Accurate sex estimation is of utmost importance in forensic anthropology and bioarchaeology. Nevertheless, traditional methods are frequently influenced by confounding factors and biases specific to certain populations. This study aims to revolutionize sex classification methods for Asian populations through the innovative integration of Orthogonal Partial Least Squares (OPLS) for dimensionality reduction and Linear Discriminant Analysis (LDA) for evaluating mandibular metrics. A collection of dry mandibles, predominantly sourced from the late 19th century to minimize the influence of modern admixture, was analyzed, measuring 16 key parameters. OPLS was utilized to isolate sex-relevant variations, followed by univariate and multivariate LDA to achieve robust classification, with cross-validation performed to ensure reliability. The results indicated cross-validated accuracies ranging from 75.7 to 87.4% for univariate LDA and from 82.5 to 85.4% for multivariate LDA, with maximum mandibular body height identified as the most significant predictor (87.4%). This pilot study establishes a reliable framework for sex estimation based on mandibular parameters in pooled Asian populations, offering significant implications for forensic and bioarchaeological applications. The effectiveness of OPLS in eliminating confounding factors was highlighted, enhancing the robustness of the findings. Future research is recommended to extend these methodologies to other Asian subgroups and develop LDA models for fragmented mandibles, thereby improving the practical utility of sex estimation techniques in forensic contexts. Valuable insights into sexual dimorphism are provided, emphasizing the potential for standardized sexing protocols across diverse Asian populations, which reinforces the importance of reliable methodologies in forensic investigations.

There is minimal published experience with naratriptan during breastfeeding. If naratriptan is required by the mother of an older infant, it is not a reason to discontinue breastfeeding, but until more data become available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.

Tinnitus, a distressing condition that can significantly impair quality of life, has been associated with several medications, including triptans. This study aimed to explore the relationship between tinnitus and specific migraine treatments, focusing on triptans and calcitonin gene-related peptide (CGRP) inhibitors. Data from the FDA Adverse Event Reporting System (FAERS) through the third quarter of 2023 were analyzed to calculate proportional reporting ratios (PRR) and reporting odds ratios (ROR) for migraine treatments, specifically triptans and CGRP inhibitors. Positive tinnitus signals were identified when PRRs or RORs were greater than 2.0, the lower bound of the 95% confidence interval exceeded 1.0, and at least three cases were reported. Intra- and inter-class analyses were conducted to compare tinnitus reports among individual drugs and drug classes. Among 47,615 tinnitus-related adverse events, 345 were associated with CGRP inhibitors and 183 with triptans. Positive tinnitus signals were observed for several CGRP inhibitors, except eptinezumab and atogepant, and for all triptans except sumatriptan. Inter-class analysis revealed no significant differences between triptans and CGRP inhibitors. However, intra-class analysis identified naratriptan, almotriptan, and frovatriptan as having notable tinnitus signals among triptans, while CGRP inhibitors did not exhibit strong signals for any specific drug. Using real-world data from FAERS and pharmacovigilance methods, this study identified tinnitus signals related to migraine treatments, particularly among certain triptans. These findings provide preliminary evidence for further investigation into the relationship between migraine medications and tinnitus.

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder caused by CAG trinucleotide expansion in the androgen receptor (AR) gene. To improve the quality of in vitro cell-based assays for the evaluation of potential drug candidates for SBMA, we developed a morphology-based phenotypic analysis for a muscle cell model of SBMA that involves multiparametric morphological profiling to quantitatively assess the therapeutic effects of drugs on muscle cell phenotype. The analysis was validated using dihydrotestosterone and pioglitazone, which have been shown to exacerbate and ameliorate the pathophysiology of SBMA, respectively. Gene expression analysis revealed activation of the JNK pathway in the SBMA cells compared to the control cells. Phenotypic analysis revealed the effect of naratriptan, a JNK inhibitor, on the phenotypic changes of SBMA cells, and the results were confirmed by LDH assays. We then trained a predictive machine learning model to classify the drug responses, and it successfully discriminated between pioglitazone-type and naratriptan-type morphological profiles based on their morphological characteristics. Our morphology-based phenotypic analysis provides a noninvasive and efficient screening method to accelerate the development of therapeutics for SBMA.

Objective: Japan has resumed its health technology assessment to decide how to reduce high-cost drug prices. While drug price rules in Japan are comprehensive, they do not necessarily capture differences in product characteristics. This study examined the drug price revision strategy in Japan using migraine treatment with triptans as an example. Cost data from fiscal years (FY) 2018, 2020, and 2022 were utilized. Methods: A cost-utility analysis was conducted from the perspective of healthcare payers, focusing on Japanese patients aged over 18 years experiencing migraines. The study employed a base-case model with probabilities derived from a network meta-analysis. Direct costs included medical and drug costs. Effectiveness was assessed using the European Quality of Life 5-dimensions-3-level questionnaire. Deterministic and probabilistic sensitivity analyses were conducted to examine the level of uncertainty. Results: In FY2018, sumatriptan and eletriptan were cost-effective; however, the other triptans were dominated by sumatriptan. In FY2020, sumatriptan and eletriptan were cost-effective, and rizatriptan was extended-dominated; nevertheless, the other triptans were dominated by sumatriptan. In FY2022, naratriptan and eletriptan were cost-effective; however, the other triptans were dominated by naratriptan. The hierarchy of triptan strategies varied in each fiscal year. Conclusions: This study provides valuable insights into the drug price revision strategy in Japan. The variations could be problematic because in Japan, formulary management of triptans, for example, those for migraine, may face revaluation every other year. Discussions regarding this issue will be further explored in the future.

The triptans class of pharmaceuticals, which was created to treat acute migraine, is made up of indole-containing drugs that bind to a subset (1B/1D) of 5-hydroxytryptamine receptors and are agonists of serotonin receptors. At the moment, naratriptan, eletriptan, zolmitriptan, rizatriptan, almotriptan, and frovatriptan are the seven types of triptans available on the market. Among these are the FDA-approved triptans, Zolmitriptan and Sumatriptan, which are selective serotonin (5-hydroxytryptamine) agonists. Zolmitriptan, a synthetic tryptamine derivative and a well-known member of the triptan family, is available as an orally disintegrating tablet, nasal spray, and tablet. There are melt formulations of rizatriptan and zolmitriptan available on the market that are easier to use and absorb, comparable to regular pills. Recently, the FDA approved zolmitriptan, a medication with tolerability comparable to sumatriptan. Whereas zolmitriptan is only available as an oral melt or tablet, sumatriptan is available as a nasal spray, oral preparation, or self-injectable kit. The only known antimigraine drugs that were widely utilized before the triptan period were ergotamine and dihydroergotamine. However, zolmitriptan binds to plasma proteins only 25% of the time because of significant first-pass degradation. Researchers have looked into fresh ideas for solving this issue and innovations to overcome its pharmacokinetic difficulties. This article emphasizes the role of zolmitriptan in the treatment of migraines, highlighting its pharmacological properties, production, metabolism, and structural features.

Around 91% of migraine patients use over-the-counter medicines to treat attacks, often without further treatment or medical consultation. This therapeutic principle is established in most countries, regardless of how the healthcare system is otherwise structured or financed. Using Germany as an example, the basis for an expansion of attack therapy with rizatriptan as an over-the-counter triptan is described. To achieve the best possible tolerability and safety in the context of self-medication, the lowest possible dose should be selected to provide the most favourable tolerability and safety profile in the context of self-medication through low dosages. The lowest approved dose of rizatriptan is 5 mg. This was investigated in three randomized controlled trials with 752 patients. The results show that rizatriptan at a dose of 5 mg is more effective than the triptans naratriptan 2.5 mg, almotriptan 12.5 mg and sumatriptan 50 mg, which were previously available for self-medication in Germany. There was no significant difference in the frequency of adverse events with rizatriptan 5 mg compared to placebo. Rizatriptan 5 mg does not have a higher side effect potential than sumatriptan 50 mg, which is already exempt from the prescription requirement. The reasons given show that rizatriptan in a dose of 5 mg for the treatment of acute migraine attacks fulfils the requirements for a transfer from prescription to pharmacy-only status at least as well as sumatriptan 50 mg, naratriptan 2.5 mg and almotriptan 12.5 mg. From a clinical care perspective, it is desirable for affected patients to have other options available for self-medication. Non-responders to other substances also have a further treatment option with rizatriptan 5 mg, with the same or even better risk-benefit profile, to treat migraine attacks safely, effectively and in a tolerable manner as part of self-medication.

Migraine is a common brain condition characterised by disabling attacks of headache with sensory sensitivities. Despite increasing understanding of migraine neurobiology and the impacts of this on therapeutic developments, there remains a need for treatment options for patients underserved by currently available therapies. The first specific drugs developed to treat migraine acutely, the serotonin-5-hydroxytryptamine [5-HT1B/1D] receptor agonists (triptans), seem to require headache onset in order to have an effect, while early treatment during mild pain before headache escalation improves short-term and long-term outcomes. Some patients find treating in the early window once headache has started but not escalated difficult, and migraine can arise from sleep or in the early hours of the morning, making prompt treatment after pain onset challenging. Triptans may be deemed unsuitable for use in patients with vascular disease and in those of older age and may not be effective in a proportion of patients. Headache is also increasingly recognised as being just one of the many facets of the migraine attack, and for some patients it is not the most disabling symptom. In many patients, painless symptoms can start prior to headache onset and can reliably warn of impending headache. There is, therefore, a need to identify therapeutic targets and agents that may be used as early as possible in the course of the attack, to prevent headache onset before it starts, and to reduce both headache and non-headache related attack burden. Early small studies using domperidone, naratriptan and dihydroergotamine have suggested that this approach could be useful; these studies were methodologically less rigorous than modern day treatment studies, of small sample size, and have not since been replicated. The emergence of novel targeted migraine treatments more recently, specifically calcitonin gene-related peptide (CGRP) receptor antagonists (gepants), has reignited interest in this strategy, with encouraging results. This review summarises historical and emerging data in this area, supporting use of the premonitory phase as an opportunity to intervene as early as possible in migraine to prevent attack-related morbidity.