Engineered human lymph node stroma model for examining interstitial fluid flow and T cell egress.

The lymph node (LN) performs essential roles in immunosurveillance throughout the body. Developing in vitro models of this key tissue is of great importance to enhancing physiological relevance in immunoengineering. The LN consists of stromal populations and immune cells, which are highly organized and bathed in constant interstitial flow.

Observations of Ramadan fasting in the initial year after bariatric surgery.

Background: Ramadan is considered to be the holiest month of the Islamic religion. Hundreds of millions of Muslims practice the commitments of Ramadan, which include the abstinence from eating and drinking during daylight hours. Although there are exemptions to fasting for medical reasons, there is very limited guidance in terms of the safety of fasting in the postoperative period after bariatric surgery.

Model discovery approach enables noninvasive measurement of intra-tumoral fluid transport in dynamic MRI.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a routine method to noninvasively quantify perfusion dynamics in tissues. The standard practice for analyzing DCE-MRI data is to fit an ordinary differential equation to each voxel. Recent advances in data science provide an opportunity to move beyond existing methods to obtain more accurate measurements of fluid properties.

Demonstration of chemotherapeutic mediated lymphatic changes in meningeal lymphatics in vitro, ex vivo, and in vivo.

Systemic chemotherapeutics target cancer cells but are also known to impact other cells away from the tumor. Questions remain whether systemic chemotherapy crosses the blood-brain barrier and causes inflammation in the periphery that impacts the central nervous system (CNS) downstream. The meningeal lymphatics are a critical component that drain cerebrospinal fluid from the CNS to the cervical lymph nodes for immunosurveillence.

Preoperative and early adjuvant weight loss medications in bariatric surgery patients with body mass index over 60 or suboptimal initial response to surgery.

Background: Few studies have examined the adjuvant use of antiobesity medications with surgery, especially in the pre- and early postoperative periods.

Objective: Evaluate the impact of adjuvant pharmacotherapy on bariatric surgery outcomes.

Setting: University hospital, United States.

Metabolic Syndrome in Adults Receiving Clozapine; The Need for Pharmacist Support.

People who are diagnosed with treatment resistant schizophrenia (TRS) are likely to have clozapine as a therapeutic management option. There is a high prevalence of metabolic syndrome in patients receiving clozapine. To mitigate against this, monitoring of weight, waist circumference, lipid profile, glycated haemoglobin (HbA1c), fasting blood glucose (FBG) and blood pressure (BP) is recommended.

Evolutionary Analysis of TCGA Data Using Over- and Under- Mutated Genes Identify Key Molecular Pathways and Cellular Functions in Lung Cancer Subtypes.

We identify critical conserved and mutated genes through a theoretical model linking a gene’s fitness contribution to its observed mutational frequency in a clinical cohort. “Passenger” gene mutations do not alter fitness and have mutational frequencies determined by gene size and the mutation rate. Driver mutations, which increase fitness (and proliferation), are observed more frequently than expected.

A Phase 1b Adaptive Androgen Deprivation Therapy Trial in Metastatic Castration Sensitive Prostate Cancer.

Background: We hypothesize that cancer survival can be improved through adapting treatment strategies to cancer evolutionary dynamics and conducted a phase 1b study in metastatic castration sensitive prostate cancer (mCSPC). Methods: Men with asymptomatic mCSPC were enrolled and proceeded with a treatment break after achieving > 75% PSA decline with LHRH analog plus an NHA. ADT was restarted at the time of PSA or radiographic progression and held again after achieving >50% PSA decline.

Evolution-based mathematical models significantly prolong response to abiraterone in metastatic castrate-resistant prostate cancer and identify strategies to further improve outcomes.

Background: Abiraterone acetate is an effective treatment for metastatic castrate-resistant prostate cancer (mCRPC), but evolution of resistance inevitably leads to progression. We present a pilot study in which abiraterone dosing is guided by evolution-informed mathematical models to delay onset of resistance.

Methods: In the study cohort, abiraterone was stopped when PSA was <50% of pretreatment value and resumed when PSA returned to baseline.

Corrigendum to 'Association between electronic cigarette use and fragility fractures among US adults' volumes 1-6 (2021) 100002.

[This corrects the article DOI: 10.1016/j.ajmo.

Association between electronic cigarette use and fragility fractures among US adults.

Background: The popularity of electronic cigarette (e-cigarette) use continues to rise in the United States. While conventional cigarette smoking is an established risk factor for osteoporosis and osteoporotic fracture, the effects of e-cigarette use on bone health are unknown. We aimed to examine the association between e-cigarette use and fragility fractures.

Early construction of the thalamocortical axon pathway requires c-Jun N-terminal kinase signaling within the ventral forebrain.

Background: Thalamocortical connectivity is essential for normal brain function. This important pathway is established during development, when thalamic axons extend a long distance through the forebrain before reaching the cerebral cortex. In this study, we identify a novel role for the c-Jun N-terminal kinase (JNK) signaling pathway in guiding thalamocortical axons through intermediate target territories.

The short- and long-term effects of dietary patterns on cardiometabolic health in adults aged 65 years or older: a systematic review.

Context: Cardiometabolic diseases are leading causes of death and morbidity. Aging increases the risk of disease development. Diet has protective and causal effects on cardiometabolic health.

A rare case of diabetic ketoacidosis presenting with severe hypertriglyceridemia requiring plasmapheresis in an adult with type-2 diabetes mellitus: Case report.

Introduction: Severe hypertriglyceridemia (HTG) is a rare complication of insulin resistance. Its presentation with diabetic ketoacidosis (DKA) has been reported in a few cases, where most patients have type-1 diabetes mellitus (DM). Our case represents a unique presentation of DKA associated with severe HTG above 10,000 mg/dL in an adult with type-2 DM.

Frequency-dependent interactions determine outcome of competition between two breast cancer cell lines.

Tumors are highly dynamic ecosystems in which diverse cancer cell subpopulations compete for space and resources. These complex, often non-linear interactions govern continuous spatial and temporal changes in the size and phenotypic properties of these subpopulations. Because intra-tumoral blood flow is often chaotic, competition for resources may be a critical selection factor in progression and prognosis.

Fighting microbial pathogens by integrating host ecosystem interactions and evolution.

Successful therapies to combat microbial diseases and cancers require incorporating ecological and evolutionary principles. Drawing upon the fields of ecology and evolutionary biology, we present a systems-based approach in which host and disease-causing factors are considered as part of a complex network of interactions, analogous to studies of "classical" ecosystems. Centering this approach around empirical examples of disease treatment, we present evidence that successful therapies invariably engage multiple interactions with other components of the host ecosystem.

Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer.

In the absence of curative therapies, treatment of metastatic castrate-resistant prostate cancer (mCRPC) using currently available drugs can be improved by integrating evolutionary principles that govern proliferation of resistant subpopulations into current treatment protocols. Here we develop what is coined as an 'evolutionary stable therapy', within the context of the mathematical model that has been used to inform the first adaptive therapy clinical trial of mCRPC. The objective of this therapy is to maintain a stable polymorphic tumor heterogeneity of sensitive and resistant cells to therapy in order to prolong treatment efficacy and progression free survival.

The Role of Brain Natriuretic Peptide as a Prognostic Marker for Sepsis.

Brain natriuretic peptide (BNP) is a neurohormone released in response to volume expansion and increased pressure. It is commonly used to assist in the diagnosis and management of heart failure. BNP can also play an important role as a biomarker in septic shock; however, elevations of BNP in conditions other than sepsis or cardiac dysfunction limits its use as the sole prognostic marker in patients hospitalized with sepsis.

When Anti-Neutrophil Cytoplasmic Antibody Fails: A Case of Anti-Neutrophil Cytoplasmic Antibody Negative Granulomatosis With Polyangiitis.

Granulomatosis with polyangiitis (GPA) is a vasculitis of small and medium-sized vessels and presents with varying signs and symptoms. It includes upper and lower airway manifestations and glomerulonephritis with a positive antineutrophil cytoplasmic antibody (ANCA) in serology in 90% of cases. However, about 10% of cases with GPA can have negative serology, often resulting in a diagnostic delay.

Extremely High Creatine Kinase Activity in Rhabdomyolysis without Acute Kidney Injury.

BACKGROUND Elevation of creatine kinase (CK) activity has been shown to be predictive of acute kidney injury (AKI) in rhabdomyolysis. Patients with extremely high CK activity with preserved renal function are uncommon. This report describes a case of non-traumatic rhabdomyolysis, with a markedly elevated CK activity, without associated AKI.

Resistance is not the end: lessons from pest management.

The "war on cancer" began over 40 years ago with the signing of the National Cancer Act of 1971. Currently, complete eradication has proven possible in early stage premetastatic disease with increasingly successful early detection and surgery protocols; however, late stage metastatic disease remains invariably fatal. One of the main causes of treatment failure in metastatic disease is the ability of cancer cells to evolve resistance to currently available therapies.