Diagnosing amyotrophic lateral sclerosis (ALS) is challenging and requires distinguishing it from conditions like distal hereditary motor neuropathy type 5 (dHMN-V). A 21-year-old female initially diagnosed with ALS showed progressive upper limb weakness extending to the lower limbs. Trio exome sequencing revealed a de novo pathogenic Berardinelli-Seip congenital lipodystrophy 2 variant (c.263A>G, p.Asn88Ser), confirming dHMN-V. Minipolymyoclonus of small amplitudes in bilateral wrists and ankles was an atypical presentation. This case underscores the importance of considering dHMN-V as a differential diagnosis in ALS-like distal upper extremity weakness.

Diagnosing amyotrophic lateral sclerosis (ALS) is challenging and requires distinguishing it from conditions like distal hereditary motor neuropathy type 5 (dHMN-V). A 21-year-old female initially diagnosed with ALS showed progressive upper limb weakness extending to the lower limbs. Trio exome sequencing revealed a de novo pathogenic Berardinelli-Seip congenital lipodystrophy 2 variant (c.263A>G, p.Asn88Ser), confirming dHMN-V. Minipolymyoclonus of small amplitudes in bilateral wrists and ankles was an atypical presentation. This case underscores the importance of considering dHMN-V as a differential diagnosis in ALS-like distal upper extremity weakness.

Diagnosing amyotrophic lateral sclerosis (ALS) is challenging and requires distinguishing it from conditions like distal hereditary motor neuropathy type 5 (dHMN-V). A 21-year-old female initially diagnosed with ALS showed progressive upper limb weakness extending to the lower limbs. Trio exome sequencing revealed a de novo pathogenic Berardinelli-Seip congenital lipodystrophy 2 variant (c.263A>G, p.Asn88Ser), confirming dHMN-V. Minipolymyoclonus of small amplitudes in bilateral wrists and ankles was an atypical presentation. This case underscores the importance of considering dHMN-V as a differential diagnosis in ALS-like distal upper extremity weakness.

Oral lichen planus (OLP) is a chronic inflammatory disease, affecting approximately 0.5% to 2% of the global population. OLP can lead to long-term oral pain, reduced quality of life, with the potential for malignant transformation. Current treatment strategies focus on symptom management and reducing the risk of malignancy. Treatment of OLP is challenging and varies from patient to patient, especially in those who do not respond to corticosteroids. The effectiveness and safety of second-line and third-line treatment options in such cases are continually compared and evaluated, and recently, the application of Janus kinase inhibitors, micro ribonucleic acids, and mesenchymal stem cell-based therapies is being assessed. As a result, the ability of clinicians to select the most appropriate treatment modalities for each patient remains crucial. This review aims to evaluate the efficacy of recent treatment modalities and key considerations to assist clinicians in selecting effective and safe treatment strategies for OLP.

Background: Circulating tumor DNA (ctDNA) is a potential biomarker in pancreatic ductal adenocarcinoma (PDAC). However, studies on residual ctDNA in patients post-chemotherapy are limited. We assessed the prognostic value of residual ctDNA in metastatic PDAC relative to that of carbohydrate antigen 19-9 (CA19-9). Methods: ctDNA analysis using a targeted next-generation sequencing panel was performed at baseline and during chemotherapy response evaluation in 53 patients. Progression-free survival (PFS) and overall survival (OS) were first evaluated based on ctDNA positivity at baseline. For further comparison, patients testing ctDNA-positive at baseline were subdivided based on residual ctDNA into ctDNA responders (no residual ctDNA post-chemotherapy) and ctDNA non-responders (residual ctDNA post-chemotherapy). Additional survival analysis was performed based on CA19-9 levels. Results: The baseline ctDNA detection rate was 56.6%. Although clinical outcomes tended to be poorer in patients with baseline ctDNA positivity than in those without, the differences were not significant. Residual ctDNA post-chemotherapy was associated with reduced PFS and OS. The prognosis of ctDNA responders was better than that of non-responders but did not significantly differ from that of ctDNA-negative individuals (no ctDNA both at baseline and during post-chemotherapy). Compared with ctDNA responses to che-motherapy, a ≥ 50% decrease in the CA19-9 level had less effect on both PFS and OSbased on hazard ratios and significance levels. ctDNA could be monitored in half of the patients whose baseline CA19-9 levels were within the reference range. Conclusions Residual ctDNA analysis post-chemotherapy is a promising approach for predicting the clinical outcomes of patients with metastatic PDAC.

Halitosis is defined as a nasty odor emanating through the mouth and is primarily related to the enhanced concentration of volatile sulfur compounds (VSCs). VSC measurements have been commonly used for experimental comparison and clinical diagnosis. As quantitative methods for comparative analyses of oral malodor, gas chromatography devices have been most commonly used to quickly and easily determine the concentration of several gas components of VSCs, which are agents primarily responsible for halitosis. The concentrations of VSCs fluctuate dynamically depending on contributing factors, including various oral/systemic conditions, intake of medicine and food/drink, oral hygiene, and even routine daily activities. Therefore, the exact analysis of VSCs requires the appropriate standardization of not only exact measurement techniques but also participant conditioning with scientific considerations. Thus, this paper describes the experimental standardizations commonly recommended in previous literature and their scientific background.

Background: To deliver therapeutics into the brain, it is imperative to overcome the issue of the blood-brain-barrier (BBB). One of the ways to circumvent the BBB is to administer therapeutics directly into the brain parenchyma. To enhance the treatment efficacy for chronic neurodegenerative disorders, repeated administration to the target location is required. However, this increases the number of operations that must be performed. In this study, we developed the IntraBrain Injector (IBI), a new implantable device to repeatedly deliver therapeutics into the brain parenchyma. Methods: We designed and fabricated IBI with medical grade materials, and evaluated the efficacy and safety of IBI in 9 beagles. The trajectory of IBI to the hippocampus was simulated prior to surgery and the device was implanted using 3D-printed adaptor and surgical guides. Ferumoxytol-labeled mesenchymal stem cells (MSCs) were injected into the hippocampus via IBI, and magnetic resonance images were taken before and after the administration to analyze the accuracy of repeated injection. Results: We compared the planned vs. insertion trajectory of IBI to the hippocampus.With a similarity of 0.990 ± 0.001 (mean ± standard deviation), precise targeting of IBI was confirmed by comparing planned vs. insertion trajectories of IBI. Multiple administrations of ferumoxytol-labeled MSCs into the hippocampus using IBI were both feasible and successful (success rate of 76.7%). Safety of initial IBI implantation, repeated administration of therapeutics, and long-term implantation have all been evaluated in this study. Conclusion Precise and repeated delivery of therapeutics into the brain parenchyma can be done without performing additional surgeries via IBI implantation.

Background and Objectives: Papillary thyroid carcinoma (PTC) with lateral neck lymph node metastasis is known as a major risk factor for tumor recurrence after surgical treatment. The aim of this study is to identify risk factors for loco-regional recurrence in patients with PTC with lateral neck lymph node metastasis, which has a high risk of recurrence.Subjects and Method This study involved 319 patients who underwent total thyroidectomy, central lymph node (LN) and lateral LN dissection due to PTC. The patients’ demographics and pathological factors, including lymph node metastasis were retrospectively reviewed. Univariate, multivariate and C-index with variable selection analyses were performed to identify factors associated with recurrence-free survival (RFS). Results: A mean follow-up of 101 months, 35 (10.9%) patients had a loco-regional recurrence. In multivariate analysis according to loco-regional recurrence, patients with a primary tumor of more than 4 cm, multifocality, vascular invasion, and bilateral lateral cervical metastasis were associated with worse RFS. In the variable selection analysis, lateral lymph node metastasis ratio was also statistically significant. Conclusion PTC with lateral neck lymph node metastasis included tumors larger than 4 cm. Multifocality, vascular invasion, high lateral lymph node metastasis ratio and bilateral neck lymph node metastasis are predictive factors of loco-regional recurrence, and these risk factors should be carefully followed-up after surgery.

The methylglyoxal (MGO) trapping constituents from Malus baccata L. were investigated using incubation of MGO and crude extract under physiological conditions followed by HPLC analysis. The peak areas of MGO trapping compounds decreased, and their chemical structures were identified by HPLC-ESI/MS. Sieboldin was identified as a major active molecule representing MGO-trapping activity of the crude extract. After reaction of sieboldin and MGO, remaining MGO was calculated by microplate assay method using imine (Schiff base) formation of 2,4-dinitrophenylhydrazine (DNPH) and aldehyde group. After 4 h incubation, sieboldin trapped over 43.8% MGO at a concentration of 0.33 mM and showed MGO scavenging activity with an RC 50 value of 0.88 mM for the incubation of 30 min under physiological conditions. It was also confirmed that sieboldin inhibited the production of advanced glycation end products (AGE) produced by bovine serum albumins (BSA)/MGO. Additionally, MGO trapping mechanism of sieboldin was more specifically identified by 1 H-, 13 C-, 2D NMR and, confirm to be attached to the position of C-3' (or 5').

no abstract available.