Supramolecular Enzyme-Peptide Gels for Localized Therapeutic Biocatalysis.

Enzyme therapeutics are often compromised by poor accumulation within target tissues, necessitating high doses that can exacerbate off-target effects. We report an injectable supramolecular enzyme-peptide gel platform for prolonged local enzyme retention . The gel is based on CATCH(+/-) ( C o- A ssembling T ags based on CH arge-complementarity), cationic and anionic peptide pairs that form β-sheet fibrils upon mixing .

A Natural deep eutectic solvent as an effective material for dual debridement and antibiofilm effects in chronic wound treatment.

In chronic wound treatment, the debridement of devitalized tissue and the eradication of the biofilm must balance aggressiveness with care to protect regenerating tissues. In this study, urea, a potent chaotropic molecule, was modulated through the formation of a Natural Deep Eutectic Solvent (NADES) with betaine to develop a new debriding material (BU) suitable for application into injured dermal tissues. To evaluate BU's debriding capacity, along with its antibiofilm effect and biocompatibility, pre-clinical to clinical methods were employed.

Association of congenital heart defects (CHD) with factors related to maternal health and pregnancy in newborns in Puerto Rico.

Background: Given the pervasive issues of obesity and diabetes both in Puerto Rico and the broader United States, there is a compelling need to investigate the intricate interplay among BMI, pregestational, and gestational maternal diabetes, and their potential impact on the occurrence of congenital heart defects (CHD) during neonatal development.

Methods: Using the comprehensive System of Vigilance and Surveillance of Congenital Defects in Puerto Rico, we conducted a focused analysis on neonates diagnosed with CHD between 2016 and 2020. Our assessment encompassed a range of variables, including maternal age, gestational age, BMI, pregestational diabetes, gestational diabetes, hypertension, history of abortion, and presence of preeclampsia.

Extracavitary primary effusion lymphoma presenting as a solitary brain mass.

Primary effusion lymphoma (PEL) is an uncommon B-cell lymphoma associated with human herpesvirus 8 and comprises 3-4% of all HIV-related lymphomas. It traditionally presents as a pleural, pericardial, and/or peritoneal effusion, though it can occasionally manifest as an extracavitary or solid mass in the absence of an effusion. The extracavitary or solid variant of primary effusion lymphoma has been reported in the skin, gastrointestinal tract, lung, and lymph nodes.

Differential outcomes of re-stratified high-risk prostate cancer patients treated with external beam radiation therapy plus high-dose-rate brachytherapy boost.

Purpose: We report outcomes of high-risk prostate cancer (PCa) patients, initially classified according to a 3-tier NCCN classification system, treated with external beam radiation therapy (EBRT) and high-dose-rate brachytherapy boost (HDR-BT). Patients were analyzed based on a re-stratification of their risk grouping using CAPRA score and a newer 5-tier NCCN classification.

Material And Methods: 471 high-risk PCa patients treated with EBRT, HDR-BT, and androgen deprivation therapy (ADT) between 1999 and 2018 were included.

Expression and purification of active shikimate dehydrogenase from Plasmodium falciparum.

Plasmodium falciparum is known to cause severe malaria, current treatment consists in artemisinin-based combination therapy, but resistance can lead to treatment failure. Knowledge concerning P. falciparum essential proteins can be used for searching new antimalarials, among these a potential candidate is shikimate dehydrogenase (SDH), an enzyme part of the shikimate pathway which is responsible for producing endogenous aromatic amino acids.

The Immunoregulatory and Regenerative Potential of Activated Human Stem Cell Secretome Mitigates Acute-on-Chronic Liver Failure in a Rat Model.

Acute-on-chronic liver failure (ACLF) is a syndrome marked by sudden liver function decline and multiorgan failure, predominantly acute kidney injury (AKY), in patients with chronic liver disease. Unregulated inflammation is a hallmark of ACLF; however, the key drivers of ACLF are not fully understood. This study explores the therapeutic properties of human mesenchymal stem cell (MSC) secretome, particularly focusing on its enhanced anti-inflammatory and pro-regenerative properties after the in vitro preconditioning of the cells.

Intramedullary Spinal Cord Tumors: Whole-Genome Sequencing to Assist Management and Prognosis.

Intramedullary spinal cord tumors (IMSCTs) harbor unique genetic mutations which may play a role in prognostication and management. To this end, we present the largest cohort of IMSCTs with genetic characterization in the literature from our multi-site institutional registry. A total of 93 IMSCT patient records were reviewed from the years 1999 to 2020.

Attention Deficit-Hyperactivity Disorder (ADHD): From Abnormal Behavior to Impairment in Synaptic Plasticity.

Attention deficit-hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high incidence in children and adolescents characterized by motor hyperactivity, impulsivity, and inattention. Magnetic resonance imaging (MRI) has revealed that neuroanatomical abnormalities such as the volume reduction in the neocortex and hippocampus are shared by several neuropsychiatric diseases such as schizophrenia, autism spectrum disorder and ADHD. Furthermore, the abnormal development and postnatal pruning of dendritic spines of neocortical neurons in schizophrenia, autism spectrum disorder and intellectual disability are well documented.

Therapeutic response to pazopanib: case report and literature review on molecular abnormalities of aggressive prolactinomas.

Introduction: Aggressive prolactinomas (APRLs) pose a significant clinical challenge due to their high rate of regrowth and potentially life-threatening complications. In this study, we present a case of a patient with an APRL who had a trial of multiple therapeutic modalities with the aim to provide a review of molecular abnormalities and management of APRLs by corroborating our experience with previous literature.

Methods: A total of 268 articles were reviewed and 46 were included.

Histone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of Plasmodium parasites.

Gene expression in malaria parasites is subject to various layers of regulation, including histone post-translational modifications (PTMs). Gene regulatory mechanisms have been extensively studied during the main developmental stages of Plasmodium parasites inside erythrocytes, from the ring stage following invasion to the schizont stage leading up to egress. However, gene regulation in merozoites that mediate the transition from one host cell to the next is an understudied area of parasite biology.

Suppression of local inflammation via galectin-anchored indoleamine 2,3-dioxygenase.

The treatment of chronic inflammation with systemically administered anti-inflammatory treatments is associated with moderate-to-severe side effects, and the efficacy of locally administered drugs is short-lived. Here we show that inflammation can be locally suppressed by a fusion protein of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO) and galectin-3 (Gal3). Gal3 anchors IDO to tissue, limiting the diffusion of IDO-Gal3 away from the injection site.

The unfolded protein response transcription factor XBP1s ameliorates Alzheimer's disease by improving synaptic function and proteostasis.

Alteration in the buffering capacity of the proteostasis network is an emerging feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is the main adaptive pathway to cope with protein folding stress at the ER. Inositol-requiring enzyme-1 (IRE1) operates as a central ER stress sensor, enabling the establishment of adaptive and repair programs through the control of the expression of the transcription factor X-box binding protein 1 (XBP1).

Anti-Inflammatory Chilean Endemic Plants.

Medicinal plants have been used since prehistoric times and continue to treat several diseases as a fundamental part of the healing process. Inflammation is a condition characterized by redness, pain, and swelling. This process is a hard response by living tissue to any injury.

Royal jelly extracellular vesicles promote wound healing by modulating underlying cellular responses.

royal jelly (RJ) is a well-known remedy in traditional medicine around the world and its versatile effects range from antibacterial to anti-inflammatory properties and pro-regenerative properties. As a glandular product, RJ has been shown to contain a substantial number of extracellular vesicles (EVs), and, in this study, we aimed to investigate the extent of involvement of RJEVs in wound healing-associated effects. Molecular analysis of RJEVs verified the presence of exosomal markers such as CD63 and syntenin, and cargo molecules MRJP1, defensin-1, and jellein-3.

Solid Fiber Inside of Capillary and Modified Fusion-Spliced Fiber Optic Microneedle Devices for Improved Light Transmission Efficiency.

Convection-enhanced delivery (CED) is a drug delivery technique used to deliver therapeutics directly to the brain and is a continually evolving technique to treat glioblastoma. Early versions of CED have proven to result in inadequate drug volume dispersed (V), increasing the likelihood of tumor recurrence. Fiber optic microneedle devices (FMDs) with the ability to deliver fluid and thermal energy simultaneously have shown an ability to increase V, but FMDs have historically had low light transmission efficiency.

Advancements in drug delivery methods for the treatment of brain disease.

The blood-brain barrier (BBB) presents a formidable obstacle to the effective delivery of systemically administered pharmacological agents to the brain, with ~5% of candidate drugs capable of effectively penetrating the BBB. A variety of biomaterials and therapeutic delivery devices have recently been developed that facilitate drug delivery to the brain. These technologies have addressed many of the limitations imposed by the BBB by: (1) designing or modifying the physiochemical properties of therapeutic compounds to allow for transport across the BBB; (2) bypassing the BBB by administration of drugs alternative routes; and (3) transiently disrupting the BBB (BBBD) using biophysical therapies.

Reproductive Justice: A Case-Based, Interactive Curriculum.

Introduction: Reproductive injustices such as forced sterilization, preventable maternal morbidity and mortality, restricted access to family planning services, and policy-driven environmental violence undermine reproductive autonomy and health outcomes, with disproportionate impact on historically marginalized communities. However, curricula focused on reproductive justice (RJ) are lacking in medical education.

Methods: We designed a novel, interactive, case-based RJ curriculum for postclerkship medical students.

Active Observation of Biochemical Recurrence without Treatment following Radical Prostatectomy: Long-Term Analysis of Outcomes.

Biochemical recurrence (BCR) following radical prostatectomy (RP) is an unreliable predictor of prostate cancer (PC) progression. This study was a retrospective cohort analysis of prospectively collected data (407/1895) of men with BCR at a tertiary referral center. Patients were assessed for active observation (AO) compared with a treatment group (TG) utilizing doubling time (DT) kinetics.

Methylphenidate Restores Behavioral and Neuroplasticity Impairments in the Prenatal Nicotine Exposure Mouse Model of ADHD: Evidence for Involvement of AMPA Receptor Subunit Composition and Synaptic Spine Morphology in the Hippocampus.

In ADHD treatment, methylphenidate (MPH) is the most frequently used medication. The present work provides evidence that MPH restored behavioral impairments and neuroplasticity due to changes in AMPAR subunit composition and distribution, as well as maturation of dendritic spines, in a prenatal nicotine exposure (PNE) ADHD mouse model. PNE animals and controls were given a single oral dose of MPH (1 mg/kg), and their behavior was tested for attention, hyperactivity, and working memory.

Social Networking Use Across Gender: Its Association with Social Connectedness and Happiness Amidst the COVID-19 Pandemic.

With the increasing popularity of social networking platforms, it serves a greater purpose that is no longer contained simply as a means of social leisure. Social networking sites (SNSs) form and maintain social interactions. Various phenomena revolve around how this usage is associated with certain behaviors, such as keeping social ties online and affecting well-being.