Olmsted syndrome causing point mutants of TRPV3 (G568C and G568D) show defects in intracellular Ca2+-mobilization and induce lysosomal defects.

TRPV3, a non-selective cation channel known to be activated by physiological temperature, is expressed in skin and is involved in different skin functions. Point mutations in TRPV3 cause severe pathological condition, known as Olmsted Syndrome (OS). Now we demonstrate that two OS-inducing point mutations (G568C and G568D) located at the lipid-water-interface region joining TM4 with the loop4 of TRPV3 cause reduced cell size and major defects in lysosomal numbers, and distribution. We detected these two mutants in the lysosome. However, G568C and G568D mutants differ from themselves and also from Wild-type in terms of Ca2+-influx in response to activation by agonist (FPP). These two mutants fail to mobilise Ca2+ from intracellular stores, especially when cytosolic Ca2+ is chelated and/or in absence of extracellular Ca2+. We demonstrate that OS-mutants cause defective pH-maintenance at the lysosomes. We propose that G568C and G568D mutants most-likely act as Ca2+-leaky channels from lysosomes with different abilities.

Polymeric Micelles as Drug Delivery System: Recent Advances, Approaches, Applications and Patents.

Administering therapeutics through the oral route is a pervasive and widely approved medication administration approach. However, it has been found that many drugs show low systemic absorption when delivered through this route. Such limitations of oral drug delivery can be overcome by polymeric micelles acting as vehicles. As a result, they improve drug absorption by protecting loaded drug substances from the gastrointestinal system's hostile conditions, allowing controlled drug release at a specific site, extending the time spent in the gut through mucoadhesion, and inhibiting the efflux pump from reducing therapeutic agent accumulation. To promote good oral absorption of a weakly water-soluble medicinal drug, the loaded medicine should be protected from the hostile atmosphere of the GI tract. Polymeric micelles can be stacked with a broad assortment of ineffectively dissolvable medications, improving bioavailability. This review discusses the major mechanism, various types, advantages, and limitations for developing the polymeric micelle system and certain micellar drug delivery system applications. The primary goal of this review is to illustrate how polymeric micelles can be used to deliver poorly water-soluble medications.

Nonextraction Treatment of Maxillary Canine and Lateral Incisor Transposition: A Case Report.

The transposition of teeth is an infrequent dental abnormality characterized by the exchange of position between two adjacent teeth. This report presents a unique case of transposition involving the maxillary right canine and lateral incisor in a 20-year-old female patient. Clinical assessment and radiographic evaluation revealed the unconventional positioning of the affected teeth. Treatment planning necessitated collaborative efforts between orthodontic specialists to achieve optimal esthetic and functional outcomes. The patient underwent a comprehensive treatment regimen, including orthodontic alignment by distal drifting of the canine and mesial shifting of the lateral incisor. Subsequent long-term follow-ups confirmed stable occlusion and satisfactory esthetics in a time period of 18 months. This case underscores the significance of precise diagnosis and a multidisciplinary approach in managing intricate dental anomalies such as tooth transposition.

A More Aesthetically Pleasing Smile: A Case Report on the Impact of Scalpel Technique on Gingival Depigmentation.

Gingival hyperpigmentation can significantly affect how the smile looks cosmetically, leading patients to seek treatment. This case report addresses the use of a scalpel approach combined with bur abrasion for gingival depigmentation in a 19-year-old female patient who was displeased with her "black" gums. A local anesthetic was required for the surgical removal of the pigmented epithelium and a thin layer of connective tissue. Post-operative care included antibiotics and analgesics, with chlorhexidine mouthwash use for optimal healing. Follow-up examinations showed successful depigmentation without complications. This simple method is a good choice for gingival pigmentation management since it provides satisfactory cosmetic results and patient satisfaction.

Misdiagnosis of an Odontogenic Infection as a Skin Lesion: The Diagnostic Dilemma.

Extraoral sinus tracts of endodontic origin might be confused for a variety of dermatological conditions. Differential diagnosis of this clinical condition plays an essential role in providing appropriate clinical care because misdiagnosis is the most prevalent cause of prolonged therapy and healing failure. As a result, every cutaneous sinus structure affecting the face or neck should be investigated for dental issues. Its diagnosis can sometimes be difficult until the treating clinician examines the potential of a dental cause. Once an appropriate diagnosis has been established, definitive treatment, consisting of root canal therapy or tooth extraction, to remove the primary source of infection is a straightforward and successful operation.

Nutriose, a Dextrin-based Natural Polysaccharide Polymer with Beneficial Activities as a Candidate for Future Drug Delivery: A Review.

Nutriose is a dextrin-based soluble fiber prepared from starch. Cereals such as maize, wheat, and barley are the primary sources of nutrients for commercial production. Nutriose is resistant to digestion by human enzymes in the stomach and small intestine. It is mostly undamaged when it enters the colon after traveling through the digestive tract, where it generates shortchain fatty acids (SCFAs) as byproducts. These SCFAs, which include butyrate, propionate, and acetate, have a number of health advantages. They foster an environment in the colon that is advantageous for gut health-promoting bacteria like lactobacilli and bifidobacteria. Nutriose fermentation leads to a more balanced composition of the gut microbiota, which may have advantages for the immune system, better digestion, and increased nutrient absorption. As a result, nutriose is currently being utilized as a prebiotic. Several publications have previously demonstrated the impact of nutriose on stimulating gut mucosal immunity and boosting colonic fermentation and excretion in rats. Nanoformulations and nutrisomes have already been prepared and evaluated in recent years. A novel nutriose-based polymeric coating mix has already been tested as a potential colon-targeting material. As a natural polysaccharide, nutriose's possible uses in pharmaceuticals may increase in the near future. The purpose of this study is to critically analyze existing data to determine the potential of nutriose as a natural polymer for various drug delivery systems.

Treatment of Vertical Maxillary Excess and Skeletal Class II Malocclusion: A Case Report.

Class II malocclusion is a recurrent problem that may occur at a young age. If treated initially, the malocclusion can be corrected by redirecting the growth without invasive modalities and avoiding orthognathic surgeries. A female patient aged 10 years three months came to the department of orthodontics having a complaint of upper front teeth placed forwardly, diagnosed with skeletal class II due to retrusive mandible and vertical maxillary excess with hyper divergent growth pattern with increased anterior facial height, with Angle's molar class II division 1 malocclusion, increased overjet of 13 mm and overbite of 7 mm, acute nasolabial angle, deep mentolabial sulcus, and hyperactive mentalis. It was treated using an activator with medium-high-pull headgear (modified Herren activator) passing through the maxillary center of resistance. A fixed mechanotherapy with high-pull headgear was given using the anterior inclined plane acrylic plate in the maxilla and McLaughlin, Bennett, and Trevisi (MBT). Begg's wrap was used for the retention plan. This case report shows the significance of proper treatment results obtained due to correct identification and planning in treating malocclusion. This case report shows the significance of proper treatment results obtained due to correct identification and planning in treating malocclusion.

Periapical Lesion: A Single-Sitting Root Canal Treatment.

The aim of root canal treatment is to disinfect the root canal completely and prevent the progression of any periapical infection. Surgical treatment of periapical lesions is associated with many complications and challenges. This article describes the management of a periapical lesion of the right lower premolar in a single-visit root canal procedure using Metapex. The patient was observed for one week for any incidences of flare-ups.

A scoping review of multigenerational impacts of grandparental exposures on mental health in grandchildren.

PURPOSE OF REVIEW: The multigenerational effects of grandparental exposures on their grandchildren's mental health and neurodevelopment are gaining research attention. We conducted a scoping review to summarize the current epidemiological studies investigating pregnancy-related and environmental factors that affected grandparental pregnancies and mental health outcomes in their grandchildren. We also identified methodological challenges that affect these multigenerational health studies and discuss opportunities for future research. RECENT FINDINGS: We performed a literature search using PubMed and Embase and included 18 articles for this review. The most investigated grandparental pregnancy-related factors were the grandparental age of pregnancy (N = 6), smoking during pregnancy (N = 4), and medication intake (N = 3). The most frequently examined grandchild outcomes were autism spectrum disorder (N = 6) and attention-deficit/hyperactivity disorder (N = 4). Among these studies, grandparental smoking and the use of diethylstilbestrol were more consistently reported to be associated with neurodevelopmental disorders, while the findings for grandparental age vary across the maternal or paternal line. Grandmaternal weight, adverse delivery outcomes, and other spatial-temporal markers of physical and social environmental stressors require further scrutiny. The current body of literature has suggested that mental and neurodevelopmental disorders may be outcomes of unfavorable exposures originating from the grandparental generation during their pregnancies. To advance the field, we recommend research efforts into setting up multigenerational studies with prospectively collected data that span through at least three generations, incorporating spatial, environmental, and biological markers for exposure assessment, expanding the outcome phenotypes evaluated, and developing a causal analytical framework including mediation analyses specific for multigenerational research.