Artificial Intelligence-Based Distinction of Actinic Keratosis and Seborrheic Keratosis.

Actinic keratosis (AK) and seborrheic keratosis (SK) represent prevalent dermatological conditions with distinct clinical characteristics and potential health implications. This article investigates recent strides in dermatological diagnostics, centered on the development and application of artificial intelligence (AI) technology for discerning between AK and SK. The objective of this study is to develop and evaluate an artificial intelligence (AI) model capable of accurately distinguishing between stage one and stage two gastric carcinoma based on pathology slides. Employing a dataset of high-resolution images obtained from Kaggle.com, consisting of 1000 AK and 1000 SK images, a novel AI model was trained using cutting-edge deep learning methodologies. The dataset underwent meticulous partitioning into training, validation, and testing subsets to ensure robustness and generalizability. The AI model showcased exceptional proficiency in distinguishing AK from SK images, attaining notable levels of accuracy, precision, recall, specificity, F1-score, and area under the curve (AUC). Insights into the etiology and clinical ramifications of AK and SK were presented, emphasizing the critical significance of precise diagnosis and tailored therapeutic approaches. The integration of AI technology into dermatological practice holds considerable potential for enhancing diagnostic precision, refining treatment decisions, and elevating patient outcomes. This article underscores the transformative impact of AI in dermatology and the importance of collaborative efforts between clinicians, researchers, and technologists in advancing the realm of dermatological diagnosis and care.

Navigating the Incidence of Postoperative Arrhythmia and Hospitalization Length: The Role of Amiodarone and Other Antiarrhythmics in Prophylaxis.

Antiarrhythmic drugs play a pivotal role in managing and preventing arrhythmias. Amiodarone, classified as a class III antiarrhythmic, has been used prophylactically to effectively prevent atrial fibrillation postoperatively in cardiac surgeries. However, there is a lack of consensus on the use of amiodarone and other antiarrhythmic drugs as prophylaxis to reduce the occurrence of all types of postoperative arrhythmias in cardiac and non-cardiac surgeries. A comprehensive PubMed query yielded 614 relevant papers, of which 52 clinical trials were analyzed. The data collection included the class of antiarrhythmics, timing or method of drug administration, surgery type, type of arrhythmia and its incidence, and hospitalization length. Statistical analyses focused on prophylactic antiarrhythmics and their respective reductions in postoperative arrhythmias and hospitalization length. Prophylactic amiodarone alone compared to placebo demonstrated a significant reduction in postoperative arrhythmia incidence in cardiac and non-cardiac surgeries (24.01%, p<0.0001), and it was the only treatment group to significantly reduce hospitalization length versus placebo (p = 0.0441). Prophylactic use of class 4 antiarrhythmics versus placebo also demonstrated a significant reduction in postoperative arrhythmia incidence (28.01%, p<0.0001), and while there was no significant statistical reduction compared to amiodarone (4%, p=0.9941), a lack of abundant data provides a case for further research on the prophylactic use of class 4 antiarrhythmics for this indication. Amiodarone prophylaxis remains a prime cornerstone of therapy in reducing postoperative arrhythmia incidence and hospitalization length. Emerging data suggests a need for a broader exploration of alternative antiarrhythmic agents and combination therapies, particularly class 4 antiarrhythmics, in both cardiac and non-cardiac surgeries. This meta-analysis depicts the effectiveness of amiodarone, among other antiarrhythmics, in postoperative arrhythmia incidence and hospitalization length reduction in cardiac and non-cardiac surgeries.

Advancing Breast Cancer Research Through Collaborative Computing: Harnessing Google Colab for Innovation.

This investigation explores the potential efficacy of machine learning algorithms (MLAs), particularly convolutional neural networks (CNNs), in distinguishing between benign and malignant breast cancer tissue through the analysis of 1000 breast cancer images gathered from Kaggle.com, a domain of publicly accessible data. The dataset was meticulously partitioned into training, validation, and testing sets to facilitate model development and evaluation. Our results reveal promising outcomes, with the developed model achieving notable precision (92%), recall (92%), accuracy (92%), sensitivity (89%), specificity (96%), an F1 score of 0.92, and an area under the curve (AUC) of 0.944. These metrics underscore the model's ability to accurately identify malignant breast cancer images. Because of limitations such as sample size and potential variations in image quality, further research, data collection, and integration of theoretical models in a real-world clinical setting are needed to expand the reliability and generalizability of these MLAs. Nonetheless, this study serves to highlight the potential use of artificial intelligence models as supporting tools for physicians to utilize in breast cancer detection.

Isolated Superior Ophthalmic Vein Thrombosis.

The purpose of this article is to report a rare case of isolated superior ophthalmic vein thrombosis. A 74-year-old female presented to the emergency department with a sudden onset of eye pain and bulging. Ophthalmological examination was remarkable for proptosis and ptosis with chemosis of the OS. Neuroimaging demonstrated an isolated superior ophthalmic vein thrombosis secondary to presumed thrombosis of the superior vein varix. Hypercoagulable, infectious, and autoimmune lab workups were unremarkable. The patient was initiated on anticoagulation with the eventual resolution of her symptoms. Isolated superior ophthalmic vein thrombosis is an uncommon diagnosis that requires urgent evaluation to prevent vision loss. Risk factors are multifactorial with infectious being the most common etiology. Our case is unique in that there was no identifiable risk factor.

Development of an Artificial Intelligence Model for the Classification of Gastric Carcinoma Stages Using Pathology Slides.

This study showcases a novel AI-driven approach to accurately differentiate between stage one and stage two gastric carcinoma based on pathology slide analysis. Gastric carcinoma, a significant contributor to cancer-related mortality globally, necessitates precise staging for optimal treatment planning and patient management. Leveraging a comprehensive dataset of 3540 high-resolution pathology images sourced from Kaggle.com, comprising an equal distribution of stage one and stage two tumors, the developed AI model demonstrates remarkable performance in tumor staging. Through the application of state-of-the-art deep learning techniques on Google's Collaboration platform, the model achieves outstanding accuracy and precision rates of 100%, accompanied by notable sensitivity (97.09%), specificity (100%), and F1-score (98.31%). Additionally, the model exhibits an impressive area under the receiver operating characteristic curve (AUC) of 0.999, indicating superior discriminatory power and robustness. By providing clinicians with an efficient and reliable tool for gastric carcinoma staging, this AI-driven approach has the potential to significantly enhance diagnostic accuracy, inform treatment decisions, and ultimately improve patient outcomes in the management of gastric carcinoma. This research contributes to the ongoing advancement of cancer diagnosis and underscores the transformative potential of artificial intelligence in clinical practice.

Case-Based Collaborative Learning in Undergraduate Radiology Teaching-Are Essential Conditions for Group Discussions Met?

BACKGROUND: Delivering case-based collaborative learning (cCBL) at scale using technology that both presents the clinical problem authentically and seeks to foster quality group discussion is a challenge, especially argumentation which is critical for effective learning. The aim of this study was to investigate the presence of essential conditions to capitalize on a technology-enhanced cCBL scenario for teaching radiology and facilitating quality group discussion. METHODS: A questionnaire was administered to 114 fourth-year medical students who completed a technology-enhanced cCBL scenario for teaching neuroradiology. It consisted of individual online pre-class work and face-to-face in-class work, where group discussion followed individual work at a workstation. Items from the "Heedful Interrelating in Collaborative Educational Settings" scale and "positive emotional engagement" questionnaire assessed the quality of social-cognitive processes and emotional engagement during the group discussions. Structured interviews were used to explore the teachers' awareness of and engagement with the technology. RESULTS: The mean scores of most "heedfulness" items were below 3.5 (7-point scale), suggesting that participants did not enter the debriefing with a mindset conducive for argumentation. However, for the affective states "interest" and "enjoyment" the mean scores were above 5. Free text comments suggested participants enjoyed the superficial interactions, but did not necessarily engage in argumentation. Structured interviews revealed teachers were aware of the possibilities of the learning dashboard and used it as a common frame of reference, but did not really succeed to use it as a springboard for discussion. CONCLUSION: A technology-enhanced cCBL scenario is useful for teaching radiology in undergraduate medical education, but the added value of acquiring in-depth knowledge will only be achieved when students are aware of the importance of an "heedful" mind-set.

Differentially co-expressed myofibre transcripts associated with abnormal myofibre proportion in chronic obstructive pulmonary disease.

BACKGROUND: Skeletal muscle dysfunction is a common extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD). Alterations in skeletal muscle myosin heavy chain expression, with reduced type I and increased type II myosin heavy chain expression, are associated with COPD severity when studied in largely male cohorts. The objectives of this study were (1) to define an abnormal myofibre proportion phenotype in both males and females with COPD and (2) to identify transcripts and transcriptional networks associated with abnormal myofibre proportion in COPD. METHODS: Forty-six participants with COPD were assessed for body composition, strength, endurance and pulmonary function. Skeletal muscle biopsies from the vastus lateralis were assayed for fibre-type distribution and cross-sectional area via immunofluorescence microscopy and RNA-sequenced to generate transcriptome-wide gene expression data. Sex-stratified k-means clustering of type I and IIx/IIax fibre proportions was used to define abnormal myofibre proportion in participants with COPD and contrasted with previously defined criteria. Single transcripts and weighted co-expression network analysis modules were tested for correlation with the abnormal myofibre proportion phenotype. RESULTS: Abnormal myofibre proportion was defined in males with COPD (n = 29) as <18% type I and/or >22% type IIx/IIax fibres and in females with COPD (n = 17) as <36% type I and/or >12% type IIx/IIax fibres. Half of the participants with COPD were classified as having an abnormal myofibre proportion. Participants with COPD and an abnormal myofibre proportion had lower median handgrip strength (26.1 vs. 34.0 kg, P = 0.022), 6-min walk distance (300 vs. 353 m, P = 0.039) and forced expiratory volume in 1 s-to-forced vital capacity ratio (0.42 vs. 0.48, P = 0.041) compared with participants with COPD and normal myofibre proportions. Twenty-nine transcripts were associated with abnormal myofibre proportions in participants with COPD, with the upregulated NEB, TPM1 and TPM2 genes having the largest fold differences. Co-expression network analysis revealed that two transcript modules were significantly positively associated with the presence of abnormal myofibre proportions. One of these co-expression modules contained genes classically associated with muscle atrophy, as well as transcripts associated with both type I and type II myofibres, and was enriched for genetic loci associated with bone mineral density. CONCLUSIONS: Our findings indicate that there are significant transcriptional alterations associated with abnormal myofibre proportions in participants with COPD. Transcripts canonically associated with both type I and type IIa fibres were enriched in a co-expression network associated with abnormal myofibre proportion, suggesting altered transcriptional regulation across multiple fibre types.

Long-term survival and functional outcomes of critically ill patients with hematologic malignancies: a Canadian multicenter prospective study.

PURPOSE: Patients with hematologic malignancy (HM) commonly develop critical illness. Their long-term survival and functional outcomes have not been well described. METHODS: We conducted a prospective, observational study of HM patients admitted to seven Canadian intensive care units (ICUs) (2018-2020). We followed survivors at 7 days, 6 months and 12 months following ICU discharge. The primary outcome was 12-month survival. We evaluated functional outcomes at 6 and 12 months using the functional independent measure (FIM) and short form (SF)-36 as well as variables associated with 12-month survival. RESULTS: We enrolled 414 patients including 35% women. The median age was 61 (interquartile range, IQR: 52-69), median Sequential Organ Failure Assessment (SOFA) score was 9 (IQR: 6-12), and 22% had moderate-severe frailty (clinical frailty scale [CFS] ≥ 6). 51% had acute leukemia, 38% lymphoma/multiple myeloma, and 40% had received a hematopoietic stem cell transplant (HCT). The most common reasons for ICU admission were acute respiratory failure (50%) and sepsis (40%). Overall, 203 (49%) were alive 7 days post-ICU discharge (ICU survivors). Twelve-month survival of the entire cohort was 21% (43% across ICU survivors). The proportion of survivors with moderate-severe frailty was 42% (at 7 days), 14% (6 months), and 8% (12 months). Median FIM at 7 days was 80 (IQR: 50-109). Physical function, pain, social function, mental health, and emotional well-being were below age- and sex-matched population scores at 6 and 12 months. Frailty, allogeneic HCT, kidney injury, and cardiac complications during ICU were associated with lower 12- month survival. CONCLUSIONS: 49% of all HM patients were alive at 7 days post-ICU discharge, and 21% at 12 months. Survival varied based upon hematologic diagnosis and frailty status. Survivors had important functional disability and impairment in emotional, physical, and general well-being.

Clinical Course and Outcomes of COVID-19 Patients Admitted to the ICU of a Tertiary Care Hospital in Central India: A Cross-Sectional Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) rapidly spread globally, leading to a pandemic significantly impacting individuals, communities, and economies worldwide. Public health measures such as social distancing, mask-wearing, and hand hygiene have been implemented globally to mitigate the spread of the virus. Many people recovered from COVID-19, but some cases needed intensive care unit (ICU) care, among whom most required mechanical ventilation (MV). MATERIALS AND METHODS: This hospital-based cross-sectional study was done among 75 clinical or reverse transcriptase-polymerase chain reaction (RT-PCR) test-confirmed cases of COVID-19 infection admitted to the ICU of a tertiary care unit in India. RESULTS: A maximum number of patients, i.e. 47 (63%), were male, and 26 (35%) belonged to the age group of 41-60 years. The most common symptom was fever at the time of admission to the hospital. Comorbidity was reported in 21 (28%) patients. The majority of patients recorded a combination of hypertension and diabetes. The majority (n =34, 45%) of the patients stayed for ≤ 3 days in the ICU, and 46 (61%) deaths were recorded in the ICU during this period. CONCLUSION: Delayed medical intervention, advanced age, male gender, and underlying health conditions like cardiovascular disease and diabetes can contribute to worse outcomes and increased mortality in COVID-19 patients.

Artificial Intelligence in Dermoscopy: Enhancing Diagnosis to Distinguish Benign and Malignant Skin Lesions.

This study presents an innovative application of artificial intelligence (AI) in distinguishing dermoscopy images depicting individuals with benign and malignant skin lesions. Leveraging the collaborative capabilities of Google's platform, the developed model exhibits remarkable efficiency in achieving accurate diagnoses. The model underwent training for a mere one hour and 33 minutes, utilizing Google's servers to render the process both cost-free and carbon-neutral. Utilizing a dataset representative of both benign and malignant cases, the AI model demonstrated commendable performance metrics. Notably, the model achieved an overall accuracy, precision, recall (sensitivity), specificity, and F1 score of 92%. These metrics underscore the model's proficiency in distinguishing between benign and malignant skin lesions. The use of Google's Collaboration platform not only expedited the training process but also exemplified a cost-effective and environmentally sustainable approach. While these findings highlight the potential of AI in dermatopathology, it is crucial to recognize the inherent limitations, including dataset representativity and variations in real-world clinical scenarios. This study contributes to the evolving landscape of AI applications in dermatologic diagnostics, showcasing a promising tool for accurate lesion classification. Further research and validation studies are recommended to enhance the model's robustness and facilitate its integration into clinical practice.

Protein glycosylation in cardiovascular health and disease.

Protein glycosylation, which involves the attachment of carbohydrates to proteins, is one of the most abundant protein co-translational and post-translational modifications. Advances in technology have substantially increased our knowledge of the biosynthetic pathways involved in protein glycosylation, as well as how changes in glycosylation can affect cell function. In addition, our understanding of the role of protein glycosylation in disease processes is growing, particularly in the context of immune system function, infectious diseases, neurodegeneration and cancer. Several decades ago, cell surface glycoproteins were found to have an important role in regulating ion transport across the cardiac sarcolemma. However, with very few exceptions, our understanding of how changes in protein glycosylation influence cardiovascular (patho)physiology remains remarkably limited. Therefore, in this Review, we aim to provide an overview of N-linked and O-linked protein glycosylation, including intracellular O-linked N-acetylglucosamine protein modification. We discuss our current understanding of how all forms of protein glycosylation contribute to normal cardiovascular function and their roles in cardiovascular disease. Finally, we highlight potential gaps in our knowledge about the effects of protein glycosylation on the heart and vascular system, highlighting areas for future research.

Do Patients Accurately Recall Pain Levels Following Sacroiliac Joint Steroid Injection? A Cohort Study of Recall Bias in Patient-reported Outcomes.

BACKGROUND: Sacroiliac joint (SIJ) injections are crucial in the diagnostic toolkit for evaluating SIJ pathology. Recall bias is an important component in patient-reported outcomes that has not been well studied in SIJ injection. OBJECTIVE: The purpose of this study was to characterize the accuracy, direction, and magnitude of pain level recall bias following SIJ steroid injection and study the factors that affect patient recollection. STUDY DESIGN: Prospective cohort study. SETTING: Level 1 academic medical center. METHODS: Using standardized questionnaires, baseline Numeric Rating Scale (NRS-11) scores were recorded for patients undergoing SIJ steroid injections at preinjection, at 4 hours postinjection, and at 24 hours postinjection. At a minimum of 2 weeks postinjection, patients were asked to recall their preinjection, 4-hour, and 24-hour postinjection NRS-11 scores. Actual and recalled NRS-11 scores were compared using paired t tests for each time interval. Multivariable linear regression was used to identify factors that correlated with consistent recall. RESULTS: Sixty patients with a mean age of 66 years (65% women) were included. Compared to their preinjection pain score, patients showed considerable improvement at both 4 hours (mean difference [MD] = 3.28; 95% CI, 2.68 - 3.89), and 24 hours (MD = 3.23; 95% CI, 2.44 - 4.03) postinjection. Patient recollection of preinjection symptoms was more severe than actual (MD = 0.65; 95% CI, 0.31 - 0.99). Patient recollection of symptoms was also more severe than actual at 4 hours (MD = 0.50; 95% CI .04 - 1.04) as well as at 24 hours postinjection (MD = 0.80; 95% CI, 0.16 - 1.44). The magnitude of recall bias was mild and did not exceed the minimal clinically important difference. There was a moderate correlation between actual and recalled pain levels when comparing preinjection with the 4-hour postinjection NRS-11 score (correlation coefficient [r] =0.64; P < 0.001) and moderate correlation when comparing preinjection with the 24-hour postinjection NRS-11 score (r = 0.62; P < 0.001). Linear regression models showed that at preinjection, patients with a lower body mass index and the presence of coexisting psychiatric diagnoses were better at recalling their pain (P < 0.05). Patients with a higher body mass index also experienced less pain relief when comparing preinjection with the 4-hour postinjection NRS-11 score (P < 0.05). LIMITATIONS: Recall pain scores were obtained via telephone surveys, which can lead to interview bias. One patient died, and 3 were lost to follow-up. We did not control for patient use of adjunctive pain relief modalities, which may modulate the overall response to injection. SIJ injections can also be diagnostic, so some patients may not have shared the same indication for injection or pain-generating diagnosis. CONCLUSIONS: Patients had favorable pain level responses to their SIJ steroid injection for both actual and recall surveys. Although patients demonstrated poor recall of absolute pain scores at preinjection, 4-hour postinjection, and 24-hour postinjection, they demonstrated robust recall of their net pain score improvement at both 4- and 24-hours postinjection. These findings suggest that there is utility in using patient recollection to describe the magnitude of pain relief following treatment for sacroiliac joint dysfunction.

Recapitulation of human pathophysiology and identification of forensic biomarkers in a translational model of chlorine inhalation injury.

Chlorine gas (Cl2) has been repeatedly used as a chemical weapon, first in World War I and most recently in Syria. Life-threatening Cl2 exposures frequently occur in domestic and occupational environments, and in transportation accidents. Modeling the human etiology of Cl2-induced acute lung injury (ALI), forensic biomarkers, and targeted countermeasures development have been hampered by inadequate large animal models. The objective of this study was to develop a translational model of Cl2-induced ALI in swine to understand toxico-pathophysiology and evaluate whether it is suitable for screening potential medical countermeasures and to identify biomarkers useful for forensic analysis. Specific pathogen-free Yorkshire swine (30-40 kg) of either sex were exposed to Cl2 (≤240 ppm for 1 h) or filtered air under anesthesia and controlled mechanical ventilation. Exposure to Cl2 resulted in severe hypoxia and hypoxemia, increased airway resistance and peak inspiratory pressure, and decreased dynamic lung compliance. Cl2 exposure resulted in increased total leucocyte and neutrophil counts in bronchoalveolar lavage fluid, vascular leakage, and pulmonary edema compared with the air-exposed group. The model recapitulated all three key histopathological features of human ALI, such as neutrophilic alveolitis, deposition of hyaline membranes, and formation of microthrombi. Free and lipid-bound 2-chlorofatty acids and chlorotyrosine-modified proteins (3-chloro-l-tyrosine and 3,5-dichloro-l-tyrosine) were detected in plasma and lung tissue after Cl2 exposure. In this study, we developed a translational swine model that recapitulates key features of human Cl2 inhalation injury and is suitable for testing medical countermeasures, and validated chlorinated fatty acids and protein adducts as biomarkers of Cl2 inhalation.NEW & NOTEWORTHY We established a swine model of chlorine gas-induced acute lung injury that exhibits several features of human acute lung injury and is suitable for screening potential medical countermeasures. We validated chlorinated fatty acids and protein adducts in plasma and lung samples as forensic biomarkers of chlorine inhalation.

Revolutionizing cancer treatment: comprehensive insights into immunotherapeutic strategies.

Cancer, characterized by the uncontrolled proliferation of aberrant cells, underscores the imperative for innovative therapeutic approaches. Immunotherapy has emerged as a pivotal constituent in cancer treatment, offering improved prognostic outcomes for a substantial patient cohort. Noteworthy for its precision, immunotherapy encompasses strategies such as adoptive cell therapy and checkpoint inhibitors, orchestrating the immune system to recognize and selectively target malignant cells. Exploiting the specificity of the immune response renders immunotherapy efficacious, as it selectively targets the body's immune milieu. Diverse mechanisms underlie cancer immunotherapies, leading to distinct toxicity profiles compared to conventional treatments. A remarkable clinical stride in the anticancer resources is immunotherapy. Remarkably, certain recalcitrant cancers like skin malignancies exhibit resistance to radiation or chemotherapy, yet respond favorably to immunotherapeutic interventions. Notably, combination therapies involving chemotherapy and immunotherapy have exhibited synergistic effects, enhancing overall therapeutic efficacy. Understanding the pivotal role of immunotherapy elucidates its complementary value, bolstering the therapeutic landscape. In this review, we elucidate the taxonomy of cancer immunotherapy, encompassing adoptive cell therapy and checkpoint inhibitors, while scrutinizing their distinct adverse event profiles. Furthermore, we expound on the unprecedented potential of immunogenic vaccines to bolster the anticancer immune response. This comprehensive analysis underscores the significance of immunotherapy in modern oncology, unveiling novel prospects for tailored therapeutic regimens.

A phenomenological exploration of the feedback experience of medical students after summative exam failure.

BACKGROUND: Preventing medical students entering cycles of underperformance following assessment is a priority due to the consequences for the student, faculty, and wider society. The benefits from feedback may be inadequately accessed by students in difficulty due to the emotional response evoked by examination failure. This study aims to explore medical students' experiences of receiving feedback after summative assessment failure and investigate the role of emotions on motivation for learning after underperformance, to better support remediation and preparation for future assessments. METHODS: This study used interpretative phenomenological analysis (IPA) to explore the experiences of four medical students who failed summative assessments. Additionally, a content analysis was conducted using Linguistic Inquiry and Word Count (LIWC) to investigate the characteristics and use of language to describe their emotional response. RESULTS: Anger, fear, anxiety, and sadness were emotions frequently experienced after examination failure. These emotions led to feelings of mistrust of the medical school and subsequent distrust in the university's assessment processes, impacting on the desire to engage with feedback. There was dissonance between the students' perceptions of what feedback should provide and what benefit feedback provided after summative assessments. The linguistic inquiry further confirmed an initial (and sometimes long lived) negative affective state after experiencing failure, and a barrier to engagement with remediation when not effectively managed. CONCLUSIONS: A range of emotions, directed at themselves and the medical school are experienced by students following exam failure. These emotions lead to a range of negative feelings and responses that affect how students make sense of and move on from the failure experience. There is a need for educators to better understand and support students to manage, reflect and contextualise their emotional responses, minimise external attribution and to enable focus on remediation and learning.

Expression of E-cadherin and N-cadherin in Epithelial-to-Mesenchymal Transition of Osteosarcoma: A Systematic Review.

Osteosarcoma (OS) is a debilitating cancer of the bone that commonly afflicts the young and old. This may be de novo or associated with tumorigenic syndromes. However, many molecular mechanisms are still being uncovered and may offer greater avenues for screening and therapy. Cadherins, including E-cadherin and N-cadherin/vimentin, are involved in epithelial-to-mesenchymal transmission (EMT), which is key for tumor invasion. A study reviewing the relationship between OS and cadherins might elucidate a potential target for therapy and screening. A robust literature review was conducted by searching PubMed with the keywords "osteosarcoma", "cadherin", "e-cadherin" and "n-cadherin". Of a preliminary 266 papers, 25 were included in the final review. Review articles and those without primary data were excluded. Loss of E-cadherin is noted in metastatic cell lines of osteosarcoma. Overexpression of E-cadherin or knockout of N-cadherin/vimentin results in loss of metastatic potential. There are several methods of gene knockout, including CRISPR-Cas9 gene editing, viral vector insertion with micro RNA complementary to long noncoding RNA within gene segments, or proteomic editing. Screening for EMT and genetic treatment of EMT is a possible avenue for the treatment of refractory osteosarcoma. Several studies were conducted ex vivo. Further testing involving in vitro therapy is necessary to validate these methods. Limitations of this study involve a lack of in vivo trials to validate methods.

Advancement in Opioid Abuse-deterrent Formulation Technologies and Regulatory Expectation.

Chronic pain is a byproduct of many diseases and conditions. Along with long-term opioid medication use in chronic pain management, misuse of this vital medication has been a topic of much debate over the last two decades. Abuse-deterrent formulations play a critical role in comprehensive opioid risk management strategies, limiting the attractiveness and drug-liking qualities of an opioid drug by limiting their bioavailability, making abuse of the tampered opioid medication less appealing or rewarding, or impeding the extraction of the opioid drug and thus impeding the administration of the opioid formulation via alternative routes. The present article covers various regulatory actions, expectations in abuse-deterrent formulation approval, and emerging opioid abuse-deterrent formulation strategies, such as incorporating physical barriers, chemical barriers, aversion agents, pH modulating release properties, novel delivery systems, agonist/antagonist combinations, and prodrugs, as potential approaches to encountering the crisis of the opioid abuse epidemic. Looking at the severity of the opioid crisis across the globe now is the right time for various regulatory agencies to come under one roof to save society from the opioid epidemic, define the policy on how and when to prescribe opioid formulations to patients, perform abuse risk assessments, and make more efforts to approve only abusedeterrent opioid medication.

Hypoxia increases persulfide and polysulfide formation by AMP kinase dependent cystathionine gamma lyase phosphorylation.

Hydropersulfide and hydropolysulfide metabolites are increasingly important reactive sulfur species (RSS) regulating numerous cellular redox dependent functions. Intracellular production of these species is known to occur through RSS interactions or through translational mechanisms involving cysteinyl t-RNA synthetases. However, regulation of these species under cell stress conditions, such as hypoxia, that are known to modulate RSS remain poorly understood. Here we define an important mechanism of increased persulfide and polysulfide production involving cystathionine gamma lyase (CSE) phosphorylation at serine 346 and threonine 355 in a substrate specific manner, under acute hypoxic conditions. Hypoxic phosphorylation of CSE occurs in an AMP kinase dependent manner increasing enzyme activity involving unique inter- and intramolecular interactions within the tetramer. Importantly, both cellular hypoxia and tissue ischemia result in AMP Kinase dependent CSE phosphorylation that regulates blood flow in ischemic tissues. Our findings reveal hypoxia molecular signaling pathways regulating CSE dependent persulfide and polysulfide production impacting tissue and cellular response to stress.

Operative Technique for Sacral Insufficiency Fractures Causing Spinopelvic Dissociation: A Case Report.

CASE: We present a case of a 54-year-old man with atraumatic, U-type sacral insufficiency and L5 compression fractures leading to spinopelvic dissociation, inability to ambulate, and bowel/bladder compromise. The patient underwent L3-4 percutaneous pedicle screw fixation with bilateral iliac bolts and percutaneous iliosacral screw fixation. Postoperatively, the patient had return of bowel/bladder function and independent ambulation at 2.5 years. CONCLUSION: Atraumatic spinopelvic dissociation is an underappreciated pathology in older patients. Here, we describe the result of our preferred treatment strategy, triangular osteosynthesis, to preserve function and independence. Despite optimal, prompt treatment, these injuries pose a difficult rehabilitation process for patients.