Reduced reward responsiveness in treatment resistant depression of middle-aged adults: Association with carotid artery stiffness and tetrahydrobiopterin.

Nearly one third of the population diagnosed with major depressive disorder (MDD) fail to respond to two or more antidepressant drugs of adequate dose and duration. This necessitates identification of confounding psychological and physiological factors that could contribute to treatment resistant depression (TRD). The present longitudinal study investigated the influence of behavioural inhibition system (BIS) and behavioural approach system (BAS) in treatment resistance. Further, the association of depression severity with physiological factors contributing to arterial stiffness was also investigated. Baseline data was acquired from 101 middle-aged (36-56 years) patients on immediate diagnosis with MDD using DSM-V criteria. Follow ups were conducted at 06 months and 12 months during treatment. Psychological assessment battery at baseline and follow ups comprised of Hamilton depression rating (HAM-D) for depression severity, WHODAS-2 and BIS-BAS score. Atherosclerosis and central arterial stiffness were measured by intima-media thickness of internal carotid artery and brachial-ankle pulse wave velocity. Physiological factors influencing central vascular function viz., body-mass index, estimated glomerular filtration rate, HbA1c, central systolic and diastolic blood pressure, heart rate and tetrahydrobiopterin were also investigated. Our results show lower reward responsiveness (BAS-RR) and higher BIS scores in TRD patients along with differentially higher intima-media thickness of left internal carotid artery. Higher depression severity at all stages of the study was correlated with lower tetrahydrobiopterin and BAS-RR scores. We, therefore, suggest that vascular depression resulting due to increased intima-media thickness of left carotid artery and lower tetrahydrobiopterin could be contributing factors for treatment resistance in middle-aged MDD patients.

Antibacterial Coatings for Titanium Implants: Recent Trends and Future Perspectives.

Titanium and its alloys are widely used as implant materials for biomedical devices owing to their high mechanical strength, biocompatibility, and corrosion resistance. However, there is a significant rise in implant-associated infections (IAIs) leading to revision surgeries, which are more complicated than the original replacement surgery. To reduce the risk of infections, numerous antibacterial agents, e.g., bioactive compounds, metal ions, nanoparticles, antimicrobial peptides, polymers, etc., have been incorporated on the surface of the titanium implant. Various coating methods and surface modification techniques, e.g., micro-arc oxidation (MAO), layer-by-layer (LbL) assembly, plasma electrolytic oxidation (PEO), anodization, magnetron sputtering, and spin coating, are exploited in the race to create a biocompatible, antibacterial titanium implant surface that can simultaneously promote tissue integration around the implant. The nature and surface morphology of implant coatings play an important role in bacterial inhibition and drug delivery. Surface modification of titanium implants with nanostructured materials, such as titanium nanotubes, enhances bone regeneration. Antimicrobial peptides loaded with antibiotics help to achieve sustained drug release and reduce the risk of antibiotic resistance. Additive manufacturing of patient-specific porous titanium implants will have a clear future direction in the development of antimicrobial titanium implants. In this review, a brief overview of the different types of coatings that are used to prevent implant-associated infections and the applications of 3D printing in the development of antibacterial titanium implants is presented.

Role of Tumor Specific niche in Colon Cancer Progression and Emerging Therapies by Targeting Tumor Microenvironment.

Colorectal cancer is the third most common form of cancer worldwide leading to escalating mortality rates and mainly includes hereditary, sporadic and colitis-associated cancer development. The escalated mortality rates is due to the limited treatment options as this form of cancer is usually not easy to diagnose in its early stages and are highly invasive leading to rapid metastasis of the malignant cells to the neighbouring tissue. In order to combat this limitation several chemotherapeutic regimens are now being combined with targeted therapies after the knowledge acquired on the inevitable effects of the tumor microenvironment on the colon cancer growth and progress. The colon tumor niche mainly consists of a large mass of tumor cells along with various immune cells, inflammatory cells, tumor macrophages and fibroblasts that infiltrate the tumor as it is a site of predominant inflammation. Among cells of the microenvironment, mesenchymal stem cells (MSCs) exhibiting ability to evolve into cancer associated fibroblasts (CAFs) have recently generated a major interest in the field. The physiological state of the tumor microenvironment is closely connected to discrete steps of tumorigenesis. The colon cancer cells elicit various factors with their direct interaction with MSCs or via paracrine fashion, which modulate these cells to promote cancer instead of performing their innate function of abating cancer progression. This review intends to highlight the necessity to exploit the cellular landscape of tumor microenvironment of colon cancer and a detailed understanding of the interactions between tumor epithelial cells and their stromal/inflammatory elements will aid in future perspectives for designing therapeutic regimens targeting tumor microenvironment to improve the clinical outcome of colon cancer.