occurrence and circulation of the main antibiotic genes (blaTEM and blaSHV) in the samples. Regular and thorough surveillance of ESBL-producing E. coli and subsequent preventive actions are essential for preventing the spread of these resistance genes in the future, which could pose serious and catastrophic health risks. Authorities should cling to the concept of One Health to minimize the risk of new varieties.

12.
Vet World ; 15(1): 205-212, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35369599

ABSTRACT

Background and Aim: Mastitis is considered a significant disease of lactating animals. There are new attitudes for recognizing genes responsible for causing this disease to overcome and change the manipulation of this problem. This study aimed to isolate and identify Staphylococcus aureus strains from mastitic bovine animals and detect some specific biofilm-forming genes (icaA, icaD, and biofilm-associated protein [bap] genes clfA, fnbA, agrI, agrII, agrIII, agrIV, and cna). Materials and Methods: A total of 121 mastitic milk samples were analyzed using biochemical tests (catalase test, oxidative-fermentative test, and coagulase test) and Gram stain. Multiplex polymerase chain reaction was applied to characterize biofilm genes (icaA, icaD, bap, clfA, and fnbA) in addition to (agrI, agrII, agrIII, agrIV, and cna). Results: Among the 121 milk samples, 35 staphylococci isolates were derived with an incidence of 28.92% (35/121); among them, 19 are coagulase positive. Ninety percent of the isolates had ica genes (icaA and icaD) while bap gene was not recognized in any isolate. In addition, the incidence of fnbA, can, and clfA was 89.5% each. The prevalence of agr specific groups (agrI, agrII, agrIII, and agrIV) was 78.9%, 52.6%, 10.5%, and 15.8%, respectively. Conclusion: This study concluded that S. aureus has variant mechanisms of pathogenicity to form biofilm devoid of carrying a specific gene.

13.
Br J Cancer ; 126(8): 1125-1139, 2022 05.
Article in English | MEDLINE | ID: mdl-34893761

ABSTRACT

Despite significant improvements in the way breast cancer is managed and treated, it continues to persist as a leading cause of death worldwide. If detected and diagnosed early, when tumours are small and localised, there is a considerably higher chance of survival. However, current methods for detection and diagnosis lack the required sensitivity and specificity for identifying breast cancer at the asymptomatic or very early stages. Thus, there is a need to develop more rapid and reliable methods, capable of detecting disease earlier, for improved disease management and patient outcome. Raman spectroscopy is a non-destructive analytical technique that can rapidly provide highly specific information on the biochemical composition and molecular structure of samples. In cancer, it has the capacity to probe very early biochemical changes that accompany malignant transformation, even prior to the onset of morphological changes, to produce a fingerprint of disease. This review explores the application of Raman spectroscopy in breast cancer, including discussion on its capabilities in analysing both ex-vivo tissue and liquid biopsy samples, and its potential in vivo applications. The review also addresses current challenges and potential future uses of this technology in cancer research and translational clinical application.


Subject(s)
Breast Neoplasms , Spectrum Analysis, Raman , Biopsy , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Female , Humans , Sensitivity and Specificity , Spectrum Analysis, Raman/methods
14.
F1000Res ; 11: 561, 2022.
Article in English | MEDLINE | ID: mdl-38481534

ABSTRACT

Background: It is of utmost importance for the elements that influence public compliance with vaccination against COVID-19 to be assessed, including misconceptions, rumors, and conspiracy theories. Hence, in this study, we aimed to estimate the distribution of the most common misconceptions regarding COVID-19 vaccines and their predictors in Saudi Arabia. Methods: We distributed an online questionnaire to participants aged 18 years or older. The survey included two sections. The first section comprised questions related to participants' demographic characteristics, level of education, and their sources of information about COVID-19. The second section assessed participants' perceptions regarding 11 of the most common misconceptions regarding COVID-19 vaccines, rated using a 5-point Likert scale. Using ordinal logistic regression, we conducted an evaluation of the relationships among different predictors including age, sex, educational level, and sources of information, as well as acceptance of misconceptions about vaccination. Results: The most widely accepted misconception was that the COVID-19 vaccine had severe side effects, with 34.8% of participants believing this misinformation. Factors that were significantly associated with acceptance or non- acceptance of misconceptions were: 1) sex, with female respondents in this survey accepting rumors significantly more often than male respondents (p<0.001); 2) educational level, especially secondary school, was associated with a significantly lower acceptance of misconceptions (p=0.001). In total, 60.5% of participants used social media as their primary source of information, which was also a significant positive predictor of acceptance of misconceptions (p=0.034). Conclusion: It is of critical importance to increase assurance regarding the safety of COVID-19 vaccines, the issue most likely to involve misconceptions, and to address the elements that affect belief in rumors among the population.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Female , Male , Humans , COVID-19 Vaccines/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , Cross-Sectional Studies , Saudi Arabia , Educational Status
15.
Immunol Lett ; 240: 1-8, 2021 12.
Article in English | MEDLINE | ID: mdl-34562551

ABSTRACT

Some COVID-19 patients suffer complications from anti-viral immune responses which can lead to both a dangerous cytokine storm and development of blood-borne factors that render severe thrombotic events more likely. The precise immune response profile is likely, therefore, to determine and predict patient outcomes and also represents a target for intervention. Anti-viral T cell exhaustion in the early stages is associated with disease progression. Dysregulation of T cell functions, which precedes cytokine storm development and neutrophil expansion in alveolar tissues heralds damaging pathology.T cell function, cytokine production and factors that attract neutrophils to the lung can be modified through targeting molecules that can modulate T cell responses. Manipulating T cell responses by targeting the PI3K/Akt/mTOR pathway could provide the means to control the immune response in COVID-19 patients. During the initial anti-viral response, T cell effector function can be enhanced by delaying anti-viral exhaustion through inhibiting PI3K and Akt. Additionally, immune dysregulation can be addressed by enhancing immune suppressor functions by targeting downstream mTOR, an important intracellular modulator of cellular metabolism. Targeting this signalling pathway also has potential to prevent formation of thrombi due to its role in platelet activation. Furthermore, this signalling pathway is essential for SARS-cov-2 virus replication in host cells and its inhibition could, therefore, reduce viral load. The ultimate goal is to identify targets that can quickly control the immune response in COVID-19 patients to improve patient outcome. Targeting different levels of the PI3K/Akt/mTOR signalling pathway could potentially achieve this during each stage of the disease.


Subject(s)
COVID-19 Drug Treatment , Phosphatidylinositol 3-Kinase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , SARS-CoV-2/pathogenicity , TOR Serine-Threonine Kinases/metabolism , Animals , COVID-19/enzymology , COVID-19/immunology , COVID-19/virology , Fibrinolytic Agents/therapeutic use , Host-Pathogen Interactions , Humans , MTOR Inhibitors/therapeutic use , Molecular Targeted Therapy , Phosphoinositide-3 Kinase Inhibitors/therapeutic use , SARS-CoV-2/immunology , Viral Load
16.
Expert Rev Mol Diagn ; 21(8): 789-807, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34148471

ABSTRACT

INTRODUCTION: Oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) are a significant health burden globally. Smoking, alcohol, and betel quid are the main risk factors. Lack of screening methods has been highlighted as a significant challenge in management. Salivary biomarkers are proposed as noninvasive diagnostic tools. The aim of this systematic review was to study salivary biomarkers reported in OSCC and OPMD. Specific objectives were to select a salivary biomarker panel suitable for early detection of OSCC and OPMD and to assess relationships between salivary biomarkers and risk factors. METHODS: Electronic literature search was conducted in academic databases (Scopus, Medline, Embase and Web of Science) without any restrictions. Following calibration, two blinded reviewers screened the studies and extracted data. A risk of bias assessment was conducted using Newcastle Ottawa scale. 295 studies were included with descriptive data analysis. EXPERT OPINION: A salivary biomarker panel including Interleukin (IL) 1ß, IL6, and IL8 was selected for OSCC and OPMD. Reported relationships between salivary biomarkers and risk factors are discussed and research gaps are highlighted. Future research should be directed to assess potential salivary biomarkers and their relationships to risk factors in order to understand the biomarker's role in disease initiation.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/diagnosis , Humans , Mouth Neoplasms/diagnosis , Mouth Neoplasms/etiology , Risk Factors , Saliva
17.
Pediatr Pulmonol ; 56(8): 2740-2750, 2021 08.
Article in English | MEDLINE | ID: mdl-34102042

ABSTRACT

Severe oligohydramnios (OH) due to prolonged loss of amniotic fluid can cause pulmonary hypoplasia. Animal model of pulmonary hypoplasia induced by amniotic fluid drainage is partly attributed to changes in mechanical compression of the lung. Although numerous studies on OH-model have demonstrated changes in several individual proteins, however, the underlying mechanisms for interrupting normal lung development in response to a decrease of amniotic fluid volume are not fully understood. In this study, we used a proteomic approach to explore differences in the expression of a wide range of proteins after induction of OH in a mouse model of pulmonary hypoplasia to find out the signaling/molecular pathways involved in fetal lung development. Liquid chromatography-massspectromery/mass spectrometry analysis found 474 proteins that were differentially expressed in OH-induced hypoplastic lungs in comparison to untouched (UnT) control. Among these proteins, we confirmed the downregulation of AKT1, SP-D, and CD200, and provided proof-of-concept for the first time about the potential role that these proteins could play in fetal lung development.


Subject(s)
Oligohydramnios , Amniotic Fluid , Animals , Disease Models, Animal , Female , Lung , Mice , Pregnancy , Proteomics
18.
Front Immunol ; 12: 763877, 2021.
Article in English | MEDLINE | ID: mdl-35069536

ABSTRACT

Malignant melanoma is an aggressive form of cancer, which can be treated with anti-CTLA-4 and anti-PD-1 checkpoint inhibitor antibodies but while anti-CTLA-4 antibodies have clear benefits for some patients with melanoma, productive responses are difficult to predict and often associated with serious immune related adverse events. Antibodies specific to CTLA-4 bind two major isoforms of CTLA-4 in humans, the receptor isoform and a second naturally secretable, soluble isoform - sCTLA-4. The primary aim here was to examine the effect of selectively blocking the function of sCTLA-4 on in vitro immune responses from volunteer healthy or melanoma patient PBMC samples. Addition of recombinant sCTLA-4 to healthy PBMC samples demonstrated sCTLA-4 to have immunosuppressive capacity comparable to recombinant CTLA4-Ig, partially reversible upon antibody blockade. Further, we identified a mechanistic relationship where melanoma patient TGFß2 serum levels correlated with sCTLA-4 levels and provided the basis for a novel protocol to enhance sCTLA-4 production and secretion by T cells with TGFß2. Finally, a comparison of selective antibody blockade of sCTLA-4 demonstrated that both healthy and melanoma patient effector cytokine responses can be significantly increased. Overall, the data support the notion that sCTLA-4 is a contributory factor in cancer immune evasion.


Subject(s)
Antibodies, Neoplasm/immunology , CTLA-4 Antigen/immunology , Immune Checkpoint Inhibitors , Melanoma , Neoplasm Proteins/immunology , Transforming Growth Factor beta2/immunology , Adult , Aged , Aged, 80 and over , Animals , Cell Line, Tumor , Female , Humans , Male , Melanoma/immunology , Melanoma/therapy , Mice , Middle Aged
19.
J Cell Physiol ; 235(11): 8210-8223, 2020 11.
Article in English | MEDLINE | ID: mdl-31970782

ABSTRACT

The underlying mechanism of normal lung organogenesis is not well understood. An increasing number of studies are demonstrating that extracellular vesicles (EVs) play critical roles in organ development by delivering microRNAs (miRNA) to neighboring and distant cells. miRNAs are important for fetal lung growth; however, the role of miRNA-EVs (miRNAs packaged inside the EVs) during fetal lung development is unexplored. The aim of this study was to examine the expression of miRNA-EVs in MLE-12, a murine lung epithelial cell line subjected to mechanical stretch in vitro with the long-term goal to investigate their potential role in the fetal lung development. Both cyclic and continuous mechanical stretch regulate miRNA differentially in EVs released from MLE-12 and intracellularly, demonstrating that mechanical signals regulate the expression of miRNA-EVs in lung epithelial cells. These results provide a proof-of-concept for the potential role that miRNA-EVs could play in the development of fetal lung.


Subject(s)
Epithelial Cells/metabolism , Extracellular Vesicles/metabolism , Gene Expression Regulation, Developmental/physiology , Lung/embryology , MicroRNAs/metabolism , Animals , Cell Line , Mice , Stress, Mechanical
20.
J Oral Implantol ; 46(2): 115-121, 2020 Apr 01.
Article in English | MEDLINE | ID: mdl-31910068

ABSTRACT

The purpose of this case report is to present implant-retained maxillary and mandibular complete overdentures in a patient with Marfan syndrome. The patient initially presented with generalized periodontitis (stage IV, grade C). Due to the progressive nature of periodontal disease, the patient elected to have implant-retained maxillary and mandibular complete dentures. Bilateral maxillary sinus augmentation was performed 6 months before full-mouth extraction, alveoloplasty, and immediate implant placement. Maxillary and mandibular immediate overdentures were delivered. After 4 months of healing, the final overdenture was fabricated. The patient was seen regularly throughout the healing process for peri-implant maintenance. Soft-tissue grafts were completed to increase the thickness of the mucosa around the implants. The patient has been followed for 2 years and is functioning well without major complications. For patients with Marfan syndrome, implant-retained prostheses are a viable treatment option in the presence of a failing dentition.


Subject(s)
Dental Implants , Marfan Syndrome , Dental Prosthesis, Implant-Supported , Denture, Overlay , Humans , Mandible , Mouth Rehabilitation
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