Mustard Gel versus Chlorhexidine Gel as Root-Canal Medicament Against Enterococcus Faecalis: An in vitro Study.

OBJECTIVE: To evaluate the efficacy of mustard gel versus chlorhexidine (CHX) gel in treating the most resistant Enterococcus faecalis (E. faecalis) bacteria as intra-canal medications. STUDY DESIGN: Randomised controlled trial (in vitro study). Place and Duration of the Study: Department of Operative Dentistry, de'Montmorency College of Dentistry, in collaboration with Lahore General Hospital, between March and October 2021. METHODOLOGY: Forty single-rooted teeth, extracted and randomly allocated, were divided into two groups. Group 1 underwent treatment with CHX gel, while Group 2 was treated with Mustard gel. Subsequently, after disinfection, each tooth was horizontally divided into three equal parts. The middle section was standardised and inoculated with a controlled strain of E. faecalis. Intra-canal medicaments were administered for seven days. Bacterial colonies were quantified as colony forming units (CFU/mL) and subjected to analysis using Statistical Package for Social Sciences (SPSS) version 25. RESULTS: The median bacterial count observed was 1,550 (range 775 - 2,500) for Group 1, contrasting with 400 (range 200 - 775) for Group 2, indicating a significant difference in bacterial count between the groups (p <0.001). CONCLUSION: Mustard gel demonstrated significantly superior efficacy compared to chlorhexidine gel against E. faecalis in root canal procedures. KEY WORDS: Chlorhexidine, Enterococcus faecalis, Mustard, Root canal medicament, Antimicrobial drug-resistance, Root canal irrigants.

An In Vitro Study Comparing the Antibacterial and Mechanical Properties of Zinc Oxide-Based Nanofillers in Orthodontic Adhesives for White Spot Lesion Prevention in Fixed Orthodontic Therapy.

Introduction Preventing enamel demineralization (white spot lesions or WSLs) around the brackets during and after orthodontic therapy has been a challenging problem. Zinc oxide (ZnO) nanoparticles (NPs) show antibacterial effects against cariogenic bacteria Streptococcus (S.) mutans. Materials and methods In this study, researchers modified Transbond XT adhesive (Sigma Aldrich, St. Louis, Missouri, USA) by adding different concentrations of ZnO nanoparticles, i.e., 0.1% and 0.5wt%, in two experimental groups and a control group. We performed Fourier transform infrared spectroscopy and scanning electron microscopy for physio-structural characterization and investigated antibacterial ability by disc diffusion and colony-forming tests. We conducted shear bond strength and adhesive remnant index to determine the mechanical characteristics. Results The development and size of the inhibition zone were greatly dependent on the concentration of ZnO nanoparticles in the disc agar diffusion test. All ZnO NP-based experimental adhesives reduced the colony numbers for S. mutans. For S. mutans, the composite comprising 0.5wt% ZnO nanoparticles significantly reduced colony counts. The control group exhibited the maximum mean shear bond strength, whereas 0.5wt% nanoparticles composite had the lowest number. Conclusion Adding ZnO as nanofillers imparts antibacterial properties to the orthodontic adhesives. An increase in the concentration of ZnO nanoparticles in orthodontic adhesive increases its antibacterial properties. We found the shear bond strength of the novel composite with up to 0.5wt% ZnO nanoparticles to be in a clinically acceptable range.

Efficacy and safety of ticagrelor monotherapy following a brief DAPT vs. prolonged 12-month DAPT in ACS patients post-PCI: a meta-analysis of RCTs.

BACKGROUND: As per current guidelines, acute coronary syndrome (ACS) patients who undergo percutaneous coronary intervention (PCI) should be started on dual antiplatelet therapy (DAPT) for a period of 12 months. OBJECTIVE: To assess the efficacy and safety of brief DAPT (up to 3 months) succeeded by ticagrelor monotherapy compared with a 12-month DAPT in ACS patients following PCI. METHODS: We systematically searched Cochrane, Embase, and PubMed to find relevant randomized clinical trials. Examined outcomes included the incidence of major adverse cerebrovascular and cardiovascular events (MACCE), bleeding events, and the composite incidence of net adverse clinical events (NACE). RESULTS: Our primary analysis included 21,927 ACS patients from six RCTs. Our pooled results indicate that following PCI in individuals with ACS, brief DAPT followed by ticagrelor did not increase the risk of MACCE (OR 0.92, 95% CI 0.79-1.07) but significantly reduced the risk of minor or major bleeding (OR 0.52, 95% CI 0.44-0.62) and NACE (OR 0.71, 95% CI 0.59-0.86) compared with a long-term DAPT within a follow-up of 12 months. CONCLUSION: Brief DAPT followed by ticagrelor monotherapy is superior to a 12-month DAPT in offering a net clinical advantage in ACS patients following PCI.

Safety and Efficacy of Camostat Mesylate for Covid-19: a systematic review and Meta-analysis of Randomized controlled trials.

BACKGROUND: Camostat mesylate, an oral serine protease inhibitor, is a powerful TMPRSS2 inhibitor and has been reported as a possible antiviral treatment against COVID-19. Therefore, we aim to assess the safety and efficacy of camostat mesylate for COVID-19 treatment. METHODS: A systematic review and meta-analysis synthesizing randomized controlled trials from PubMed, Scopus, Embase, Cochrane, Web of Science, clinical trials.gov, and medrxiv until June 2023. The outcomes were pooled using Mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous outcomes. The protocol is registered in PROSPERO with ID CRD42023439633. RESULTS: Nine RCTs, including 1,623 patients, were included in this analysis. There was no difference between camostat mesylate and placebo in producing negative PCR test results at 1-7 days (RR: 0.76, 95% CI: [0.54, 1.06] P = 0.1), 8-14 days (RR: 1.02, 95% CI: [0.84, 1.23] P = 0.87), or 15-21 days (RR: 0.99, 95% CI: [0.82, 1.19] P = 0.90); clinical resolution of symptoms at 1-7 days (RR: 0.94 (95% CI: 0.58, 1.53) P = 0.81), 8-14 days (RR: 0.91, 95% CI: [0.74, 1.11] P = 0.33, ), or 15-21 days (RR: 0.77, 95% CI: [0.40, 1.51] P = 0.45); and time to symptom improvement (MD:-0.38 weeks (95% CI: [-1.42, 0.66] P = 0.47, I2 = 85%). CONCLUSION: Camostat mesylate did not improve clinical outcomes in patients with COVID-19, compared to placebo.

QSPR Analysis of Drugs for Treatment of Schizophrenia Using Topological Indices.

Schizophrenia is a chronic psychotic disorder characterized primarily by cognitive deficits. Drugs and therapies are helpful in managing the symptoms, mostly with long-term compliance. There is a pressing need to design more efficient drugs with fewer adverse effects. Solubility, metabolic stability, toxicity, permeability, and transporter effects are important parameters in the efficacy of drug design, which in turn depend upon different physical and chemical characteristics of drugs. In recent years, there has been growing interest in developing computational tools for the discovery and development of drugs for schizophrenia. Some of these methods use machine learning algorithms to predict the efficacy and side effects of the potential drugs. Other studies have used computer simulations to understand the molecular mechanisms underlying the disease and identify new targets for drug development. Topological indices are numeric quantities linked to the chemical structure of drugs and predict the properties, reactivity, and stability of drugs through the quantitative structure-property relationship (QSPR). This work is aimed at using statistical techniques to link QSPR correlating properties with connectivity indices using linear regression. The QSPR model gives quite a better estimation of the properties of drugs, such as melting point, boiling point, enthalpy, flash point, molar refractivity, refractive index, complexity, molecular weight, and refractivity. Results are validated by comparing actual values to estimated values for the drugs.

QSPR Modeling of Fungicides Using Topological Descriptors.

A topological index is a real number that is obtained from a chemical graph's structure. Determining the physiochemical and biological characteristics of a variety of medications is useful since it more accurately represents the theoretical characteristics of organic molecules. This is accomplished using degree-based topological indices. The QSPR research has improved the structural understanding of the physiochemical properties of fungicides. Thirteen fungicides are examined for some of their physiochemical properties, and a QSPR model is built using nine of the drugs' topological indices. Here, we examine the degree to which the topological indices and physiochemical attributes are connected. To do this, we create networks connecting each of the topological indices to the properties of fungicides and computationally construct topological indices of the drugs mentioned above. According to this QSPR model, the melting point, boiling point, flash point, complexity, surface tension, etc. of fungicides are strongly connected. It was discovered that the topological indices (TIs) applied to the fungicides more accurately represent their theoretical features and show a strong correlation with their physical attributes.

Late Presentation of Peritonitis Post Jejunal Perforation Due to Flank Stab Wound.

Abdominal trauma injuries are caused by many mechanisms including blunt and penetrating trauma injuries. Penetrating injuries are far more common than blunt injuries. Subsequently, the most affected organ during such injuries is small intestine perforations. As far as we know, there were no cases reported before about jejunal injury due to penetrating trauma. We present a case of a 20-year-old male with a stab wound injury who was initially stable in the emergency department (ED). After a set of investigations were done, the patient was discharged home. Yet, the patient presented again with late signs of peritonitis. Imaging was done and showed pneumoperitoneum. Thereafter, the patient was rushed to the operation room (OR) where the jejunal repair was performed. ED physicians must be vigilant regarding any signs of deterioration in penetrating trauma patients and should provide clear instructions to patients regarding any symptoms of the acute abdomen before any discharge.

Computing Topological Invariants of Deep Neural Networks.

A deep neural network has multiple layers to learn more complex patterns and is built to simulate the activity of the human brain. Currently, it provides the best solutions to many problems in image recognition, speech recognition, and natural language processing. The present study deals with the topological properties of deep neural networks. The topological index is a numeric quantity associated to the connectivity of the network and is correlated to the efficiency and accuracy of the output of the network. Different degree-related topological indices such as Zagreb index, Randic index, atom-bond connectivity index, geometric-arithmetic index, forgotten index, multiple Zagreb indices, and hyper-Zagreb index of deep neural network with a finite number of hidden layers are computed in this study.

A Rare Complication of Perforated Appendicitis: A Case of Necrotizing Fasciitis.

Acute appendicitis is considered one of the most common surgical emergencies with low morbidity and mortality. However, delay in the diagnosis may lead to perforation of the appendix. Hence, complications may arise, including necrotizing fasciitis, a rare complication of a perforated appendix. We present a case of perforated appendicitis complicated by necrotizing fasciitis leading to rapid deterioration. A 75-year-old male patient presented to our emergency room with a three-day history of right lower quadrant abdominal pain and abdominal distention. On admission, computed tomography (CT) scan showed a perforated appendix and peri-appendicular abscess. An exploratory laparotomy was performed. The appendix was resected and the wound closed. The patient was recovering well and tolerating food after the procedure. However, the patient developed progressive erythema/swelling over the right flank with new-onset leukocytosis. The diagnosis of necrotizing fasciitis was suspected and confirmed by careful evaluation and laboratory/radiological tests. Antibiotics were changed to clindamycin and piperacillin/tazobactam, and the patient was taken back to the operation room (OR) for surgical debridement. Postoperatively, the patient was shifted to the intensive care unit (ICU). He developed hearing impairment, which improved after the cessation of clindamycin. He was discharged in good condition after three weeks of hospital stay. This case report highlights the importance of maintaining a high index of suspicion for necrotizing soft tissue infection in immunocompromised patients with perforated appendicitis and being cautious when prescribing clindamycin to patients at risk of hearing loss.

Association of Root Hair Length and Density with Yield-Related Traits and Expression Patterns of TaRSL4 Underpinning Root Hair Length in Spring Wheat.

Root hairs play an important role in absorbing water and nutrients in crop plants. Here we optimized high-throughput root hair length (RHL) and root hair density (RHD) phenotyping in wheat using a portable Dinolite™ microscope. A collection of 24 century wide spring wheat cultivars released between 1911 and 2016 were phenotyped for RHL and RHD. The results revealed significant variations for both traits with five and six-fold variation for RHL and RHD, respectively. RHL ranged from 1.01 mm to 1.77 mm with an average of 1.39 mm, and RHD ranged from 17.08 mm-2 to 20.8 mm-2 with an average of 19.6 mm-2. Agronomic and physiological traits collected from five different environments and their best linear unbiased predictions (BLUPs) were correlated with RHL and RHD, and results revealed that relative-water contents (RWC), biomass and grain per spike (GpS) were positively correlated with RHL in both water-limited and well-watered conditions. While RHD was negatively correlated with grain yield (GY) in four environments and their BLUPs. Both RHL and RHD had positive correlation indicating the possibility of simultaneous selection of both phenotypes during wheat breeding. The expression pattern of TaRSL4 gene involved in regulation of root hair length was determined in all 24 wheat cultivars based on RNA-seq data, which indicated the differentially higher expression of the A- and D- homeologues of the gene in roots, while B-homeologue was consistently expressed in both leaf and roots. The results were validated by qRT-PCR and the expression of TaRSL4 was consistently high in rainfed cultivars such as Chakwal-50, Rawal-87, and Margallah-99. Overall, the new phenotyping method for RHL and RHD along with correlations with morphological and physiological traits in spring wheat cultivars improved our understanding for selection of these phenotypes in wheat breeding.

Epidemiology and molecular characterization of re-emerged virulent strains of Peste des Petits Ruminants virus among sheep in Kassala State, Eastern Sudan.

BACKGROUND: Peste des Petits Ruminants (PPR) is a severe contagious viral disease, which mainly affects small ruminants. PPR is caused by a Morbillivirus that belongs to the family Paramyxoviridae. In this study 12 suspected PPR outbreaks among sheep and goats were investigated in four localities in Kassala State, Eastern Sudan, during 2015-2017. The causative agent was confirmed by a Sandwich Enzyme-Linked Immunosorbent Assay (sELISA), and a Reverse Transcription Polymerase Chain Reaction (RT-PCR) targeting a partial sequence of nucleocapsid protein gene (N- gene) and a partial sequence of fusion protein gene (F- gene). Sequencing and phylogenetic analysis were carried out on six N- gene based RT-PCR products selected from two outbreaks occurred on border and inner localities of Kassala State to determine the circulating lineages of PPRV strains. Identity percentages were determined between isolates in this study and previous Sudanese, and other (African and Asian) isolates which clustered along with them. RESULTS: Out of 30 samples, 22 (73.3%) were positive using sandwich ELISA. From 22 s ELISA positive samples, 17 (77.3%) were positive by Ngene based RT-PCR and only 7(43.8%) out of 16 positive samples by N gene based RT-PCR were positive using Fgene based RT-PCR. The sequencing and phylogenetic analysis confirmed involvement of the lineage IV of PPRV in outbreaks among small ruminants in Kassala State and high identity percentage between our isolates and previous Sudanese and other (African and Asian) isolates. CONCLUSIONS: The present study demonstrates that genetic relationship between PPRV strains circulating in sheep in Kassala State, Eastern Sudan, and PPRV strains characterized as lineage IV in neighboring African countries such as Eretria,Ethiopia, Egypt, and other Asian countries.

Prosthodontics dental materials: From conventional to unconventional.

New inventions and innovations in the field of dentistry have potential applications to satisfy the patient's demand. In prosthodontics, a dental prosthesis plays a major role in improving the quality of oral health care. Currently, the trends have shifted towards the implants and implant-supported prosthesis for the replacement of missing teeth. Conventional dentures are patient's preference mainly due to financial constraints. In an attempt to find solutions to current problems, we have come across new materials zirconium, titanium and new inventions like flexible dentures, fenestrated dentures, and CAD/CAM fabricated dentures. Using the progress of past five years in the field of prosthodontics, this comprehensive review focuses on denture base materials, denture liners, removable partial dentures, fixed prosthesis such as crown and bridge materials, implant-supported a fixed denture, artificial teeth materials, impression materials, and ingenious alternatives to conventional dentures. This article also sheds some light on the current promising researches and gives insight into the problems that can be the focus of future researches.

The Pressing Need to Raise Awareness about Osteoarthritis Care among Elderly Females in Pakistan: A Cross-sectional Study.

Introduction Osteoarthritis (OA) is the single-most common cause of physical disability among adults. In view of its promising management modalities, an analysis of the level of awareness among the suspected individuals and their attitudes is crucial to assess the level of their implementation. This study aimed to do that among the female population in Karachi, Pakistan. Methods This cross-sectional study was conducted among 316 elderly females (≥60 years) in Karachi in 2018. Data were collected via a structured questionnaire, which included sections titled: demographics, knowledge, attitudes, and practices. Data were analyzed using the Statistical Package for Social Sciences (version 20.20, IBM, Armonk, New York, US), and chi-square tests were used to assess the connection between OA care and socioeconomic statuses. Mean and standard deviation were calculated for quantitative variables. Results A considerable portion (48%, n = 152) of the participants were from a lower socioeconomic background, and 51% of them had a history of joint pain. Significantly, 63% of the participants (n = 199) attributed their joint pain to age, while nearly half attributed it to their diet and exercise habits. A major segment (73%, n = 230) of the participants, irrespective of their socioeconomic backgrounds, had visited a doctor for their joint complaints. Around 65% of the participants said they would never undergo a knee-joint replacement, regardless of how worse their symptoms might get. Additionally, 36% of the participants were unsatisfied with their current treatment, while more than half of the participants said that medication would improve their condition. Conclusions Our results demonstrate a connection between the lack of awareness about OA and the factors negatively affecting its management. They also point towards areas that require focused efforts for better awareness.

Evaluation of methods to reduce background using the Python-based ELISA_QC program.

Almost all immunological approaches [immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), Western blot], that are used to quantitate specific proteins have had to address high backgrounds due to non-specific reactivity. We report here for the first time a quantitative comparison of methods for reduction of the background of commercial biotinylated antibodies using the Python-based ELISA_QC program. This is demonstrated using a recombinant humanized anti-cocaine monoclonal antibody. Several approaches, such as adjustment of the incubation time and the concentration of blocking agent, as well as the dilution of secondary antibodies, have been explored to address this issue. In this report, systematic comparisons of two different methods, contrasted with other more traditional methods to address this problem are provided. Addition of heparin (HP) at 1 µg/ml to the wash buffer prior to addition of the secondary biotinylated antibody reduced the elevated background absorbance values (from a mean of 0.313 ±â€¯0.015 to 0.137 ±â€¯0.002). A novel immunodepletion (ID) method also reduced the background (from a mean of 0.331 ±â€¯0.010 to 0.146 ±â€¯0.013). Overall, the ID method generated more similar results at each concentration of the ELISA standard curve to that using the standard lot 1 than the HP method, as analyzed by the Python-based ELISA_QC program. We conclude that the ID method, while more laborious, provides the best solution to resolve the high background seen with specific lots of biotinylated secondary antibody.

Estrogen and soy isoflavonoids decrease sensitivity of medulloblastoma and central nervous system primitive neuroectodermal tumor cells to chemotherapeutic cytotoxicity.

BACKGROUND: Our previous studies demonstrated that growth and migration of medulloblastoma (MB), the most common malignant brain tumor in children, are stimulated by 17ß-estradiol. The growth stimulating effects of estrogens are mediated through ERß and insulin-like growth factor 1 signaling to inhibit caspase 3 activity and reduce tumor cell apoptosis. The objective of this study was to determine whether estrogens decreased sensitivity of MB cells to cytotoxic actions of chemotherapeutic drugs. METHODS: Using in vitro cell viability and clonogenic survival assays, concentration response analysis was used to determine whether the cytoprotective effects of estradiol protected human D283 Med MB cells from the cytotoxic actions of the MB chemotherapeutic drugs cisplatin, vincristine, or lomustine. Additional experiments were done to determine whether the ER antagonist fulvestrant or the selective ER modulator tamoxifen blocked the cytoprotective actions of estradiol. ER-selective agonists and antagonists were used to define receptor specificity, and the impacts of the soy-derived phytoestrogens genistein, daidzein, and s-equol on chemosensitivity were evaluated. RESULTS: In D283 Med cells the presence of 10 nM estradiol increased the IC50 for cisplatin-induced inhibition of viability 2-fold from ~5 µM to >10 µM. In clonogenic survival assays estradiol decreased the chemosensitivity of D283 Med cells exposed to cisplatin, lomustine and vincristine. The ERß selective agonist DPN and low physiological concentrations of the soy-derived phytoestrogens genistein, daidzein, and s-equol also decreased sensitivity of D283 Med cells to cisplatin. The protective effects of estradiol were blocked by the antiestrogens 4-hydroxytamoxifen, fulvestrant (ICI 182,780) and the ERß selective antagonist PPHTP. Whereas estradiol also decreased chemosensitivity of PFSK-1 cells, estradiol increased sensitivity of Daoy cell to cisplatin, suggesting that ERß mediated effects may vary in different MB celltypes. CONCLUSIONS: These findings demonstrate that E2 and environmental estrogens decrease sensitivity of MB to cytotoxic chemotherapeutics, and that ERß selective and non-selective inhibition of estrogen receptor activity blocks these cytoprotective actions. These findings support the therapeutic potential of antiestrogen adjuvant therapies for MB, and findings that soy phytoestrogens also decrease sensitivity of MB cells to cytotoxic chemotherapeutics suggest that decreased exposure to environmental estrogens may benefit MB patient responses to chemotherapy.

Characterization of a recombinant humanized anti-cocaine monoclonal antibody produced from multiple clones for the selection of a master cell bank candidate.

We have generated a humanized anti-cocaine monoclonal antibody (mAb), which is at an advanced stage of pre-clinical development. We report here in vitro binding affinity studies, and in vivo pharmacokinetic and efficacy studies of the recombinant mAb. The overall aim was to characterize the recombinant antibody from each of the three highest producing transfected clones and to select one to establish a master cell bank. In mAb pharmacokinetic studies, after injection with h2E2 (120 mg/kg iv) blood was collected from the tail tip of mice over 28 days. Antibody concentrations were quantified using ELISA. The h2E2 concentration as a function of time was fit using a two-compartment pharmacokinetic model. To test in vivo efficacy, mice were injected with h2E2 (120 mg/kg iv), then one hour later injected with an equimolar dose of cocaine. Blood and brain were collected 5 min after cocaine administration. Cocaine concentrations were quantified using LC/MS. The affinity of the antibody for cocaine was determined using a [3H] cocaine binding assay. All three antibodies had long elimination half-lives, 2-5 nM Kd for cocaine, and prevented cocaine's entry into the brain by sequestering it in the plasma. Pharmacokinetic and radioligand binding assays supported designation of the highest producing clone 85 as the master cell bank candidate. Overall, the recombinant h2E2 showed favorable binding properties, pharmacokinetics, and in vivo efficacy.

Severe isolated primary hypoparathyroidism in an adult.

A man aged 42 years, presented with 3 years history of paraesthesias in hands and feet and muscle cramps off and on, progressing to severe carpopedal spasm, a couple of times, relieved by intravenous calcium gluconate at the emergency reception of the hospital. On examination, Trousseau's sign and Chvostek's sign were positive. Thyroid gland was not enlarged. Right eye showed mature cataract. Total serum calcium, corrected serum calcium, serum phosphate, ionized serum calcium, serum alkaline phosphatase, serum parathormone (PTH) level were deranged favouring hypoparathyroidism. He was diagnosed to be suffering from isolated primary hypoparathyroidism and put on alfacalcidol and oral calcium carbonate, with which he is asymptomatic now.