Long-acting injectable ART to advance health equity: a descriptive analysis of US clinic perspectives on barriers, needed support and programme goals for implementation from applications to the ALAI UP Project.

Introduction: Approval of the first long-acting injectable antiretroviral therapy (LAI ART) medication heralded a new era of HIV treatment. However, the years since approval have been marked by implementation challenges. The "Accelerating Implementation of Multilevel Strategies to Advance Long-Acting Injectable for Underserved Populations (ALAI UP Project)" aims to accelerate the systematic and equitable delivery of LAI ART.

Hepatitis C Cascade of Care in a Multidisciplinary Substance Use Bridge Clinic Model in Tennessee.

Many barriers prevent individuals with substance use disorders from receiving hepatitis C virus (HCV) treatment. This study describes 96 patients with active HCV treated in an opioid use disorder bridge clinic model. Of 33 patients who initiated treatment, 25 patients completed treatment, and 13 patients achieved sustained virologic response.

The role of pharmacogenetics in the treatment of major depressive disorder: a critical review.

Pharmacological therapy represents one of the essential approaches to treatment of Major Depressive Disorder (MDD). However, currently available antidepressant medications show high rates of first-level treatment non-response, and several attempts are often required to find an effective molecule for a specific patient in clinical practice. In this context, pharmacogenetic analyses could represent a valuable tool to identify appropriate pharmacological treatment quickly and more effectively.

Glaucoma-associated Optineurin mutations increase transmitophagy in a vertebrate optic nerve.

We previously described a process referred to as transmitophagy where mitochondria shed by retinal ganglion cell (RGC) axons are transferred to and degraded by surrounding astrocytes in the optic nerve head of mice. Since the mitophagy receptor Optineurin (OPTN) is one of few large-effect glaucoma genes and axonal damage occurs at the optic nerve head in glaucoma, here we explored whether OPTN mutations perturb transmitophagy. Live-imaging of optic nerves revealed that diverse human mutant but not wildtype OPTN increase stationary mitochondria and mitophagy machinery and their colocalization within, and in the case of the glaucoma-associated OPTN mutations also outside of, RGC axons.

Bone Metastasis Initiation Is Coupled with Bone Remodeling through Osteogenic Differentiation of NG2+ Cells.

Unlabelled: The bone microenvironment is dynamic and undergoes remodeling in normal and pathologic conditions. Whether such remodeling affects disseminated tumor cells (DTC) and bone metastasis remains poorly understood. Here, we demonstrated that pathologic fractures increase metastatic colonization around the injury.

Metabolite discovery through global annotation of untargeted metabolomics data.

Liquid chromatography-high-resolution mass spectrometry (LC-MS)-based metabolomics aims to identify and quantify all metabolites, but most LC-MS peaks remain unidentified. Here we present a global network optimization approach, NetID, to annotate untargeted LC-MS metabolomics data. The approach aims to generate, for all experimentally observed ion peaks, annotations that match the measured masses, retention times and (when available) tandem mass spectrometry fragmentation patterns.

The bone microenvironment increases phenotypic plasticity of ER breast cancer cells.

Estrogen receptor-positive (ER) breast cancer exhibits a strong bone tropism in metastasis. How the bone microenvironment (BME) impacts ER signaling and endocrine therapy remains poorly understood. Here, we discover that the osteogenic niche transiently and reversibly reduces ER expression and activities specifically in bone micrometastases (BMMs), leading to endocrine resistance.

Exploiting bone niches: progression of disseminated tumor cells to metastasis.

Many solid cancers metastasize to the bone and bone marrow (BM). This process may occur even before the diagnosis of primary tumors, as evidenced by the discovery of disseminated tumor cells (DTCs) in patients without occult malignancies. The cellular fates and metastatic progression of DTCs are determined by complicated interactions between cancer cells and BM niches.

Unique cellular protrusions mediate breast cancer cell migration by tethering to osteogenic cells.

Migration and invasion are key properties of metastatic cancer cells. These properties can be acquired through intrinsic reprogramming processes such as epithelial-mesenchymal transition. In this study, we discovered an alternative "migration-by-tethering" mechanism through which cancer cells gain the momentum to migrate by adhering to mesenchymal stem cells or osteoblasts.

Resistance to natural killer cell immunosurveillance confers a selective advantage to polyclonal metastasis.

Polyclonal metastases frequently arise from clusters of circulating tumor cells (CTCs). CTC clusters metastasize better than single CTCs, but the underlying molecular mechanisms are poorly understood. Here, we show that polyclonal metastatic seeds exhibit higher resistance to natural killer (NK) cell killing.

Sex Differences in the Relationship between PTSD Spectrum Symptoms and Autistic Traits in a Sample of University Students.

Background: While growing literature is stressing the link between Autistic Traits (AT) and trauma-/stress-related disorders, in both conditions significant differences have been separately reported.

Objective: This study aims to evaluate the relationship between AT and trauma-/stress-related symptoms with respect to sex.

Methods: 178 university students were assessed with the Structured Clinical Interview for DSM-5, the Trauma and Loss Spectrum (TALS) and the Adult Autism Subthreshold Spectrum (AdAS).

The broad autism phenotype in real-life: clinical and functional correlates of autism spectrum symptoms and rumination among parents of patients with autism spectrum disorder.

Objective: Increasing literature reported higher rates of psychiatric disorders in parents of children with autism spectrum disorder (ASD), as well as of autistic-like features in social and cognitive functioning. However, little attention has been paid to the association between autistic traits (AT) and global functioning in this population. The aim of the present work was to investigate clinical and functional correlates of AT among parents of ASD children, with a specific focus on ruminative thinking.

Emotional Blunting, Cognitive Impairment, Bone Fractures, and Bleeding as Possible Side Effects of Long-Term Use of SSRIs.

Objective: Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are amongst the most prescribed drugs worldwide not only for psychiatric conditions, but also for medical purposes. Converging data gathered throughout the decades following their development would indicate that SSRIs have a broader side effect profile than previously assumed. Therefore, the aim of the present paper was to to review available literature highlighting less common side effects emerging with their long-term use.

Intra-iliac Artery Injection for Efficient and Selective Modeling of Microscopic Bone Metastasis.

Intra-iliac artery (IIA) injection is an efficient approach to introduce metastatic lesions of various cancer cells in animals. Compared to the widely used intra-cardiac and intra-tibial injections, IIA injection brings several advantages. First, it can deliver a large quantity of cancer cells specifically to hind limb bones, thereby providing spatiotemporally synchronized early-stage colonization events and allowing robust quantification and swift detection of disseminated tumor cells.

The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells.

Breast cancer bone micrometastases can remain asymptomatic for years before progressing into overt lesions. The biology of this process, including the microenvironment niche and supporting pathways, is unclear. We find that bone micrometastases predominantly reside in a niche that exhibits features of osteogenesis.

Malignant hypomelanotic melanoma of mules. A histologic, immunohistochemical and ultrastructural study of a case with unknown primary site and widespread metastases.

An unusual case of malignant hypomelanotic melanoma occurred in a 15-year-old gray mantle mule with unknown primary site and widespread metastatic growth is described. An ante-mortem examination, the presence of subcutaneous nodules was noted; histologically they are constituted by spindle or polygonal-shaped tumour cells with rare black granules in the cytoplasm; the immunohistochemical procedures showed a large expression of S-100, vimentin and HMB-45 antibodies, suggesting thus a diagnosis of malignant melanoma. Ultrastructural findings, obtained on formalin-fixed paraffin-embedded material, showed characteristic melanosomes and irregular fibrillary centers in nuclei of neoplastic cells.

Conduction velocity study in type 1 diabetic patients.

The role of metabolic abnormalities in the development of diabetic neuropathy is controversial. To investigate the peripheral nerve function and the influence of hyperglycemia on nerve conduction in insulin-dependent diabetes, a one-year neurophysiological study was carried out in 30 type 1 diabetic patients ranging in age from 2-16 years. During the 12-month follow-up period the glycosylated hemoglobin determination, motor conduction velocity of the peroneal nerve and the motor and sensory conduction of the tibial nerve were assessed 3 times, at the beginning of the study and every 6 months thereafter.