Unraveling the Puzzle of Therapeutic Peptides: A Promising Frontier in Huntington's Disease Treatment.

Huntington's disease (HD) is a neurodegenerative genetic disorder characterized by a mutation in the huntingtin (HTT) gene, resulting in the production of a mutant huntingtin protein (mHTT). The accumulation of mHTT leads to the development of toxic aggregates in neurons, causing cell dysfunction and, eventually, cell death. Peptide therapeutics target various aspects of HD pathology, including mHTT reduction and aggregation inhibition, extended CAG mRNA degradation, and modulation of dysregulated signaling pathways, such as BDNF/TrkB signaling. In addition, these peptide therapeutics also target the detrimental interactions of mHTT with InsP3R1, CaM, or Caspase-6 proteins to mitigate HD. This Perspective provides a detailed perspective on anti-HD therapeutic peptides, highlighting their design, structural characteristics, neuroprotective effects, and specific mechanisms of action. Peptide therapeutics for HD exhibit promise in preclinical models, but further investigation is required to confirm their effectiveness as viable therapeutic strategies, recognizing that no approved peptide therapy for HD currently exists.

Oxytosis/Ferroptosis in Neurodegeneration: the Underlying Role of Master Regulator Glutathione Peroxidase 4 (GPX4).

Oxytosis/ferroptosis is an iron-dependent oxidative form of cell death triggered by lethal accumulation of phospholipid hydroperoxides (PLOOHs) in membranes. Failure of the intricate PLOOH repair system is a principle cause of ferroptotic cell death. Glutathione peroxidase 4 (GPX4) is distinctly vital for converting PLOOHs in membranes to non-toxic alcohols. As such, GPX4 is known as the master regulator of oxytosis/ferroptosis. Ferroptosis has been implicated in a number of disorders such as neurodegenerative diseases (amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), etc.), ischemia/reperfusion injury, and kidney degeneration. Reduced function of GPX4 is frequently observed in degenerative disorders. In this study, we examine how diminished GPX4 function may be a critical event in triggering oxytosis/ferroptosis to perpetuate or initiate the neurodegenerative diseases and assess the possible therapeutic importance of oxytosis/ferroptosis in neurodegenerative disorders. These discoveries are important for advancing our understanding of neurodegenerative diseases because oxytosis/ferroptosis may provide a new target to slow the course of the disease.

Nicotine Intake in Adult Pod E-cigarette Users: Impact of User and Device Characteristics.

INTRODUCTION: This study examined user behavior, e-cigarette dependence, and device characteristics on nicotine intake among users of pod-mod e-cigarettes. AIMS AND METHODS: In 2019-2020, people who use pod-mods in the San Francisco Bay Area completed questionnaires and provided a urine sample for analysis of total nicotine equivalents (TNE). The relationship between TNE and e-cigarette use, e-cigarette brands, e-liquid nicotine strength, e-cigarette dependence, and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), as a measure of combustible cigarette exposure, were examined. RESULTS: Of 100 participants (64% male, 71% in the 18-34 age group, 45% white), 53 used JUUL primarily, 12 used Puff Bar primarily, and 35 used other brands, including Suorin; 48 participants reported current cigarette smoking. Participants most often reported use of e-liquid with 4.5%-6.0% nicotine (68%), fruit (35%), tobacco (28%), and menthol or mint flavors (26%), used e-cigarettes on 25.5 (SD = 6.3) days a month, 10.2 (SD = 14.2) times a day, and 40% used 1-2 pods/cartridges per week. In bivariate analysis, urinary TNE was higher with greater frequency (days used) and intensity (number of pods used) of e-cigarette use, e-cigarette dependence, and combustible cigarette use. In multivariable analysis, days of e-cigarette use in the last 30 days, number of pods used per week, and NNAL levels were significantly associated with TNE. There was no significant impact of e-liquid nicotine strength on TNE. CONCLUSIONS: Nicotine intake among people who used pod-mod e-cigarettes increased with e-cigarette consumption and e-cigarette dependence, but not with e-liquid nicotine strength. Our findings may inform whether FDA adopts a nicotine standard for e-cigarettes. IMPLICATIONS: The study examined how device and user characteristics influence nicotine intake among pod-mod e-cigarette users. Nicotine intake increased with frequency (days of e-cigarette use in past 30 days) intensity of use (number of pods used per day) and e-cigarette dependence but not with the flavor or nicotine concentration of the e-liquids. Regulation of nicotine concentration of e-liquids is unlikely to influence nicotine exposure among adult experienced pod-mod users.

Anxiety Related to Nonsurgical Root Canal Treatment: A Systematic Review.

INTRODUCTION: Anxiety is an emotion characterized by feelings of tension, worried thoughts, and physical changes. Dental anxiety has been associated with pain, fear, care avoidance, and more invasive treatments including nonsurgical root canal treatment (NSRCT). The very words root canal are deeply embedded in societal consciousness. Better understanding of dental anxiety may prevent treatment avoidance. The purpose of this study was to conduct a systematic review of NSRCT-associated anxiety. METHODS: Inclusion/exclusion criteria defined MEDLINE, Cochrane Library, psychINFO, manual, and citation searches. Title lists and abstracts were read to determine utility; data were extracted, summarized, and compiled into an evidence table, and meta-analyses were performed. RESULTS: Defined searching produced 835 titles; 36 articles were included, mostly representing modern populations from countries with very high human development indices. Major sources of heterogeneity included differing study aims, outcome measures, clinical settings, locations, operators, sample selection, and sample size. Meta-analysis of 18 articles including 1989 subjects gave a pretreatment anxiety rating of 39 (standard deviation, 9) on a normalized 100-point scale. Meta-analysis of 4 articles including 232 subjects gave a post-treatment anxiety rating of 27 (standard deviation, 5) on a normalized 100-point scale, representing a 30% reduction. A L'Abbe plot of 5 studies also showed that anxiety decreased after NSRCT. Limited data indicated that gender, age, and prior NSRCT experience influenced NSRCT-associated anxiety. NSRCT-associated anxiety was ranked high among dental treatments, often close to oral surgery. CONCLUSIONS: NSRCT-associated anxiety was generally moderate. Anxiety decreased after NSRCT. Limited evidence suggested that anxiety is influenced by patient and treatment factors.

Effect of Fractionated Dose of Radiotherapy on Oral Mucosa in Head and Neck Cancer Patients: A Cytological Assessment.

BACKGROUND: Cancer therapy couples with it a plethora of complications of short and long term effects which can be so distressing that patient may tolerate only lower less-effective doses of therapy, may postpone treatments or will discontinue treatment entirely. Fractionated dose of radiotherapy coupled with therapy induce local or systemic infections due to high cellular turnover rates of the oral mucosa, diverse and complex microflora and trauma to oral tissues. Several mucosal abnormalities often results in epithelial and glandular destruction and inflammation, which can be so devastating that it may cause atypical changes on the area exposed to radiation. Thus, the aim of this study was to investigate the feasibility of using cytological evaluation to detect oral epithelial atypia among Head and Neck cancer patients receiving fractionated dose of radiotherapy. METHODS: Study was conducted on 125 head and neck cancer patients receiving radiotherapy. Subjects were divided into 5 study groups on the basis of fractionated dose of radiotherapy from 10th-50th fractions respectively. Mucosal changes were evaluated by exfoliative cytology and atypical changes and inflammatory cell infiltration were assessed. RESULTS: Without prior knowledge of the subjects' group, oral epithelial atypia was detected with increase fractionated dose of radiation. Dense inflammatory nfiltrate were identified in nearly all study groups irrespective of dose of radiotherapy. CONCLUSION: Cytological atypia and inflammatory infiltrates were detected after exposure to radiotherapy.

Ultrastructural analysis of oral exfoliated epithelial cells of tobacco smokers and betel nut chewers: A scanning electron microscopy study.

BACKGROUND: The study was undertaken to correlate epithelial surface pattern changes of oral exfoliated cells of tobacco smokers and betel nut chewers and also to compare them with patients of oral squamous cell carcinoma (OSCC) and healthy individuals. MATERIALS AND METHODS: In this cross-sectional study, a total of fifty persons were included in the study, out of which thirty formed the study group (15 each tobacco smokers and betel nut chewers) and twenty formed the control group (ten each of OSCC patients - positive control and ten normal buccal mucosa - negative control). Their oral exfoliated cells were scraped, fixed, and studied under scanning electron microscope (SEM). The statistical analysis was determined using ANOVA, Tukey honestly significant difference, Chi-square test, and statistical SPASS software, P < 0.05. RESULTS: OSCC, Individual cell modifications, intercellular relationships and surface characteristics observed by scanning electron microscopy between OSCC, tobacco smokers, betel nut chewers compared to normal oral mucosa have been tabulated. CONCLUSION: In normal oral mucosa, cell surface morphology depends on the state of keratinization of the tissue. Thus, it could prove helpful in detecting any carcinomatous change at its incipient stage and also give an insight into the ultra-structural details of cellular differentiations in epithelial tissues.

Fibrous dysplasia of the palate: report of a case and review of palatal swellings.

Fibrous dysplasia is a benign fibroosseous lesion characterised by the replacement of normal bone by excessive proliferation of cellular fibrous connective tissue which is slowly replaced by bone, osteoid, or cementum-like material. It causes bone pain, deformities, and pathological fractures. Fibrous dysplasia (FD) is a sporadic benign skeletal disorder that can affect one bone (monostotic form) or multiple bones (polyostotic form). In this paper, we present case of a monostotic fibrous dysplasia on the hard palate of 14-year-old girl and a tabular review of common palatal swellings.

Audit of leiomyoma uterus at Khyber teaching hospital Peshawar.

BACKGROUND: Fibroid is the commonest tumor of the reproductive tract and frequently encountered problem in gynecological practice. This study was carried out to observe the frequency of fibroids in relation to age, parity and clinical manifestations along with a critical review of its management. METHODS: This study was carried out over a period of one year from 1st January to 31st December 2000 in Gynae "A" unit of Khyber teaching hospital, Peshawar. All patients presenting with fibroid uterus were included in the study. Data collection included age, parity, menstrual pattern, presenting symptoms, medical and surgical treatment history. Diagnostic criteria were clinical and ultrasonography. Evaluation of medical treatment and surgery were carried out. Management outcome of minimal invasive surgery was also observed. RESULTS AND CONCLUSION: Total 146 cases were observed. Greater frequency was found in late reproductive and perimenopausal years (65.7%). There were 34.2% cases in reproductive age group. Majority was multiparous (72%) and 28% were nulliparous. Infertility was noticed in 16%. Myomas were mostly symptomatic (70%). Menstrual symptoms were commonest (81.5%), pain was second common symptom (27.3%). About 24% presented with abdominal mass and hyaline degeneration were in 50% of cases. Leiomyomas were multiple in 63.1% and commonest variety was interstitial (60.4%). Familial factor noticed in 5.4%, clinical diagnosis was made in 58.2% of cases, while ultrasound was used in 40.4% of patients, conservative treatment was given in 37.6% including medical therapy (8.2%). Surgery was performed in (62.3%). Myomectomy (10.2%) and hysterectomy was carried out in 52.05%. Minimal invasive surgery was not possible in our set up.