Perioperative management of phaeochromocytoma with stress cardiomyopathy and aberrant vascular drainage.

The following case discusses the surgical considerations for a patient presenting with cardiogenic shock secondary to a phaeochromocytoma crisis with stress cardiomyopathy. The patient underwent an interval laparoscopic adrenalectomy. Pneumoperitoneum insufflation was performed at lower pressures; manipulation of the adrenal tumour was minimised, and the adrenal vein was ligated early. However, as intraoperative blood pressure (BP) remained elevated and rising, further gentle dissection revealed an aberrant inferior phrenic vein draining the adrenal nodule. BP was finally reduced following ligation of the inferior phrenic vein, demonstrating the clinical significance of an unusual dual venous drainage from the adrenal nodule in this patient.

Artificial Intelligence and Healthcare: A Journey through History, Present Innovations, and Future Possibilities.

Artificial intelligence (AI) has emerged as a powerful tool in healthcare significantly impacting practices from diagnostics to treatment delivery and patient management. This article examines the progress of AI in healthcare, starting from the field's inception in the 1960s to present-day innovative applications in areas such as precision medicine, robotic surgery, and drug development. In addition, the impact of the COVID-19 pandemic on the acceleration of the use of AI in technologies such as telemedicine and chatbots to enhance accessibility and improve medical education is also explored. Looking forward, the paper speculates on the promising future of AI in healthcare while critically addressing the ethical and societal considerations that accompany the integration of AI technologies. Furthermore, the potential to mitigate health disparities and the ethical implications surrounding data usage and patient privacy are discussed, emphasizing the need for evolving guidelines to govern AI's application in healthcare.

Navigating Post-Traumatic Osteoporosis: A Comprehensive Review of Epidemiology, Pathophysiology, Diagnosis, Treatment, and Future Directions.

Post-traumatic osteoporosis (PTO) presents a significant challenge in clinical practice, characterized by demineralization and decreased skeletal integrity following severe traumatic injuries. This literature review manuscript addresses the knowledge gaps surrounding PTO, encompassing its epidemiology, pathophysiology, risk factors, diagnosis, treatment, prognosis, and future directions. This review emphasizes the complexity of the etiology of PTO, highlighting the dysregulation of biomineralization processes, inflammatory cytokine involvement, hormonal imbalances, glucocorticoid effects, vitamin D deficiency, and disuse osteoporosis. Moreover, it underscores the importance of multidisciplinary approaches for risk mitigation and advocates for improved diagnostic strategies to differentiate PTO from other musculoskeletal pathologies. This manuscript discusses various treatment modalities, including pharmacotherapy, dietary management, and physical rehabilitation, while also acknowledging the limited evidence on their long-term effectiveness and outcomes in PTO patients. Future directions in research are outlined, emphasizing the need for a deeper understanding of the molecular mechanisms underlying PTO and the evaluation of treatment strategies' efficacy. Overall, this review provides a comprehensive overview of PTO and highlights avenues for future investigation to enhance clinical management and patient outcomes.

Long Non-Coding RNAs as Determinants of Thyroid Cancer Phenotypes: Investigating Differential Gene Expression Patterns and Novel Biomarker Discovery.

Thyroid Cancer (TC) is the most common endocrine malignancy, with increasing incidence globally. Papillary thyroid cancer (PTC), a differentiated form of TC, accounts for approximately 90% of TC and occurs predominantly in women of childbearing age. Although responsive to current treatments, recurrence of PTC by middle age is common and is much more refractive to treatment. Undifferentiated TC, particularly anaplastic thyroid cancer (ATC), is the most aggressive TC subtype, characterized by it being resistant and unresponsive to all therapeutic and surgical interventions. Further, ATC is one of the most aggressive and lethal malignancies across all cancer types. Despite the differences in therapeutic needs in differentiated vs. undifferentiated TC subtypes, there is a critical unmet need for the identification of molecular biomarkers that can aid in early diagnosis, prognosis, and actionable therapeutic targets for intervention. Advances in the field of cancer genomics have enabled for the elucidation of differential gene expression patterns between tumors and healthy tissue. A novel category of molecules, known as non-coding RNAs, can themselves be differentially expressed, and extensively contribute to the up- and downregulation of protein coding genes, serving as master orchestrators of regulated and dysregulated gene expression patterns. These non-coding RNAs have been identified for their roles in driving carcinogenic patterns at various stages of tumor development and have become attractive targets for study. The identification of specific genes that are differentially expressed can give insight into mechanisms that drive carcinogenic patterns, filling the gaps of deciphering molecular and cellular processes that modulate TC subtypes, outside of well-known driver mutations.

Dysregulated Expression Patterns of Circular RNAs in Cancer: Uncovering Molecular Mechanisms and Biomarker Potential.

Circular RNAs (circRNAs) are stable, enclosed, non-coding RNA molecules with dynamic regulatory propensity. Their biogenesis involves a back-splicing process, forming a highly stable and operational RNA molecule. Dysregulated circRNA expression can drive carcinogenic and tumorigenic transformation through the orchestration of epigenetic modifications via extensive RNA and protein-binding domains. These multi-ranged functional capabilities have unveiled extensive identification of previously unknown molecular and cellular patterns of cancer cells. Reliable circRNA expression patterns can aid in early disease detection and provide criteria for genome-specific personalized medicine. Studies described in this review have revealed the novelty of circRNAs and their biological ss as prognostic and diagnostic biomarkers.

Association of extended core sampling with delayed intervention and pathologic outcomes for active surveillance patients A population-based analysis.

INTRODUCTION: Combined systematic plus targeted biopsy sampling improves detection of clinically significant prostate cancer (PCa). Our objective was to evaluate whether extended core sampling at initial biopsy in active surveillance (AS) patients is associated with subsequent AS discontinuation and pathologic outcomes. METHODS: National Comprehensive Cancer Network (NCCN) low- and favorable-intermediate-risk (FIR) AS patients diagnosed between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) Prostate with Watchful Waiting database. Prostate biopsy sampling was operationalized as: standard (10-12 cores), extended (13-20 cores), or super-extended (21+ cores). Sensitivity analyses using differing cutoffs was performed. Outcomes included delayed definitive intervention (radical prostatectomy [RP]/radiotherapy) and pathologic upgrading and/or downgrading in delayed RP patients. Multivariable logistic regression modelling adjusted for sociodemographic/oncologic variables was performed. RESULTS: This cohort included 42 459 patients (low-risk: 28 411; FIR:14 048); 25-29% and 3-5% of patients underwent extended and super-extended core sampling, respectively, at diagnosis. Extended core sampling was associated with decreased odds of definitive intervention in low (odds ratio [OR] 0.89, p=0.003) and grade group 2 (GG2) FIR (OR 0.83, p=0.002) patients. Super-extended sampling was associated with decreased odds of definitive intervention in prostate-specific antigen (PSA) 10-20 FIR patients (OR 0.65, p=0.02). Super-extended sampling was associated with decreased odds of upgrading to ≥GG2 disease in low-risk (OR 0.45, p=0.032) and to ≥GG3 disease in GG2 FIR patients (OR 0.67, p=0.044). CONCLUSIONS: This population-based analysis demonstrates that extended/super-extended sampling at diagnosis is associated with significantly decreased odds of AS discontinuation and pathologic upgrading in low/FIR AS patients. This highlights the significance of extended tissue sampling at initial biopsy to appropriately risk-stratify AS patients and minimize AS discontinuation rates.

Intraductal Prostate Cancer Affinity for Lymphatic-Predominant Metastases Through 18F-DCFPyL‒Prostate-Specific Membrane Antigen‒Positron Emission Tomography/CT Scans in Pretreatment Prostate Cancer Patients.

PURPOSE: Intraductal prostate cancer (IDC) is linked to unfavorable oncologic outcomes, marked by distinctive cellular intrinsic pathway changes and intricate immunosuppressive microenvironments that could impact the way cancer spreads. The aim of this study was to determine whether the presence of IDC in prostate biopsy specimens obtained from patients before primary prostate cancer (PCa) treatment is associated with a lymph node metastatic propensity in prostate-specific membrane antigen (PSMA)‒positron emission tomography (PET)/CT. MATERIALS AND METHODS: This was a cross-sectional analysis of all PCa patients undergoing a pretreatment 18F-DCFPyL-PSMA-PET/CT between January 1, 2016, and August 2021 at The Princess Margaret Cancer Centre. Outcomes were presence of any metastasis in the overall cohort, presence of lymphatic vs no metastases, and presence of lymphatic vs bone metastasis among patients who underwent PSMA-PET/CT as PCa primary staging. The associations between IDC presence on the prostate biopsy and the study outcomes were evaluated using univariable and multivariable logistic regression analyses. RESULTS: The cohort consisted of 120 patients. IDC and cribriform pattern were observed in 55 (46%) and 48 (40%) prostate biopsies, respectively. Overall, 52 patients (43%) had evidence of metastasis. Presence of IDC on biopsy was associated with increased odds of overall metastasis (odds ratio: 2.47, 95% CI: 1.09-5.61, P = .03). Of the 52 patients with evidence of metastasis, 41 (79%) had evidence of lymphatic metastasis. Presence of IDC on biopsy was associated with significantly increased odds of lymphatic metastasis vs nonmetastases (odds ratio: 3.03, 95% CI: 1.24-7.40, P = .01). CONCLUSIONS: The identification of IDC morphology in prostate biopsy specimens has been observed to be significantly linked with lymph node metastasis on 18F-DCFPyL-PET/CT imaging in a PCa pretreatment staging setting. We found that presence of IDC in prostate biopsy appears to be a marker for lymph node metastasis on 18F-DCFPyL-PET/CT.

Sustained silencing peanut allergy by xanthopurpurin is associated with suppression of peripheral and bone marrow IgE-producing B cell.

Introduction: Peanut allergy is an immunoglobulin E (IgE) mediated food allergy. Rubia cordifolia L. (R. cordifolia), a Chinese herbal medicine, protects against peanut-induced anaphylaxis by suppressing IgE production in vivo. This study aims to identify IgE-inhibitory compounds from the water extract of R. cordifolia and investigate the underlying mechanisms using in vitro and in vivo models. Methods: Compounds were isolated from R. cordifolia water extract and their bioactivity on IgE production was assessed using a human myeloma U266 cell line. The purified active compound, xanthopurpurin (XPP), was identified by LC-MS and NMR. Peanut-allergic C3H/HeJ mice were orally administered with or without XPP at 200µg or 400µg per mouse per day for 4 weeks. Serum peanut-specific IgE levels, symptom scores, body temperatures, and plasma histamine levels were measured at challenge. Cytokines in splenocyte cultures were determined by ELISA, and IgE + B cells were analyzed by flow cytometry. Acute and sub-chronic toxicity were evaluated. IL-4 promoter DNA methylation, RNA-Seq, and qPCR analysis were performed to determine the regulatory mechanisms of XPP. Results: XPP significantly and dose-dependently suppressed the IgE production in U266 cells. XPP significantly reduced peanut-specific IgE (>80%, p <0.01), and plasma histamine levels and protected the mice against peanut-allergic reactions in both early and late treatment experiments (p < 0.05, n=9). XPP showed a strong protective effect even 5 weeks after discontinuing the treatment. XPP significantly reduced the IL-4 level without affecting IgG or IgA and IFN-γ production. Flow cytometry data showed that XPP reduced peripheral and bone marrow IgE + B cells compared to the untreated group. XPP increased IL-4 promoter methylation. RNA-Seq and RT-PCR experiments revealed that XPP regulated the gene expression of CCND1, DUSP4, SDC1, ETS1, PTPRC, and IL6R, which are related to plasma cell IgE production. All safety testing results were in the normal range. Conclusions: XPP successfully protected peanut-allergic mice against peanut anaphylaxis by suppressing IgE production. XPP suppresses murine IgE-producing B cell numbers and inhibits IgE production and associated genes in human plasma cells. XPP may be a potential therapy for IgE-mediated food allergy.

A Review of the Past, Present, and Future of the Monkeypox Virus: Challenges, Opportunities, and Lessons from COVID-19 for Global Health Security.

Monkeypox, a rare but significant zoonotic and orthopoxviral disease, has garnered increasing attention due to its potential for human-to-human transmission and its recent resurgence in multiple countries throughout Europe, North America, and Oceania. The disease has emerged as a novel threat to the global health systems that are still striving to recover from the major shocks of the COVID-19 pandemic. The unusual manifestation of the illness highlights a substantial knowledge deficit and necessitates the immediate development of a public health action strategy, considering the epidemiological differences observed in the ongoing outbreak and the appearance of cases in non-endemic nations. This literature review aims to synthesize existing knowledge on monkeypox, encompassing its historical context, etiology, epidemiology, surveillance, prevention, transmission, clinical presentation, diagnosis, treatments, and recent outbreak. Particular attention is given to both advances and gaps in our understanding of monkeypox, and we point toward future directions for research and intervention efforts as pertains to vaccine development and distribution. Lastly, we will also review the recent outbreak through a sociopolitical lens as relates to decision-making strategies, especially given the lessons learned from COVID-19.

Mesorectal nodal metastasis with seminal vesicle invasion in biochemically recurrent prostate cancer.

OBJECTIVES: To determine the prevalence and predictors of mesorectal lymph node (MLN) metastases on prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) in patients with biochemically recurrent prostate cancer (PCa) following radical therapy. MATERIALS AND METHODS: This was a cross-sectional analysis of all PCa patients with biochemical failure following radical prostatectomy or radiotherapy who underwent an 18 F-DCFPyL-PSMA-PET/CT at the Princess Margaret Cancer Centre between December 2018 and February 2021. Lesions with PSMA scores ≥2 were considered positive for PCa involvement (PROMISE classification). Predictors of MLN metastasis were evaluated using univariable and multivariable logistic regression analyses. RESULTS: Our cohort consisted of 686 patients. The primary treatment method was radical prostatectomy and radiotherapy in 528 (77.0%) and 158 patients (23.0%), respectively. The median serum PSA level was 1.15 ng/mL. Overall, 384 patients (56.0%) had a positive scan. Seventy-eight patients (11.3%) had MLN metastasis, with 48/78 (61.5%) having MLN involvement as the only site of metastasis. On multivariable analysis, presence of pT3b disease (odds ratio 4.31, 95% confidence interval 1.44-14.2; P = 0.011) was significantly associated with increased odds of MLN metastasis, whereas surgical factors (radical prostatectomy vs radiotherapy; performance/extent of pelvic nodal dissection), surgical margin positivity, and Gleason Grade were not. CONCLUSIONS: In this study, 11.3% of PCa patients with biochemical failure had MLN metastasis on 18 F-DCFPyL-PET/CT. pT3b disease was associated with 4.31-fold significantly increased odds of MLN metastasis. These findings suggest alternate drainage routes for PCa cells, either via alternate lymphatic drainage from the seminal vesicles themselves or secondary to direct extension from posteriorly located tumours invading the seminal vesicles.

Lymphotropic Pattern of Prostate-specific Membrane Antigen-detected Metastases Among Biochemically Recurrent Radical Prostatectomy Patients with Cribriform Disease.

BACKGROUND: Cribriform morphology portends worse oncologic outcomes, and has unique cellular intrinsic pathway alterations and tumor microenvironments that may impact metastatic spread patterns. OBJECTIVE: To determine whether the presence of cribriform morphology in prostatectomy specimens of patients with biochemical recurrence after radical prostatectomy (RP) is associated with the presence of metastasis on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and a distinct pattern of spread. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional analysis was conducted of all prostate cancer patients with biochemical recurrence after RP undergoing 18F-DCFPyL-PET/CT between December 2018 and February 2021 at the Princess Margaret Cancer Centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were presence of any metastasis in the overall cohort and lymphatic versus bone/visceral metastases among patients with metastatic disease. The associations between the presence of intraductal (IDC) and/or invasive cribriform (ICC) carcinoma on the RP specimen and study outcomes were evaluated using logistic regression analyses. RESULTS AND LIMITATIONS: The cohort included 176 patients. IDC and ICC were observed in 77 (43.8%) and 80 (45.5%) RP specimens, respectively. The median time from RP to PSMA-PET/CT was 5.0 yr. The median serum prostate-specific antigen level at PSMA-PET/CT was 1.12 ng/ml. Overall, metastasis was observed in 77 patients, of whom 58 were had lymphatic-only metastasis. On a multivariable analysis, presence of IDC on RP was associated with increased odds of overall metastasis (odds ratio [OR]: 2.17; 95% confidence interval [CI]: 1.07-4.45; p = 0.033). Presence of ICC on RP was associated with significantly increased odds of lymphatic versus bone/visceral metastases (OR: 3.13; 95% CI: 1.09-21.7; p = 0.004). CONCLUSIONS: Presence of cribriform morphology on RP specimens of patients with biochemical failure after RP is associated with increased odds of PSMA-PET/CT-detected metastases with a lymphatic predominant pattern of spread. These findings have implications for the design and evaluation of post-RP salvage therapies. PATIENT SUMMARY: We found that microscopic cribriform appearance correlates with disease spread on imaging in prostate cancer patients with recurrence and has a predilection for spread to lymph nodes, as opposed to bone or visceral organs.

Interactome of Long Non-Coding RNAs: Transcriptomic Expression Patterns and Shaping Cancer Cell Phenotypes.

RNA biology has gained extensive recognition in the last two decades due to the identification of novel transcriptomic elements and molecular functions. Cancer arises, in part, due to the accumulation of mutations that greatly contribute to genomic instability. However, the identification of differential gene expression patterns of wild-type loci has exceeded the boundaries of mutational study and has significantly contributed to the identification of molecular mechanisms that drive carcinogenic transformation. Non-coding RNA molecules have provided a novel avenue of exploration, providing additional routes for evaluating genomic and epigenomic regulation. Of particular focus, long non-coding RNA molecule expression has been demonstrated to govern and direct cellular activity, thus evidencing a correlation between aberrant long non-coding RNA expression and the pathological transformation of cells. lncRNA classification, structure, function, and therapeutic utilization have expanded cancer studies and molecular targeting, and understanding the lncRNA interactome aids in defining the unique transcriptomic signatures of cancer cell phenotypes.

Androgen Receptor Activation Induces Senescence in Thyroid Cancer Cells.

Thyroid cancer (TC) is the most common endocrine malignancy, with an approximately three-fold higher incidence in women. TCGA data indicate that androgen receptor (AR) RNA is significantly downregulated in PTC. In this study, AR-expressing 8505C (anaplastic TC) (84E7) and K1 (papillary TC) cells experienced an 80% decrease in proliferation over 6 days of exposure to physiological levels of 5α-dihydrotestosterone (DHT). In 84E7, continuous AR activation resulted in G1 growth arrest, accompanied by a flattened, vacuolized cell morphology, with enlargement of the cell and the nuclear area, which is indicative of senescence; this was substantiated by an increase in senescence-associated ß-galactosidase activity, total RNA and protein content, and reactive oxygen species. Additionally, the expression of tumor suppressor proteins p16, p21, and p27 was significantly increased. A non-inflammatory senescence-associated secretory profile was induced, significantly decreasing inflammatory cytokines and chemokines such as IL-6, IL-8, TNF, RANTES, and MCP-1; this is consistent with the lower incidence of thyroid inflammation and cancer in men. Migration increased six-fold, which is consistent with the clinical observation of increased lymph node metastasis in men. Proteolytic invasion potential was not significantly altered, which is consistent with unchanged MMP/TIMP expression. Our studies provide evidence that the induction of senescence is a novel function of AR activation in thyroid cancer cells, and may underlie the protective role of AR activation in the decreased incidence of TC in men.

Molecular Docking and Network Pharmacology Interaction Analysis of Gingko Biloba (EGB761) Extract with Dual Target Inhibitory Mechanism in Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the most common type of neurodegenerative dementia affecting people in their later years of life. The AD prevalence rate has significantly increased due to a lack of early detection technology and low therapeutic efficacy. Despite recent scientific advances, some aspects of AD pathological targets still require special attention. Certain traditionally consumed phytocompounds have been used for thousands of years to treat such pathologies. The standard extract of Gingko biloba (EGB761) is a combination of 13 macro phyto-compounds and various other micro phytocompounds that have shown greater therapeutic potential against the pathology of AD. OBJECTIVE: Strong physiological evidence of cognitive health preservation has been observed in elderly people who keep an active lifestyle. According to some theories, consuming certain medicinal extracts helps build cognitive reserve. We outline the research employing EGB761 as a dual target for AD. METHODS: This study investigates various inhibitory targets against AD using computational approaches such as molecular docking, network pharmacology, ADMET (full form), and bioactivity prediction of the selected compounds. RESULTS: After interaction studies were done for all the phytoconstituents of EGB761, it was concluded that all four of the phytocompounds (kaempferol, isorhamnetin, quercetin, and ginkgotoxin) showed the maximum inhibitory activity against acetylcholinesterase (AChE) and GSK3ß. CONCLUSION: The highly active phytocompounds of EGB761, especially quercetin, kaempferol, and isorhamnetin, have better activity against AChE and GSK3ß than its reported synthetic drug, according to molecular docking and network pharmacology research. These compounds may act on multiple targets in the protein network of AD. The AChE theory was primarily responsible for EGB761's therapeutic efficacy in treating AD.

Recent Updates on Corticosteroid-Induced Neuropsychiatric Disorders and Theranostic Advancements through Gene Editing Tools.

The vast use of corticosteroids (CCSs) globally has led to an increase in CCS-induced neuropsychiatric disorders (NPDs), a very common manifestation in patients after CCS consumption. These neuropsychiatric disorders range from depression, insomnia, and bipolar disorders to panic attacks, overt psychosis, and many other cognitive changes in such subjects. Though their therapeutic importance in treating and improving many clinical symptoms overrides the complications that arise after their consumption, still, there has been an alarming rise in NPD cases in recent years, and they are seen as the greatest public health challenge globally; therefore, these potential side effects cannot be ignored. It has also been observed that many of the neuronal functional activities are regulated and controlled by genomic variants with epigenetic factors (DNA methylation, non-coding RNA, and histone modeling, etc.), and any alterations in these regulatory mechanisms affect normal cerebral development and functioning. This study explores a general overview of emerging concerns of CCS-induced NPDs, the effective molecular biology approaches that can revitalize NPD therapy in an extremely specialized, reliable, and effective manner, and the possible gene-editing-based therapeutic strategies to either prevent or cure NPDs in the future.

Age related differences in primary testicular lymphoma: A population based cohort study.

INTRODUCTION: Primary testicular non-Hodgkin's lymphoma (PTL) is a very rare disease, comprising 1% of all non-Hodgkin's lymphoma and <5% of all cases of testicular tumors. With a median age at diagnosis of 67 years, PTL is the most common testicular malignancy in men aged >60 years. There is limited published data on PTL incidence and outcomes in younger patients. The aim of this study is to compare the clinical parameters and survival outcomes between the patients older and younger than 50. METHODS: The SEER database was queried for all patients diagnosed with PTL between 1983 and 2017. Data collected consisted of demographic, and clinical parameters, including staging, pathological assessments, and survival data. Patients were stratified according to their age and compared. RESULTS: There was a total of 1,581 patients diagnosed with PTL between the year 2000 and 2017, of whom 215 (13.6%) were younger than 50 years old. The median age at diagnosis was 41 (interquartile range [IQR] 1-50), and 72 (IQR 51-95) years old for patients ≤50 and patients > 50 years of age, respectively. Comparison of younger and older patients detected similarities in disease laterality (92% vs. 94%, P = 0.38) and Ann Arbor stage I to II at diagnosis (76% vs. 75%, P = 0.59). The most common diffuse large B-cell lymphoma (DLBCL) subtype was more common in older patients (61% vs. 87%, P < 0.001). Radical orchiectomy (71% vs. 79%, P = 0.004) and radiation treatment (40% vs. 37%, P = 0.49) rates were comparable between both groups. However, a higher proportion of younger patients underwent chemotherapy (83% vs. 72%, P < 0.001). Patients ≤50 and >50 years old had a hazard ratio (HR) of 0.63 (95% CI: 0.57-0.71) and 0.34 (95% CI: 0.31-0.37), respectively, for 10-year OS with a median survival time for patients >50 of 5.75 years (95% CI: 5.25-6.33), P < 0.001. Patients ≤50 years old had a HR of 0.33 (95% CI: 0.26-0.40) compared to HR of 0.40 (95% CI: 0.37-0.43) in patients >50 years old for cumulative disease-specific mortality (DSM, P = 0.0204). Age >50 years was associated with worse DSM with a HR of 1.39 (95% CI: 1.05- 1.86, P = 0.024). Ann Arbor stage II and higher was also associated with worse DSM, while undergoing surgery, radiotherapy, and chemotherapy were associated with improved DSM. CONCLUSIONS: PTL is the most common testicular malignancy in men older than 60 years of age, but more than a quarter of the patients are younger than 60 and more than 13% are ≤50 years. Younger patients are more likely to receive chemotherapy and radiation, and overall do better in terms of DSM. Being younger, having a lower Ann Arbor stage and being treated with chemotherapy and radiotherapy increase the chances of survival.

Natural sources and encapsulating materials for probiotics delivery systems: Recent applications and challenges in functional food development.

Probiotics are known as the live microorganisms which upon adequate administration elicit a health beneficial response inside the host by decreasing the luminal pH, eliminating the pathogenic bacteria in the gut as well as producing short chain fatty acids (SCFA). With advancements in research; probiotics have been explored as potential ingredients in foods. However, their use and applications in food industry have been limited due to restrictions of maintaining the viability of probiotic cells and targeting the successful delivery to gut. Encapsulation techniques have significant influence on increasing the viability rates of probiotic cells with the successful delivery of cells to the target site. Moreover, encapsulating techniques also prevent the live cells from harsh physiological conditions of gut. This review discusses several encapsulating techniques as well as materials derived from natural sources and nutraceutical compounds. In addition to this, this paper also comprehensively discusses the factors affecting the probiotics viability and evaluation of successful release and survival of probiotics under simulated gastric, intestinal conditions as well as bile, acid tolerant conditions. Lastly applications and challenges of using encapsulated bacteria in food industry for the development of novel functional foods have also been discussed in detail too. Future studies must include investigating the use of encapsulated bacterial formulations in in-vivo models for effective health beneficial properties as well as exploring the mechanisms behind the successful release of these formulations in gut, hence helping us to understand the encapsulation of probiotic cells in a meticulous manner.

MEG3 Expression Indicates Lymph Node Metastasis and Presence of Cancer-Associated Fibroblasts in Papillary Thyroid Cancer.

Papillary thyroid cancer is the most common endocrine malignancy, occurring at an incidence rate of 12.9 per 100,000 in the US adult population. While the overall 10-year survival of PTC nears 95%, the presence of lymph node metastasis (LNM) or capsular invasion indicates the need for extensive neck dissection with possible adjuvant radioactive iodine therapy. While imaging modalities such as ultrasound and CT are currently in use for the detection of suspicious cervical lymph nodes, their sensitivities for tumor-positive nodes are low. Therefore, advancements in preoperative detection of LNM may optimize the surgical and medical management of patients with thyroid cancer. To this end, we analyzed bulk RNA-sequencing datasets to identify candidate markers highly predictive of LNM. We identified MEG3, a long-noncoding RNA previously described as a tumor suppressor when expressed in malignant cells, as highly associated with LNM tissue. Furthermore, the expression of MEG3 was highly predictive of tumor infiltration with cancer-associated fibroblasts, and single-cell RNA-sequencing data revealed the expression of MEG3 was isolated to cancer-associated fibroblasts (CAFs) in the most aggressive form of thyroid cancers. Our findings suggest that MEG3 expression, specifically in CAFs, is highly associated with LNM and may be a driver of aggressive disease.

The role of prophylactic prostatectomy as a primary prevention strategy in high-risk germline mutation carriers.

PURPOSE OF REVIEW: Men with high-risk germline mutations are at significantly higher risk of developing and dying from prostate cancer. Current screening and treatment paradigms may lead to missed opportunities for cure. Herein we review the current literature on prevention, screening and treatment of these carriers and explore the potential role of prophylactic prostatectomy in primary prevention of prostate cancer mortality. RECENT FINDINGS: Prostate-specific antigen (PSA)-based screening has demonstrated marginal benefits in prostate cancer (PCa) survival and uncertainty remains on its true benefit among high-risk carriers. Recent results indicate that PCa in BRCA 2 carriers occurs at a higher incidence, younger age and progresses more rapidly compared with noncarriers. An intensified screening protocol of MRI and PSA in young carriers demonstrated how using PSA values alone may be insufficient. Current evidence indicates that high-risk carriers have worse survival outcomes after undergoing radical treatment for screening detected disease when compared with noncarriers. SUMMARY: Prophylactic prostatectomy within the context of a clinical trial is a reasonable primary prevention option for discussion with high-risk carriers, especially BRCA2 carriers during the shared decision-making process. Limitations exist in the current strategies of early PSA screening followed by radical treatment in this group.