Immunohistochemical Evaluation of Cathepsin B, L, and S Expression in Breast Cancer Patients.

Purpose: Cysteine cathepsins are proteases that play a role in normal cellular physiology and neoplastic transformation. Elevated expression and enzymatic activity of cathepsins in breast cancer (BCa) indicates their potential as a target for tumor imaging. In particular cathepsin B (CTSB), L (CTSL), and S (CTSS) are used as targets for near-infrared (NIR) fluorescence imaging (FI), a technique that allows real-time intraoperative tumor visualization and resection margin assessment.

Severe drought exposure in utero associates to children's epigenetic age acceleration in a global climate change hot spot.

The goal of this study is to examine the association between in utero drought exposure and epigenetic age acceleration (EAA) in a global climate change hot spot. Calculations of EAA in adults using DNA methylation have been found to accurately predict chronic disease and longevity. However, fewer studies have examined EAA in children, and drought exposure in utero has not been investigated.

Peripheral cortical bone density predicts vertebral bone mineral properties in spine fusion surgery patients.

Spine fusion surgery is one of the most common orthopedic procedures, with over 400,000 performed annually to correct deformities and pain. However, complications occur in approximately one third of cases. While many of these complications may be related to poor bone quality, it is difficult to detect bone abnormalities prior to surgery.

Mineral Nutrition of Samburu Adolescents: A Comparative Study of Pastoralist Communities in Kenya.

Objectives: This study aimed to characterize mineral nutrition (copper, magnesium, selenium, and zinc) in Samburu pastoralist youth, in the context of differential cultural transitions due to uneven changes in educational access, herding intensity, polygyny, and access to wild, domesticated, and market-sourced foods.

Materials And Methods: Whole dried blood spots were collected in a total of 161 youth (highlands, = 97; lowlands, = 64) to assess concentrations of: cadmium, copper, lead, magnesium, mercury, selenium, and zinc. Concentrations were determined through Inductively Coupled Mass Spectrometry.

Epigenetic mechanisms underlying the association between maternal climate stress and child growth: characterizing severe drought and its impact on a Kenyan community engaging in a climate change-sensitive livelihood.

Pastoralists in East Africa are among the world's most vulnerable communities to climate change, already living near their upper thermal limits and engaging in a climate-sensitive livelihood in a climate change global hot spot. Pregnant women and children are even more at risk. Here, we report the findings of a study characterizing Samburu pastoralist women's experiences of severe drought and outcomes in their children (N = 213, 1.

Cysteine Cathepsins in Breast Cancer: Promising Targets for Fluorescence-Guided Surgery.

The majority of breast cancer patients is treated with breast-conserving surgery (BCS) combined with adjuvant radiation therapy. Up to 40% of patients has a tumor-positive resection margin after BCS, which necessitates re-resection or additional boost radiation. Cathepsin-targeted near-infrared fluorescence imaging during BCS could be used to detect residual cancer in the surgical cavity and guide additional resection, thereby preventing tumor-positive resection margins and associated mutilating treatments.

Formulation of a Thermosensitive Imaging Hydrogel for Topical Application and Rapid Visualization of Tumor Margins in the Surgical Cavity.

Background: Tumor-positive surgical margins during primary breast cancer (BCa) surgery are associated with a two-fold increase in the risk of local recurrence when compared with tumor-negative margins. Pathological microscopic evaluation of the samples only assesses about 1/10 of 1% of the entire volume of the removed BCa specimens, leading to margin under-sampling and potential local recurrence in patients with pathologically clean margins, i.e.

Golgi membrane protein Erd1 Is essential for recycling a subset of Golgi glycosyltransferases.

Protein glycosylation in the Golgi is a sequential process that requires proper distribution of transmembrane glycosyltransferase enzymes in the appropriate Golgi compartments. Some of the cytosolic machinery required for the steady-state localization of some Golgi enzymes are known but existing models do not explain how many of these enzymes are localized. Here, we uncover the role of an integral membrane protein in yeast, Erd1, as a key facilitator of Golgi glycosyltransferase recycling by directly interacting with both the Golgi enzymes and the cytosolic receptor, Vps74.

Using an unmanned aerial vehicle water sampler to gather data in a pit-lake mining environment to assess closure and monitoring.

Residual pit lakes from mining are often dangerous to sample for water quality. Thus, pit lakes may be rarely (or never) sampled. This study developed new technology in which water-sampling devices, mounted on an unmanned aerial vehicle (UAV), were used to sample three pit lakes in Nevada, USA, during 1 week in 2017.

Family socioeconomic status and child telomere length among the Samburu of Kenya.

Previous research in high-income countries suggests that children from families with lower socioeconomic status (SES) tend to have shorter telomere length - a biomarker of stress and cell aging - than children from families with greater social and economic resources. However, little is known about predictors of child telomere length in low-income settings. Data for the current study are from a sample of 214 Samburu children aged 1-9 years.

Heavy metal blood concentrations in association with sociocultural characteristics, anthropometry and anemia among Kenyan adolescents.

Objectives: To measure heavy metal concentrations among Kenyan youth and quantify associations with sociocultural, demographic, and health factors as well as anthropometry.

Methods: Using data from a study of semi-nomadic pastoralists in Samburu County, Kenya, we measured blood concentrations of lead (Pb), mercury (Hg), and cadmium (Cd) in 161 adolescents. We identified sociocultural, demographic and health characteristics associated with each metal and quantified the association between metals and adolescent anthropometry.

Lifetime stress and war exposure timing may predict methylation changes at NR3C1 based on a pilot study in a warrior cohort in a small-scale society in Kenya.

Objectives: Candidate gene methylation studies of NR3C1 have identified associations with psychosocial adversity, including war trauma. This pilot study (sample sizes from 22 to 45 for primary analyses) examined NR3C1 methylation in a group of Kenyan pastoralist young men in relation to culturally relevant traumatic experiences, including participation in coalitional lethal gun violence.

Methods: Adolescent and young adult Samburu men ("warriors") were recruited for participation.

Hypomethylating Agent Azacitidine Is Effective in Treating Brain Metastasis Triple-Negative Breast Cancer Through Regulation of DNA Methylation of Keratin 18 Gene.

Breast cancer patients presenting with symptomatic brain metastases have poor prognosis, and current chemotherapeutic agents are largely ineffective. In this study, we evaluated the hypomethylating agent azacitidine (AZA) for its potential as a novel therapeutic in preclinical models of brain metastasis of breast cancer. We used the parental triple-negative breast cancer MDA-MB-231 (231) cells and their brain colonizing counterpart (231Br) to ascertain phenotypic differences in response to AZA.

A Protease-Activated Fluorescent Probe Allows Rapid Visualization of Keratinocyte Carcinoma during Excision.

Keratinocyte carcinomas, including basal and squamous cell carcinomas, are the most common human cancers worldwide. While 75% of all keratinocyte carcinoma (4 million annual cases in the United States) are treated with conventional excision, this surgical modality has much lower cure rates than Mohs micrographic surgery, likely due to the bread-loaf histopathologic assessment that visualizes <1% of the tissue margins. A quenched protease-activated fluorescent probe 6qcNIR, which produces a signal only in the protease-rich tumor microenvironment, was topically applied to 90 specimens immediately following excision.

Prosocial Emotion, Adolescence, and Warfare : DNA Methylation Associates with Culturally Salient Combat Variables.

Examining the costs and motivations of warfare is key to conundrums concerning the relevance of this troubling phenomenon to the evolution of social attachment and cooperation, particularly during adolescence and young adulthood-the developmental time period during which many participants are first recruited for warfare. The study focuses on Samburu, a pastoralist society of approximately 200,000 people occupying northern Kenya's semi-arid and arid lands, asking what role the emotionally sensitized, peer-driven adolescent life stage may have played in the cultural and genetic coevolution of coalitional lethal aggression. Research in small-scale societies provides unparalleled opportunities for sharply defined variables, particularly in age generation societies in which all young men are initiated into "warriorhood.

Molecular imaging and validation of margins in surgically excised nonmelanoma skin cancer specimens.

In an effort to increase the efficiency and cure rate of nonmelanoma skin cancer (NMSC) excisions, we have developed a point-of-care method of imaging and evaluation of skin cancer margins. We evaluate the skin surgical specimens using a smart, near-infrared probe (6qcNIR) that fluoresces in the presence of cathepsin proteases overexpressed in NMSC. Imaging is done with an inverted, flying-spot fluorescence scanner that reduces scatter, giving a 70% improved step response as compared to a conventional imaging system.

Rapid visualization of nonmelanoma skin cancer.

Background: Mohs micrographic surgery examines all margins of the resected sample and has a 99% cure rate. However, many nonmelanoma skin cancers (NMSCs) are not readily amenable to Mohs micrographic surgery. This defines an unmet clinical need to assess the completeness of non-Mohs micrographic surgery resections during surgery to prevent re-excision/recurrence.

Documenting the health consequences of endemic warfare in three pastoralist communities of northern Kenya: a conceptual framework.

Violent conflict represents the third most important source of mortality around the world, yet violence-related mortality remains profoundly undercounted (Krug, Dahlberg, Mercy, Zwi, & Lozano, 2002). As a step toward documenting the consequences of even the "smallest wars" we offer a conceptual framework for a recently initiated project that comparatively examines the direct and indirect consequences of intercommunity violence among Pokot, Samburu, and Turkana herding communities of Northern Kenya. While a substantial body of work has accumulated on the social responses to this violence very little is known about the differential impacts on community health.