Occurrence of Depression and its Association with Oral Health in Elderly People Living in Old Age Homes of Mathura.

Introduction: Depression can affect oral health as a result of neglecting oral hygiene procedures which leads to an increased risk of dental caries and periodontal disease. Aim: To determine relationship between oral health and depression among elder people residing in old age homes of Mathura city. Materials and Methods: The study was conducted among 500 subjects aged ≥60 years where dental condition, number of missing teeth, removable denture wearing, teeth mobility, periodontal condition, pocket depth, loss of attachment, and depression according to the Patient Health Questionnaire-9 scale were assessed. Results: Regression analysis showed a positive relationship of the PHQ-9 value with DMFT and MT. Conclusion: Among people aged 60 years and over, severity of depression increased with higher number of MT and DT.

Role of Lipid Packing Defects in Determining Membrane Interactions of Antimicrobial Polymers.

Understanding the emergence and role of lipid packing defects in the detection and subsequent partitioning of antimicrobial agents into bacterial membranes is essential for gaining insights into general antimicrobial mechanisms. Herein, using methacrylate polymers as a model platform, we investigate the effects of inclusion of various functional groups in the biomimetic antimicrobial polymer design on the aspects of lipid packing defects in model bacterial membranes. Two antimicrobial polymers are considered: ternary polymers composed of cationic, hydrophobic, and polar moieties and binary polymers with only cationic and hydrophobic moieties. We find that differing modes of insertion of these two polymers lead to different packing defects in the bacterial membrane. While insertion of both binary and ternary polymers leads to an enhanced number of deep defects in the upper leaflet, shallow defects are moderately enhanced upon interaction with ternary polymers only. We provide conclusive evidence that insertion of antimicrobial polymers in bacterial membrane is preceded by sensing of interfacial lipid packing defects. Our simulation results show that the hydrophobic groups are inserted at a single colocalized deep defect site for both binary and ternary polymers. However, the presence of polar groups in the ternary polymers use the shallow defects close to the lipid-water interface, in addition, to insert into the membrane, which leads to a more folded conformation of the ternary polymer in the membrane environment, and hence a different membrane partitioning mechanism compared to the binary polymer, which acquires an amphiphilic conformation.

Towards designing globular antimicrobial peptide mimics: role of polar functional groups in biomimetic ternary antimicrobial polymers.

Using atomistic molecular dynamics simulations, we study the interaction of ternary methacrylate polymers, composed of charged cationic, hydrophobic and neutral polar groups, with model bacterial membrane. Our simulation data shows that the random ternary polymers can penetrate deep into the membrane interior and partitioning of even a single polymer has a pronounced effect on the membrane structure. Lipid reorganization, on polymer binding, shows a strong affinity of the ternary polymer for anionic POPG lipids and the same is compared with the control case of binary polymers (only cationic and hydrophobic groups). While binary polymers exhibit strong propensity of acquired amphiphilic conformations upon membrane insertion, our results strongly suggest that such amphiphilic conformations are absent in the case of random ternary polymers. The ternary polymers adopt a more folded conformation, staying aligned in the direction of the membrane normal and subsequently penetrating deeper into the membrane interior suggesting a novel membrane partitioning mechanism without amphiphilic conformations. Finally, we also examine the interactions of ternary polymer aggregates with model bacterial membranes, which show that replacing some of the hydrophobic groups by polar groups leads to weakly held ternary aggregates enabling them to undergo rapid partitioning and insertion into membrane interior. Our work thus underscores the role of inclusion of polar groups into the framework of traditional binary biomimetic antimicrobial polymers and suggests different mode of partitioning into bacterial membranes, mimicking antimicrobial mechanism of globular antimicrobial peptides like Defensin.

The function of peptide-mimetic anionic groups and salt bridges in the antimicrobial activity and conformation of cationic amphiphilic copolymers.

Herein we report the synthesis of ternary statistical methacrylate copolymers comprising cationic ammonium (amino-ethyl methacrylate: AEMA), carboxylic acid (propanoic acid methacrylate: PAMA) and hydrophobic (ethyl methacrylate: EMA) side chain monomers, to study the functional role of anionic groups on their antimicrobial and hemolytic activities as well as the conformation of polymer chains. The hydrophobic monomer EMA was maintained at 40 mol% in all the polymers, with different percentages of cationic ammonium (AEMA) and anionic carboxylate (PAMA) side chains, resulting in different total net charge for the polymers. The antimicrobial and hemolytic activities of the copolymer were determined by the net charge of +3 or larger, suggesting that there was no distinct effect of the anionic carboxylate groups on the antimicrobial and hemolytic activities of the copolymers. However, the pH titration and atomic molecular dynamics simulations suggest that anionic groups may play a strong role in controlling the polymer conformation. This was achieved via formation of salt bridges between cationic and anionic groups, transiently crosslinking the polymer chain allowing dynamic switching between compact and extended conformations. These results suggest that inclusion of functional groups in general, other than the canonical hydrophobic and cationic groups in antimicrobial agents, may have broader implications in acquiring functional structures required for adequate antimicrobial activity. In order to explain the implications, we propose a molecular model in which formation of intra-chain, transient salt bridges, due to the presence of both anionic and cationic groups along the polymer, may function as "adhesives" which facilitate compact packing of the polymer chain to enable functional group interaction but without rigidly locking down the overall polymer structure, which may adversely affect their functional roles.

Aggregation of methacrylate-based ternary biomimetic antimicrobial polymers in solution.

Using detailed atomistic simulations, we explore the morphological characteristics of aggregates formed in solution phase by ternary biomimetic antimicrobial (AM) methacrylate polymers, composed of hydrophobic, charged cationic and polar functional groups and compare it with aggregate morphologies of binary methacrylate polymers, composed only of hydrophobic and charged cationic functional groups. The effect of sequence of the constituent functional groups on aggregate conformation is also studied by considering random and block sequences along the polymer backbone. Our results show that while binary polymers tend to form robust aggregates, replacing some of the hydrophobic groups with overall charge neutral polar groups weakens the aggregate considerably, leading to increased conformational fluctuations and formation of loose-packed, open aggregates, particularly in the case of random ternary polymers. Interaction energy calculations clearly suggest that the role of inclusion of polar groups in ternary polymers is two-fold: (1) to reduce possible strong local concentration of hydrophobic groups and 'smear' the overall hydrophobicity along the polymer backbone to increase the solubility of the polymers (2) to compensate the loss of attractive hydrophobic interactions by forming attractive electrostatic interactions with the charged groups and contribute to aggregation formation, albeit weak. Given that most of the naturally occurring AM peptides have contributions from all the three functional groups, this study elucidates the functionally tuneable role of inclusion of polar groups in the way AM agents interact with each other in solution phase, which can eventually dictate their partitioning behaviour into bacterial and mammalian membranes.

Importance of being cross-linked for the bacterial cell wall.

The bacterial cell wall is primarily composed of a mesh of glycan strands cross-linked by peptide bridges and is essential for safeguarding the cell. The structure of the cell wall has to be stiff enough to bear the high turgor pressure and sufficiently tough to ensure protection against failure. Here we explore the role of various design features of the cell in enhancing the toughness of the cell wall. We explain how the glycan strand length distribution, the degree of cross-linking and the placement of the cross-links on the glycan strands can act in tandem to ensure that the cell wall offers sufficient resistance to propagation of cracks. Further, we suggest a possible mechanism by which peptide bond hydrolysis, via judicious cleaving of peptide cross-links, can act to mitigate this risk of failure. We also study the reinforcing effect of MreB cytoskeleton, which can offer a degree of safety to the cell wall. However, we show that the cross-linked structure of the cell wall is its primary line of defense against mechanical failure.

Modeling cell-substrate de-adhesion dynamics under fluid shear.

Changes in cell-substrate adhesion are believed to signal the onset of cancer metastasis, but such changes must be quantified against background levels of intrinsic heterogeneity between cells. Variations in cell-substrate adhesion strengths can be probed through biophysical measurements of cell detachment from substrates upon the application of an external force. Here, we investigate, theoretically and experimentally, the detachment of cells adhered to substrates when these cells are subjected to fluid shear. We present a theoretical framework within which we calculate the fraction of detached cells as a function of shear stress for fast ramps as well as the decay in this fraction at fixed shear stress as a function of time. Using HEK and 3T3 fibroblast cells as experimental model systems, we extract characteristic force scales for cell adhesion as well as characteristic detachment times. We estimate force-scales of ∼500 pN associated to a single focal contact, and characteristic time-scales of [Formula: see text] s representing cell-spread-area dependent mean first passage times to the detached state at intermediate values of the shear stress. Variations in adhesion across cell types are especially prominent when cell detachment is probed by applying a time-varying shear stress. These methods can be applied to characterizing changes in cell adhesion in a variety of contexts, including metastasis.