Nanoenzymes: A Radiant Hope for the Early Diagnosis and Effective Treatment of Breast and Ovarian Cancers.

Breast and ovarian cancers, despite having chemotherapy and surgical treatment, still have the lowest survival rate. Experimental stages using nanoenzymes/nanozymes for ovarian cancer diagnosis and treatment are being carried out, and correspondingly the current treatment approaches to treat breast cancer have a lot of adverse side effects, which is the reason why researchers and scientists are looking for new strategies with less side effects. Nanoenzymes have intrinsic enzyme-like activities and can reduce the shortcomings of naturally occurring enzymes due to the ease of storage, high stability, less expensive, and enhanced efficiency. In this review, we have discussed various ways in which nanoenzymes are being used to diagnose and treat breast and ovarian cancer. For breast cancer, nanoenzymes and their multi-enzymatic properties can control the level of reactive oxygen species (ROS) in cells or tissues, for example, oxidase (OXD) and peroxidase (POD) activity can be used to generate ROS, while catalase (CAT) or superoxide dismutase (SOD) activity can scavenge ROS. In the case of ovarian cancer, most commonly nanoceria is being investigated, and also when folic acid is combined with nanoceria there are additional advantages like inhibition of beta galactosidase. Nanocarriers are also used to deliver small interfering RNA that are effective in cancer treatment. Studies have shown that iron oxide nanoparticles are actively being used for drug delivery, similarly ferritin carriers are used for the delivery of nanozymes. Hypoxia is a major factor in ovarian cancer, therefore MnO2-based nanozymes are being used as a therapy. For cancer diagnosis and screening, nanozymes are being used in sonodynamic cancer therapy for cancer diagnosis and screening, whereas biomedical imaging and folic acid gold particles are also being used for image guided treatments. Nanozyme biosensors have been developed to detect ovarian cancer. This review article summarizes a detailed insight into breast and ovarian cancers in light of nanozymes-based diagnostic and therapeutic approaches.

Incidentally Diagnosed Low-Grade Primary Peritoneal Serous Carcinoma Within the Umbilical Hernia Sac in a Male: A Report of an Extremely Rare Case and Review of the Literature.

Primary peritoneal serous carcinoma (PPSC) is a rare tumor that develops in the peritoneum. PPSC originates from embryonic nests of Müllerian cells in the peritoneum, which are also present in the epithelium of the ovary. This similarity explains the histopathological resemblance between PPSC and low-grade serous ovarian carcinoma. While PPSC primarily affects women, it is an extremely rare occurrence in males, and it is believed that the significant difference in diagnosis rates between males and females is due to the inhibition of Müllerian system growth by substances produced by male Sertoli cells. These substances are present at higher levels in males, which may prevent the development of Müllerian system-derived tumors in men. We describe a 65-year-old male patient who presented for elective bariatric surgery and umbilical hernia repair, and an incidental finding of low-grade PPSC was made based on hernia sac pathology. The patient underwent further management, including tumor debulking and hyperthermic intraperitoneal chemotherapy (HIPEC), with positive outcomes. Long-term follow-up and oral letrozole treatment are planned.

Multidrug resistance among uropathogenic clonal group A E. Coli isolates from Pakistani women with uncomplicated urinary tract infections.

OBJECTIVE: Multi-drug resistance (MDR) has notably increased in community acquired uropathogens causing urinary tract infections (UTIs), predominantly Escherichia coli. Uropathogenic E. coli causes 80% of uncomplicated community acquired UTIs, particularly in pre-menopausal women. Considering this high prevalence and the potential to spread antimicrobial resistant genes, the current study was conducted to investigate the presence of clinically important strains of E. coli in Pakistani women having uncomplicated cystitis and pyelonephritis. Women belonging to low-income groups were exclusively included in the study. Seventy-four isolates from urine samples were processed, phylotyped, and screened for the presence of two Single Nucleotide Polymorphisms (SNPs) particularly associated with a clinically important clonal group A of E. coli (CgA) followed by antibiotic susceptibility testing and genome sequence analysis. RESULTS: Phylogroup B2 was most prevalent in patients and 44% of isolates were positive for the presence of CgA specific SNPs in Fumarate hydratase and DNA gyrase subunit B genes. Antibiotic susceptibility testing showed widespread resistance to trimethoprim-sulfamethoxazole and extended-spectrum beta-lactamase production. The infection analysis revealed the phylogroup B2 to be more pathogenic as compared to the other groups. The genome sequence of E. coli strain U17 revealed genes encoding virulence, multidrug resistance, and host colonization mechanisms. CONCLUSIONS: Our research findings not only validate the significant occurrence of multidrug-resistant clonal group A E. coli (CgA) in premenopausal Pakistani women suffering from cystitis and pyelonephritis but also reveal the presence of genes associated withvirulence, and drug efflux pumps. The detection of highly pathogenic, antimicrobial-resistant phylogroup B2 and CgA E. coli strains is likely to help in understanding the epidemiology of the pathogen and may ultimately help to reduce the impact of these strains on human health. Furthermore, the findings of this study will particularly help to reduce the prevalence of uncomplicated UTIs and the cost associated with their treatment in women belonging to low-income groups.

Early post-operative outcomes of robot-assisted pyeloplasty in patients with unilateral ureteropelvic junction obstruction.

INTRODUCTION: Ureteropelvic junction obstruction (UPJO) is a commonly encountered abnormality and it can lead to serious consequences such as renal dysplasia eventually resulting in loss of kidney. Hence, early diagnosis and timely management remains the cornerstone of the treatment. The most anticipated technique amongst modern day urologist is the robot-assisted laparoscopic pyeloplasty (RALP). The study aims to determine early post-operative outcomes of robot-assisted laparoscopic transperitoneal pyeloplasty procedure in patients presenting with unilateral ureteropelvic junction obstruction to establish the local perspective. METHODOLOGY: This is a descriptive study involving patients with ureteropelvic junction obstruction in a tertiary care facility in Karachi; Sindh Institute of Urology and Transplant (SIUT). A total of 46 participants were recruited. Robot-assisted laparoscopic transperitoneal dismembered Hynes-Anderson pyeloplasty was performed by a single surgeon with over 3 years of experience in the presence of the researcher. Early postoperative outcome total operative time, length of hospital stay, console time and blood loss were noted by the researcher as per operational definition. Data were analyzed on SPSS Version 22. RESULTS: Mean age in our study was 46.51 years with the standard deviation of ± 10.87. Whereas, mean length of hospital stay, total operative time, total blood loss, console time, pre-hemoglobin, posthemoglobin, height, weight and BMI in our study was 1.19 ± 0.40 days, 64.58 ± 17.59 min, 9.56 ± 6.13 ml, 30.17 ± 4.99 min, 12.66 ± 1.47 ml, 11.79 ± 1.93 ml, 165.62 ± 8.23 cm, 68.34 ± 8.23 kg and 24.85 ± 3.34 kg/m2, respectively. CONCLUSION: Recent advancements in technology have yielded the latest RALP technique which has been proven significantly better than existing approaches and similar results are reported by this study demonstrating improvement in peri-operative and post-operative outcomes ultimately ameliorating the quality of life of patients with UPJO.

Knowledge of head and neck cancer among medical students in the UK.

Head and neck cancer (HNC) refers to malignancies found in mucosal surfaces anywhere from the paranasal sinuses to the larynx, including the various glands and cavities. Between the years 2016 and 2018, there were about 3900 new cases every year in women and 8600 in men, making it the thirteenth most common cancer in women and fourth most common in men. The aim of our study was to evaluate the amount and type of teaching United Kingdom (UK) medical students receive on HNC, and to assess their current knowledge of these cancers. An online survey distributed via university representatives was responded to by 311 final year medical students from 25 medical schools across the UK. Regarding HNC teaching, 72 students (23.2%) reported receiving no teaching at their medical school. Of the 239 who reported receiving teaching, 169 (54.3%) received it in the format of a non-interactive, large group lecture. A total of 271 respondents (87.1%) believed that medical students at their university would benefit from more teaching on HNC. Based on our sample, there appears to be an overall dissatisfaction and lack of confidence surrounding HNC in the undergraduate curriculum. With its increasing prevalence in the UK, it is vital that red-flag symptoms and referral criteria are understood by the future medical workforce.

Spotlight on El-Zahrawi, Father of Modern Surgery: Reflections on His Impact on Contemporary Medicine and the Need for Greater Medical Education on Pivotal Figures in Medicine.

Issue: For students in the preclinical years of medical school, it is easy to overlook the narrative component of medicine and become occupied with learning the vast sea of information about the human body. There are limited, if any, options to learn about historical figures in medicine and how they can inform our future in clinical medicine. Evidence: There is an apparent lack of education offered on pivotal figures in medicine across many institutions. The few instances that medical history has been incorporated into the curriculum are further discussed. Implications: In order to incorporate cultural competency in our delivery of care, it is important to consider the diversity of the population we will be serving and how we can prepare to help patients feel heard in their unique issues. In this paper, we propose learning about the true history of certain medical practices, rather than the "colonial" version often utilized in textbooks and lectures, as a means of diversifying students' perspectives of the origins of these practices as well as giving credit where it is due. The time period during which many of these medical practices were cultivated is referred to as the Islamic Golden Age, but scholars who made contributions belonged to many different faiths and cultural backgrounds. El-Zahrawi was a Muslim physician whose principal work, Kitab-at-Tasrif, contains topics on medicine, surgery, midwifery, pharmacology, therapeutics, diet, psychotherapy, and medical chemistry. He pioneered numerous techniques in surgery and invented surgical devices that are still used to this day.

Incidentaloma on Staging CT Revealed to Be Breast to Renal Tumour-to-Tumour Metastasis.

Tumour-to-tumour metastases (TTM) are a rare phenomenon in which a primary tumour has metastasised within another distant primary tumour. We present the case of a 63-year-old female who presented with right-sided breast cancer. An incidental left-sided renal mass was detected on staging CT of the thorax, abdomen, and pelvis (CT-TAP). The patient had no evidence of metastases below the diaphragm. Histology following a radical left nephrectomy revealed metastatic breast cancer within a renal cell carcinoma (RCC). The patient underwent chemotherapy and surgery for right-sided breast cancer. Follow-up imaging demonstrated the metastatic spread of the breast cancer. This is an unusual case of TTM from breast to an initially occult RCC primary.

Skin Lesion Segmentation Using an Ensemble of Different Image Processing Methods.

In recent times, there has been a huge increase in the average number of cases of skin cancer per year, which sometimes become life threatening for humans. Early detection of various skin diseases through automated detection techniques plays a crucial role. However, the presence of numerous artefacts makes this task challenging. Dermoscopic images exhibit various variations, including hair artefacts, markers, and ill-defined boundaries. These artefacts make automatic analysis of skin lesion quite a difficult task. To address these issues, it is essential to have an accurate and efficient automated method which will delineate a skin lesion from the rest of the image. Unfortunately, due to the presence of several types of skin artefacts, there is no such thresholding method that can provide a sufficient segmentation result for every type of skin lesion. To overcome this limitation, an ensemble-based method is proposed that selects the optimal thresholding based on an objective function. A group of state-of-the-art different thresholding methods such as Otsu, Kapur, Harris hawk, and grey level are used. The proposed method obtained superior results (dice score = 0.89 with p-value ≤ 0.05) as compared to other state-of-the-art methods (Otsu = 0.79, Kapur = 0.80, Harris hawk = 0.60, grey level = 0.69, active contour model = 0.72). The experiments conducted in this study utilize the ISIC 2016 dataset, which is publicly available and specifically designed for skin-related research. Accurate segmentation will help in the early detection of many skin diseases.

A Case of Hypertriglyceridemia-Induced Acute Pancreatitis in the Setting of Alcohol Abuse.

Acute pancreatitis (AP) is the painful inflammation of the pancreas. It is commonly associated with gallstones, excessive alcohol use, and certain medications. We report a case of hypertriglyceridemia-induced pancreatitis in a 35-year-old African American male with a history of alcohol abuse, tobacco use, and hyperlipidemia who presented with abdominal pain and intractable vomiting. During history taking, he reported chronic alcohol abuse over the past 10 years. On physical examination, he was ill-looking, with a dry mucous membrane and reproducible epigastric tenderness. Laboratory testing indicated markedly elevated triglycerides and lipase levels. Computed Tomography imaging showed signs of pancreatic inflammation. He was treated with aggressive intravenous fluid hydration, insulin infusion, and pain control medications. He demonstrated significant improvement and then transitioned to oral fibrates. Community resources for alcohol abuse treatment were provided and a referral was made to endocrinology for outpatient follow-up. This case highlights acute pancreatitis in a person with high alcohol use with elevated triglyceride and explores possible associations between these three.

Mass Spectrometry based identification of site-specific proteomic alterations and potential pathways underlying the pathophysiology of schizophrenia.

BACKGROUND: Schizophrenia (SZ) is a complex multifactorial disorder that affects 1% of the population worldwide with no available effective treatment. Although proteomic alterations are reported in SZ however proteomic expression aberrations among different brain regions are not fully determined. Therefore, the present study aimed spatial differential protein expression profiling of three distinct regions of SZ brain and identification of associated affected biological pathways in SZ progression. METHODS AND RESULTS: Comparative protein expression profiling of three distinct autopsied human brain regions (i.e., substantia nigra, hippocampus and prefrontal cortex) of SZ was performed with respective healthy controls. Using two-dimensional electrophoresis (2DE)-based nano liquid chromatography tandem mass spectrometry (Nano-LC MS /MS) analysis, 1443 proteins were identified out of which 58 connote to be significantly dysregulated, representing 26 of substantia nigra,14 of hippocampus and 18 of prefrontal cortex. The 58 differentially expressed proteins were further analyzed using Ingenuity pathway analysis (IPA). The IPA analysis provided protein-protein interaction networks of several proteins including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kb), extracellular signal regulated kinases 1/2 (ERK1/2), alpha serine / Threonine-protein kinase (AKT1), cellular tumor antigen p53 (TP53) and amyloid precursor protein (APP), holding prime positions in networks and interacts with most of the identified proteins and their closely interacting partners. CONCLUSION: These findings provide conceptual insights of novel SZ related pathways and the cross talk of co and contra regulated proteins. This spatial proteomic analysis will further broaden the conceptual framework for schizophrenia research in future.

Unveiling Sex Differences in Tricuspid Valve Disease: A Systematic Review and Meta-Analysis of Surgical Management.

Tricuspid regurgitation (TR) is a heart condition where blood flows backward through the tricuspid valve. Tricuspid valve disease constitutes a major valvular heart condition that is receiving heightened attention due to tailored treatment options and sex-specific differences in treatment outcomes. The study aims to investigate whether biological sex has a significant influence on the development, progression, and treatment outcomes of tricuspid valve disease in adults. We conducted a comprehensive search to identify studies examining the impact of sex on the pathophysiology of TR as well as treatment outcomes in patients with TR. We searched PUBMED/MEDLINE, SCOPUS, and Excerpta Medica dataBASE (EMBASE) from inception to September 2023 to identify relevant studies. Twelve studies totaling 22,574 patients met our eligibility criteria. These studies were categorized into three subgroups: patients with TR without intervention (3,848 patients, with 48.1% males and 51.9% females), those who underwent open heart surgery (17,498 patients: 46.2% males and 53.8% females), and those who underwent transcatheter tricuspid valve repair/replacement (TTVR; 1,687 patients: 41.6% males and 58.4% females). Analysis revealed no major differences in terms of TR etiology. Males tended to have a slightly lower mean age difference (mean difference (MD): -0.60 years; 95% confidence interval (CI) (-1.49, -0.04); p = 0.10) but had more frequent chronic lung disease (risk ratio (RR): 1.12, 95% CI (1.01, 1.25), p = 0.03). Males showed higher baseline TR volume (MD: 4.11, 95% CI (0.53, 7.68), p = 0.02) and lower left ventricular ejection fraction (MD: -5.85, 95% CI (-6.97, -4.73), p < 0.00001). Following open heart surgery for TR treatment, males required more frequent permanent pacemaker implantation (PPM; RR: 1.57, 95% CI (1.21, 2.03), p = 0.0006). Similarly, TTVR showed a higher need for PPM in males (RR: 1.45, 95% CI (1.10, 1.93), p = 0.010). In-hospital mortality exhibited no sex differences, but males had a slightly elevated late mortality risk. Sex differences in TR patients were notable in baseline characteristics, with males having a higher risk of certain conditions. The more frequent requirement for PPM was a major sex-based difference in terms of prognosis.

Spice-Derived Bioactive Compounds Confer Colorectal Cancer Prevention via Modulation of Gut Microbiota.

Colorectal cancer (CRC) is the second most frequent cause of cancer-related mortality among all types of malignancies. Sedentary lifestyles, obesity, smoking, red and processed meat, low-fiber diets, inflammatory bowel disease, and gut dysbiosis are the most important risk factors associated with CRC pathogenesis. Alterations in gut microbiota are positively correlated with colorectal carcinogenesis, as these can dysregulate the immune response, alter the gut's metabolic profile, modify the molecular processes in colonocytes, and initiate mutagenesis. Changes in the daily diet, and the addition of plant-based nutraceuticals, have the ability to modulate the composition and functionality of the gut microbiota, maintaining gut homeostasis and regulating host immune and inflammatory responses. Spices are one of the fundamental components of the human diet that are used for their bioactive properties (i.e., antimicrobial, antioxidant, and anti-inflammatory effects) and these exert beneficial effects on health, improving digestion and showing anti-inflammatory, immunomodulatory, and glucose- and cholesterol-lowering activities, as well as possessing properties that affect cognition and mood. The anti-inflammatory and immunomodulatory properties of spices could be useful in the prevention of various types of cancers that affect the digestive system. This review is designed to summarize the reciprocal interactions between dietary spices and the gut microbiota, and highlight the impact of dietary spices and their bioactive compounds on colorectal carcinogenesis by targeting the gut microbiota.

Association of Chest Pain Protocol-Discordant Discharge With Outcomes Among Emergency Department Patients With Modest Elevations of High-Sensitivity Troponin.

Importance: Accelerated diagnostic protocols (ADPs) for chest pain using high-sensitivity troponin (hsTn) levels have excellent sensitivity and negative predictive value for rapid risk stratification of patients with chest pain. However, little is known about the outcomes of patients who are discharged despite abnormal ADP results, ie, after "ruling-in" with a modest elevation of hsTn. Objective: To determine outcomes of patients discharged following ADP, including those who were ruled in with modestly elevated levels of hsTnT but discharged nonetheless. Design, Setting, and Participants: This retrospective cohort study included patients with chest pain who presented to the emergency departments (EDs) of a large multisite health system ED between January 2017 to September 2019. Patients were assessed using an ADP, had a peak hsTnT level measured between the limit of quantitation and 52 ng/L, were discharged, and had follow-up in the electronic medical record. Data analysis was conducted from January 2017 to September 2019. Exposures: Application of an hsTnT ADP. Main Outcomes and Measures: Thirty-day major adverse cardiac events (MACE), including myocardial infarction, urgent coronary revascularization, and all-cause death, comparing patients who were discharged following ADP-concordant vs ADP-discordant results. Results: Of 10 342 patients with chest pain (mean [SD] age 51 [17] years; 5902 [57%] women) discharged following ADP, 29 (0.28%) had MACE. Patients with MACE were older (median [IQR] age, 66 [53-75] years vs 50 [38-62] years; P < .001) and more likely to have prior CAD (12 [41.4%] vs 1805 [17.5%]; P = .002) and hyperlipidemia (13 [44.8%] vs 2248 [21.8%]; P = .006). Additionally, patients with MACE were 5-fold more likely to have been discharged despite ADP discordance (16 [55.2%] vs 1145 [11.1%]; P < .001). A multivariable logistic regression analysis revealed only ADP discordance was independently associated with MACE (odds ratio, 6.42 [95% CI, 2.94-14.0]; P < .001). When stratified by peak hsTnT level, there were no differences in MACE between ADP-concordant and -discordant discharges provided the peak hsTnT measured was less than 12 ng/L. In contrast, patients with peak hsTnT level between 12 and 51 ng/L were significantly more likely to have MACE if they were discharged after ADP-discordant vs -concordant hsTnT series (14 of 609 [2.30%] vs 5 of 1047 [0.48%]; P < .002). Notably, a HEART (history, electrocardiogram, age, risk factors, troponin) score of 4 or greater retrospectively identified the most ADP-discordant discharges (13 of 16 [81.3%]) who had MACE. Conclusions and Relevance: In this cohort study, an hsTnT ADP identified patients who could be discharged from the ED with low 30-day risk of MACE, provided the discharge was based on ADP-concordant "rule-out." Conversely, the rate of MACE was significantly higher among patients discharged despite ADP discordance. Most patients with ADP-discordant discharges who experienced MACE had a HEART score of 4 or greater, suggesting that application of this score may augment discharge decisions of patients despite ADP-discordant troponin series.

Psoralen downregulates osteoarthritis chondrocyte inflammation via an estrogen-like effect and attenuates osteoarthritis.

Estrogen and its receptor play a positive role in the development of osteoarthritis (OA). Psoralen is a plant-derived estrogen analog. This study aimed to verify whether psoralen inhibits OA through an estrogen-like effect. First, human primary chondrocytes in the late stage of OA were extracted to complete collagen type II immunofluorescence staining and cell proliferation experiments. Subsequently, estrogen, psoralen and estrogen receptor antagonists were co-cultured with OA chondrocytes, and RT-PCR was performed to detect the gene expression. A rabbit OA model was subsequently made by anterior cruciate ligament transection (ACLT). They were set as Sham group, OA group and Psoralen group, respectively. The articular cartilage samples were taken after 5 weeks of treatment, and the effect was observed by gross observation, histological staining, micro-CT scanning of subchondral bone. The results of cellular experiments displayed that the cultured cells were positive for collagen II fluorescence staining and 12 µg/mL psoralen was selected as the optimal concentration. In addition, psoralen had effects similar to estrogen, promoting the expression of estrogen tar-get genes CTSD, PGR and TFF1 and decreasing the expression of the inflammation-related gene TNF- α, IL-1ß and IL-6. The effect of psoralen was blocked after the use of an estrogen receptor antagonist. Further animal experiments indicated that the psoralen group showed less destruction of cartilage tissue and decreased OASRI scores compared with the OA group. A subchondral bone CT scan demonstrated that psoralen significantly increased subchondral bone mineral density (BMD), trabecular thickness and trabecular number and decreased trabecular separation. In summary, psoralen inhibits the inflammatory production of chondrocytes, which is related to estrogen-like effect, and can be used to attenuate the progression of OA.

Heterogeneity in the prevalence of premature hypertension among Asian American populations compared with white individuals: A National Health Interview Survey study.

Background: Differences in prevalence of risk factors such as hypertension may explain heterogeneity in cardiovascular risk across Asian American populations. Methods: We used National Health Interview Survey (NHIS) data from 2006 to 2018 among White, Chinese, Asian Indian, Filipino, and 'other Asians' (Japanese, Korean, and Vietnamese). Unadjusted and adjusted odds ratios (aOR) with 95% confidence intervals were reported using logistic regression models for the association between race and self-reported premature hypertension (age <50 years old). Models were adjusted for sex, education, body mass index, smoking status, diabetes, and coronary heart disease. Results: We studied 99,864 participants with history of hypertension (mean age, 59.3 ± 0.1; 50% women, 90% US born). Asian Indians had higher prevalence of premature hypertension (37%) compared with Filipinos (27%), 'other Asians' (26%), Whites (25%), and Chinese (21%). Compared with Whites, Chinese individuals had lower odds of premature hypertension (aOR = 0.79, 0.63-0.98), but Asian Indians had higher odds (aOR = 1.85, 1.48-2.31). Compared with Chinese, odds of premature hypertension was higher for Asian Indians (aOR = 2.39, 1.74-3.27), Filipinos (aOR = 1.53, 1.16-2.04), and 'other Asians' (OR = 1.32, 1.03-1.70; aOR = 1.59, 1.20-2.10). Overall prevalence of hypertension was lower among Asian Indians (aOR = 0.52, 0.46-0.58) and 'other Asians' (aOR = 0.74, 0.68-0.79) compared with Whites. Conclusions: There is heterogeneity in the risk of hypertension across Asian Americans by age. Asian Indians and 'other Asians' had higher prevalence of premature hypertension and lower prevalence of overall hypertension, which may call for earlier screening for risk factors among these populations.

Evaluating Cancer Pain Characteristics and Treatment Factors in the Emergency Department: A Retrospective Cohort Study.

Objectives: To identify patient characteristics and treatment factors of patients presenting to the emergency department (ED) with cancer-related pain that may affect patient outcomes. Methods: We conducted a retrospective cohort study to evaluate adult patients with active cancer, who presented to the ED with a chief complaint of pain between June first, 2012 and January first, 2016. We utilized multivariable logistic regression to evaluate the association of several exposure variables, including disease and demographic characteristics, primary pain site, and treatment methods, on ED disposition and revisit rate. Results: We included 483 patients with active cancer with a chief complaint of pain. Patients with severe pain on arrival tended to be younger than those who did not present with severe pain (median: 58 vs 62 respectively, OR 8.0 p < 0.01). Patients with high ECOG scores (3-4) with severe pain on arrival (≥7 out of 10) had less improvement in their pain than the rest of our cohort (OR 8.4, p < 0.01). Also, those with musculoskeletal pain had significantly less improvement in reported pain than all other pain types (delta pain -2.1 vs -3.4, OR 2.3, p = 0.025) Long delays in initial analgesic administration were associated with increased rates of subsequent admission (OR 3.4) [p = 0.014]. Although opioid analgesics led to greater decreases in pain than non-opioid analgesics, patients treated with opioids were more likely to be admitted (43% vs 34.5% AOR 1.51, p = 0.048). Conclusion: Our study showed that delays in analgesic administration, poor functional status, and the presence of musculoskeletal (MSK) pain significantly influenced outcomes for this patient cohort. These findings suggest the development of specific protocols and tools to address cancer-related pain in the ED may be necessary.

The Efficacy of S-Adenosyl Methionine and Probiotic Supplementation on Depression: A Synergistic Approach.

Depression is a common and serious health issue affecting around 280 million people around the world. Suicidal ideation more frequently occurs in people with moderate to severe depression. Psychotherapy and pharmacological drugs are the mainstay of available treatment options for depressive disorders. However, pharmacological options do not offer complete cure, especially in moderate to severe depression, and are often seen with a range of adverse events. S-adenosyl methionine (SAMe) supplementation has been widely studied, and an impressive collection of literature published over the last few decades suggests its antidepressant efficacy. Probiotics have gained significant attention due to their wide array of clinical uses, and multiple studies have explored the link between probiotic species and mood disorders. Gut dysbiosis is one of the risk factors in depression by inducing systemic inflammation accompanied by an imbalance in neurotransmitter production. Thus, concomitant administration of probiotics may be an effective treatment strategy in patients with depressed mood, particularly in resistant cases, as these can aid in dysbiosis, possibly resulting in the attenuation of systemic inflammatory processes and the improvement of the therapeutic efficacy of SAMe. The current review highlights the therapeutic roles of SAMe and probiotics in depression, their mechanistic targets, and their possible synergistic effects and may help in the development of food supplements consisting of a combination of SAMe and probiotics with new dosage forms that may improve their bioavailability.

Emerin regulation of nuclear stiffness is required for fast amoeboid migration in confined environments.

When metastasizing, tumor cells must traverse environments with diverse physicochemical properties. Recently, the cell nucleus has emerged as a major regulator of the transition from mesenchymal to fast amoeboid (leader bleb-based) migration. Here, we demonstrate that increasing nuclear stiffness through elevating lamin A, inhibits fast amoeboid migration in melanoma cells. Importantly, nuclei may respond to force through stiffening. A key factor in this process is the inner nuclear membrane (INM) protein emerin. Accordingly, we determined the role of emerin in regulating fast amoeboid migration. Strikingly, we found that both the up- and downregulation of emerin results in an inhibition of fast amoeboid migration. However, when key Src phosphorylation sites were removed, upregulation of emerin no longer inhibited fast amoeboid migration. Interestingly, as measured by using a Src biosensor, activity of Src was low in cells within a confined environment. Thus, the fast amoeboid migration of melanoma cells depends on the precise calibration of emerin activity.