Deaths in Immigration and Customs Enforcement (ICE) detention: A Fiscal Year (FY) 2021-2023 update.

Background: This study describes the deaths of individuals in Immigration and Customs Enforcement (ICE) detention between FY2021-2023, updating a report from FY2018-2020, which identified an increased death rate amidst the COVID-19 pandemic. Methods: Data was extracted from death reports published online by ICE. Causes of deaths were recorded, and death rates per 100,000 admissions were calculated using population statistics reported by ICE. Reports of individuals released from ICE custody just prior to death were also identified and described. Results: There were 12 deaths reported from FY2021-2023, compared to 38 deaths from FY2018-2020. The death rate per 100,000 admissions in ICE detention was 3.251 in FY2021, 0.939 in FY2022, and 1.457 in FY2023, compared with a pandemic-era high of 10.833 in FY2020. Suicide caused 1 of 12 (8.3%) deaths in FY2021-2023 compared with 9 of 38 (23.7%) deaths in FY2018-2020. COVID-19 was contributory in 3 of 11 (25%) medical deaths in FY2021-2023, compared with 8 of 11 (72.7%) in the COVID-era months of FY2020 (p = 0.030). Overall, 4 of 11 (36.3%) medical deaths in FY2021-2023 resulted from cardiac arrest in detention facilities, compared with 6 of 29 (20.3%) in FY2018-2020. Three deaths of hospitalized individuals released from ICE custody with grave prognoses were identified. Conclusions: The death rate among individuals in ICE custody decreased in FY2021-2023, which may be explained in part by the release of vulnerable individuals following recent federal legal determinations (e.g., Fraihat v. ICE). Identification of medically complex individuals released from ICE custody just prior to death and not reported by ICE indicates that reported deaths underestimate total deaths associated with ICE detention. Attentive monitoring of mortality outcomes following release from ICE custody is warranted.

Less-lethal law enforcement weapons: clinical management of associated injuries in the emergency department.

Less-lethal weapons and tactics are being increasingly used by law enforcement to minimize the reliance on more-lethal force. While these methods are designated as "less-lethal," they can cause morbidity and mortality when deployed. Knowledge of these weapons and tactics can help direct the workup and management of patients with injuries from these methods and can protect clinicians from secondary exposure and injuries. This issue reviews the most common less-lethal weapons and tactics used by law enforcement, describes their mechanism of action, and discusses associated common injury patterns. Recommendations are provided for the evaluation and management of these patients in the emergency department.

A fully defined 3D matrix for ex vivo expansion of human colonic organoids from biopsy tissue.

Intestinal organoids have widespread research and biomedical applications, such as disease modeling, drug testing and regenerative medicine. However, the transition towards clinical use has in part been hampered by the dependency on animal tumor-derived basement membrane extracts (BMEs), which are poorly defined and ill-suited for regulatory approval due to their origin and batch-to-batch variability. In order to overcome these limitations, and to enable clinical translation, we tested the use of a fully defined hydrogel matrix, QGel CN99, to establish and expand intestinal organoids directly from human colonic biopsies. We achieved efficient de novo establishment, expansion and organoid maintenance, while also demonstrating sustained genetic stability. Additionally, we were able to preserve stemness and differentiation capacity, with transcriptomic profiles resembling normal colonic epithelium. All data proved comparable to organoids cultured in the BME-benchmark Matrigel. The application of a fully defined hydrogel, completely bypassing the use of BMEs, will drastically improve the reproducibility and scalability of organoid studies, but also advance translational applications in personalized medicine and stem cell-based regenerative therapies.

Why Didn't You Text Me? Poststudy Trends From the DepoText Trial.

OBJECTIVE: To evaluate the longitudinal impact of a 9-month text message intervention on participant adherence beyond the intervention to highly effective contraceptive methods among urban adolescent and young adult women enrolled in the DepoText randomized control trial (RCT). STUDY DESIGN: Retrospective longitudinal cohort study of long-term follow-up data from the DepoText RCT. Sixty-seven female participants (aged 13-21 years) using depot medroxyprogesterone acetate (DMPA) were recruited from an urban academic adolescent practice in Baltimore, Maryland. The principal outcome measured was a comparison of contraceptive method choice between the control and intervention groups during the 20 months postintervention. RESULTS: Intervention participants were 3.65 times more likely to continue using DMPA or a more efficacious method at the 20-month postintervention evaluation (odds ratio 3.65, 95% CI 1.26-10.08; P = .015). CONCLUSION: Participation in the DepoText trial was associated with continued use of DMPA or a more effective contraceptive method almost 20 months after the intervention exposure ended.

Adverse Childhood Experiences Among Hispanic Children in Immigrant Families Versus US-Native Families.

OBJECTIVES: To examine the prevalence of child and family characteristics associated with adverse childhood experiences (ACEs) in Hispanic children in immigrant families compared with Hispanic children in US-native families. METHODS: Data were from the nationally representative 2011-2012 National Survey of Children's Health. Parent-reported child ACE exposure was classified as no ACEs (0), low ACEs (1), or high ACEs (≥2). By using multinomial logistic regression, we evaluated the odds of low or high ACE exposure versus no ACE exposure by immigrant family status and child and family characteristics (eg, insurance status, child health status, or household-to-income ratio). RESULTS: The study sample included 12 162 Hispanic children. More children in immigrant families lived ≤200% of the federal poverty level compared with children in US-native families (80% vs 47%, respectively; P < .001). Thirty percent of children in US-native families reported high ACEs compared with only 16% of children in immigrant families (P < .001). The odds of high ACE exposure versus no ACE exposure for children in immigrant families compared with US-native children was 0.46 (95% confidence interval: 0.34-0.61). Child and family characteristics did not explain the difference in odds of ACE exposure by immigrant family status. CONCLUSIONS: Children in immigrant families had significantly lower odds of ACE exposure despite higher prevalence of poverty. This may not reflect a true health advantage in this population. There may be unmeasured factors that buffer children in immigrant families from ACE exposure, or ACE questions may not capture the adverse experiences specific to immigrant families.

Perceived Social Support, Parental Notification, and Parental Engagement after Pelvic Inflammatory Disease among Urban Adolescent and Young Adults.

BACKGROUND: Urban adolescent and young adult women often require adult support throughout their transition to adulthood particularly regarding seeking healthcare. While confidentiality is crucial feature of care delivery, successful adherence to treatment can be multi-factorial. The purpose of this study is to determine factors associated with parental notification and engagement in self-care of young women diagnosed with Pelvic Inflammatory Disease (PID). METHODS: This study utilizes data from 187 participants in the Technology Enhanced Community Health Nursing (TECH-N) study, a randomized controlled trial of an intervention to prevent recurrent STIs after a diagnosis of mild-moderate PID. Participants were recruited from pediatric ambulatory settings provided baseline demographic, reproductive history, and perceived social support using an audio computerized self-interview at baseline and parental notification collected during a two-week follow-up interview, served as the primary outcome. RESULTS: Sixty-five percent of participants informed a parent of their PID diagnosis, 74% of whom reported receiving supportive care. Participants who reported a higher sense of responsibility to others were 17% less likely to inform a parent of their diagnosis. CONCLUSION: Most urban young women with PID notify parents of their diagnosis and obtain support for self-management in the outpatient setting. While autonomy is a critical milestone for transition to young adulthood, these data suggest that proactive youth-managed parental engagement may be an underutilized resource for young women diagnosed with PID.

Understanding Adolescent Nonresponsiveness to Text Messages: Lessons from the DepoText Trial.

Urban adolescents face economic, social, and behavioral challenges in adhering to long-term contraceptive use. Use of text messaging reminders has the potential to increase adherence to family planning appointments and to educate patients about safe sexual health practices; however, nonresponsiveness to messages is difficult to interpret and may jeopardize programmatic success. We aimed to understand why adolescent girls enrolled in a randomized, controlled pilot trial (DepoText) designed to increase attendance at family planning visits were periodically nonresponsive to text messages through conducting structured interviews with participants whose text reply rates were less than 100 % during the trial period. Qualitative and quantitative data were collected and classified using descriptive data analysis. Reasons for nonresponsiveness, barriers to continuous cell phone coverage, cell phone plan characteristics, and attitudes toward the DepoText program were the primary endpoints of interest. Most participants (78%) attributed instances of nonresponsiveness to being away from the phone or due to a personal conflict such as school or work. Service interruption due to bill nonpayment (44%), phone loss (28%), and cell phone number change (28%) were significant barriers to continuous coverage during the trial period, and many respondents indicated that the downturn in the economy made it more difficult to maintain their cell phone plan. Almost a third reported having to choose between cell phone and other payments, but the vast majority (88%) considered their cell phone a "need" rather than a "want." Participants universally expressed satisfaction with the text messaging program and reported feeling more connected to the clinic (96%) through the messages serving as reminders (64%), encouragement to assume personal responsibility for their health care (12%), and enhanced personal connection with the clinic staff (4%). Our study suggests that a text messaging program can be used in an urban clinical setting to communicate with adolescent girls about family planning services. While economic barriers to continuous cell phone coverage do exist, adolescents indicate that the text message reminder system can be a valuable tool for enhancing clinic connectedness and promoting autonomy in care-seeking behavior.

Flow shear stress regulates endothelial barrier function and expression of angiogenic factors in a 3D microfluidic tumor vascular model.

Endothelial cells lining blood vessels are exposed to various hemodynamic forces associated with blood flow. These include fluid shear, the tangential force derived from the friction of blood flowing across the luminal cell surface, tensile stress due to deformation of the vessel wall by transvascular flow, and normal stress caused by the hydrodynamic pressure differential across the vessel wall. While it is well known that these fluid forces induce changes in endothelial morphology, cytoskeletal remodeling, and altered gene expression, the effect of flow on endothelial organization within the context of the tumor microenvironment is largely unknown. Using a previously established microfluidic tumor vascular model, the objective of this study was to investigate the effect of normal (4 dyn/cm(2)), low (1 dyn/cm(2)), and high (10 dyn/cm(2)) microvascular wall shear stress (WSS) on tumor-endothelial paracrine signaling associated with angiogenesis. It is hypothesized that high WSS will alter the endothelial phenotype such that vascular permeability and tumor-expressed angiogenic factors are reduced. Results demonstrate that endothelial permeability decreases as a function of increasing WSS, while co-culture with tumor cells increases permeability relative to mono-cultures. This response is likely due to shear stress-mediated endothelial cell alignment and tumor-VEGF-induced permeability. In addition, gene expression analysis revealed that high WSS (10 dyn/cm(2)) significantly down-regulates tumor-expressed MMP9, HIF1, VEGFA, ANG1, and ANG2, all of which are important factors implicated in tumor angiogenesis. This result was not observed in tumor mono-cultures or static conditioned media experiments, suggesting a flow-mediated paracrine signaling mechanism exists with surrounding tumor cells that elicits a change in expression of angiogenic factors. Findings from this work have significant implications regarding low blood velocities commonly seen in the tumor vasculature, suggesting high shear stress-regulation of angiogenic activity is lacking in many vessels, thereby driving tumor angiogenesis.

Three-dimensional microfluidic collagen hydrogels for investigating flow-mediated tumor-endothelial signaling and vascular organization.

Hyperpermeable tumor vessels are responsible for elevated interstitial fluid pressure and altered flow patterns within the tumor microenvironment. These aberrant hydrodynamic stresses may enhance tumor development by stimulating the angiogenic activity of endothelial cells lining the tumor vasculature. However, it is currently not known to what extent shear forces affect endothelial organization or paracrine signaling during tumor angiogenesis. The objective of this study was to develop a three-dimensional (3D), in vitro microfluidic tumor vascular model for coculture of tumor and endothelial cells under varying flow shear stress conditions. A central microchannel embedded within a collagen hydrogel functions as a single neovessel through which tumor-relevant hydrodynamic stresses are introduced and quantified using microparticle image velocimetry (µ-PIV). This is the first use of µ-PIV in a tumor representative, 3D collagen matrix comprised of cylindrical microchannels, rather than planar geometries, to experimentally measure flow velocity and shear stress. Results demonstrate that endothelial cells develop a confluent endothelium on the microchannel lumen that maintains integrity under physiological flow shear stresses. Furthermore, this system provides downstream molecular analysis capability, as demonstrated by quantitative RT-PCR, in which, tumor cells significantly increase expression of proangiogenic genes in response to coculture with endothelial cells under low flow conditions. This work demonstrates that the microfluidic in vitro cell culture model can withstand a range of physiological flow rates and permit quantitative measurement of wall shear stress at the fluid-collagen interface using µ-PIV optical flow diagnostics, ultimately serving as a versatile platform for elucidating the role of fluid forces on tumor-endothelial cross talk.

Flow measurements in a blood-perfused collagen vessel using x-ray micro-particle image velocimetry.

Blood-perfused tissue models are joining the emerging field of tumor engineering because they provide new avenues for modulation of the tumor microenvironment and preclinical evaluation of the therapeutic potential of new treatments. The characterization of fluid flow parameters in such in-vitro perfused tissue models is a critical step towards better understanding and manipulating the tumor microenvironment. However, traditional optical flow measurement methods are inapplicable because of the opacity of blood and the thickness of the tissue sample. In order to overcome the limitations of optical method we demonstrate the feasibility of using phase-contrast x-ray imaging to perform microscale particle image velocimetry (PIV) measurements of flow in blood perfused hydrated tissue-representative microvessels. However, phase contrast x-ray images significantly depart from the traditional PIV image paradigm, as they have high intensity background, very low signal-to-noise ratio, and volume integration effects. Hence, in order to achieve accurate measurements special attention must be paid to the image processing and PIV cross-correlation methodologies. Therefore we develop and demonstrate a methodology that incorporates image preprocessing as well as advanced PIV cross-correlation methods to result in measured velocities within experimental uncertainty.

Microfluidic culture models to study the hydrodynamics of tumor progression and therapeutic response.

The integration of tissue engineering strategies with microfluidic technologies has enabled the design of in vitro microfluidic culture models that better adapt to morphological changes in tissue structure and function over time. These biomimetic microfluidic scaffolds accurately mimic native 3D microenvironments, as well as permit precise and simultaneous control of chemical gradients, hydrodynamic stresses, and cellular niches within the system. The recent application of microfluidic in vitro culture models to cancer research offers enormous potential to aid in the development of improved therapeutic strategies by supporting the investigation of tumor angiogenesis and metastasis under physiologically relevant flow conditions. The intrinsic material properties and fluid mechanics of microfluidic culture models enable high-throughput anti-cancer drug screening, permit well-defined and controllable input parameters to monitor tumor cell response to various hydrodynamic conditions or treatment modalities, as well as provide a platform for elucidating fundamental mechanisms of tumor physiology. This review highlights recent developments and future applications of microfluidic culture models to study tumor progression and therapeutic targeting under conditions of hydrodynamic stress relevant to the complex tumor microenvironment.

In vitro angiogenesis induced by tumor-endothelial cell co-culture in bilayered, collagen I hydrogel bioengineered tumors.

Although successful remission has been achieved when cancer is diagnosed and treated during its earliest stages of development, a tumor that has established neovascularization poses a significantly greater risk of mortality. The inability to recapitulate the complexities of a maturing in vivo tumor microenvironment in an in vitro setting has frustrated attempts to identify and test anti-angiogenesis therapies that are effective at permanently halting cancer progression. We have established an in vitro tumor angiogenesis model driven solely by paracrine signaling between MDA-MB-231 breast cancer cells and telomerase-immortalized human microvascular endothelial (TIME) cells co-cultured in a spatially relevant manner. The bilayered bioengineered tumor model consists of TIME cells cultured as an endothelium on the surface of an acellular collagen I hydrogel under which MDA-MB-231 cells are cultured in a separate collagen I hydrogel. Results showed that TIME cells co-cultured with the MDA-MB-231 cells demonstrated a significant increase in cell number, rapidly developed an elongated morphology, and invasively sprouted into the underlying acellular collagen I layer. Comparatively, bioengineered tumors cultured with less aggressive MCF7 breast cancer cells did not elicit an angiogenic response. Angiogenic sprouting was demonstrated by the formation of a complex capillary-like tubule network beneath the surface of a confluent endothelial monolayer with lumen formation and anastomosing branches. In vitro angiogenesis was dependent on vascular endothelial growth factor secretion, matrix concentration, and duration of co-culture. Basic fibroblast growth factor supplemented to the co-cultures augmented angiogenic sprouting. The development of improved preclinical tumor angiogenesis models, such as the one presented here, is critical for accurate evaluation and refinement of anti-angiogenesis therapies.

Cross-talk between endothelial and breast cancer cells regulates reciprocal expression of angiogenic factors in vitro.

Reciprocal growth factor exchange between endothelial and malignant cells within the tumor microenvironment may directly stimulate neovascularization; however, the role of host vasculature in regulating tumor cell activity is not well understood. While previous studies have examined the angiogenic response of endothelial cells to tumor-secreted factors, few have explored tumor response to endothelial cells. Using an in vitro co-culture system, we investigated the influence of endothelial cells on the angiogenic phenotype of breast cancer cells. Specifically, VEGF, ANG1, and ANG2 gene and protein expression were assessed. When co-cultured with microvascular endothelial cells (HMEC-1), breast cancer cells (MDA-MB-231) significantly increased expression of ANG2 mRNA (20-fold relative to MDA-MB-231 monoculture). Moreover, MDA-MB-231/HMEC-1 co-cultures produced significantly increased levels of ANG2 (up to 580 pg/ml) and VEGF protein (up to 38,400 pg/ml) while ANG1 protein expression was decreased relative to MDA-MB-231 monocultures. Thus, the ratio of ANG1:ANG2 protein, a critical indicator of neovascularization, shifted in favor of ANG2, a phenomenon known to correlate with vessel destabilization and sprouting in vivo. This angiogenic response was not observed in nonmalignant breast epithelial cells (MCF-10A), where absolute protein levels of MCF-10A/HMEC-1 co-cultures were an order of magnitude less than that of the MDA-MB-231/HMEC-1 co-cultures. Results were further verified with a functional angiogenesis assay demonstrating well-defined microvascular endothelial cell (TIME) tube formation when cultured in media collected from MDA-MB-231/HMEC-1 co-cultures. This study demonstrates that the angiogenic activity of malignant mammary epithelial cells is significantly enhanced by the presence of endothelial cells.

3D in vitro bioengineered tumors based on collagen I hydrogels.

Cells cultured within a three-dimensional (3D) in vitro environment have the ability to acquire phenotypes and respond to stimuli analogous to in vivo biological systems. This approach has been utilized in tissue engineering and can also be applied to the development of a physiologically relevant in vitro tumor model. In this study, collagen I hydrogels cultured with MDA-MB-231 human breast cancer cells were bioengineered as a platform for in vitro solid tumor development. The cell-cell and cell-matrix interactions present during in vivo tissue progression were encouraged within the 3D hydrogel architecture, and the biocompatibility of collagen I supported unconfined cellular proliferation. The development of necrosis beyond a depth of ~150-200 µm and the expression of hypoxia-inducible factor (HIF)-1α were demonstrated in the in vitro bioengineered tumors. Oxygen and nutrient diffusion limitations through the collagen I matrix as well as competition for available nutrients resulted in growing levels of intra-cellular hypoxia, quantified by a statistically significant (p < 0.01) upregulation of HIF-1α gene expression. The bioengineered tumors also demonstrated promising angiogenic potential with a statistically significant (p < 0.001) upregulation of vascular endothelial growth factor (VEGF)-A gene expression. In addition, comparable gene expression analysis demonstrated a statistically significant increase of HIF-1α (p < 0.05) and VEGF-A (p < 0.001) by MDA-MB-231 cells cultured in the 3D collagen I hydrogels compared to cells cultured in a monolayer on two-dimensional tissue culture polystyrene. The results presented in this study demonstrate the capacity of collagen I hydrogels to facilitate the development of 3D in vitro bioengineered tumors that are representative of the pre-vascularized stages of in vivo solid tumor progression.

Photothermal response of human and murine cancer cells to multiwalled carbon nanotubes after laser irradiation.

This study demonstrates the capability of multiwalled carbon nanotubes (MWNTs) coupled with laser irradiation to enhance treatment of cancer cells through enhanced and more controlled thermal deposition, increased tumor injury, and diminished heat shock protein (HSP) expression. We also explored the potential promise of MWNTs as drug delivery agents by observing the degree of intracellular uptake of these nanoparticles. To determine the heat generation capability of MWNTs, the absorption spectra and temperature rise during heating were measured. Higher optical absorption was observed for MWNTs in water compared with water alone. For identical laser parameters, MWNT-containing samples produced a significantly greater temperature elevation compared to samples treated with laser alone. Human prostate cancer (PC3) and murine renal carcinoma (RENCA) cells were irradiated with a 1,064-nm laser with an irradiance of 15.3 W/cm(2) for 2 heating durations (1.5 and 5 minutes) alone or in combination with MWNT inclusion. Cytotoxicity and HSP expression following laser heating was used to determine the efficacy of laser treatment alone or in combination with MWNTs. No toxicity was observed for MWNTs alone. Inclusion of MWNTs dramatically decreased cell viability and HSP expression when combined with laser irradiation. MWNT cell internalization was measured using fluorescence and transmission electron microscopy following incubation of MWNTs with cells. With increasing incubation duration, a greater number of MWNTs were observed in cellular vacuoles and nuclei. These findings offer an initial proof of concept for the application of MWNTs in cancer therapy.

Long-term survival following a single treatment of kidney tumors with multiwalled carbon nanotubes and near-infrared radiation.

Multiwalled carbon nanotubes (MWCNTs) exhibit physical properties that render them ideal candidates for application as noninvasive mediators of photothermal cancer ablation. Here, we demonstrate that use of MWCNTs to generate heat in response to near-infrared radiation (NIR) results in thermal destruction of kidney cancer in vitro and in vivo. We document the thermal effects of the therapy through magnetic resonance temperature-mapping and heat shock protein-reactive immunohistochemistry. Our results demonstrate that use of MWCNTs enables ablation of tumors with low laser powers (3 W/cm(2)) and very short treatment times (a single 30-sec treatment) with minimal local toxicity and no evident systemic toxicity. These treatment parameters resulted in complete ablation of tumors and a >3.5-month durable remission in 80% of mice treated with 100 microg of MWCNT. Use of MWCNTs with NIR may be effective in anticancer therapy.