Dental Caries: Unveiling the State-of-the-Art Insights and Crafting Hypotheses for Oral Health.

The pathophysiological understanding of dental caries explains that the primary factor responsible is linked to an imbalance in microbial composition within the oral cavity, stemming from both artificial and natural sources. Streptococcus mutans (S. mutans) is the most accountable and prevalent pathogen for caries development among the diverse pool. S. mutans, an acidogenic bacterium, lowers oral pH through the metabolic conversion of dietary sugar into organic acids, leading to enamel demineralization and dental caries. Numerous antibacterial interventions have been employed in the past to address this issue. However, adopting such an approach poses the risk of exacerbating concerns related to Antimicrobial Resistance (AMR) and long-term oral cytotoxicity. In response to this, a sustainable strategy is suggested, involving the utilization of L-Arginine (L-Arg) as a probiotic nutrient supplement for non-pathogenic microbes. It will help in creating a natural competitive environment against the pathogenic microbes responsible for initiating dental caries. The hypothesis involves utilizing a combination of a nutrient supplement and the repurposed drug Piceatannol, specifically for its anti-biofilm properties. This combination synergistically improves the effectiveness of the therapy by converting the complex microbial biofilm into a planktonic state.

Ameliorating Gonorrhea: Recent Therapeutic Adaptations and Scope to Improve its Prevailing Condition.

BACKGROUND: Gonorrhea is a sexually transmitted infection (STI) caused by the bacteria Neisseria gonorrhoeae. According to recent research, the prevalence of gonorrhea has been increasing in many parts of the world, with some areas reporting high rates of antibiotic resistance. In the United States, the Centers for Disease Control and Prevention (CDC) reported that the number of reported gonorrhea cases increased by 56% between 2015 and 2019. Globally, the World Health Organization (WHO) estimated that there were 87 million new cases of gonorrhea in 2016, with the highest burden of infection in low- and middle-income countries. Research has also shown that gonorrhea is becoming increasingly resistant to conventional antibiotics, increasing the prevalence of gonorrhea. This raises concerns and challenges in disease management. OBJECTIVES: The present review gives updated insight on the current state of the disease, challenges, and shortcomings of existing approaches along with the modern and alternative direction like vaccine development, its challenges, and scope to confront the existing state of drug resistance and increased rate of incidence. Alternative strategies like immunotherapy and phage therapy along with recent antibiotics researched for the treatment of gonorrhea. CONCLUSION: The review provides a thorough insight into the current state of the disease and various available methods used currently and recommended by WHO. To overcome disease prevalence, various alternate therapies are coming into the limelight. However, scientists and researchers show a lack of interest in the drug development and research of gonorrhea, due to less commercial scope, lack of funding, and limited scope in the scientific scenario. These hurdles need to be overcome to meet the WHO vision of reducing gonorrhea by 90% by 2030. So, there is a need to optimize the drug therapy (optimizing dosing schedule, and precision monitoring) to reduce the chance of drug resistance. Also, there is a wide scope for drug and therapeutic system development.

Unraveling the role of glial cell line-derived neurotrophic factor in the treatment of Parkinson's disease.

Parkinson's disease is the second most common neurodegenerative condition with its prevalence projected to 8.9 million individuals globally in the year 2019. Parkinson's disease affects both motor and certain non-motor functions of an individual. Numerous research has focused on the neuroprotective effect of the glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease. Discovered in 1993, GDNF is a neurotrophic factor identified from the glial cells which was found to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. Given this property, recent studies have focused on the exogenous administration of GDNF for relieving Parkinson's disease-related symptoms both at a pre-clinical and a clinical level. This review will focus on enumerating the molecular connection between Parkinson's disease and GDNF and shed light on all the available drug delivery approaches to facilitate the selective delivery of GDNF into the brain paving the way as a potential therapeutic candidate for Parkinson's disease in the future.

Atherosclerosis Potential Drug Targets: Current Scenario and Future Perspectives.

BACKGROUND: The global burden of atherosclerosis and its implication to cause coronary heart disease and ischemic cardiac problems is the most prevalent cause of morbidity and hospitalization. In the US, there has been an increase in the number of patients with cardiac problems in the last decade, and still remains the primary cause of death in Europe as well as in the US. OBJECTIVES: Even though therapeutic interventions and early diagnosis the formation of the fatty lesion and its subsequent steps are possible, the therapeutic management of the disease remains questionable when clinical data is observed. There is still scope for proper target identification and biomarker recognition, which can serve as a baseline to develop efficient pharmacological agent and delivery systems so that the disease incidence and prevalence can be controlled. The present article highlights the current pathophysiological state of the disease and emerging strategies that are applied to manage the disease. FINDINGS: This article gives an insight into the limitations of various conventionally used therapeutic agents for disease treatment. The emerging strategies that could prove efficacious in disease treatment. This article also gives an insight into current discoveries in the field of cellular and molecular biology, such as the genetic role in causing dyslipidemia and the role of immune cells and the role of non-coding small RNA, which can set the future direction to develop therapeutics interventions for atherosclerosis.

Exploring Applications of Flexible Vesicular Systems as Transdermal Drug Delivery.

Deformable lipidic-nano carriers are a category of advanced liposomal formulations. Deformable lipidic-nano carriers have a specific character to transform by rearranging the lipidic backbone to squeeze themself through a pore opening ten times smaller than their diameter when exposed to a variable condition like hydration gradient as these have potentially been used as a non-invasive delivery system to transdermally migrate various therapeutic agents for over three decades. Despite their vast application in transdermal drug delivery system, non-uniformity to express their chemical nature still exist and authors use various terms synonymously and interchangeably with each other. The present study delineates the terminologies used to express different derived deformable vesicular carriers to harmonize the terminological use. It also includes the effectiveness of deformable nanocarriers like Transferosomes, Ethosomes, Menthosomes, Invasomes, and Glycerosomes in skin conditions like basal cell carcinoma, fungal and viral infections, and hyperpigmentation disorders, along with others. Various review and research articles were selected from the 'Pubmed' database. The keywords like Transferosomes, Flexi-vesicular system, ultra-deformable vesicles, and nano-vesicular systems were used to extract the data. The data was reviewed and compiled to categorically classify different flexible vesicular systems. The composition of the different vesicular systems is identified and a report of various pathological conditions where the use of flexible lipid nanocarrier systems was implemented is compiled. The review also offers suggestive approaches where the applicability of these systems can be explored further.

Review of Progress in Diagnostic Studies of Autism Spectrum Disorder Using Neuroimaging.

This review article summarizes the recent advances in the diagnostic studies of autism spectrum disorders (ASDs) considering some of the most influential research articles from the last two decades. ASD is a heterogeneous neurodevelopmental disorder characterized by abnormalities in social interaction, communication, and behavioral patterns as well as some unique strengths and differences. The current diagnosis systems are based on autism diagnostic observation schedule (ADOS) or autism diagnostic interview-revised (ADI-R), but biological markers are also important for an effective diagnosis of ASDs. The amalgamation of neuroimaging techniques, such as structural and functional magnetic resonance imaging (sMRI and fMRI), with machine-learning and deep-learning approaches helps throw new light on typical biological markers of ASDs at the early stage of life. To assess the performance of a deep neural network, we develop a light-weighted CNN model for ASD classification. The overall accuracy, precision, and F1-score of the proposed model are 99.92%, 99.93% and 99.92%, respectively. All the neuroimaging studies we have reviewed can be divided into 3 categories, viz. thickness, volume and functional connectivity-based studies. We conclude with a discussion of the major findings of considered studies and promising directions for future research in this field.

Impedimetric Chemosensing of Volatile Organic Compounds Released from Li-Ion Batteries.

Detection of toxic and flammable gases and volatile organic compounds (VOCs) released from Li-ion batteries during thermal runaway can generate an early warning. A submicron (∼0.15 µm)-thick poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) sensor film is coated on a platinum electrode through a facile aqueous dispersion. The resulting sensor reliably detected different volatile organic compounds (VOCs) released during the early stages of thermal runaway of lithium-ion batteries (LIBs) even at low concentrations. The single-electrode sensor utilizes impedance spectroscopy to measure ethyl methyl carbonate and methyl formate concentrations at 5, 15, and 30 ppm independently and in various combinations using ethanol as a reference. In contrast to DC resistance measurement, which provides a single parameter, impedance spectroscopy provides a wealth of information, including impedance and phase angle at multiple frequencies as well as fitted charge transfer resistance and constant-phase elements. Different analytes influence the measurement of different parameters to varying degrees, enabling distinction using a single sensing material. The response time for ethyl methyl carbonate was measured to be 6 s. Three principal components (PCs) preserve more than 95% of information and efficiently enable discrimination of different classes of analytes. Application of low-power PEDOT:PSS-based gas sensors will facilitate cost-effective early detection of VOCs and provide early warning to battery management systems (BMS), potentially mitigating catastrophic thermal runaway events.

Implant esthetic restoration in ridge deficiencies in cases of trauma: a case report.

The long-term success of implant therapy does not depend solely on osseointegration, but the gingival architecture surrounding the implant system. It becomes very important to restore the gingival tissues in the areas that enhance one's esthetics. The esthetic zone can be defined as any dentoalveolar area of esthetic concern to the patient. The anterior maxillary teeth in the esthetic zone usually extend from first premolar to first premolar, but in some individuals can extend as far distally as the first molar. The patients requiring esthetic reconstruction at the site of trauma pose a great problem in implant placement and prosthetic restoration as scar tissue interferes with the same. To be successful, an implant-supported restoration should meet biological, mechanical, and esthetic goals. The most challenging situation is when esthetics is of prime concern in deficient ridge cases. This clinical report presents problems faced during implant placement and the sequential procedure to rehabilitate with an implant that was esthetically harmonized at the site of trauma.

Blue-shift of surface plasmon resonance in a metal nanoslit array structure.

The adsorption of a self-assembled monolayer of molecules on a metal surface commonly causes a red-shift in its surface plasmon resonance. We report that the anomalous dispersion of surface plasmons in a Au nanoslit array structure can cause a blue-shift of optical transmission upon adsorption of a non-absorbing self-assembled monolayer of molecules. We develop a simple model that explains the blue-shift observed in the transmission spectra with monolayer adsorption in terms of the interplay of anomalous dispersion and the cavity resonance of surface plasmons in the nanoslit array.

Charge density effects on the aggregation properties of poly(p-phenylene-ethynylene)-based anionic polyelectrolytes.

This work shows that low charge density poly(p-phenylene-ethynylene)s (PPE-SO3Na-L and PPE-CO2Na-L), which feature sulfonate and carboxylate groups on every other phenyl ring, form aggregates in water, whereas high charge density poly(p-phenylene-ethynylene)s (PPE-SO3Na-H and PPE-CO2Na-H), which possess sulfonate or carboxylate groups on every phenyl ring, do not aggregate in water. The formation of aggregates of PPE-SO3Na-L and PPE-CO2Na-L is demonstrated by comparing the concentration and temperature dependence of their steady-state spectra in water to that in DMSO, in which the two polymers do not aggregate. For the weak polyelectrolytes PPE-CO2Na-H and PPE-CO2Na-L, the solution pH was changed to vary the charge density. In addition, the cationic surfactant, octadecyltrimethyl ammonium, is shown to dissociate the low charge density polymer aggregates and to form supramolecular complexes with each of the different polyelectrolytes. Fluorescence correlation spectroscopy was applied to provide insight into the sizes of aggregates under different solution conditions.

Dependence of fluorescence quenching of a poly(p-phenyleneethynylene) polyelectrolyte on the electrostatic and hydrophobic properties of the quencher.

This study investigates the fluorescence quenching of a poly(p-phenyleneethynylene) (1) based polyelectrolyte by positively charged and neutral macromolecules. This work shows that the change in the fluorescence yield of 1 depends on a number of factors, including electrostatic, hydrophobic, and energy transfer interactions with the quencher and also changes in the solution conditions such as concentration and ionic strength. The fluorescence quenching is attributed to the formation of aggregates that form upon addition of different quenchers to a solution of 1 and/or the solution conditions. The extent of 1's aggregation is shown to depend on the type of interaction between the polymer and the quencher, the concentration of the polymer, and the ionic strength of the solution.

Solvation and aggregation of polyphenylethynylene based anionic polyelectrolytes in dilute solutions.

The absorption and fluorescence properties of a polyphenylethynylene based conjugated polyelectrolyte with sulfonate solubilizing groups (PP2) are shown to change dramatically with solution conditions because of the equilibrium between unaggregated and aggregated forms of the polymer. The fluorescence of PP2 is strongly quenched on addition of counterions such as Na+, K+, Li+, and TBA+, an effect which arises from the creation of salt stabilized aggregates. The formation of aggregates has been further corroborated by concentration and temperature studies in water and comparisons to dimethylsulfoxide solvent, in which the polymer does not aggregate. In aqueous solutions, the addition of the cationic surfactant, octadecyltrimethyl ammonium, causes the polymer aggregates to dissociate and creates polymer/surfactant aggregates that have spectral properties like that of the unaggregated polymer.

Fluorescence quenching mechanism of a polyphenylene polyelectrolyte with other macromolecules: cytochrome c and dendrimers.

This study investigates the fluorescence quenching of a polyphenyl based polyelectrolyte by positively charged macromolecules (proteins and dendrimers). This work shows that the fluorescence quenching of the dendrimer materials does not involve energy transfer or electron transfer but is correlated to the overall charge on the dendrimer and its size. The quenching is hypothesized to result from conformational changes that occur upon binding the polyelectrolyte to the protein or dendrimer. This mechanism is qualitatively different from that invoked for small-molecule analytes.