A multifunctional silk-hyaluronic acid self-healing hydrogel laden with alternatively activated macrophage-derived exosomes reshape microenvironment of diabetic wound and accelerate healing.

The impairment of phenotype switching of pro-inflammatory M1 to pro-healing M2 macrophage induced by hyperglycemic microenvironment often elevates oxidative stress, impairs angiogenesis, and leads to chronic non-healing wounds in diabetic patients. Administration of M2 macrophage-derived exosomes (M2Exo) at wound site is known to polarize M1 to M2 macrophage and can accelerate wound healing by enhancing collagen deposition, angiogenesis, and re-epithelialization. In the present study, M2Exo were conjugated with oxidized hyaluronic acid and mixed with PEGylated silk fibroin to develop self-healing Exo-gel to achieve an efficient therapy for diabetic wounds. Exo-gel depicted porous networked morphology with self-healing and excellent water retention behaviour. Fibroblast cells treated with Exo-gel showed significant uptake of M2Exo that increased their proliferation and migration in vitro. Interestingly, in a diabetic wound model of wistar rats, Exo-gel treatment induced 75 % wound closure within 7 days with complete epithelial layer regeneration by modulating cytokine levels, stimulating fibroblast-keratinocyte interaction and migration, angiogenesis, and organized collagen deposition. Taken together, this study suggests that Exo-gel depict properties of an excellent wound healing matrix and can be used as a therapeutic alternative to treat chronic non-healing diabetic wounds.

Gut microbiota and epigenetics in colorectal cancer: implications for carcinogenesis and therapeutic intervention.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. The occurrence of CRC is associated with various genetic and epigenetic mutations in intestinal epithelial cells that transform them into adenocarcinomas. There is increasing evidence indicating the gut microbiota plays a crucial role in the regulation of host physiological processes. Alterations in gut microbiota composition are responsible for initiating carcinogenesis through diverse epigenetic modifications, including histone modifications, ncRNAs and DNA methylation. This work was designed to comprehensively review recent findings to provide insight into the associations between the gut microbiota and CRC at an epigenetic level. These scientific insights can be used in the future to develop effective strategies for early detection and treatment of CRC.

Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide. It happens when certain changes occur in the cells lining the intestine, turning them into cancerous growths. Recent studies suggest the collection of microbes in our gut, called the gut microbiota, plays a big role in how our body works. Dysregulation in gut microbiota composition is responsible for the development of colorectal cancer. This work provides a closer look at these recent discoveries to better understand how gut microbes might influence the development of colorectal cancer by affecting gene function. Understanding this connection may facilitate early diagnosis and treatment of colorectal cancer.

Tumor Antigen-Primed Dendritic Cell-Derived Exosome Synergizes with Colony Stimulating Factor-1 Receptor Inhibitor by Modulating the Tumor Microenvironment and Systemic Immunity.

Dendritic cell-derived exosomes (Dex) have overcome the disadvantages associated with dendritic cell (DC) vaccines, such as cost effectiveness, stability, and sensitivity to the systemic microenvironment. However, in clinical trials, Dex failed to provide satisfactory results because of many reasons, including inadequate maturation of DC as well as the immunosuppressive tumor microenvironment (TME). Hence, culturing DCs in the presence of a maturation cocktail showed an induced expression of MHCs and co-stimulatory molecules. Additionally, targeting the colony stimulating factor-1 (CSF-1)/CSF-1 receptor (CSF-1R) signaling pathway by a CSF-1R inhibitor could deplete tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) which are responsible for immunosuppressive TME. Hence, in this study, mDexTA were isolated from bone marrow-derived DC cultured in the presence of a novel maturation cocktail and tumor antigen. mDexTA showed elevated expression of major histocompatibility complexes (MHCs) and co-stimulatory molecules and was found capable of activating naïve DC and T cells in vitro more efficiently when compared to imDexTA isolated from immature DCs. In addition, PLX-3397, a small molecule inhibitor of CSF-1/CSF-1R, was used in combination to enhance the antitumor efficacy of mDexTA. PLX-3397 showed dose-dependent toxicity against bone marrow-derived macrophages (BMDMs). In the B16-F10 murine melanoma model, we found that the combination treatment delayed tumor growth and improved survival compared to the mice treated with mDexTA alone by enhancing the CD8 T cells infiltration in TME. mDexTA when combined with PLX-3397 modulated the TME by shifting the Th1/Th2 toward a dominant Th1 population and depleting the TAMs and MDSCs. Interestingly, PLX-3397-induced FoxP3 expression was diminished when it was used in combination with mDexTA. Combination treatment also induced favorable systemic antitumor immunity in the spleen and lymph node. In conclusion, our findings provide insights into the synergy between mDexTA-based immunotherapy and PLX-3397 as the combination overcame the disadvantages associated with monotherapy and offer a therapeutic strategy for the treatment of solid tumors including melanoma.

Ponatinib delays the growth of solid tumours by remodelling immunosuppressive tumour microenvironment through the inhibition of induced PD-L1 expression.

BACKGROUND: Therapeutic modalities including chemo, radiation, immunotherapy, etc. induce PD-L1 expression that facilitates the adaptive immune resistance to evade the antitumour immune response. IFN-γ and hypoxia are some of the crucial inducers of PD-L1 expression in tumour and systemic microenvironment which regulate the expression of PD-L1 via various factors including HIF-1α and MAPK signalling. Hence, inhibition of these factors is crucial to regulate the induced PD-L1 expression and to achieve a durable therapeutic outcome by averting the immunosuppression. METHODS: B16-F10 melanoma, 4T1 breast carcinoma, and GL261 glioblastoma murine models were established to investigate the in vivo antitumour efficacy of Ponatinib. Western blot, immunohistochemistry, and ELISA were performed to determine the effect of Ponatinib on the immunomodulation of tumour microenvironment (TME). CTL assay and flow cytometry were such as p-MAPK, p-JNK, p-Erk, and cleaved caspase-3 carried out to evaluate the systemic immunity induced by Ponatinib. RNA sequencing, immunofluorescence and Western blot analysis were used to determine the mechanism of PD-L1 regulation by Ponatinib. Antitumour immunity induced by Ponatinib were compared with Dasatinib. RESULTS: Here, Ponatinib treatment delayed the growth of tumours by inhibiting PD-L1 and modulating TME. It also downregulated the level of PD-L1 downstream signalling molecules. Ponatinib enhanced the CD8 T cell infiltration, regulated Th1/Th2 ratio and depleted tumour associated macrophages (TAMs) in TME. It induced a favourable systemic antitumour immunity by enhancing CD8 T cell population, tumour specific CTL activity, balancing the Th1/Th2 ratio and lowering PD-L1 expression. Ponatinib inhibited FoxP3 expression in tumour and spleen. RNA sequencing data revealed that Ponatinib treatment downregulated the genes related to transcription including HIF-1α. Further mechanistic studies showed that it inhibited the IFN-γ and hypoxia induced PD-L1 expression via regulating HIF-1α. Dasatinib was used as control to prove that Ponatinib induced antitumour immunity is via PD-L1 inhibition mediated T cell activation. CONCLUSIONS: RNA sequencing data along with rigorous in vitro and in vivo studies revealed a novel molecular mechanism by which Ponatinib can inhibit the induced PD-L1 levels via regulating HIF-1α expression which leads to modulation of tumour microenvironment. Thus, our study provides a novel therapeutic insight of Ponatinib for the treatment of solid tumours where it can be used alone or in combination with other drugs which are known to induce PD-L1 expression and generate adaptive resistance.

Multifaceted Nano-DEV-IL for Sustained Release of IL-12 to Avert the Immunosuppressive Tumor Microenvironment and IL-12-Associated Toxicities.

Interleukin-12 (IL-12) demonstrates potent antitumor activity by enhancing Th1/Th2 response, facilitating cytotoxic T-cell (CTL) recruitment into tumors, inhibiting tumor angiogenesis, and depleting immunosuppressive cells in the tumor microenvironment (TME). Despite having encouraging preclinical and some clinical results, further development of IL-12 is limited because dose-limiting toxicity is observed in early clinical trials with systemic administration of recombinant human IL-12. Hence, strategies aiming to lower the toxicity and to improve response rates are unmet needs. In this study, IL-12 was encapsulated in extracellular vesicles derived from mature dendritic cells (DEVs) activated with tumor antigens. IL-12-encapsulated DEVs (DEV-IL) delayed the growth of murine glioblastoma by facilitating the recruitment of CD8 T-cells, NK-cells, and DCs and effectively depleting immunosuppressive cells in the TME. DEV-IL shifted the Th1/Th2 ratio toward dominating Th1 cytokines which further led to the inhibition of angiogenesis. In addition, DEV-IL also modulated systemic immunity by enhancing CTL activity and the levels of proinflammatory cytokines in the spleen. Interestingly, DEV-IL did not impart hepatic and immunotoxicity which was observed with free IL-12 administration. Hence, our study established DEV-IL as a potent platform for the sustained delivery of cytokines and could be a promising immunotherapeutic strategy for the treatment of cancer.

Repurposing Ponatinib as a PD-L1 Inhibitor Revealed by Drug Repurposing Screening and Validation by In Vitro and In Vivo Experiments.

Cancer treatment by inhibiting the PD-1/PD-L1 pathway using monoclonal antibodies has made great advances as it showed long-lasting antitumor responses in a wide range of cancers. However, antibodies exhibit several disadvantages, which include low permeability, immune-related adverse effects, complex synthetic procedures, and high treatment costs. Hence, small-molecule inhibitors can be used as alternatives; however, no small molecule with in vivo activity has been reported. In addition, there are many challenges in developing a new drug, including the timeline and escalating cost. Therefore, repurposing an approved drug offers advantages over the development of an entirely new drug. Herein, we identify an FDA-approved small-molecule drug, Ponatinib, as a PD-L1 inhibitor via virtual drug screening of the ZINC database. Ponatinib showed stable binding with PD-L1, with the highest binding energy among all of the screened FDA-approved drugs. The binding of Ponatinib with PD-L1 was supported by a fluorescence quenching assay and immunofluorescence study. Further, we compared the in vivo antitumor efficacy of Ponatinib with a commercially available anti-PD-L1 antibody in the murine melanoma model. Ponatinib was found to be more efficient in delaying tumor growth than the anti-PD-L1 antibody. Furthermore, Ponatinib also reduced the expression of PD-L1 in tumors and increased the T-cell population. Interestingly, splenocytes isolated from Ponatinib-treated mice showed enhanced cytotoxic T-cell (CTL) activity against B16-F10 cells. However, Ponatinib itself did not have any direct toxic effect on cancer cells in vitro. These findings suggest that Ponatinib can be used as a potent small-molecule inhibitor of PD-L1 to overcome the disadvantages associated with antibodies.

Structurally stable and surface-textured polylactic acid/copolymer/poly (ε-caprolactone) blend-based electrospun constructs with tunable hydroxyapatite responsiveness.

Functionally-designed nanotextured and copolymer (COP) mediated PLA/PCL (70:30 w/w) blend-based interface-engineered electrospun mats (EMs) based constructs, with phase-specific interactions, have been successfully developed. The thermal stability of constructs remained up to ∼300-350 °C, while the crystallinity reduced to ∼12-23 %, indicating enhanced pliability. The tensile strength increased by ∼75 % without much compromise in the tensile modulus whereas the dynamic relaxation response of the constructs shifted to lower temperatures upon the incorporation of ≥ 2.5 phr (parts per hundred parts of resin) of COP. The zeta potential evaluated from radial surface exposure intensity could be manipulated by controlling the extent of COP content (-60 mV for ∼5 phr COP) which in turn led to the dynamics of site-specific charge neutralization driven attachment of Ca2+ ions (∼13 % for ∼5 phr COP) of the nano-hydroxyapatite (n-HA). Such uniformly dispersed, n-HA attached, and surface-decorated (COP ≤ 5 phr) EMs enabled the selective L929 fibroblast cell attachment (∼200 % cell viability for ∼2.5 phr COP). Thus, the approach may prove to augment the biomineralization of Ca and apatite-driven healing kinetics amongst implant-seeking and inflammation-prone sites and thereby, paving a new pathway for controlled and targeted healing of bone, cartilage, dental gums, and other sites demanding n-HA and/or calcium-phosphorus assisted healing mechanism.

SARS-CoV-2 Spike Protein-Activated Dendritic Cell-Derived Extracellular Vesicles Induce Antiviral Immunity in Mice.

The onset and spread of the SARS-CoV-2 virus have created an unprecedented universal crisis. Although vaccines have been developed against the parental SARS-CoV-2, outbreaks of the disease still occur through the appearance of different variants, suggesting a continuous need for improved and effective therapeutic strategies. Therefore, we developed a novel nanovesicle presenting Spike protein on the surface of the dendritic cell-derived extracellular vesicles (DEVs) for use as a potential vaccine platform against SARS-CoV-2. DEVs express peptide/MHC-I (pMHC-I) complexes, CCR-7, on their surface. The immunogenicity and efficacy of the Spike-activated DEVs were tested in mice and compared with free Spike protein. A 1/10 Spike equivalent dose of DEVs showed a superior potency in inducing anti-Spike IgG titers in blood of mice when compared to dendritic cells or free Spike protein treatment. Moreover, DEV-induced sera effectively reduced viral infection by 55-60% within 15 days of booster dose administration. Furthermore, a 1/10 Spike equivalent dose of DEV-treated mice was found to be equally effective in inducing CD19+CD38+ T-cells in the spleen and lymph node; CD8 cells in the bone marrow, spleen, and lymph node; and CD4+CD25+ T-cells in the spleen and lymph node after 90 days of treatment. Thus, our results support the immunogenic nature of DEVs, demonstrating that a low dose of DEVs induces antibodies to inhibit SARS-CoV-2 infection in vitro, therefore warranting further investigations.

Brachytherapy via a depot of biopolymer-bound 131I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours.

Locally advanced pancreatic tumours are highly resistant to conventional radiochemotherapy. Here we show that such resistance can be surmounted by an injectable depot of thermally responsive elastin-like polypeptide (ELP) conjugated with iodine-131 radionuclides (131I-ELP) when combined with systemically delivered nanoparticle albumin-bound paclitaxel. This combination therapy induced complete tumour regressions in diverse subcutaneous and orthotopic mouse models of locoregional pancreatic tumours. 131I-ELP brachytherapy was effective independently of the paclitaxel formulation and dose, but external beam radiotherapy (EBRT) only achieved tumour-growth inhibition when co-administered with nanoparticle paclitaxel. Histological analyses revealed that 131I-ELP brachytherapy led to changes in the expression of intercellular collagen and junctional proteins within the tumour microenvironment. These changes, which differed from those of EBRT-treated tumours, correlated with the improved delivery and accumulation of paclitaxel nanoparticles within the tumour. Our findings support the further translational development of 131I-ELP depots for the synergistic treatment of localized pancreatic cancer.

Recombinant protein polymers as carriers of chemotherapeutic agents.

Chemotherapy is the standard of care for the treatment of cancer and infectious diseases. However, its use is associated with severe toxicity and resistance arising mainly due to non-specificity, resulting in disease progression. The advancement in recombinant technology has led to the synthesis of genetically engineered protein polymers like Elastin-like polypeptide (ELP), Silk-like polypeptide (SLP), hybrid protein polymers with specific sequences to impart precisely controlled properties and to target proteins that have provided satisfactory preclinical outcomes. Such protein polymers have been exploited for the formulation and delivery of chemotherapeutics for biomedical applications. The use of such polymers has not only solved the limitation of conventional chemotherapy but has also improved the therapeutic index of typical drug delivery systems. This review, therefore, summarizes the development of such advanced recombinant protein polymers designed to deliver chemotherapeutics and also discusses the key challenges associated with their current usage and their application in the future.

Designing suture-proof cell-attachable copolymer-mediated and curcumin- ß-cyclodextrin inclusion complex loaded aliphatic polyester-based electrospun antibacterial constructs.

The paper demonstrates curcumin/ß-cyclodextrin-based inclusion complex (IC) loaded polyvinyl alcohol (PVA) dip-coated and copolymer-compatibilized polylactic acid (PLA)/poly(ε-caprolactone) (PCL) blend-based electrospun mats (EMs) as antibacterial, and suture-resistant constructs, to overcome the present challenges in developing structurally-stable, biocompatible, pliable, and stand-alone multifunctional-biomedical-devices. The thermal, microstructural, and viscoelastic characterization confirmed the presence of H-bonding interactions between IC and PVA moieties and between IC incorporated PVA matrix with the copolymer-mediated nanotextured PLA/PCL blend-based EMs. IC release and surface PVA erosion induced a decrease in modulus (>4-fold) and strength (>2-fold) of constructs (post-release). Mechanistically new and architectural-framework-defined PVA-gelation induced bi-axially diverted suture-failure (post-release) and resulted in a significant enhancement in suture-retention-strength (>3-fold), energy (>5-fold), and displacement (>2-fold) for ~20 wt% IC-loaded-PVA-coated EM-constructs. The fabricated EM-constructs exhibited improvement in surface-hydrophilicity (contact angle ~45°), surface nano-roughness (~ 600 nm), surface area (~34 m2/g), pore volume (~3.6 × 10-2 cc/g), IC release efficacy (~20 % burst release), antibacterial activity (adherent bacteria <10 %) against E. coli and S. aureus, and L929 fibroblast-cell-viability (~135 %), which varied as a function of IC-content in the PVA matrix. Our study conceptually establishes a novel and efficient technique for designing antibacterial, suture-resistant engineered-EM-constructs with tunable properties for their potential use in wound-dressings, periodontal-membranes, drug-delivery, and regenerative-systems.

Genetically Engineered Nanoparticles of Asymmetric Triblock Polypeptide with a Platinum(IV) Cargo Outperforms a Platinum(II) Analog and Free Drug in a Murine Cancer Model.

The development of platinum(Pt)-drugs for cancer therapy has stalled, as no new Pt-drugs have been approved in over a decade. Packaging small molecule drugs into nanoparticles is a way to enhance their therapeutic efficacy. To date, there has been no direct comparison of relative merits of the choice of Pt oxidation state in the same nanoparticle system that would allow its optimal design. To address this lacuna, we designed a recombinant asymmetric triblock polypeptide (ATBP) that self-assembles into rod-shaped micelles and chelates Pt(II) or enables covalent conjugation of Pt(IV) with similar morphology and stability. Both ATBP-Pt(II) and ATBP-Pt(IV) nanoparticles enhanced the half-life of Pt by ∼45-fold, but ATBP-Pt(IV) had superior tumor regression efficacy compared to ATBP-Pt(II) and cisplatin. These results suggest loading Pt(IV) into genetically engineered nanoparticles may yield a new generation of more effective platinum-drug nanoformulations.

A novel, minimally invasive implant to assist in repeated intraocular drug delivery.

The standard of care for posterior segment disorders such as wet age-related macular degeneration, diabetic macular oedema and retinal vascular occlusions is pharmacotherapy by intravitreal drug delivery. Since the therapeutic effect of these drugs lasts only around 4 to 8 weeks, repeated intravitreal injections are required. Pain is experienced by the patients during injection as the needle courses through the sclera and choroid. The current work describes the design and development of a novel anodized titanium alloy implant that allows for intravitreal injections through the implant so that the needle transverses only the conjunctiva, thus minimizing discomfort to the patient. Both ex-vivo testing of the implant in enucleated goat's eye as well as in-vivo validation in rabbit eyes was carried out. The implant was placed through pars plana via a minor surgical procedure and was sutured to the sclera and covered with conjunctiva. Subsequent intravitreal injections were administered under topical anaesthesia with a 30-gauge needle through the implant thus delivering the drug into the vitreous cavity. Repeated intravitreal injections were administered every 2 weeks via the implant for 3 months in 4 rabbits. Apart from cataract in 1 rabbit, no complications were observed. There was no evidence of intra-ocular inflammation or infection at final follow-up. Histopathological analysis did not reveal any inflammation or necrosis around the area of implant. The implants were subsequently removed at 5 months and scleral wound was closed with a single suture. The sclera and overlying conjunctiva healed well and no intraocular complications were observed after removal.

Cellphone enabled point-of-care assessment of breast tumor cytology and molecular HER2 expression from fine-needle aspirates.

Management of breast cancer in limited-resource settings is hindered by a lack of low-cost, logistically sustainable approaches toward molecular and cellular diagnostic pathology services that are needed to guide therapy. To address these limitations, we have developed a multimodal cellphone-based platform-the EpiView-D4-that can evaluate both cellular morphology and molecular expression of clinically relevant biomarkers directly from fine-needle aspiration (FNA) of breast tissue specimens within 1 h. The EpiView-D4 is comprised of two components: (1) an immunodiagnostic chip built upon a "non-fouling" polymer brush-coating (the "D4") which quantifies expression of protein biomarkers directly from crude cell lysates, and (2) a custom cellphone-based optical microscope ("EpiView") designed for imaging cytology preparations and D4 assay readout. As a proof-of-concept, we used the EpiView-D4 for assessment of human epidermal growth factor receptor-2 (HER2) expression and validated the performance using cancer cell lines, animal models, and human tissue specimens. We found that FNA cytology specimens (prepared in less than 5 min with rapid staining kits) imaged by the EpiView-D4 were adequate for assessment of lesional cellularity and tumor content. We also found our device could reliably distinguish between HER2 expression levels across multiple different cell lines and animal xenografts. In a pilot study with human tissue (n = 19), we were able to accurately categorize HER2-negative and HER2-positve tumors from FNA specimens. Taken together, the EpiView-D4 offers a promising alternative to invasive-and often unavailable-pathology services and may enable the democratization of effective breast cancer management in limited-resource settings.

Fabrication of In Situ Layered Hydrogel Scaffold for the Co-delivery of PGDF-BB/Chlorhexidine to Regulate Proinflammatory Cytokines, Growth Factors, and MMP-9 in a Diabetic Skin Defect Albino Rat Model.

Diabetes mellitus (DM)-associated impairments in wound healing include prolonged inflammation, the overexpression of matrix metalloproteases (MMPs), and low levels of growth factors at the wound site. To this end, a layer-by-layer scaffold (SL-B-L) made of cross-linked silk fibroin and hyaluronic acid is developed to deliver chlorhexidine, an antimicrobial agent and an MMP-9 inhibitor, along with the PDGF-BB protein. SL-B-L exhibited highly porous morphology. Diabetic rats treated with SL-B-L demonstrated an early wound closure, a fully reconstructed epithelial layer by 14 days, and reduced levels of IL-6, TNF-α, TGF-ß1, and MMP-9. Interestingly, SL-B-L treatment increased angiogenesis, the bioavailability of collagen, DNA content, and VEGF-A levels. Furthermore, enhanced keratinocyte-fibroblast interaction along with ordered collagen deposition was observed in SL-B-L-treated rats. Most interestingly, when compared with a clinically used scaffold SEESKIN+, SL-B-L outperformed in promoting wound healing in a diabetic rat model by regulating the inflammation while delivering growth factor and the MMP-9 inhibitor.

A comparison of cost and cost-effectiveness analysis of two- implant-retained overdentures versus other removable prosthodontic treatment options for edentulous mandible: A systematic review.

AIM: The aim of this study was to examine systematically the data published on the cost and cost-effectiveness of mandibular two-implant-retained overdentures compared to other removable prosthodontic treatment options for edentulous mandible. SETTINGS AND DESIGN: It is a systematic review which analyses the available data from the prospective and retrospective studies and randomized clinical trials to find out costs and cost effectiveness of different removable treatment modalities for completely edentulous mandible. The study protocol was decided according to PRISMA guidelines. MATERIALS AND METHODS: The search was limited to English literature only and included an electronic search through PubMed Central, Cochrane Central Register of Controlled Trials, and complemented by hand-searching. All clinical trials published up to August 2019 were included (without any starting limit). Two independent investigators extracted the data and assessed the studies. STATISTICAL ANALYSIS USED: No meta-analysis was conducted because of the high heterogeneity of data. RESULTS: Out of the initial 509 records, only nine studies were included. The risks of bias of individual studies were assessed. Six studies presented data on cost and cost analysis only. The rest three articles provided data on cost-effectiveness. The overall costs of implant overdentures were higher than the conventional complete dentures. However, implant overdentures were more cost-effective when compared to conventional complete dentures. Single-implant overdentures are also less expensive than two-implant overdentures. Overdentures supported by two or four mini-implants were also reported as more cost-effective than conventional two-implant-supported overdentures. CONCLUSIONS: Two-implant-retained overdentures are more expensive but cost-effective than the conventional complete dentures. Two- or four-mini-implant-retained overdentures are less expensive than two-implant-retained overdentures, but there is a lack of long-term data on aftercare cost and survival rate of mini-implants. Single-implant overdentures are also less expensive than the two-implant-retained overdentures. The differences of the aftercare costs of different attachment systems for implant overdentures were not significant. There is a need of further studies on comparative cost-effectiveness of different types of implant overdentures.

A study on the evaluation of bite force, prosthetic and nutritional status in adult cleft patients in Kolkata.

CONTEXT: Altered orofacial morphology and poor dental status affects the dietary intake of cleft patient, making susceptible to nutritional imbalance. Oral health care planning for this population is impossible without the evaluation of stomatognathic functional status as well as prosthetic and nutritional status and need. AIMS: The aim of this study was to evaluate prosthetic status and prosthetic treatment need, bite force and nutritional status, in adult cleft patients and to compare them with the adult noncleft population of similar definition. SETTINGS AND DESIGN: Cleft (n = 250) and noncleft (n = 250) individuals of either sex, aged 18 years or above, excluding severe medically compromised and differently abled, were examined and individual biteforce was measured after obtaining written consent and ethical clearance from the two institutions in Kolkata. SUBJECTS AND METHODS: A "raw data sheet" was prepared according to the parameters of the "Oral Health Surveys: Basic methods," World Health Organization (1997) for evaluation of prosthetic status and need, dentition status and Mini-Nutritional Assessment, Nestlé (1994) for the evaluation nutritional status. A Gnathodynamometer was used to record bite force. STATISTICAL ANALYSIS USED: Statistical analysis was performed using SPSS 20.0.1, Graph Pad Prism version 5, Student's t-test, and Chi-square test. RESULTS: The mean bite force of frontal area in cleft group (3.4356 ± 0.9457 kgf) was found to be significantly lower (P < 0.0001) than in noncleft (22.8749 ± 5.3644 kgf) group. The difference of mean bite force in the right side (2.4576 ± 0.6131 kgf) and left side (1.2708 ± 0.1036 kgf) in cleft group was found to be statistically significant (P < 0.0001). Prosthetic need in maxillary arch was found to be significantly (χ2: 490.0000; P < 0.0001) higher in cleft than in noncleft group. Nutritional status was observed to be significantly (χ2: 179.4049; P < 0.0001) higher "at risk" in cleft than in noncleft group. CONCLUSIONS: Lack of adequate Government concern leading to significantly higher prosthetic need and lower prosthetic status, hence lower bite force resulting lower nutritional status in adult cleft patients in Kolkata.

A study on the accuracy of horizontal condylar guidance values in edentulous patients using preprosthetic diagnostic radiographs.

CONTEXT: Determination of horizontal condylar guidance (HCG) by various clinical and radiographic methods was performed by several investigators. If a correlation between HCG values using lateral radiographic tracing and protrusive interocclusal records can be established, the necessity of performing elaborate recording procedures can be eliminated. AIMS: The aim of this study is to evaluate and to compare the correlation between HCG values in edentulous people using the protrusive interocclusal records mounted on a semi-adjustable articulator with the manual tracing of panoramic radiograph and lateral cephalogram. MATERIALS AND METHODS: A total of 20 completely edentulous individuals of either sex from 45 to 75 years (mean age 63.15 years) fulfilling the inclusion criteria were included in this in vivo study. In all the participants, HCG angles were determined clinically using protrusive interocclusal records and semi-adjustable articulator after intraoral gothic arch tracing. Radiographically, it was obtained by cephalometric tracing of panoramic radiograph and lateral cephalogram. RESULTS: The present study shows mean HCG ± standard deviation (SD) of 28.17° ± 5.99° for interocclusal protrusive record while cephalometric tracing method yielded HCG ± SD of 38.95° ± 4.77° and 35.2° ± 4.94° for lateral cephalogram and orthopantomogram, respectively. A statistically significant positive correlation (P < 0.0001) was found among these three methods. CONCLUSION: HCG can be successfully determined in edentulous participants by using three aforementioned methods. HCG values from cephalometric tracing of diagnostic radiographs can be used as an adjunct to the clinical method but cannot be used independently for programming a semi-adjustable articulator.

A comparative analysis of salivary factors and maxillary denture retention in different arch forms: An in vivo study.

AIMS: This study aims to find the effect of change in different salivary factors before and after complete denture insertion and to measure the maxillary denture retention in different arch forms. MATERIALS AND METHODS: Thirty completely edentulous individuals (10 each of square, tapered, and ovoid arch form of maxilla) belonging to the age group of 40-70 years were selected. Salivary factors (flow, density, pH, viscosity, and total protein) were evaluated before and after denture insertion. Retention of maxillary denture was measured in all the different arch forms. STATISTICAL ANALYSIS: Student's independent sample's t-test was applied. The correlation was analyzed by Pearson's correlation analysis. RESULTS: While mean flow rate and pH of saliva increased, mean viscosity, total protein, and density of saliva decreased after maxillary complete denture insertion. A positive correlation was found between retention and total maxillary basal surface area. Retention value was found to be greatest in square type and least in tapered type. CONCLUSIONS: Complete denture acts as a mechanical stimulant thus increasing flow rate and pH immediately after complete denture insertion. Density, total protein, and viscosity of saliva decreased after complete denture insertion which may be due to increase in water content of saliva. The retention of maxillary complete denture does not seem to depend on the rate of change of the salivary factors, before and after complete denture insertion. Total basal surface area and maxillary denture retention values were highest in square arch form and least in tapered arch form.