Cathepsin-K inhibition enhances anti-cancerous activity within oral squamous cell carcinoma cells: Uncloaking the potency of new K21 formulation.

BACKGROUND: The ability of cancer cells to be invasive and metastasize depend on several factors, of which the action of protease activity takes center stage in disease progression. PURPOSE/OBJECTIVE: To analyze function of new K21 molecule in the invasive process of oral squamous cell carcinoma (OSCC) cell line. MATERIALS & METHODS: The Fusobacterium (ATCC 23726) streaks were made, and pellets were resuspended in Cal27 (ATCC CRL-2095) OSCC cell line spheroid cell microplate. Cells were seeded and Lysotracker staining performed for CathepsinK red channel. Cell and morphology were evaluated using Transmission Electron microscopy. Thiobarbituric acid assay was performed. OSCC was analyzed for Mic60. Raman spectra were collected from the cancer cell line. L929 dermal fibroblast cells were used for Scratch Assay. ELISA muti arrays were used for cytokines and matrix molecules. Internalization ability of fibroblast cells were also analyzed. Structure of K21 as a surfactant molecule with best docked poses were presented. RESULTS: Decrease in lysosomal staining was observed after 15 and 30 min of 0.1% treatment. Tumor clusters were associated with cell membrane destruction in K21 primed cells. There was functional silencing of Mic60 via K21, especially with 1% concentration with reduced cell migration and invasiveness. Raman intensity differences were seen at 700 cm-1, 1200 cm-1 and 1600 cm-1 regions. EVs were detected within presence of fibroblast cells amongst K21 groups. Wound area and wound closure showed the progress of wound healing. CONCLUSION: Over expression of CatK can be reduced by a newly developed targeted K21 based drug delivery system leading to reduced migration and adhesion of oral squamous cell carcinoma cells. The K21 drug formulation can have great potential for cancer therapies due to targeting and cytotoxicity effects.

A Novel Coated Suture Displays Antimicrobial Activity Without Compromising Structural Properties.

BACKGROUND: Treated or coated sutures promise to prevent contamination of wounds. PURPOSE: The purpose of the study was to coat surgical sutures with a new quaternary ammonium silane (QAS) antimicrobial compound at two different application temperatures and then to evaluate the resulting structural, physical, mechanical, and biological properties. STUDY DESIGN, SETTING, SAMPLE: In vitro and in vivo studies were conducted using male albino Wistar rats approved by the Joint Ethical Committee of IMU and Postgraduate Medical Institute, Lahore. Only suture samples, coated uniformly with verified presence of the compound and of adequate length were used. Samples which were not coated uniformly and with inadequate length or damaged were excluded. PREDICTOR VARIABLE: Predictor variables were sutures with and without QAS coatings and different temperatures. Sutures were coated with QAS at 0.5 and 1.0% wt/vol using the dip coating technique and sutures with and without QAS coating were tested at 25 and 40 °C temperatures. MAIN OUTCOME VARIABLE(S): Outcome variables of structural and physico-mechanical properties of QAS-coated and non-coated sutures were measured using Fourier transform infrared spectroscopy (for structural changes), confocal laser and scanning electron (for diameter changes), and tensile strength/modulus (for mechanical testing). Biologic outcome variables were tested (bacterial viability); macrophage cultures from Wistar rats were tested (M1/M2 polarization detecting IL-6 and IL-10). Macrophage cells were analyzed with CD80+ (M1) and CD163+ (M2). Chemotaxis index was calculated as a ratio of quantitative fluorescence of cells. COVARIATES: Not applicable. ANALYSES: Ordinal data among groups were compared using the Wilcoxon Mann-Whitney U test along with the comparison of histological analysis using the Wilcoxon Sign-rank test (P < .05). RESULTS: Fourier transform infrared spectroscopy peak at 1490 cm-1 confirmed the presence of QAS on suture's surfaces with a significant increase (P < .05) in diameter (0.99 ± 0.5-mm) and weight (0.77 ± 0.02-mg) observed for 1% QAS groups treated at 40 °C. Non-coated samples heated at 25 °C had significantly (P < .05) less diameters (0.22 ± 0.03-mm) and weights (0.26 ± 0.06-mg). Highest tensile strength/modulus was observed for 0.5% QAS-coated samples which also had significantly higher antibacterial characteristics than other sutures (P < .05). QAS-coated sutures significantly increased M1 and M2 markers. CONCLUSION AND RELEVANCE: QAS coating conferred antibacterial action properties without compromising the physical and mechanical properties of the suture.

Use of endoscope in teaching of otolaryngology residents about site and size of tympanic membrane perforation and its impact on degree of hearing loss in adult patients: A cross sectional study.

OBJECTIVE: To determine the association between site and size of perforation of the tympanic membrane and the level of conductive hearing. METHODS: The cross-sectional study was conducted from November 2015 to October 2016 at Aga Khan University Hospital Karachi and comprised patients with tympanic membrane perforation without any other middle-ear disease. Karl-Storz Rigid Endoscope attached to a camera was used to take pictures of the tympanic membrane. Site of the perforation was determined using a vertical line to divide the membrane into two anterior and posterior halves. Size of the perforation was calculated as a percentage of the total membrane using Image J software. Data analysis was done using Stata 12. RESULTS: Of the 55 patients, 29(53%) were males and 26(47%) were females. The overall mean age was 33+/-15 years. With every 5% increase in the size of perforation, the hearing loss increased by 1 decibel. A difference of 5.5 decibels was noted between anterior and posterior perforations of similar size. CONCLUSION: Hearing loss increased with increase in the size of perforation.

Collagen based barrier membranes for periodontal guided bone regeneration applications.

Certain cell populations within periodontal tissues possess the ability to induce regeneration, provided they have the opportunity to populate the wound or defect. Guided regeneration techniques have been investigated for regenerating periodontal tissues and such therapies usually utilize barrier membranes. Various natural and synthetic barrier membranes have been fabricated and tested to prevent epithelial and connective tissue cells from invading while allowing periodontal cells to selectively migrate into the defect. This paper focuses on the literature relevant to the use and potential of resorbable collagen membranes in GBR procedures, sites of periodontal and intrabony defects, in cases of socket and alveolar ridge preservation and at implant sites. The results of their use in GBR procedures has shown them to be effective and comparable with non-resorbable membranes with regards to clinical attachment gain, probing depth reduction and defect bone filling. They have also shown to prevent epithelial ingrowth into the defect space during the initial wound healing phase postsurgically. Collagen membranes have also been used for root coverage and GBR procedures and have shown good success rates comparable to subepithelial connective tissue grafts and expanded-polytetrafluoroethylene (e-PTFE) membranes. The future for periodontal tissue engineering is very exciting with the use of barrier membranes expected to continue playing a critical role. However, long-term clinical trials are required to further evaluate and confirm the efficacy of the available collagen barrier membranes for periodontal and bone regeneration use.

Identification And Endodontic Treatment Of Threecanalled Maxillary First Premolar.

Maxillary premolars exhibit variable root canal morphology, but it is quite rare to find three canals in their root system. The aim of this case report is to present the diagnosis and clinical management of a patient with anatomical variation of having three root canals in the maxillary first premolar. Three-canalled maxillary premolars are quite an endodontic challenge. A discussion is provided here to facilitate the early recognition of these canals, access cavity modifications for better intra-canal preparation and obturation procedures. Clinicians are required to be aware of the anatomical variations they may encounter when dealing with maxillary premolars and should be trained to apply this knowledge in the clinical scenario.

Oral antimicrobial peptides: Types and role in the oral cavity.

Antimicrobial peptides (AMPs) are a wide-ranging class of host-defense molecules that act early to contest against microbial invasion and challenge. These are small cationic peptides that play an important in the development of innate immunity. In the oral cavity, the AMPs are produced by the salivary glands and the oral epithelium and serve defensive purposes. The aim of this review was to discuss the types and functions of oral AMPs and their role in combating microorganisms and infections in the oral cavity.

Ways to manage hepatitis C without cirrhosis: Treatment by comparison of coded eastern medicine hepcinal with interferon alpha 2b and ribavirin.

Hepatitis C virus (HCV) infection is a serious and significant global health problem in the Pakistan and elsewhere. In majority of cases HCV infection remains asymptomatic but in advance cases it may progress to fibrosis of liver, shrinkage of liver cells or failure of liver. The hepatitis C may progress to cause liver cirrhosis that mostly develop in 20% of the affected patients in 20 years with an increased risk in male, alcoholic drink, immune-compromised and who acquire HCV infection after the age of 40 years. This was an open-label prospective study conducted on 66 clinically and immunologically diagnosed cases of HCV infection. In Hepcinal treated group, there were significant improvement in HCV associated symptoms compared to control group (p<0.05). While Interferon therapy resulted in significant improvement in serological response (55.88%) compared to Hepcinal treated patients (46.88%). It was concluded that Hepcinal has shown better clinical response but no significant serological response (p=0.3244) and it might be an alternative therapy to treat hepatitis C infection and to prevent its progression into chronic ailment.

Clinical efficacy of polyherbal formulation Eezpain spray for muscular pain relief.

The topical herbal formulation Eezpain spray consisting of natural ingredients that have been clinically proved for its analgesic and anti-inflammatory activity. The designed formulation on application knee and wrist joints, back of neck and shoulder, forearms and lower back exhibited significant efficacy. A total of 20 subjects both male and female applied Eezpain spray consisting of Gaultheria oil, Eucalyptus oil, Turpentine oil, Clove Oil, Menthol and Camphor. All the active materials are cited that these have analgesic activity in myalgia and neuralgia. The study design was prospective and opens as pilot study followed the inclusion and exclusion criteria. All the sign and symptoms were noted at baseline and at the end of 14 days treatment performance was evaluated. The statistical analysis was done by using Microsoft Excel2007 and SPSS version 18.0. It is concluded that Eezpain spray has shown efficacy in mild to moderate cases on applying locally to the affected parts to relieve pain from different ailments.

Comparative clinical study on the efficacy of biocor plus compared with simvastatin for the management of hypercholesterolemia.

Hypercholestriolemia is major risk factor that enhances the incidence of cardiovascular disease and coronary artery disease. The present study was conducted to normalize the lipid profile in the blood by using Biocor Plus for hypercholesterolemia compared with Simvastatin. It was prospective randomized case control study conducted on 70 diagnosed patients of hypercholesterolemia at Sohail Memorial Hospital, Karachi and Amir Habib Medical Center and Maternity Home, Karachi. Patients of both genders (30-70 years) with clinical diagnosis of Hypercholesterolemia. Sample sizes for this study included total of 70 subjects. There was statistically significant difference when comparing the effectiveness of test drug, Biocor Plus to control drug, Simvastatin for the treatment of primary hypercholesterolemia. This is clearly evident that the herbal coded test drug, Biocor Plus possesses a therapeutic value for the treatment of primary hypercholesterolemia. There were no untoward or significant side effects associated with the use of Biocor Plus that proved its good acceptability by the patients. Moreover there was subjective feeling of wellbeing regarding breathlessness and chest tightness or pressure in the patients taking Biocor Plus. This makes an interesting point to focus on this effective alternative drug for primary hypercholesterolemia.

CBCT in Dental Implantology: A Key Tool for Preventing Peri-Implantitis and Enhancing Patient Outcomes.

(1) Introduction: Trust is a cornerstone of the patient-physician relationships. Unforeseen complications in the health care system could jeopardize patients' trust in their physicians. (2) Aim: This article presents a quantitative figure regarding foreseeing the necessity of a three-dimensional quantitative visualization of bone structure and concurrently preparing for an ancillary procedure by a dentist to successfully perform the surgery that could minimize unforeseen complications; (3) Materials and method: This retrospective study has been derived based on an analysis of 1134 patients who had received 4800 dental implants from January 2001 to August 2020, out of which 200 cases were randomly selected for this study. Each procedure during implant treatment was categorized as OPG (Orthopantomography) or OPG with CBCT as per all the procedures which included and were coded as follows, 1: Surgery & Restoration, 2: GBR (Guided Bone Regeneration), 3: GTR (Guided Tissue Regeneration), 4: Block Bone Graft, 5: Spreading, 6: Splitting, 7: Internal Sinus, 8: External Sinus, 9: PRF (Platelet Rich Fibrin). Any of the 200 cases in which implant placement could not have been performed for reasons related to a lack of CBCT were selected for this study. The surgery was aborted halfway through without implant placement in these cases due to a lack of bone quantity and/or lack of primary stability. These cases were registered for re-evaluation and statistical analysis; (4) Results: 7% of the cases that used OPG alone led the surgeon to unexpectedly abort in the middle of the surgery without implant placement. All (100%) of the patients who had CBCT during treatment planning were able to receive implants during the surgery. None of the patients left the surgery without receiving implants if CBCT was used (0%); (5) Discussion: Radiographic image quality is defined as the amount of information within the image that allows the radiologist to make a diagnostic decision with a particular level of certainty (Martin et al., 1999) and hence the importance of CBCT. The unexpected 7% of devastating situations for patients who started surgery but did not have implant placement led to [A] aborting the surgery, [B] procedural difficulties requiring an alternative treatment plan, [C] a negative impact on the patient's behavior, and [D] wanting to change doctor due to a lack of trust; (6) Conclusion: This study indicates that in implant dentistry patients' mistrust could be avoided by 7% if CBCT is obtained. It also shows the significance of cone-beam computed tomography as an adjunct to panoramic radiography during the diagnosis and treatment planning phase. The use of panoramic radiography alone can lead to a 7% likelihood of misdiagnosis. A lack of CBCT during treatment planning negatively affects the outcome of surgical procedures.

Riding Toward Danger: A Scoping Review of Burns Associated With Personal Mobility Devices, Including Electric Bikes (E-Bikes) and Electric Scooters (E-Scooters).

Burn injuries related to lithium-ion batteries from personal mobility devices, such as electric bikes and electric scooters, have emerged as a global concern. By examining the literature, this study aims to provide an overview of the demographics, patterns, and outcomes of personal mobility device-associated burns. A Singaporean cohort revealed burns resulting predominantly from fires occurring due to the combustion of unattended personal mobility device batteries during charging. In contrast, an Israeli cohort showed a higher total body surface area and highlighted the vulnerability of limbs to burn injuries in such incidents. A Beijing cohort, consisting of pediatric patients indicated potential child safety concerns regarding personal mobility device usage. Finally, a Shanghai cohort demonstrated the potential dangers of personal mobility device battery chargers. The observed differences between those experiencing burn injuries and the broader population of personal mobility device riders in terms of age and gender suggest that younger males may be at higher risk, perhaps due to risky practices such as leaving personal mobility devices unattended while charging. This review emphasizes the need for safety education, adherence to regulations, and responsible consumer choices to mitigate burn injuries. Recommendations include promoting child safety measures, using certified personal mobility devices, and cautious handling of DIY conversion kits. Further large-scale studies are essential to gain comprehensive insights and develop effective safety strategies to protect personal mobility device riders from burn injuries.

Long-Term Follow-Up of Patients with Chronic Kidney Disease: Renal Function Decline and Associated Risk Factors.

Evaluating the chronic course of chronic kidney disease (CKD) and identifying associated risk factors is essential for effective management. This study aims to identify risk factors and monitor the decline in renal function through prolonged follow-up of CKD patients. This retrospective cohort study included 410 CKD patients diagnosed between 2015 and 2022. Data collected included demographics, comorbidities, and repeated measurements of glomerular filtration rate (GFR) and proteinuria. Statistical analyses examined the association between GFR decline and risk factors such as age, diabetes, hypertension, and proteinuria during the follow-up period. The cohort showed a progressive decline in GFR over time. Significant associations were found between GFR decline and age, diabetes, hypertension, and higher proteinuria levels (P < 0.001). Age was associated with a 0.32 ml/min decline in GFR per 1.73 m², while the coefficients for hypertension and diabetes were -2.98 and -4.21, respectively. A strong correlation was found between proteinuria and GFR decline (ß = -6.78, P < 0.001). Early identification and management of risk factors are crucial for slowing CKD progression. These findings underscore the need for targeted interventions to preserve renal function and improve patient outcomes.

Assessment of Long-Term Pulmonary Function and Quality of Life in Patients with Chronic Obstructive Pulmonary Disease (COPD).

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition portrayed by persistent airflow limitation and correlated symptoms. Despite advances in treatment, COPD remains a significant global health burden, necessitating ongoing research to understand its long-standing impact on pulmonary function and quality of life (QoL). Methods: This longitudinal research enrolled 200 COPD and followed them over a 5-year period. Baseline assessments included spirometry to measure forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), along with standardized questionnaires assessing QoL. Follow-up assessments were conducted annually, and statistical analysis was performed to examine changes in pulmonary function and QoL over time. Results: Significant declines in FEV1 and FVC were observed at each follow-up time point compared to the baseline, indicating progressive deterioration in lung function. QoL scores, as assessed by the St. George's Respiratory Questionnaire and the COPD Assessment Test, also worsened progressively over the research period. Conclusion: Current conclusions underscore the progressive nature of COPD, highlighting the importance of proactive management strategies aimed at preserving lung function and improving QoL. Early intervention and ongoing monitoring are essential in optimizing outcomes for COPD subjects and reducing the disease burden on individuals and healthcare systems.

Assessment of Postoperative Complications and Outcomes in Patients Undergoing Laparoscopic Cholecystectomy.

Introduction: A common surgical technique for gallbladder disorders is laparoscopic cholecystectomy (LC), which has the benefits of less postoperative discomfort and quicker recovery. The purpose of this retrospective research was to assess postoperative outcomes and complications in patients having laparoscopic correction. Methods: In total, 200 patients who had LC at the tertiary care center between 2017 and 2022 were the subjects of a retrospective investigation. We gathered and examined data on preoperative conditions, surgical specifics, postoperative results, and demographics. Results: Notable findings from the study were as follows: (1) The average age of the patients was 47.5 years (±12.3), and there were strong correlations (P < 0.001) between age and problems. (2) Significant correlations were found between many covariates and postoperative outcomes, such as a 10% readmission rate and a mean hospital stay of 3.6 days (±1.2) (P < 0.05). (3) Different relationships were seen between the complications (P values ranging from 0.021 to <0.001), including wound infections (6%) and bile duct injuries (2.5%). Conclusion: To enhance patient care, a thorough assessment and focused treatments are required. This study sheds light on the frequency of postoperative problems and outcomes in patients receiving LC.

Three-Dimensional Printing Methods for Bioceramic-Based Scaffold Fabrication for Craniomaxillofacial Bone Tissue Engineering.

Three-dimensional printing (3DP) technology has revolutionized the field of the use of bioceramics for maxillofacial and periodontal applications, offering unprecedented control over the shape, size, and structure of bioceramic implants. In addition, bioceramics have become attractive materials for these applications due to their biocompatibility, biostability, and favorable mechanical properties. However, despite their advantages, bioceramic implants are still associated with inferior biological performance issues after implantation, such as slow osseointegration, inadequate tissue response, and an increased risk of implant failure. To address these challenges, researchers have been developing strategies to improve the biological performance of 3D-printed bioceramic implants. The purpose of this review is to provide an overview of 3DP techniques and strategies for bioceramic materials designed for bone regeneration. The review also addresses the use and incorporation of active biomolecules in 3D-printed bioceramic constructs to stimulate bone regeneration. By controlling the surface roughness and chemical composition of the implant, the construct can be tailored to promote osseointegration and reduce the risk of adverse tissue reactions. Additionally, growth factors, such as bone morphogenic proteins (rhBMP-2) and pharmacologic agent (dipyridamole), can be incorporated to promote the growth of new bone tissue. Incorporating porosity into bioceramic constructs can improve bone tissue formation and the overall biological response of the implant. As such, employing surface modification, combining with other materials, and incorporating the 3DP workflow can lead to better patient healing outcomes.

Unravelling the Programmed Inflammation and Tissue Repair by a Multipotential Antimicrobial K21 Silane.

AIMS AND OBJECTIVES: To examine if a novel antimicrobial silane K21 can alter macrophage polarisation and affect fibroblast proliferation by deciphering the molecular pathways for programmed healing using a combined in vitro and in vivo (animal) burn model. MATERIALS AND METHODS: An injectable silane-based antimicrobial aimed to modulate macrophage polarisation was manufactured. Experimental analysis included colorimetric cell migration assays on gingival fibroblasts, macrophage phagocytosis characterisation, immunofluorescence staining, triacylglycerol accumulation within macrophages by LCMS, cellular metabolic/proliferation assays, macrophage exposure quantification with morphology assessment using FE-SEM, Raman spectral analysis, RNA isolation for relative gene expression and animal study model to morphometrically and microscopically analyse partial thickness burn wound healing under QAS/K21. RESULTS: M1 and M2 polarisation both appeared exaggerated under QAS/K21 treatment. The wounds treated with K21 had depicted accelerated healing as compared to control (P < .05) in dorsal skin of rabbits. Relative gene expression results demonstrate reduced cytokine and anti-inflammatory response under the influence of K21. While M1 expression, TG accumulation, and associated characterisations demonstrate the programmed inflammatory potential of K21. CONCLUSION: the antimicrobial and reparative efficacy of K21 silane aids in programmed inflammation for enhanced tissue healing and repair.

Effects of Riboflavin Collagen Crosslinker on Dentin Adhesive Bonding Efficiency: A Systematic Review and Meta-Analysis.

The aim of this study was to evaluate published data regarding riboflavin (RF) as a cross-linker for improved adhesive bond strength to dentin and to analyze previous studies for optimal concentration of riboflavin range suitable for dentin bond. Saliva and distilled water were used as storage media and aging time was 24 h and 6 months. Results of meta-analysis were synthesized using a statistical method of inverse variance in random effects with a 95% Confidence Interval (CI). Cochrane review manager 5.4.1 was used to determine results of the meta-analysis. In total, 3172 articles were found from search databases "PubMed", "Scopus", and "Google Scholar". Six of the fifteen studies were eligible for meta-analysis. Micro tensile strength shows significant improvement with the addition of riboflavin (p < 0.05) compared to without the addition of riboflavin from with 95% CI. A significant difference has been found in micro tensile bond strength between use of the riboflavin cross-linker and without use of the riboflavin crosslinker in the dentin adhesive system. With a 95% confidence interval (CI), the I2 for micro tensile strength was 89% with strong heterogeneity, Chi2 = 44.76, df = 5 (p < 0.00001), and overall effect size is Z = 2.22 (p = 0.03) after immediate aging. Chiang et al. 2013 shows maximum mean differences which is 38.50 [17.93-59.07]. After 6 months of aging in distilled water or artificial saliva micro tensile bond strength has been increased with the addition of riboflavin (p < 0.05). It can be clearly seen that pooled effect and 95% CI did not cross the line of no effect. With a 95% confidence interval (CI), the I2 for micro tensile strength was 96% with strong heterogeneity, Chi2 = 117.56, df = 5 (p < 0.00001), and overall effect size is Z = 2.30 (p = 0.02). Subgroup analysis proved a similar effect of distilled water and artificial saliva as storage media on micro tensile bond strength after incorporating riboflavin as a collagen crosslinker. An artificial saliva aged forest plot also showed considerable heterogeneity with I2 = 96%; Tau2 = 257.32; Chi2 = 94.37; df = 2 (p < 0.00001); test for overall effect, Z = 1.06 (p = 0.29). Riboflavin prior to or with bonding is recommended to improve the bonding of different adhesive systems.

Vacuum cleaner friction injuries in paediatrics: A 10 year review of national trends.

Our regional burns service has gained experience in managing paediatric hand friction burns due to vacuum cleaners (VC). We aimed to evaluate our 10 year experience managing these injuries as well as reviewing national data trends in order to identify those at risk of injury. MATERIALS AND METHODS: A International Burns Injury Database (IBID) request was made to review the number of burn injuries recorded due to Vacuum cleaner injuries (VCIs). In addition, a local IBID request was made to identify the number of burn injuries managed within our regional burns service. RESULTS: We identified 288 VCIs which have increasingly occurred in England and Wales between 1996-2020 and 32 children who sustained these injuries within our regional burns service. A general theme from both national and local data highlighted that these injuries occurred in males (78%, n=25) with a mean age of 20 months (9 months-4.5 years) affecting children's hands (94%). In 25 cases (78%) these injuries involved an interphalangeal joint. 85% (n = 27) of injuries were deep dermal/full thickness with eleven children (34%) undergoing surgical excision and skin grafts. DISCUSSION: Significant paediatric burn injuries can be sustained from VCs. Greater awareness is indicated for these injuries and legislation should be considered in order to improve the safety of vacuum cleaners. International burn societies are urged to collect data of these injuries in order to co-ordinate improved prevention strategies and change within the VC industry.