Effect of exercise on fatigue and depression in breastcancer women undergoing chemotherapy: a systematic review and meta-analysis.

This meta-analysis examined the effectiveness of exercise interventions in reducing fatigue and depression among women undergoing chemotherapy for breast cancer. The study followed PRISMA guidelines and analysed seven randomized controlled trials between 2016 and 2022. The results showed that exercise can substantially reduce fatigue levels (MD: -0.40, CI: -0.66, -0.14, P: 0.003), a common side effect of chemotherapy. Although depression did not significantly change (MD: -0.39, CI: -0.98, 0.20, P: 0.19), this study highlights the positive impact of exercise on mental health outcomes. The control group also experienced decreased quality of life (MD: 0.18, CI: 0.01-0.35, P: 0.03), emphasizing the importance of incorporating exercise interventions to improve overall well-being during breast cancer treatment. In addition to primary outcomes, the study revealed that exercise positively affected secondary aspects such as cognitive fatigue, social function, physical function, constipation, and dyspnoea.

Concordance With Screening and Treatment Guidelines for Chronic Kidney Disease in Type 2 Diabetes.

Importance: Chronic kidney disease (CKD) is an often-asymptomatic complication of type 2 diabetes (T2D) that requires annual screening to diagnose. Patient-level factors linked to inadequate screening and treatment can inform implementation strategies to facilitate guideline-recommended CKD care. Objective: To identify risk factors for nonconcordance with guideline-recommended CKD screening and treatment in patients with T2D. Design, Setting, and Participants: This retrospective cohort study was performed at 20 health care systems contributing data to the US National Patient-Centered Clinical Research Network. To evaluate concordance with CKD screening guidelines, adults with an outpatient clinician visit linked to T2D diagnosis between January 1, 2015, and December 31, 2020, and without known CKD were included. A separate analysis reviewed prescription of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in adults with CKD (estimated glomerular filtration rate [eGFR] of 30-90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio [UACR] of 200-5000 mg/g) and an outpatient clinician visit for T2D between October 1, 2019, and December 31, 2020. Data were analyzed from July 8, 2022, through June 22, 2023. Exposures: Demographics, lifestyle factors, comorbidities, medications, and laboratory results. Main Outcomes and Measures: Screening required measurement of creatinine levels and UACR within 15 months of the index visit. Treatment reflected prescription of ACEIs or ARBs and SGLT2 inhibitors within 12 months before or 6 months following the index visit. Results: Concordance with CKD screening guidelines was assessed in 316 234 adults (median age, 59 [IQR, 50-67] years), of whom 51.5% were women; 21.7%, Black; 10.3%, Hispanic; and 67.6%, White. Only 24.9% received creatinine and UACR screening, 56.5% received 1 screening measurement, and 18.6% received neither. Hispanic ethnicity was associated with lack of screening (relative risk [RR], 1.16 [95% CI, 1.14-1.18]). In contrast, heart failure, peripheral arterial disease, and hypertension were associated with a lower risk of nonconcordance. In 4215 patients with CKD and albuminuria, 3288 (78.0%) received an ACEI or ARB; 194 (4.6%), an SGLT2 inhibitor; and 885 (21.0%), neither therapy. Peripheral arterial disease and lower eGFR were associated with lack of CKD treatment, while diuretic or statin prescription and hypertension were associated with treatment. Conclusions and Relevance: In this cohort study of patients with T2D, fewer than one-quarter received recommended CKD screening. In patients with CKD and albuminuria, 21.0% did not receive an SGLT2 inhibitor or an ACEI or an ARB, despite compelling indications. Patient-level factors may inform implementation strategies to improve CKD screening and treatment in people with T2D.

The multifaceted functions of long non-coding RNA HOTAIR in neuropathologies and its potential as a prognostic marker and therapeutic biotarget.

Long non-coding RNAs (lncRNAs) are progressively being perceived as prominent molecular agents controlling multiple aspects of neuronal (patho)physiology. Amongst these is the HOX transcript antisense intergenic RNA, often abbreviated as HOTAIR. HOTAIR epigenetically regulates its target genes via its interaction with two different chromatin-modifying agents; histone methyltransferase polycomb-repressive complex 2 and histone demethylase lysine-specific demethylase 1. Parenthetically, HOTAIR elicits trans-acting sponging function against multiple micro-RNA species. Oncological research studies have confirmed the pathogenic functions of HOTAIR in multiple cancer types, such as gliomas and proposed it as a pro-oncological lncRNA. In fact, its expression has been suggested to be a predictor of the severity/grade of gliomas, and as a prognostic biomarker. Moreover, a propound influence of HOTAIR in other aspects of brain heath and disease states is just beginning to be unravelled. The objective of this review is to recapitulate all the relevant data pertaining to the regulatory roles of HOTAIR in neuronal (patho)physiology. To this end, we discuss the pathogenic mechanisms of HOTAIR in multiple neuronal diseases, such as neurodegeneration, traumatic brain injury and neuropsychiatric disorders. Finally, we also summarize the results from the studies incriminating HOTAIR in the pathogeneses of gliomas and other brain cancers. Implications of HOTAIR serving as a suitable therapeutic target in neuropathologies are also discussed.

Effect of Microwave-Based Dry Blanching on Drying of Potato Slices: A Comparative Study.

Microwave (MW)-based dry blanching can inactivate oxidative enzymes like peroxidase (POD) and polyphenol oxidase (PPO) rapidly and retain a higher amount of water-soluble nutrients, like ascorbic acid. This study compared the MW-based dry blanching of potato slices of various thicknesses (5, 8, and 10 mm) with conventional methods (water and steam blanching). The time required for water and steam blanching was longer than that required for MW blanching. Potato slices of 10 mm thickness required a longer blanching duration compared with slices of a lesser thickness (5 and 8 mm). The MW-blanched samples (77.37-83.5%) retained a higher content of ascorbic acid, followed by steam-blanched (69.15-74.92%) and water-blanched (67.18-71.54%) samples. The Page, modified Page, Midilli-Kucuk, and Hii, Law, and Cloke models predicted the thin layer drying of potato slices (5 mm thickness) better with a higher coefficient of determination values (0.9607-0.9976) compared to Fick's and Exponential models (0.8942-0.9444).

Breaking Bad: Spontaneous Rupture of Incisional Hernia.

Spontaneous bowel evisceration from a ruptured, long-standing abdominal wall hernia is a very rare complication with significant morbidity and mortality, usually occurring in incisional or recurrent groin hernias. In this case report, we elucidate an unexpected scenario of spontaneous incisional hernia rupture leading to bowel evisceration, detailing the clinical presentation, diagnostic workup, and surgical management. By highlighting this rare complication, we emphasise the significance of vigilance in monitoring hernia patients and the necessity of expedited surgical intervention to prevent complications, optimise outcomes, and minimise morbidity.

Roles of HOTAIR Long Non-coding RNA in Gliomas and Other CNS Disorders.

HOX transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA (lncRNA) which is increasingly being perceived as a tremendous molecular mediator of brain pathophysiology at multiple levels. Epigenetic regulation of target gene expression carried out by HOTAIR is thorough modulation of chromatin modifiers; histone methyltransferase polycomb repressive complex 2 (PRC2) and histone demethylase lysine-specific demethylase 1 (LSD1). Incidentally, HOTAIR was the first lncRNA shown to elicit sponging of specific microRNA (miRNA or miR) species in a trans-acting manner. It has been extensively studied in various cancers, including gliomas and is regarded as a prominent pro-tumorigenic and pro-oncogenic lncRNA. Indeed, the expression of HOTAIR may serve as glioma grade predictor and prognostic biomarker. The objective of this timely review is not only to outline the multifaceted pathogenic roles of HOTAIR in the development and pathophysiology of gliomas and brain cancers, but also to delineate the research findings implicating it as a critical regulator of overall brain pathophysiology. While the major focus is on neuro-oncology, wherein HOTAIR represents a particularly potent underlying pathogenic player and a suitable therapeutic target, mechanisms underlying the regulatory actions of HOTAIR in neurodegeneration, traumatic, hypoxic and ischemic brain injuries, and neuropsychiatric disorders are also presented.

Health Status in Heart Failure and Cancer: Analysis of the Medicare Health Outcomes Survey 2016-2020.

BACKGROUND: People with heart failure (HF) and cancer experience impaired physical and mental health status. However, health-related quality of life (HRQOL) has not been directly compared between these conditions in a contemporary population of older people. OBJECTIVES: The authors sought to compare HRQOL in people with HF vs those with lung, colorectal, breast, and prostate cancers. METHODS: The authors performed a pooled analysis of Medicare Health Outcomes Survey data from 2016 to 2020 in participants ≥65 years of age with a self-reported history of HF or active treatment for lung, colon, breast, or prostate cancer. They used the Veterans RAND-12 physical component score (PCS) and mental component score (MCS), which range from 0-100 with a mean score of 50 (based on the U.S. general population) and an SD of 10. The authors used pairwise Student's t-tests to evaluate for differences in PCS and MCS between groups. RESULTS: Among participants with HF (n = 71,025; 54% female, 16% Black), mean PCS was 29.5 and mean MCS 47.9. Mean PCS was lower in people with HF compared with lung (31.2; n = 4,165), colorectal (35.6; n = 4,270), breast (37.7; n = 14,542), and prostate (39.6; n = 17,670) cancer (all P < 0.001). Participants with HF had a significantly lower mean MCS than those with lung (31.2), colon (50.0), breast (52.0), and prostate (53.0) cancer (all P < 0.001). CONCLUSIONS: People with HF experience worse HRQOL than those with cancer actively receiving treatment. The pervasiveness of low HRQOL in HF underscores the need to implement evidence-based interventions that target physical and mental health status and scale multidisciplinary clinics.

Synchronized wearables for the detection of haemodynamic states via electrocardiography and multispectral photoplethysmography.

Cardiovascular health is typically monitored by measuring blood pressure. Here we describe a wireless on-skin system consisting of synchronized sensors for chest electrocardiography and peripheral multispectral photoplethysmography for the continuous monitoring of metrics related to vascular resistance, cardiac output and blood-pressure regulation. We used data from the sensors to train a support-vector-machine model for the classification of haemodynamic states (resulting from exposure to heat or cold, physical exercise, breath holding, performing the Valsalva manoeuvre or from vasopressor administration during post-operative hypotension) that independently affect blood pressure, cardiac output and vascular resistance. The model classified the haemodynamic states on the basis of an unseen subset of sensor data for 10 healthy individuals, 20 patients with hypertension undergoing haemodynamic stimuli and 15 patients recovering from cardiac surgery, with an average precision of 0.878 and an overall area under the receiver operating characteristic curve of 0.958. The multinodal sensor system may provide clinically actionable insights into haemodynamic states for use in the management of cardiovascular disease.

Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Patients Treated With P2Y12 Inhibitors.

Background The ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) was a large, pragmatic, randomized controlled trial that found no difference between high- versus low-dose aspirin for secondary prevention of atherosclerotic cardiovascular disease. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. Methods and Results Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). The primary effectiveness end point was a composite of death, myocardial infarction, or stroke; and the primary safety end point was major bleeding requiring blood transfusions. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non-P2Y12 groups. Of 13 815 (91.6%) participants with available data, 3051 (22.1%) were receiving clopidogrel (2849 [93.4%]) or prasugrel (203 [6.7%]) at baseline. P2Y12 inhibitor use was associated with higher risk of the primary effectiveness end point (10.86% versus 6.31%; adjusted hazard ratio [HR], 1.40 [95% CI, 1.22-1.62]) but was not associated with bleeding (0.95% versus 0.53%; adjusted HR, 1.42 [95% CI, 0.91-2.22]). We found no interaction in the relative effectiveness and safety of high- versus low-dose aspirin by P2Y12 inhibitor use. Overall, dose switching or discontinuation was more common in the high-dose compared with low-dose aspirin group, but the pattern was not modified by P2Y12 inhibitor use. Conclusions In this prespecified analysis of ADAPTABLE, we found that the relative effectiveness and safety of high- versus low-dose aspirin was not modified by baseline P2Y12 inhibitor use. Registration https://www.clinical.trials.gov. Unique identifier: NCT02697916.

"I Just Wanted Nothing More Than to Get in a Real Shower": Patient Experience of the Inpatient Wait for a Heart Transplant.

BACKGROUND: Patients waiting for heart transplant may be hospitalized for weeks to months before undergoing transplantation. This high-stress period is further complicated by restrictions of daily privileges including diet, rooming, access to the outdoors, and hygiene (eg, limited in ability to shower). However, there is a paucity of research on the experience of this waiting period. We sought to describe the inpatient experience among patients awaiting heart transplantation and to better understand the needs of inpatients waiting for heart transplant. METHODS AND RESULTS: We conducted in-depth, semistructured phone interviews with a purposeful sample of patients who received a heart transplant in the past 10 years and waited in the hospital for at least 2 weeks before surgery. Using the prior literature, the lived experience of the lead author, and input from qualitative experts, we developed an interview guide. Interviews were recorded, transcribed, and analyzed in an iterative process until theoretical saturation was achieved. A 3-person coding team identified, discussed, and reconciled emergent themes. We conducted interviews with 15 patients. Overarching themes included food, hygiene, relationship with health care professionals, living environment, and stressors. Patients reported that strong bonds were formed between the patients and the staff, and the overwhelming majority only had positive comments about these relationships. However, many expressed negative comments about the experience of the food and limitations in personal hygiene. Other stressors included the unknown length of the waiting period, lack of communication about position on the transplant list, worry about family, and concerns that their life must be saved by the death of another. Many participants described that they would benefit from more interaction with recent heart transplant recipients. CONCLUSIONS: Hospitals and care units have the opportunity to make small changes that could greatly benefit the experience of waiting for a heart transplant, as well as the experience of hospitalization more generally.

Racial and Ethnic Differences in Cardiac Surveillance Evaluation of Patients Treated With Anthracycline-Based Chemotherapy.

Background Anthracyclines remain a key treatment for many malignancies but can increase the risk of heart failure or cardiomyopathy. Specific guidelines recommend echocardiography and serum cardiac biomarkers such as BNP (B-type natriuretic peptide) or NT-proBNP (N-terminal proBNP) evaluation before and 6 to 12 months after treatment. Our objective was to evaluate associations between racial and ethnic groups in cardiac surveillance of survivors of cancer after exposure to anthracyclines. Methods and Results Adult patients in the OneFlorida Consortium without prior cardiovascular disease who received at least 2 cycles of anthracyclines were included in the analysis. Multivariable logistic regression was performed to estimate the odds ratios (ORs) and 95% CIs for receiving cardiac surveillance at baseline before anthracycline therapy, 6 months after, and 12 months after anthracycline exposure among different racial and ethnic groups. Among the entire cohort of 5430 patients, 63.4% had a baseline echocardiogram, with 22.3% receiving an echocardiogram at 6 months and 25% at 12 months. Non-Hispanic Black (NHB) patients had a lower likelihood of receiving a baseline echocardiogram than Non-Hispanic White (NHW) patients (OR, 0.75 [95% CI, 0.63-0.88]; P=0.0006) or any baseline cardiac surveillance (OR, 0.76 [95% CI, 0.64-0.89]; P=0.001). Compared with NHW patients, Hispanic patients received significantly less cardiac surveillance at the 6-month (OR, 0.84 [95% CI, 0.72-0.98]; P=0.03) and 12-month (OR, 0.85 [95% CI, 0.74-0.98]; P=0.03) time points, respectively. Conclusions There were significant racial and ethnic differences in cardiac surveillance among survivors of cancer at baseline and following anthracycline-based treatment in NHB and Hispanic cohorts. Health care providers need to be cognizant of these social inequities and initiate efforts to ensure recommended cardiac surveillance occurs following anthracyclines.

Molecular mechanisms of neuroprotective offerings by rosmarinic acid against neurodegenerative and other CNS pathologies.

Rosmarinic acid (RA) is a natural phenolic compound present in culinary herbs of the Boraginaceae, Lamiaceae/Labiatae, and Nepetoideae families. While the medicinal applications of these plants have been known for ages, RA has only been relatively recently established as an effective ameliorative agent against various disorders including cardiac diseases, cancer, and neuropathologies. In particular, several studies have confirmed the neuroprotective potential of RA in multiple cellular and animal models, as well as in clinical studies. The neuroprotective effects mediated by RA stem from its multimodal actions on a plethora of cellular and molecular pathways; including oxidative, bioenergetic, neuroinflammatory, and synaptic signaling. In recent years, RA has garnered tremendous interest as an ideal therapeutic candidate for treating neurodegenerative diseases. This review first briefly discusses the pharmacokinetics of RA and then proceeds to detail the neuroprotective mechanisms of RA at the molecular levels. Finally, the authors focus on the ameliorative potential of RA against several central nervous system (CNS) disorders, ranging from neuropsychological stress and epilepsy to neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Parkinson's disease, Lewy body dementia, and amyotrophic lateral sclerosis.

Diet as a modifiable factor in tumorigenesis: Focus on microbiome-derived bile acid metabolites and short-chain fatty acids.

Several lines of evidences have implicated the resident microbiome as a key factor in the modulation of host physiology and pathophysiology; including the resistance to cancers. Gut microbiome heavily influences host lipid homeostasis by their modulatory effects on the metabolism of bile acids (BAs). Microbiota-derived BA metabolites such as deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) are implicated in the pathogeneses of various cancer types. The pathogenic mechanisms are multimodal in nature, with widespread influences on the host immunes system, cell survival and growth signalling and DNA damage. On the other hand, short-chain fatty acids (SCFAs) produced by the resident microbial activity on indigestible dietary fibres as well as during intermittent fasting regimens (such as the Ramazan fasting) elicit upregulation of the beneficial anti-inflammatory and anticancer pathways in the host. The present review first provides a brief overview of the molecular mechanisms of microbiota-derived lipid metabolites in promotion of tumour development. The authors then discuss the potential of diet as a therapeutic route for beneficial alteration of microbiota and the consequent changes in the production of SCFAs, particularly butyrate, in relation to the cancer prevention and treatment.

Mortality Prediction in Patients With or Without Heart Failure Using a Machine Learning Model.

Background: Most risk prediction models are confined to specific medical conditions, thus limiting their application to general medical populations. Objectives: The MARKER-HF (Machine learning Assessment of RisK and EaRly mortality in Heart Failure) risk model was developed in heart failure (HF) patients. We assessed the ability of MARKER-HF to predict 1-year mortality in a large community-based hospital registry database including patients with and without HF. Methods: This study included 41,749 consecutive patients who underwent echocardiography in a tertiary referral hospital (4,640 patients with and 37,109 without HF). Patients without HF were further subdivided into those with (n = 22,946) and without cardiovascular disease (n = 14,163) and also into cohorts based on recent acute coronary syndrome or history of atrial fibrillation, chronic obstructive pulmonary disease, chronic kidney disease, diabetes mellitus, hypertension, or malignancy. Results: The median age of the 41,749 patients was 65 years, and 56.2% were male. The receiver operated area under the curves for MARKER-HF prediction of 1-year mortality of patients with HF was 0.729 (95% CI: 0.706-0.752) and for patients without HF was 0.770 (95% CI: 0.760-0.780). MARKER-HF prediction of mortality was consistent across subgroups with and without cardiovascular disease and in patients diagnosed with acute coronary syndrome, atrial fibrillation, chronic obstructive pulmonary disease, chronic kidney disease, diabetes mellitus, or hypertension. Patients with malignancy demonstrated higher mortality at a given MARKER-HF score than did patients in the other groups. Conclusions: MARKER-HF predicts mortality for patients with HF as well as for patients suffering from a variety of diseases.

Smart Nanoformulations for Brain Cancer Theranostics: Challenges and Promises.

Despite their low prevalence, brain tumors are among the most lethal cancers. They are extremely difficult to diagnose, monitor and treat. Conventional anti-cancer strategies such as radio- and chemotherapy have largely failed, and to date, the development of even a single effective therapeutic strategy against central nervous system (CNS) tumors has remained elusive. There are several factors responsible for this. Brain cancers are a heterogeneous group of diseases with variable origins, biochemical properties and degrees of invasiveness. High-grade gliomas are amongst the most metastatic and invasive cancers, which is another reason for therapeutic failure in their case. Moreover, crossing the blood brain and the blood brain tumor barriers has been a significant hindrance in the development of efficient CNS therapeutics. Cancer nanomedicine, which encompasses the application of nanotechnology for diagnosis, monitoring and therapy of cancers, is a rapidly evolving field of translational medicine. Nanoformulations, because of their extreme versatility and manipulative potential, are emerging candidates for tumor targeting, penetration and treatment in the brain. Moreover, suitable nanocarriers can be commissioned for theranostics, a combinatorial personalized approach for simultaneous imaging and therapy. This review first details the recent advances in novel bioengineering techniques that provide promising avenues for circumventing the hurdles of delivering the diagnostic/therapeutic agent to the CNS. The authors then describe in detail the tremendous potential of utilizing nanotechnology, particularly nano-theranostics for brain cancer imaging and therapy, and outline the different categories of recently developed next-generation smart nanoformulations that have exceptional potential for making a breakthrough in clinical neuro-oncology therapeutics.

Direct Comparison of Diagnostic Accuracy of Fast Kilovoltage Switching Dual-Energy Computed Tomography and Magnetic Resonance Imaging for Detection of Enhancement in Renal Masses.

PURPOSE: The aim of the study was to compare diagnostic accuracy of dual-energy computed tomography (DECT) and magnetic resonance imaging (MRI) to detect enhancement in renal masses. METHODS: Adults renal masses of 10 mm or greater with both fast kilovoltage potential switching DECT and contrast-enhanced MRI performed within 12 months were retrospectively included. Two blinded radiologists independently evaluated for enhancement subjectively (5-point Likert scales) and quantitatively (signal intensity ratio ≥15% for MRI, iodine concentration ≥1.2 or ≥2.0 mg/mL for DECT). Per-lesion diagnostic accuracy, with histologic reference standard for solid masses, was expressed as the area under the receiver operator curve (AUC) for each index test. Differences were evaluated for statistical significance using the DeLong test. RESULTS: We included 24 patients with 41 masses: 17 solid renal masses and 24 Bosniak 1 or 2 cysts. There was no significant difference in diagnostic accuracy comparing subjective enhancement by MRI and using iodine overlay DECT for reader 1 (AUC 0.99 vs 0.99, P = 0.38) or reader 2 (AUC 1.00 vs 0.94, P = 0.12) Interobserver agreement was κ = 0.61 for DECT and κ = 0.71 for MRI. There was no significant difference either in accuracy between quantitative assessment using signal intensity ratio or iodine concentration for reader 1 (AUC 0.94 vs 0.94, P = 0.88) or reader 2 (AUC 0.97 vs 0.92, P = 0.16). False-negative results in both subjective and quantitative assessment were nearly exclusively seen in papillary renal cell carcinoma, occurring with both DECT and MRI. CONCLUSIONS: We detected no significant differences in accuracy for detecting enhancement in renal masses comparing MRI and DECT. Our results require further investigation in larger sample sizes, but suggest that DECT may be comparable to MRI for detection of enhancement in renal masses.

Bioplatforms in liquid biopsy: advances in the techniques for isolation, characterization and clinical applications.

Tissue biopsy analysis has conventionally been the gold standard for cancer prognosis, diagnosis and prediction of responses/resistances to treatments. The existing biopsy procedures used in clinical practice are, however, invasive, painful and often associated with pitfalls like poor recovery of tumor cells and infeasibility for repetition in single patients. To circumvent these limitations, alternative non-invasive, rapid and economical, yet sturdy, consistent and dependable, biopsy techniques are required. Liquid biopsy is an emerging technology that fulfills these criteria and potentially much more in terms of subject-specific real-time monitoring of cancer progression, determination of tumor heterogeneity and treatment responses, and specific identification of the type and stages of cancers. The present review first briefly revisits the state-of-the-art technique of liquid biopsy and then proceeds to address in detail, the advances in the potential clinical applications of four major biological agencies present in liquid biopsy samples (circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes and tumor-educated platelets (TEPs)). Finally, the authors conclude with the limitations that need to be addressed in order for liquid biopsy to effectively replace the conventional invasive biopsy methods in the clinical settings.

Mycobacterium tuberculosis Methyltransferase Rv1515c Can Suppress Host Defense Mechanisms by Modulating Immune Functions Utilizing a Multipronged Mechanism.

Mycobacterium tuberculosis (M. tb) gene Rv1515c encodes a conserved hypothetical protein exclusively present within organisms of MTB complex and absent in non-pathogenic mycobacteria. In silico analysis revealed that Rv1515c contain S-adenosylmethionine binding site and methyltransferase domain. The DNA binding and DNA methyltransferase activity of Rv1515c was confirmed in vitro. Knock-in of Rv1515c in a model mycobacteria M. smegmatis (M. s_Rv1515c) resulted in remarkable physiological and morphological changes and conferred the recombinant strain with an ability to adapt to various stress conditions, including resistance to TB drugs. M. s_Rv1515c was phagocytosed at a greater rate and displayed extended intra-macrophage survival in vitro. Recombinant M. s_Rv1515c contributed to enhanced virulence by suppressing the host defense mechanisms including RNS and ROS production, and apoptotic clearance. M. s_Rv1515c, while suppressing the phagolysosomal maturation, modulated pro-inflammatory cytokine production and also inhibited antigen presentation by downregulating the expression of MHC-I/MHC-II and co-stimulatory signals CD80 and CD86. Mice infected with M. s_Rv1515c produced more Treg cells than vector control (M. s_Vc) and exhibited reduced effector T cell responses, along-with reduced expression of macrophage activation markers in the chronic phase of infection. M. s_Rv1515c was able to survive in the major organs of mice up to 7 weeks post-infection. These results indicate a crucial role of Rv1515c in M. tb pathogenesis.

Macrophage: A Cell With Many Faces and Functions in Tuberculosis.

Mycobacterium tuberculosis (Mtb) is the causative agent of human tuberculosis (TB) which primarily infects the macrophages. Nearly a quarter of the world's population is infected latently by Mtb. Only around 5%-10% of those infected develop active TB disease, particularly during suppressed host immune conditions or comorbidity such as HIV, hinting toward the heterogeneity of Mtb infection. The aerosolized Mtb first reaches the lungs, and the resident alveolar macrophages (AMs) are among the first cells to encounter the Mtb infection. Evidence suggests that early clearance of Mtb infection is associated with robust innate immune responses in resident macrophages. In addition to lung-resident macrophage subsets, the recruited monocytes and monocyte-derived macrophages (MDMs) have been suggested to have a protective role during Mtb infection. Mtb, by virtue of its unique cell surface lipids and secreted protein effectors, can evade killing by the innate immune cells and preferentially establish a niche within the AMs. Continuous efforts to delineate the determinants of host defense mechanisms have brought to the center stage the crucial role of macrophage phenotypical variations for functional adaptations in TB. The morphological and functional heterogeneity and plasticity of the macrophages aid in confining the dissemination of Mtb. However, during a suppressed or hyperactivated immune state, the Mtb virulence factors can affect macrophage homeostasis which may skew to favor pathogen growth, causing active TB. This mini-review is aimed at summarizing the interplay of Mtb pathomechanisms in the macrophages and the implications of macrophage heterogeneity and plasticity during Mtb infection.

Comparison of 5 Rectal Preparation Strategies for Prostate MRI and Impact on Image Quality.

PURPOSE: To compare 5 different rectal preparation strategies for prostate MRI. METHODS: This 5-arm quality-assurance study evaluated 56 patients per arm (280 patients) including: no preparation, clear-fluids diet (CFD) beginning at 00:00 hours on the day of MRI, Fleet®-enema, enema + CFD, enema + CFD + IV-antispasmodic agent. The study was powered to 0.80 with alpha-error of 0.05. Three blinded radiologists independently evaluated T2-Weighted (T2W) and Diffusion Weighed Imaging (DWI) for: rectal diameter (maximal AP diameter), rectal content (stool, fluid, gas), rectal motion, T2W/DWI image quality, T2W image sharpness and DWI susceptibility artifact using 5-point Likert scales. Overall comparisons were performed using analysis of variance (ANOVA) and Kruskal-Wallis, with pair-wise comparisons using paired t-tests and Wilcoxon sign-rank tests. RESULTS: Rectal diameter and amount of gas were lower in enema compared to non-enema groups (p < 0.001), with smallest diameter and least gas in the enema + CFD + IV-antispasmodic group (p = 0.022-<0.001). T2W image quality and sharpness were highest in the enema + CFD groups (p < 0.001) with no difference comparing enema + CFD with/without IV-antispasmodic (p = 0.064, 0.084). Motion artifact was least in enema + CFD + IV-antispasmodic group compared to all other groups (p < 0.001), followed by the enema + CFD group (p = 0.008-<0.001). DWI image quality was highest (p < 0.001) and DWI susceptibility artifact lowest (p < 0.001) in the enema + CFD groups (p < 0.001) and did not differ comparing enema + CFD with/without anti-spasmodic (p = 0.058-0.202). CONCLUSIONS: Use of enema + clear-fluids diet before prostate MRI yields the highest T2W and DWI image quality with the least DWI artifact. IV-antispasmodic use reduces motion on T2W but does not improve image quality on T2W or DWI, or lessen DWI artifact compared to enema + clear-fluids diet.