The induction of bone formation by 3D-printed PLGA microsphere scaffolds in a calvarial orthotopic mouse model: a pilot study.

Polymeric biodegradable microspheres are readily utilized to support targeted drug delivery for various diseases clinically. 3D printed tissue engineering scaffolds from polymer filaments with embedded microspheres or nanoparticles, as well as bulk microsphere scaffolds, have been investigated for regenerative medicine and tissue engineering. However, 3D printed scaffolds consisting only of a homogenous microsphere size with an optimized architecture that includes a unique micro- and macroporosity, have been challenging to produce and hence, have not been assessed in the literature yet.

Expanding Environmental Care Competencies for Future and Current Healthcare Providers.

The multiple impacts of the environment on the health of populations can oftentimes be clouded by the daily care practices of healthcare providers. This case study describes an innovative graduate level elective course that uses a problem-based approach to apply evidence-based principles of environmental health to the care of populations. Initial implementation of the course, over two cohorts in 2023, had primarily second-degree undergraduate nursing students.

Characterization of the TLR9-Activating Potential of LNA-Modified Antisense Oligonucleotides.

Early characterization of the immunostimulatory potential of therapeutic antisense oligonucleotides (ASOs) is crucial. At present, little is known about the toll-like receptor 9 (TLR9)-mediated immunostimulatory potential of third-generation locked nucleic acid (LNA)-modified ASOs. In this study, we have systematically investigated the TLR9-activating potential of LNA-modified oligonucleotides using different mouse and human cell culture systems.

Human angiotensin-converting enzyme 2-specific antisense oligonucleotides reduce infection with SARS-CoV-2 variants.

Background: The Spike protein mutation severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to decreased protective effect of various vaccines and mAbs, suggesting that blocking SARS-CoV-2 infection by targeting host factors would make the therapy more resilient against virus mutations. Angiotensin-converting enzyme 2 (ACE2) is the host receptor of SARS-CoV-2 and its variants, as well as many other coronaviruses. Downregulation of ACE2 expression in the respiratory tract may prevent viral infection.

"Be more positive and more kind to your own bodies": Adolescent and young adult preferences for how parents can support their children with weight-related pressures.

Body dissatisfaction is a key factor contributing to the development of disordered eating, and body dissatisfaction is often influenced by media, peer, and parental pressures during adolescence. Little research has explored ways in which parents can help their children manage pressures from social media and their peers. The present study used the MyVoice National Poll of Youth, a large text-message cohort of young people (14-24 years old) in the United States, to collect and examine qualitative data about their experiences with parental weight-related communication and how they think parents can best support their children regarding messages they see/hear surrounding weight, body shape and size by their peers and media sources.

The 3D-McMap Guidelines: Three-Dimensional Multicomposite Microsphere Adaptive Printing.

Microspheres, synthesized from diverse natural or synthetic polymers, are readily utilized in biomedical tissue engineering to improve the healing of various tissues. Their ability to encapsulate growth factors, therapeutics, and natural biomolecules, which can aid tissue regeneration, makes microspheres invaluable for future clinical therapies. While microsphere-supplemented scaffolds have been investigated, a pure microsphere scaffold with an optimized architecture has been challenging to create via 3D printing methods due to issues that prevent consistent deposition of microsphere-based materials and their ability to maintain the shape of the 3D-printed structure.

CerS6-dependent ceramide synthesis in hypothalamic neurons promotes ER/mitochondrial stress and impairs glucose homeostasis in obese mice.

Dysregulation of hypothalamic ceramides has been associated with disrupted neuronal pathways in control of energy and glucose homeostasis. However, the specific ceramide species promoting neuronal lipotoxicity in obesity have remained obscure. Here, we find increased expression of the C ceramide-producing ceramide synthase (CerS)6 in cultured hypothalamic neurons exposed to palmitate in vitro and in the hypothalamus of obese mice.

Parallel Chondrogenesis and Osteogenesis Tissue Morphogenesis in Muscle Tissue via Combinations of TGF-β Supergene Family Members.

Objective: This study aimed to decipher the temporal and spatial signaling code for clinical cartilage and bone regeneration. We investigated the effects of continuous equal dosages of a single, dual, or triplicate growth factor combination of bone morphogenetic protein (BMP)-2, transforming growth factor (TGF)-β3, and/or BMP-7 on muscle tissue over a culturing period. The hypothesis was that specific growth factor combinations at specific time points direct tissue transformation toward endochondral bone or cartilage formation.

BRAF in-frame deletion mutants differ in their dimerization propensity, HSP90 dependence, and druggability.

In-frame exon 12 deletions are increasingly identified in various tumor types. The resultant BRAF oncoproteins usually lack five amino acids in the β3-αC helix linker and sometimes contain de novo insertions. The dimerization status of BRAF oncoproteins, their precise pathomechanism, and their direct druggability by RAF inhibitors (RAFi) has been under debate.

Antisense Oligonucleotide Therapy Decreases IL-1β Expression and Prolongs Survival in Mutant Nlrp3 Mice.

Antisense oligonucleotides (ASOs) are a novel therapeutic strategy that targets a specific gene and suppresses its expression. The cryopyrin-associated periodic syndromes (CAPS) are a spectrum of autoinflammatory diseases characterized by systemic and tissue inflammation that is caused by heterozygous gain-of-function mutations in the nucleotide-binding and oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) gene. The aim of this study was to investigate the efficacy of an Nlrp3-specific ASO treatment in CAPS.

Dual TLR9 and PD-L1 targeting unleashes dendritic cells to induce durable antitumor immunity.

Background: Although immune checkpoint inhibitors have been a breakthrough in clinical oncology, these therapies fail to produce durable responses in a significant fraction of patients. This lack of long-term efficacy may be due to a poor pre-existing network linking innate and adaptive immunity. Here, we present an antisense oligonucleotide (ASO)-based strategy that dually targets toll-like receptor 9 (TLR9) and programmed cell death ligand 1 (PD-L1), aiming to overcome resistance to anti-PD-L1 monoclonal therapy.

Osteochondrogenesis by TGF-β3, BMP-2 and noggin growth factor combinations in an muscle tissue model: Temporal function changes affecting tissue morphogenesis.

In the absence of clear molecular insight, the biological mechanism behind the use of growth factors applied in osteochondral regeneration is still unresolved. The present study aimed to resolve whether multiple growth factors applied to muscle tissue , such as TGF-β3, BMP-2 and Noggin, can lead to appropriate tissue morphogenesis with a specific osteochondrogenic nature, thereby revealing the underlying molecular interaction mechanisms during the differentiation process. Interestingly, although the results showed the typical modulatory effect of BMP-2 and TGF-β3 on the osteochondral process, and Noggin seemingly downregulated specific signals such as BMP-2 activity, we also discovered a synergistic effect between TGF-β3 and Noggin that positively influenced tissue morphogenesis.

STAT3 signaling induced by the IL-6 family of cytokines modulates angiogenesis.

Aberrant angiogenesis is a hallmark of cardiovascular and retinal neovascular disease. The STAT3 signaling pathway represents a potential pharmacological target for these diseases due to its impact on angiogenesis. Surprisingly, some STAT3 activators, such as the IL-6 cytokine family member oncostatin M (OSM), enhance angiogenesis, whereas others, such as ciliary neurotropic factor (CNTF), reduce it.

The intellectual capital supporting nurse practice in a post-emergency state: A case study.

Aim: To explore the resources supporting current nurse practice in the post-emergency country of Liberia, using the nursing intellectual capital framework, as nurses work to meet the targets set by Government of Liberia's Essential Package of Health Services.

Design: Case study.

Methods: Data were collected in Liberia February-June 2019.

Profiling Biomarkers in HIV Glomerular Disease - Potential for the Non-Invasive Diagnosis of HIVAN?

Background: There is a wide spectrum of kidney pathology in human immunodeficiency virus (HIV) infection, affecting all structures of the kidney. The histology of HIV chronic kidney disease (CKD) is diverse, ranging from HIV-associated nephropathy (HIVAN) to focal glomerulosclerosis (FSGS), HIV-immune complex disease (HIV-ICD), other glomerulopathies and tubulo-interstitial nephritis. Definitive diagnosis is by kidney biopsy, an invasive procedure.

Gaps and Opportunities in HIV Service Delivery in High Volume HIV Care Centers in Liberia: Lessons From the Field.

Background: Human Immunodeficiency Virus (HIV) infection continues to have a profound humanitarian and public health impact in western and central Africa, a region that risks being left behind in the global response to ending the AIDS epidemic. In Liberia, where the health system is being rebuilt following protracted civil wars and an Ebola virus disease outbreak, the Resilient and Responsive Health System (RRHS) is assisting with quality HIV services delivery through support from PEPFAR and HRSA but gaps remain across the cascade of care from diagnosis to viral load suppression.

Objective: To highlight gaps in HIV service delivery in Liberia, identify opportunities and offer recommendations for improving the quality of service delivery.

Facing COVID-19 in Liberia: Adaptations of the Resilient and Responsive Health Systems Initiative.

The 5-year Resilient and Responsive Health Systems (RRHS)-Liberia Initiative, funded by PEPFAR via HRSA, launched in 2017 and was designed to support the implementation of Liberia's National Health Workforce Program as a means to improving HIV-related health outcomes. The COVID-19 pandemic, arrived in Liberia just five years after Ebola and during RRHS-Liberia's fourth year, impacted educational programs and threatened the project's continued work. This paper presents the challenges that the COVID-19 pandemic posed to the RRHS partners, as well as adaptations they made to maintain progress towards project goals: 1) contributing to Liberia's 95-95-95 HIV targets via direct service delivery, and 2) building a resilient and responsive health workforce in Liberia via instruction and training.

Normal Physiologic Birth Continuing Professional Development: From a National Health Priority to Expanded Capacity.

Background: The Republic of Liberia has experienced many barriers to maintaining the quality of its healthcare workforce. The Resilient and Responsive Health Systems (RRHS) Initiative supported by the U.S.

Structure, Process, and Outcomes of Liberian National Nursing and Midwifery Curricular Revisions.

Background: The Republic of Liberia has had major disruptions to the education of its health care cadres. Post Ebola, the Resilient and Responsive Health Systems (RRHS) initiative began a new era of capacity building with the support of PEPFAR and HRSA. Nursing and Midwifery serve as the largest healthcare cadres in Liberia.

CHOP-ASO Ameliorates Glomerular and Tubular Damage on Top of ACE Inhibition in Diabetic Kidney Disease.

Background: Maladaptive endoplasmic reticulum stress signaling in diabetic kidney disease (DKD) is linked to increased glomerular and tubular expression of the cell-death-promoting transcription factor C/EBP homologous protein (CHOP). Here, we determined whether locked nucleic acid (LNA)-modified antisense oligonucleotides (ASOs) targeting CHOP ameliorate experimental DKD.

Methods: We determined the efficacy of CHOP-ASO in the early and late stages of experimental DKD (in 8- or 16-week-old db/db mice, respectively) alone or with an angiotensin-converting enzyme inhibitor (ACEi), after an in vivo dose-escalation study.

How clinicians manage routinely low supplies of personal protective equipment.

Background: Recommended personal protective equipment (PPE) is routinely limited or unavailable in low-income countries, but there is limited research as to how clinicians adapt to that scarcity, despite the implications for patients and workers.

Methods: This is a qualitative secondary analysis of case study data collected in Liberia in 2019. Data from the parent study were included in this analysis if it addressed availability and use of PPE in the clinical setting.

Investigation of the Activity of Antisense Oligonucleotides Targeting Multiple Genes by RNA-Sequencing.

Locked nucleic acid-modified antisense oligonucleotides (ASOs) can achieve strongly different degrees of target knockdown despite having similar biophysical properties and 100% homology with their target. The determinants for this observation remain largely unknown. We used multi-specific ASOs that have 100% sequence complementarity with a common target () and a different number of diverse targets and investigated their effect on gene expression in a cell line by RNA-sequencing.

Sensitivity and Resistance of Oncogenic RAS-Driven Tumors to Dual MEK and ERK Inhibition.

Oncogenic mutations in family genes arise frequently in metastatic human cancers. Here we developed new mouse and cellular models of oncogenic Hras-driven undifferentiated pleomorphic sarcoma metastasis and of Kras-driven pancreatic ductal adenocarcinoma metastasis. Through analyses of these cells and of human oncogenic KRAS-, NRAS- and BRAF-driven cancer cell lines we identified that resistance to single MEK inhibitor and ERK inhibitor treatments arise rapidly but combination therapy completely blocks the emergence of resistance.

Infection Prevention and Control in Liberia 5 Years After Ebola: A Case Study.

Background: Effective management of health emergencies is an important strategy to improve health worldwide. One way to manage health emergencies is to build and sustain national capacities. The Ebola epidemic of 2014 to 2015 resulted in greater infection prevention and control (IPC) capacity in Liberia, but few studies have investigated if and how that capacity was sustained.