The Genetic and Molecular Drivers of Multiple Myeloma: Current Insights, Clinical Implications, and the Path Forward.

Background: Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of malignant plasma cells within the bone marrow. The disease's complexity is underpinned by a variety of genetic and molecular abnormalities that drive its progression.

Methods: This review was conducted through a state-of-The-art literature search, primarily utilizing PubMed to gather peer-reviewed articles.

FaMMily Affairs: Dissecting inherited contributions to multiple myeloma risk.

Etiological links to multiple myeloma (MM) remain poorly understood, though emerging evidence suggests a significant hereditary component. This review integrates current literature on inherited factors contributing to MM risk, synthesizing both epidemiologic and genomic data. We examine familial clustering patterns, assess genome-wide association studies (GWAS) that reveal common genetic variants linked to MM, and explore rare, high-penetrance variants in key susceptibility genes.

Mechanosensitive nuclear uptake of chemotherapy.

The nucleus is at the nexus of mechanotransduction and the final barrier for most first line chemotherapeutics. Here, we study the intersection between nuclear-cytoskeletal coupling and chemotherapy nuclear internalization. We find that chronic and acute modulation of intracellular filaments changes nuclear influx of doxorubicin (DOX).

Protein-Specific Crowding Accelerates Aging in Protein Condensates.

Macromolecular crowding agents, such as poly(ethylene glycol) (PEG), are often used to mimic cellular cytoplasm in protein assembly studies. Despite the perception that crowding agents have an inert nature, we demonstrate and quantitatively explore the diverse effects of PEG on the phase separation and maturation of protein condensates. We use two model proteins, the FG domain of Nup98 and bovine serum albumin (BSA), which represent an intrinsically disordered protein and a protein with a well-established secondary structure, respectively.

Interaction-Dependent Secondary Structure of Peptides in Biomolecular Condensates.

Biomolecular condensates provide a mechanism for compartmentalization of biomolecules in eukaryotic cells. These liquid-like condensates are formed via liquid-liquid phase separation, by a plethora of interactions, and can mediate several biological processes in healthy cells. Expansions of dipeptide repeat proteins, DPRs, in which arginine rich DPRs like poly-proline-arginine (PR), and poly-glycine-arginine (GR), partition RNA into condensates can however induce cell toxicity.

Occupational Noise Exposure in Foot and Ankle Surgery and the Risk of Noise-Induced Hearing Loss.

Background: Occupational exposure to high levels of noise increases the risk of noise-induced hearing loss (NIHL), resulting in significant long-term quality of life implications. Hearing protection is recommended if occupational noise exposure routinely exceeds 85 decibels (dB). The purpose of this study was to determine if foot and ankle surgeons are exposed to excessive levels of noise, thus putting them at an increased risk for NIHL.

Initial Safety of Total Talus Replacement Used to Treat Talar Avascular Necrosis.

Background: Total talus replacement (TTR) implants are designed to replace the diseased talar anatomy, reduce pain, maintain ankle range of motion, and restore ankle function after conservative treatments have failed. Currently TTR implants are produced by 3D printing a patient-specific implant designed from the patient's preoperative anatomy. TTR surgery using patient-specific implants is a relatively new technique that remains understudied in the literature.

An Evaluation of Oral Anticoagulant Safety Indicators by England's Community Pharmacies.

Background: Anticoagulants are life-saving medicines that can prevent strokes for patients diagnosed with atrial fibrillation (AF) as well as treating patients with venous thromboembolism (VTE), but when used incorrectly, they are frequently associated with patient harm.

Aim: To evaluate the impact of community pharmacy teams on optimising patient knowledge and awareness and improving medication safety from the use of anticoagulants.

Methods: Two national audits, consisting of 17 questions assessing and improving patients' understanding of anticoagulant therapy, identifying high-risk patients, and contacting prescribers when clinically appropriate were incentivised for England's community pharmacies in 2021-2022 and 2023-2024 using the Pharmacy Quality Scheme (PQS) commissioned by NHS England.

Health-Related Quality of Life After Neonatal Treatment of Symptomatic Tetralogy of Fallot: Insights from the Congenital Cardiac Research Collaborative.

To evaluate the association between initial management strategy of neonatal symptomatic Tetralogy of Fallot (sTOF) and later health-related quality of life (HRQOL) outcomes. We performed a multicenter, cross-sectional evaluation of a previously assembled cohort of infants with sTOF who underwent initial intervention at ≤ 30 days of age, between 2005 and 2017. Eligible patients' parents/guardians completed an age-appropriate Pediatric Quality of Life Inventory, a Pediatric Quality of Life Inventory Cardiac Module Heart Disease Symptoms Scale, and a parental survey.

A randomized, active-controlled, multi-centric, phase-II clinical study to assess safety and immunogenicity of a fully liquid DTwP-HepB-IPV-Hib hexavalent vaccine (HEXASIIL®) in Indian toddlers.

Background: Combination vaccines are effective in simplifying complex vaccination schedules involving multiple vaccines. A fully liquid hexavalent diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)- hepatitis B (HepB)-inactivated poliovirus (IPV)-Haemophilus influenzae b (Hib) vaccine (HEXASIIL®), manufactured by Serum Institute of India Pvt. Ltd.

The Influence of Resilience on Outcomes After Total Ankle Arthroplasty.

Background: Resiliency is the ability to recover from stressful events and has been shown to correlate with patient outcomes following certain orthopaedic procedures. The purpose of this study was to determine the relationship between resiliency and outcomes following TAA.

Methods: A retrospective analysis of patients undergoing primary TAA between April 2015 and September 2022 was performed (N = 83).

Systemic Factors Affecting Prognosis in Periodontics: Part II.

This study gives an insight into certain systemic conditions and factors such as nutrition, age, hematological disorders, hypertension, smoking, obesity, and metabolic syndrome that have a notable effect on the periodontium. The review highlights the importance of taking these factors into consideration in periodontal therapy and their impact on the prognosis of periodontal therapies. The other systemic factors are discussed in detail elsewhere in the special issue.

Repurposing antidiabetic drugs for Alzheimer's disease: A review of preclinical and clinical evidence and overcoming challenges.

Repurposing antidiabetic drugs for the treatment of Alzheimer's disease (AD) has emerged as a promising therapeutic strategy. This review examines the potential of repurposing antidiabetic drugs for AD treatment, focusing on preclinical evidence, clinical trials, and observational studies. In addition, the review aims to explore challenges and opportunities in repurposing antidiabetic drugs for AD, emphasizing the importance of well-designed clinical trials that consider patient selection criteria, refined outcome measures, adverse effects, and combination therapies to enhance therapeutic efficacy.

A standard set of outcome measures for the comprehensive assessment of oral health and occlusion in individuals with osteogenesis imperfecta.

Background: Osteogenesis imperfecta (OI) is a group of inherited connective tissue disorders of varying severity characterized by bone fragility. The primary objective of this international multidisciplinary collaboration initiative was to reach a consensus for a standardized set of clinician and patient-reported outcome measures, as well as associated measuring instruments for dental care of individuals with OI, based on the aspects considered important by both experts and patients. This project is a subsequent to the Key4OI project initiated by the Care4BrittleBones foundation which aims to develop a standard set of outcome measures covering a large domain of factors affecting quality of life for people with OI.

Self-Blinking Thioflavin T for Super-resolution Imaging.

Thioflavin T (ThT) is a typical dye used to visualize the aggregation and formation of fibrillar structures, e.g., amyloid fibrils and peptide nanofibrils.

Ketomimetic Nutrients Trigger a Dual Metabolic Defense in Breast Cancer Cells.

While the triggers for the metastatic transformation of breast cancer (BC) cells remain unknown, recent evidence suggests that intrinsic cellular metabolism could be a crucial driver of migratory disposition and chemoresistance. Aiming to decode the molecular mechanisms involved in BC cell metabolic maneuvering, we study how a ketomimetic (ketone body rich, low glucose) medium affects Doxorubicin (DOX) susceptibility and invasive disposition of BC cells. We quantified glycocalyx sialylation and found an inverse correlation with DOX-induced cytotoxicity and DOX internalization.

Charting the Course: Sequencing Immunotherapy for Multiple Myeloma.

Multiple chimeric antigen receptor (CAR) T-cell and bispecific antibody (bsAb) therapies have been approved, demonstrating impressive clinical efficacy in relapsed/refractory multiple myeloma (MM). Currently, these treatment share overlapping approval indications in the relapsed/refractory space, highlighting the importance of optimal selection and sequencing to maximize clinical efficacy. For patients previously unexposed to T-cell-directed therapies, several factors should be weighed when both options are available.

CAR T-cell toxicities: from bedside to bench, how novel toxicities inform laboratory investigations.

Multiple chimeric antigen receptor (CAR) T-cell therapies are US Food and Drug Administration-approved, and several are under development. Although effective for some cancers, toxicities remain a limitation. The most common toxicities, that is, cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, are well described.