Pediatric Anesthesia Exposure: Decoding Its Neurodevelopmental Implications and Navigating the Nuances.

General anesthesia is fundamental in pediatric medical interventions, but its potential neurodevelopmental impact on children has raised concerns, necessitating a thorough investigation. This systematic review aimed to assess the association between pediatric anesthesia exposure and neurodevelopmental outcomes, focusing on dosage effects and identifying high-risk groups. The study involved an extensive literature search across PubMed, Medline, and Google Scholar, selecting 40 relevant studies from an initial pool of 2,000, based on inclusion criteria that focused on children under 18 years exposed to anesthesia, excluding those with major comorbidities or perioperative physiological insults. It was observed that while a single exposure to anesthesia had minimal impact on general neurodevelopment, repeated or prolonged exposures posed greater concerns. Despite these findings, the study identified gaps in certain areas like adaptive behavior and sensory cognition due to limited data. The conclusion drawn is that although the evidence on anesthesia-induced neurotoxicity in children remains inconclusive, the implications of pediatric anesthesia exposure are significant enough to warrant careful consideration by healthcare professionals, who should balance the procedural benefits against the risks. This study also calls for future research to standardize methodologies and employ consistent, validated neurodevelopmental measurement tools.

The application of artificial intelligence in diabetic retinopathy screening: a Saudi Arabian perspective.

Introduction: Diabetic retinopathy (DR) is the leading cause of preventable blindness in Saudi Arabia. With a prevalence of up to 40% of patients with diabetes, DR constitutes a significant public health burden on the country. Saudi Arabia has not yet established a national screening program for DR. Mounting evidence shows that Artificial intelligence (AI)-based DR screening programs are slowly becoming superior to traditional screening, with the COVID-19 pandemic accelerating research into this topic as well as changing the outlook of the public toward it. The main objective of this study is to evaluate the perception and acceptance of AI in DR screening among eye care professionals in Saudi Arabia. Methods: A cross-sectional study using a self-administered online-based questionnaire was distributed by email through the registry of the Saudi Commission For Health Specialties (SCFHS). 309 ophthalmologists and physicians involved in diabetic eye care in Saudi Arabia participated in the study. Data analysis was done by SPSS, and a value of p < 0.05 was considered significant for statistical purposes. Results: 54% of participants rated their level of AI knowledge as above average and 63% believed that AI and telemedicine are interchangeable. 66% believed that AI would decrease the workforce of physicians. 79% expected clinical efficiency to increase with AI. Around 50% of participants expected AI to be implemented in the next 5 years. Discussion: Most participants reported good knowledge about AI. Physicians with more clinical experience and those who used e-health apps in clinical practice regarded their AI knowledge as higher than their peers. Perceived knowledge was strongly related to acceptance of the benefits of AI-based DR screening. In general, there was a positive attitude toward AI-based DR screening. However, concerns related to the labor market and data confidentiality were evident. There should be further education and awareness about the topic.

Brain-inhabiting bacteria and neurodegenerative diseases: the "brain microbiome" theory.

Controversies surrounding the validity of the toxic proteinopathy theory of Alzheimer's disease have led the scientific community to seek alternative theories in the pathogenesis of neurodegenerative disorders (ND). Recent studies have provided evidence of a microbiome in the central nervous system. Some have hypothesized that brain-inhabiting organisms induce chronic neuroinflammation, leading to the development of a spectrum of NDs. Bacteria such as Chlamydia pneumoniae, Helicobacter pylori, and Cutibacterium acnes have been found to inhabit the brains of ND patients. Furthermore, several fungi, including Candida and Malassezia species, have been identified in the central nervous system of these patients. However, there remains several limitations to the brain microbiome hypothesis. Varying results across the literature, concerns regarding sample contamination, and the presence of exogenous deoxyribonucleic acids have led to doubts about the hypothesis. These results provide valuable insight into the pathogenesis of NDs. Herein, we provide a review of the evidence for and against the brain microbiome theory and describe the difficulties facing the hypothesis. Additionally, we define possible mechanisms of bacterial invasion of the brain and organism-related neurodegeneration in NDs and the potential therapeutic premises of this theory.

Aberrant Expression of Claudins in Head and Neck Carcinomas and Their Prognostic and Therapeutic Value: A Narrative Review.

Head and neck carcinomas have been associated with poor prognosis. Recent studies have highlighted the role of claudins' expression in tumors throughout the body, and their prognostic and therapeutic role. Understanding the role of claudins and how their expression affects the progression of carcinomas in the head and neck region may allow for advances in the prognosis and management of this type of cancer. Several studies have highlighted the aberrant expression of the proteins in carcinomas in this region. Specifically, the overexpression of claudin-1 and downregulation of claudins-4, -7, and -17 have been linked with poor survival in oral squamous cell carcinoma patients. In laryngeal squamous cell carcinoma, increased levels of claudins-1 and reduced levels of claudins-3, -8, and -11 have been linked with poor outcomes. Targeting these proteins has shown promising outcomes as therapeutic in preclinical studies. However, studies remain extremely limited in nasal and hypopharyngeal carcinomas. In this review, we survey the available literature describing the aberrant expression of various claudins in carcinomas in this region, while highlighting their potential prognostic and therapeutic value. Then, we describe some molecular mechanisms involved in the aberrant expression of claudins and how they can be utilized as therapeutic targets.

Expression of Claudins in Preneoplastic Conditions of the Gastrointestinal Tract: A Review.

Premalignant lesions of the gastrointestinal tract are a group of disorders which act as the harbinger of malignant tumors. They are the ground-zero of neoplastic transformation, and their identification and management offer patients the best opportunity of blocking the progress of cancer. However, diagnoses of some of these conditions are hard to make, and their clinical importance is difficult to assess. Recent reports indicated that several claudin proteins have altered expressions in many cancers, including esophageal, gastric, colon, liver, and pancreatic cancers. The early identification of the aberrant expression of these proteins could lead to the early diagnosis and management of gastrointestinal tumors. Specifically, claudins -1, -2, -3, -4, and -18 are frequently overexpressed in gastrointestinal preneoplastic lesions. These altered expressions have shown clinical value in several tumors, providing diagnostic and prognostic information. In this article, we review the literature on the aberrant expression of claudins in preneoplastic lesions of the gastrointestinal tract. Additionally, we summarize their diagnostic and prognostic implications.

The Risk of Latent Tuberculosis Infection Among Healthcare Workers at a General Hospital in Bisha, the Kingdom of Saudi Arabia.

Background and objective Tuberculosis (TB) is a global health issue, often preceded by a latent tuberculosis infection (LTBI) in individuals. Significant global and local efforts have recently been directed toward this infection, focusing on TB control and eradication. This study aimed to assess the magnitude of LTBI among healthcare workers (HCWs) in the Kingdom of Saudi Arabia, by evaluating its prevalence and associated risk factors. Methods An analytical cross-sectional study was conducted among HCWs at the King Abdullah Hospital (KAH), from January to August 2018, by using two surveys: the first one involved data related to HCW demographics and the tuberculin skin test (TST) readings, and the second involved a questionnaire that assessed LTBI risk factors. Results Out of the total 561 HCWs who participated in the study, 66 had an induration reading of more than 10 mm in TST. Many factors were associated with LTBI cases, but multivariate analysis showed that age, gender, and nationality were statistically significant risk factors. Conclusion Given the nature of their work, HCWs are at a greater risk of TB and LTBI. At the same time, HCWs are uniquely positioned to play a crucial role in halting the spread of TB. Gaps in preventive measures may result in the increased spread of TB. Our study assessed risk factors associated with the increased risk of LTBI and proposed possible ways of addressing them.

The Incidence of Needlestick and Sharps Injuries Among Healthcare Workers in a Tertiary Care Hospital: A Cross-Sectional Study.

Background Needlestick injuries (NSIs) and sharps injuries (SIs) remain significant hazards in most healthcare facilities that expose healthcare workers (HCWs) to blood-borne pathogens (e.g., HIV, hepatitis B, and hepatitis C). This study aims to review the incidence of NSIs and SIs in King Fahad Medical City (KFMC) and correlate this incidence with several parameters related to the event, including age, sex, length of work experience, type of injury, type of instrument causing the injury, type of activity during which the injury happened, nature of the job of the HCWs, and location within the hospital where the injury happened. Methodology This cross-sectional study involves all self-reported documents related to needlestick and sharp injuries among HCWs at King Fahad Medical City (KFMC) in Riyadh, Kingdom of Saudi Arabia, from January 2017 to December 2020. The data of 389 reports of needlestick and sharp injuries detailing incidence and site, shift, type, and instrument related to the incidents were reported to the infection control department for coding and analysis using the Statistical Package for the Social Sciences (SPSS) version 22 (IBM SPSS Statistics, Armonk, NY, USA). Results Our data showed that NSIs/SIs could be caused by a wide range of objects used by healthcare workers, including needles, suture needles, scalpels, and sharp devices. Remarkably, the most common cause of NSIs was handling the sharp object (38.8%), followed by disposing of the sharp object (19.3%). Furthermore, nurses were found to be the highest at-risk category of HCWs experiencing NSIs (49.9%), while medical waste handlers (1.5%) and dentists (1.3%) were least likely to incur injuries. Conclusion This study sheds some light on the incidence rates of NCIs and SIs at KFMC and correlates these rates with several demographical, occupational, and experiential parameters related to these events.

The Clinical Significance of CD163+ Tumor-Associated Macrophages (TAMs) in Laryngeal Squamous Cell Carcinoma.

Background and objective The tumor's microenvironment is currently considered an important indicator of the tumor's prognosis, treatment failure, and recurrence. CD163+ tumor-associated macrophages (TAMs) are a marker of poor prognosis in many types of human cancers. In the present study, the expression of CD163+ TAMs was analyzed in laryngeal squamous cell carcinomas (LSCCs) using immunohistochemistry, and this expression was correlated with the clinical and pathological characteristics of LSCC patients. Materials and methods One commercial human larynx microarray with 80 cases of LSCCs, was used for this study. For comparison with normal laryngeal mucosa, a second microarray carrying normal tissues from all human anatomical sites, including normal laryngeal tissues, was used. Immunohistochemical staining was performed, and the primary antibody was a mouse monoclonal against human CD136. The absence of the primary antibody was used as a negative control. The percentage of positive cells was categorized into five scores: 0 (0%); 1, (1%-10%); 2, (11%-50%); 3, (51%-80%); and 4, (>80%). A case was scored as positive for CD163 with a score >= 1. The χ2 test was used to assess the CD163 expression in LSCC cases (N=80). A statistically significant difference was defined as P 0.05. Results The human larynx microarray containing 80 cases of LSCCs was used for this study. The age of the cancer patients in this array was in the range of 39 to 72, with a median of 53. LSCC grades were distributed as follows: 25 patients were designated as grade I, 43 were designated as grade II, and 6 were designated as grade III. Two tumors' (2/80) cores were missing from the microarray. Six tumors on the microarray did not have a grade designation reported by the manufacturer of the array. The expression of CD163 in normal, benign, unmatched laryngeal tissue was absent. In cancer cases, on the other hand, a significant number of LSCCs had TAMs that were positive for CD163 (87% positive tumors, with an IHC score ranging from 1 to 4, χ2=30.634; p<0.001). The rest of the LSCC cases (10 in total) had negative CD163 expression (score of 0). Conclusion A significant majority of LSCCs were found to have CD163+ TAMs expression using tissue microarrays (TMAs). This expression is positively correlated with the tumor's grade, clinical manifestation, and TNM staging. Morphologic evidence shows that the majority of LSCCs express the highest range of immunohistochemistry (IHC) scores for CD163 protein in the membranes and cytoplasm of their TAMs. This study provides evidence of the clinical significance of CD163+TAMs in LSCCs and proposes further studies to pinpoint the exact role of these cells in LSCC patients.

Detection of Increased Expression of Claudin-1 in Triple-Negative Breast Cancer: Analysis and Clinical-Pathological Correlation.

Background Triple-negative breast cancer (TNBC) is a highly aggressive disease that lacks therapeutic targets and prognostic biomarkers. Claudin-1 is a well-described tight junction protein with prognostic value in many human cancers. Aims The need for the discovery of biomarkers of TNBC disease was a major reason for this study. Claudin-1 is a tight junction protein that has shown promising results in the prognosis and management of cancer in general. In the breast, claudin-1 expression and significance have shown variable results, especially in TNBC patients. Our study assessed expression of claudin-1 in a group of TNBC patients, and correlated this expression with clinical-pathological parameters, and with the expression of ß-catenin. Materials and methods Tissues from a group of 52 TNBC patients were retrieved from the archives of the community hospital. All related information including demographical, pathologic and clinical data were retrieved. Immunohistochemistry assays of a rabbit polyclonal antibody anti-human claudin-1 were applied using the avidin-biotin peroxidase methodology. Results A statistically significant majority of TNBC cases positively expressed claudin-1 (81%, χ2=13.705; p<0.001). Most TNBC cases had grade 2 ß-catenin expression (77.5%; p<0.001), and positive expression for claudin-1 correlated with that of ß-catenin (χ2= 23.757; p<0.001). Claudin-1 and ß-catenin expressions within tumour cells shared several features including absent or weakness of membranous expression, and redistribution of both proteins to the cytoplasm of tumour cells, and in some cases to the nuclei of these cells. Claudin-1 expression also correlates with adverse survival outcomes, where only four of 20 claudin-1-positive patients who received neo-adjuvant chemotherapy (NAC) achieved pathological complete response (pCR). Conclusions The above presents a complex role of claudin-1 in TNBC patients. In this study, claudin-1 expression was associated with poor prognostic features including invasion, metastases and adverse clinical outcomes. Claudin-1 expression in TNBC correlated with the expression of ß-catenin, an important oncogene and a major contributor to the epithelial mesenchymal transition (EMT) phenomenon. Overall, the above results may serve as an impetus for further mechanistic studies to assess the exact role of claudin-1 in TNBC and its possible use in the management of this subset of breast cancer.

Claudins in genitourinary tract neoplasms: mechanisms, prognosis, and therapeutic prospects.

Genitourinary (GU) cancers are among the most prevalent neoplasms in the world, with bladder cancers constituting 3% of global cancer diagnoses. However, several pathogenetic mechanisms remain controversial and unclear. Claudins, for example, have been shown to play a significant role in several cancers of the human body. Their role in GU cancers has not been extensively studied. Aberrant expression of claudins -1, -2, -3, -4, -7, and -11 has been expressed in urothelial cell carcinomas. In prostate cancers, altered levels of claudins -1, -2, -3, -4, and -5 have been reported. Furthermore, the levels of claudins -1, -2, -3, -4, -6, -7, -8, and -10 have been studied in renal cell carcinomas. Specifically, claudins -7 and -8 have proven especially useful in differentiating between chromophobe renal cell carcinomas and oncocytomas. Several of these claudins also correlate with clinicopathologic parameters and prognosis in GU cancers. Although mechanisms underpinning aberrant expression of claudins in GU cancers are unclear, epigenetic changes, tumor necrosis factor-ɑ, and the p63 protein have been implicated. Claudins also provide therapeutic value through tailored immunotherapy via molecular subtyping and providing therapeutic targets, which have shown positive outcomes in preclinical studies. In this review, we aim to summarize the literature describing aberrant expression of claudins in urothelial, prostatic, and renal cell carcinomas. Then, we describe the mechanisms underlying these changes and the therapeutic value of claudins. Understanding the scope of claudins in GU cancers paves the way for several diagnostic, prognostic, and therapeutic innovations.

Filamin-A expression in laryngeal squamous cell carcinoma and its clinical significance.

BACKGROUND: Laryngeal squamous cell carcinomas (LSCCs) are tumours with a high incidence of treatment failure and recurrence. Recent strategies to improve the five-year survival rate and to decrease the rates of recurrence and metastases did not improve outcomes significantly. Research efforts in recent years have started focusing on discovering biomarkers of prognosis and management in LSCCs. Filamin-A reportedly has been associated with metastatic disease in a recent study. Analysis of this protein's expression in LSCCs is lacking in the literature. MATERIALS AND METHODS: This study analysed the expression of filamin-A, using immunohistochemistry, in a tissue microarray of 80 cases of laryngeal squamous cell cancers. Clinical-pathological parameters were analysed according to filamin-A expression in the tissue microarray. Furthermore, a review of possible mechanisms of this protein in cancer, in general, was presented, along with a review of the protein's expression in other head and neck tumours. RESULTS: A significant majority of laryngeal squamous cell cancers exhibited positive expression of filamin-A protein. All the filamin-A positive tumours expressed it in their cytoplasm. Significant correlation between filamin-A expression and grade, stage, lymph node status and metastases were found. CONCLUSION: The above may suggest an important role for filamin-A in LSCCs. Overall, filamin-A expression in laryngeal cancer is in line with evidence seen in other head and neck cancers. Further studies are in order to pinpoint the exact role of this protein in LSCCs, and its possible utilization in the management of these difficult-to-treat tumours.

KI-67 LI Expression in Triple-Negative Breast Cancer Patients and Its Significance.

PURPOSE: Triple-negative breast cancer (TNBC) is a subset of breast cancer which is known to carry a poor prognosis because of lack of targets for hormonal therapy. Research efforts have focused in recent years on discovering biomarkers of management in TNBCs. KI-67 Labelling Index (LI) is a nuclear protein which has proven to play diagnostic and prognostic roles in many cancers. MATERIALS AND METHODS: We analysed the expression of KI-67 LI by immunohistochemistry in TNBC cases from the University hospital. This expression was cross-checked against clinical-pathological criteria of TNBC patients and against Vimentin expression in TNBC patients with significant KI-67 expression. RESULTS: KI-67 LI was significantly expressed in the majority of TNBC cases. This expression was significantly correlated with lymph node metastases, tumour invasion, high tumour nuclear grade, clinical stage, adverse survival outcome, and failure to achieve pathological complete response. TNBCs' KI-67 LI expression was also correlated with Vimentin expression, the mesenchymal chief marker of the EMT phenomenon. CONCLUSION: Collectively, our study presents a strong argument for the use of KI-67 LI as a biomarker of aggressive, metastatic TNBC disease with poor outcome. This study, along with mounting evidence in the scientific literature, presents a case for the use of this nuclear protein in diagnosis, prognosis, and follow-up of patients with this difficult diagnosis.

Expression of Claudin-1 in laryngeal squamous cell carcinomas (LSCCs) and its significance.

BACKGROUND: A large body of scientific evidence points to the important roles of tight junction proteins in tumor development, progression and dissemination. The larynx has only a few studies, analyzing the role of this group of junctional proteins in its oncogenesis. In this study, the author sheds some light on the expression and possible role of claudin-1 in laryngeal squamous cell carcinomas. MATERIALS AND METHODS: This study analyzed the expression of claudin-1, using immunohistochemistry, in a tissue microarray of 80 cases of laryngeal squamous cell cancers. Clinicopathological parameters were analyzed according to claudin-1 expression in the tissue microarray. Furthermore, the expression of slug/snail1, an Epithelial-Mesenchymal Transition (EMT) linked protein, was analyzed by immunohistochemistry in the same microarray, and the expressions of the two proteins were assessed for correlation. RESULTS: A significant majority of laryngeal squamous cell cancers exhibited positive expression of claudin-1 proteins. The majority of those tumors expressed claudin-1 in their cytoplasm. The overall majority of those same tumors also exhibited a cytoplasmic shift of the slug-snail-1 protein from the nuclei to the cytoplasm. There was also evidence of correlation of the two proteins' expressions in the cytoplasm of laryngeal tumors. CONCLUSION: The above may suggest a role for claudin-1 in the development and progression of laryngeal squamous cell carcinoma. Overall, claudin-1's aberrant expression in laryngeal cancer is in line with evidence seen in other head and neck cancers. Its co-expression with slug/snail-1 in LSCC patients should be investigated further to understand the nature of the relationship of the two proteins in LSCC and their possible contribution to its development and progression.

Regional functional and structural abnormalities within the aorta as a potential driver of vascular disease in metabolic syndrome.

NEW FINDINGS: What is the central question of this study? Is aortic dysfunction, a significant contributor to cardiovascular disease in metabolic syndrome, expressed uniformly across both the thoracic and abdominal aorta? What is the main finding and its importance? Our study shows that, in the setting of metabolic syndrome, functional and structural deficits in the aorta are differentially expressed along its length, with the abdominal portion displaying more extensive vascular abnormalities. It is, therefore, likely that early interventional strategies targeting the abdominal aorta might alleviate cardiovascular pathologies driven by the metabolic syndrome. ABSTRACT: The extent of vascular dysfunction associated with metabolic syndrome might vary along the length of the aorta. In this study, we investigated regional functional and structural changes in the thoracic and abdominal aorta of a rat model of metabolic syndrome, namely, high-fat diet (HFD) streptozotocin-induced diabetes mellitus (HFD-D). Four-week-old male Wistar albino rats were fed with either HFD or control diet (CD) for 10 weeks. At week 6, 40 mg/kg streptozotocin and its vehicle were injected i.p. into HFD and CD groups, respectively. At the end of the feeding period, rats were euthanised and aortic segments collected for assessment of vascular functional responses and histomorphometry. Tail-cuff systolic blood pressures (154 ± 6  vs. 110 ± 4 mmHg) and areas under the curve for oral glucose and i.p. insulin tolerance tests were greater in HFD-D versus CD rats. Abdominal aortic vasoconstriction in response to noradrenaline and KCl was greater in HFD-D compared with CD rats. Thoracic vasoconstrictor responses to noradrenaline, but not KCl, were greater in the HFD-D group. Abdominal, but not thoracic, endothelium-dependent vasorelaxation in response to acetylcholine was blunted in HFD-D relative to CD rats; however, nitric oxide-dependent vasorelaxation in HFD-D rats was impaired in both thoracic and abdominal segments. The abdominal aorta of HFD-D rats showed deranged interlamellar spacing and increased lipid plaque deposition. In conclusion, vascular dysfunction in metabolic syndrome is expressed differentially along the length of the aorta, with the abdominal aorta exhibiting increased susceptibility to vasoconstrictors and greater deficits in endothelium-dependent relaxation. These vascular functional abnormalities could potentially underlie the development of hypertensive cardiovascular disease associated with the metabolic syndrome.

Endobronchial biopsy in the final diagnosis of chronic obstructive pulmonary disease and asthma: a clinicopathological study.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are chronic conditions with an increasing prevalence in developing countries. The evaluation of endobronchial biopsies has emerged as a tool to differentiate between both conditions via the measurement of the reticular basement membrane (RBM) thickness with various conclusions drawn from different studies. OBJECTIVES: Compare the thickness of the RBM between asthma and COPD and evaluate other histomorphological features in both groups. DESIGN: Prospective, descriptive and analytical. SETTING: University teaching hospital. PATIENTS AND METHODS: The study included patients with COPD and irreversible and reversible asthma with diagnosis based on clinical assessment, pulmonary function tests and high-resolution computed tomography scans. Endobronchial biopsies were obtained from all patients and, using a light microscope and a computerized image analyzer, the thickness of the reticular basement membrane was calculated in all patients. We also made a qualitative assessment of other histo-morphological features. MAIN OUTCOME MEASURES: Mean RBM thickness. SAMPLE SIZE: Thirty male patients. RESULTS: The mean RBM thickness in asthmatic patients was 8.9 (2.4) micro m. The mean RBM thickness in COPD patients was 5.3 (1.1) micro m. However, there was no thickening of the RBM in patients with reversible asthma. The RBM was significantly thicker in patients with irreversible asthma than in patients with COPD or reversible asthma. There were no significant differences in epithelial desquamation or metaplasia, mucosal or submucosal inflammation, the presence of eosinophils, submucosal glandular hyperplasia or submucosal smooth muscle hyperplasia between groups. CONCLUSIONS: The thickness of the RBM is the only reproducible histopathological feature to differentiate COPD from irreversible asthma. LIMITATIONS: The study included a limited number of patients. A qualitative approach was used to compare epithelial cell injury, inflammation, submucosal glandular and muscular hyperplasia. CONFLICT OF INTEREST: None.

Claudin-1 role in colon cancer: An update and a review.

Tight junction proteins are essential for sealing the cellular sheets and controlling para-cellular ion flux. Our understanding of the role that tight junction proteins, particularly claudins, play in cellular functions and pathologic conditions is continuously expanding. Particularly, the role of claudin-1 in oncogenesis in multiple locations in the human body is coming to light. This review will shed light on the role of claudin-1 in colon cancer. It will address the mechanisms through which claudin-1 becomes dysregulated in colon cancer. This will provide a platform to address results of claudin-1 expression in the third most common malignant tumour worldwide. Furthermore, it will provide updates about possible use of this biomarker in the surveillance of difficult colon maladies, such as inflammatory bowel disease. The use of claudin-1 as a biomarker of diagnostic and prognostic values will provide Medicine with much needed ammunition in the fight against cancer and will bring about, with added refinements, a new chapter in the era of personalized medicine to tackle this disease and match its destructive course with equally powerful and specifically targeted therapies.

Progression of matrixin and cardiokine expression patterns in an ovine model of heart failure and recovery.

BACKGROUND: The molecular mechanisms underlying the geometrical changes of the left ventricle during the progression to heart failure and recovery are not well defined. OBJECTIVE: Here we investigate the involvement of matrixins and cardiokines in an ovine model of pressure-induced left ventricular failure (LVF). METHODS: Fifteen sheep underwent supracoronary aortic banding with an inflatable cuff. A controlled and progressive increase of LV pressure was monitored echocardiographically. Endomyocardial biopsies were collected throughout the development of LVF and subsequent recovery after pressure unloading. RESULTS: Thirteen sheep developed LVF with a subsequent recovery. Peak left ventricular hypertrophy (LVH) and dilatation (LVD) occurred at 31.5 ± 1.6 weeks and 102.7 ± 2.2 weeks post-banding respectively, with an increase in LV internal diameter in diastole (LVIDd 5.11 ± 0.12 compared to the control 3.37 ± 0.07 cm, p<0.001), with preserved LV ejection fraction (LVEF). Reduced LVEF became evident 116.5 ± 2.7 weeks post-banding. Clinical and echocardiographic improvements were observed following deflation of the aortic banding cuff. By 138.1 ± 3.1 weeks cardiac performance recovered with restoration of LVEF. Significant changes in the expression of matrix metalloproteinases (MMP)-1, -2, -3, vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF)-2, interferon (INF)-α-2 and soluble CD40 ligand (sCD40L) were observed throughout the progression to failure and recovery. CONCLUSIONS: We used an ovine model to study reversible LV remodelling without interruption and found significant changes in matrixin and cardiokine expression during LV progression to failure and recovery.

Analysis of the distribution and expression of claudin-1 tight junction protein in the oral cavity.

BACKGROUND: Claudins are the main sealing proteins of the intercellular tight junctions and play an important role in cancer cell progression and dissemination. The authors have previously shown that overexpression of claudin-1 is associated with angiolymphatic and perineural invasion, consistent with aggressive tumor behavior and with advanced stage disease in oral squamous cell carcinomas (OSCCs). Our goal in this study was to examine claudin-1 expression in a tissue microarray of OSCCs taken from multiple sites within the oral cavity. MATERIALS AND METHODS: This study examined and compared the expression of claudin-1 by immunohistochemistry in 60 tissue samples (49 OSCCs and 10 cases of non-neoplastic tissue, single core per case) were analyzed for claudin-1 expression by immunohistochemistry. The tumors included SCCs from the tongue (n=28), the cheek (n=9), gingival (n=4), lip (n=3), and oral cavity (n=5). Nonmalignant normal oral mucosa from the tongue (unmatched cases, n=2). Cancer adjacent tissue samples were taken from the tongue (n=6), gingival (n=2), and palate (n=1). RESULTS: This study demonstrates the expression of claudin-1 protein across a sample of OSCCs originating from multiple locations in the oral cavity. The highest expression of claudin-1 was observed in well-differentiated OSCCs, whereas poorly differentiated OSCCs exhibited mostly negative staining for claudin-1. In addition, we hereby report differential pattern of expression among tumors of different sites within the oral cavity, and between benign and cancerous samples. Our understanding of the exact function and role of claudin-1 in tumorigenesis is expanding exponentially.

Claudin-1 expression in squamous cell carcinomas of different organs: comparative study of cancerous tissues and normal controls.

Claudins are the main sealing proteins of the intercellular tight junctions and play an important role in cancer cell progression and dissemination. This study examined and compared the expression of claudin-1 by immunohistochemistry in 60 squamous cell carcinomas of different tissue types and normal 33 controls, arranged in 2 tissue microarray slides. A score was generated to classify claudin-1 expression into negative, low, medium, and high. Most squamous cell carcinomas (91.67%) showed positive membranous staining. Medium to high claudin-1 expression was prevalent in carcinomas from the head-neck, skin, and genitourinary regions and was less frequent in other locations. An inverse correlation was noted between claudin-1 expression and tumor grade in tumors of the genitourinary and breast-gynecologic regions. Of the normal organs, significant claudin-1 expression was present mainly in the skin whereas other epithelial tissues had only minimal to low expression levels. Claudin-1 expression in squamous cell carcinoma varies in organ-specific manner reflecting influence of local factors and different mechanisms of claudin-1 expression. Knowledge of this fact is important in planning biologic therapy targeting claudin-1.

Claudins in human cancer: a review.

Claudins are tight junction proteins that are critical for the sealing of cellular sheets and controlling paracellular ion flux. The claudin family of proteins is composed of at least 24 closely related transmembrane proteins, most of them are well characterized at the gene and protein levels. The claudins are present in variety of normal tissues, hyperplastic conditions, benign neoplasms, and cancers that exhibit epithelial differentiation. Loss of claudins expression has also been reported in several malignancies as well. Differential expression of various members of the claudins family in cancers can be used in confirming the histologic identity of certain cancers and excluding others. Examples include the use of immunohistochemical detection of claudins to differentiate between oncocytoma and chromophobe renal cell carcinoma, endometrial endometrioid carcinoma and seropapillary carcinoma, mesothelioma and metastatic adenocarcinoma, hepatocellular and biliary tract carcinomas, and between intestinal-type and diffuse-type gastric carcinoma. Expression of certain claudins can also be used as markers that can predict patient's prognosis. Thus, it seems that attempts to identify expression claudins in cancers are becoming increasingly useful in histologic diagnosis of tumors as well as means to assess patient's prognosis.