The Natural Products Targeting on Allergic Rhinitis: From Traditional Medicine to Modern Drug Discovery.

More than 500 million people suffer from allergic rhinitis (AR) in the world. Current treatments include oral antihistamines and intranasal corticosteroids; however, they often cause side effects and are unsuitable for long-term exposure. Natural products could work as a feasible alternative, and this study aimed to review the efficacies and mechanisms of natural substances in AR therapies by examining previous literature. Fifty-seven studies were collected and classified into plants, fungi, and minerals decoction; clinical trials were organized separately. The majority of the natural products showed their efficacies by two mechanisms: anti-inflammation regulating diverse mediators and anti-oxidation controlling the activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway stimulated by reactive oxygen species (ROS). The main AR factors modified by natural products included interleukin (IL)-4, IL-5, IL-13, interferon-gamma (IFN-γ), tumor necrosis factor-α (TNF-α), cyclooxygenase 2 (COX-2), and phospho-ERK1/2 (p-ERK1/2). Although further studies are required to verify their efficacies and safeties, natural products can significantly contribute to the treatment of AR.

Negative α-synuclein pathology in the submandibular gland of patients carrying PRKN pathogenic variants.

INTRODUCTION: Alpha-synuclein (AS) pathology in the peripheral nervous tissue is a potential pathological biomarker in Parkinson disease (PD). Several studies reported the excellent specificity of the AS pathology of the submandibular gland (SMG) biopsy in PD. PRKN pathogenic variant is one of the major genetic causes of young-onset PD without Lewy pathology in the brain. In this study, we evaluated peripheral AS pathology in the SMG biopsy of patients with PRKN pathogenic variants. METHODS: We enrolled three young-onset PD patients with PRKN pathogenic variants. Two patients were compound heterozygous for trans-exon 3 and 4 deletions and one patient was heterozygous for an exon 2 duplication. We obtained two submandibular gland tissues with core needle biopsy (18G). The neural structures were identified using neurofilament (NF) immunostaining and the neural tissue in the adjacent section were stained with 129 phophorylated α-synuclein (pAS) antibody. RESULTS: pAS staining in the SMG was negative in all cases with the PRKN pathogenic variants. CONCLUSIONS: Our data may support the high specificity of the AS pathology of SMG in α-synuclein associated parkinsonism. Future studies evaluating peripheral neural tissue including the SMG in the elderly healthy population are required to validate the role of peripheral AS pathology as a biomarker in PD.

Alternating Hemiplegia of Childhood in Korea: a Case Report.

Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disorder characterized by recurrent paroxysmal hemiplegic attacks that affect one or the other side of the body. Up to 74% of patients with AHC have a pathologic variant in the ATP1A3 gene. After the introduction of next-generation sequencing, intermediate cases and atypical cases have expanded the clinical spectrum of ATP1A3-related disorders. Herein, we report the first case of AHC in Korea. A 33-year-old man visited our hospital with recurrent hemiplegic and dystonic episode after his first birthday. He was completely normal between episodes and did not have any ataxia, but brain magnetic resonance imaging showed cerebellar atrophy. He also had pes planovalgus deformity. Whole exome sequencing revealed a heterozygous G947R variant in the ATP1A3 gene (c.2839G > C, rs398122887), which is a known pathologic variant. This atypical case of AHC demonstrates the importance of the clinical approach in diagnosing ATP1A3-related disorders.

Patient selected goals and satisfaction after bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

Assessing patient goals is crucial in understanding patient centered outcomes and satisfaction. However, patient goals may change throughout treatment. Our objective is to identify the changes in patient-selected goals of Parkinson's disease (PD) patients undergoing bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and examine the relationship among patient-selected goal achievement, standard DBS outcome measures, and overall patient satisfaction. Seventy-five patients undergoing bilateral STN-DBS listed three patient-selected goals before surgery. After six months, patients were asked to restate the three goals and to rate the degree of goal achievement and the overall satisfaction of surgery. The three most frequently selected goals were "dyskinesia", "gait disorder", and "medication off duration". After six months, 80.0% of patients could not accurately recall their pre-DBS goals. "Dyskinesia" was the most consistently selected goal, more patients selected "tremor" and "less medication" at post-DBS compared to pre-DBS, and less patients selected "gait disorder" at post-DBS compared to pre-DBS. 74.7% of patients reported overall satisfaction by stating they were "very much" or "much better after surgery". Patient satisfaction significantly correlated with goal achievement (r = 0.640; p < 0.001). Interestingly, change in UPDRS motor scores did not correlate with patient satisfaction (r = 0.100; p = 0.395). Although recalled goals do not accurately represent the pre-surgical goals, the achievement score for recalled goals significantly correlated with patient satisfaction. Patient goals change due to many reasons. Therefore, follow-up patient counseling to discuss goals and outcomes is important in improving patient satisfaction after STN-DBS.

Prospective cohort study of patients with early gastric cancer to detect prodromal Parkinson disease (EGC-PPD): A study protocol and baseline characteristics.

The aim of the current study is to determine the predictive value of alpha-synuclein (AS) aggregation in stomach surgical specimens in combination with selected clinical prodromal markers (CPMs) for development of Parkinson disease (PD) in a normal population. We organized a prospective, long-term, clinicopathologic cohort of patients without neurological diseases who received a radical operation for early gastric cancer (EGC) between ages 50 and 65 years. The participants will be followed for up to 10 years and screened for CPMs and motor symptoms by annual telephone interview. If a participant reports one or more positive answers to screening questions about motor symptoms, they will be regarded as having possible parkinsonism. A movement disorder specialist will then evaluate whether that participant has PD. The primary outcome is the development of PD during the 10-year follow-up. The recruitment period has been completed, and the baseline clinical characteristics are compared between participants with and without possible parkinsonism. A total of 718 participants (mean age: 60.1 ±â€¯5.9) was recruited. The motor symptom screening questionnaire revealed 65 patients with possible parkinsonism (9.0%) at baseline. Patients with possible parkinsonism answered that they had subjective loss of smell more than those without parkinsonism at the time of recruitment (18.5% vs 8.3%) and operation (15.4% vs 6.3%). However, the objective odor discrimination test showed no difference between patients with and without possible parkinsonism. Baseline assessments revealed a sufficient number of patients with possible parkinsonism, which will be confirmed as PD or not in subsequent follow-up visits.

Submandibular gland is a suitable site for alpha synuclein pathology in Parkinson disease.

OBJECTIVE: To validate the role of α-synuclein (AS) pathology in submandibular gland (SMG) as a biomarker for Parkinson disease (PD). METHODS: We performed ultrasonography (USG) guided core needle biopsy of SMG in PD patients and procured SMG biopsy tissues or surgical excision specimens from non-PD patients as controls. Then, we compared AS deposition in the SMG tissues between the PD patients and the controls. We recruited 16 PD patients in this study. In each individual, two core needle biopsy tissues were obtained from the left submandibular gland under USG guidance. Fourteen sex and age-matched controls who did not have PD and dementia but received a core needle biopsy or surgical resection of the SMG due to SMG diseases were procured from the pathology archive. Biopsy tissues and surgical specimens were immuno-stained with serine 129 phosphorylated AS (pAS) antibody for microscopic examination. pAS deposition in neural structures such as ganglion cells and neurites was considered as positive. RESULTS: No serious complication occurred during and after the SMG biopsy. We found glandular parenchyma and neural structures in all biopsied SMG tissues from the patients and the controls. Nine out of 16 PD patients (56.2%) were positive for pAS staining, while none of the controls were positive (0%). CONCLUSIONS: SMG core needle biopsy can reliably and safely obtain sufficient glandular parenchyma and neural structures to evaluate the α-synuclein pathology. AS pathology in SMG has high specificity and good sensitivity as a biomarker for PD.

Non-Motor Symptom Burdens Are Not Associated with Iron Accumulation in Early Parkinson's Disease: a Quantitative Susceptibility Mapping Study.

BACKGROUND: Quantitative susceptibility mapping (QSM) has been used to measure iron accumulation in the deep nuclei of patients with Parkinson's disease (PD). This study examined the relationship between non-motor symptoms (NMSs) and iron accumulation in the deep nuclei of patients with PD. METHODS: The QSM data were acquired from 3-Tesla magnetic resonance imaging (MRI) in 29 patients with early PD and 19 normal controls. The Korean version of the NMS scale (K-NMSS) was used for evaluation of NMSs in patients. The patients were divided into high NMS and low NMS groups. The region-of-interest analyses were performed in the following deep nuclei: red nucleus, substantia nigra pars compacta, substantia nigra pars reticulata, dentate nucleus, globus pallidus, putamen, and head of the caudate nucleus. RESULTS: Thirteen patients had high NMS scores (total K-NMSS score, mean = 32.1), and 16 had low NMS scores (10.6). The QSM values in the deep were not different among the patients with high NMS scores, low NMS scores, and controls. The QSM values were not correlated linearly with K-NMSS total score after adjusting the age at acquisition of brain MRI. CONCLUSION: The study demonstrated that the NMS burdens are not associated with iron accumulation in the deep nuclei of patients with PD. These results suggest that future neuroimaging studies on the pathology of NMSs in PD should use more specific and detailed clinical tools and recruit PD patients with severe NMSs.

Fundamental limit of alpha-synuclein pathology in gastrointestinal biopsy as a pathologic biomarker of Parkinson's disease: Comparison with surgical specimens.

OBJECTIVE: Alpha-synuclein (AS) accumulation identified by immunohistochemistry (IHC) of gastrointestinal (GI) tract biopsies is considered as a potential pathologic biomarker for Parkinson's disease (PD). We compared AS IHC findings in biopsy specimens and surgically resected full-depth specimens to examine the reliability of GI tract biopsies. METHODS: We included patients with PD who had undergone operation of the GI tract for treatment of tumors. Controls were matched with age at operation, gender, and surgical resection site. We compared AS accumulation using phosphorylated AS (pAS) IHC between patients and controls, and within individuals between surgical and biopsy specimens. RESULTS: A total of 33 patients with PD were categorized into either the stomach (N = 12) or colorectal group (N = 21). The frequency of pAS positivity in gastric surgical specimens was 58.3% (7/12) and 8.3% (1/12) in the patient and control groups, respectively (p = 0.027). The frequency of pAS positivity in colorectal surgical specimens was identical in the patient and control group (23.8% [5/21] in each). Intriguingly, immunostaining results for biopsy specimens were not concordant with those for surgical specimens. There was no significant difference in the frequency of pAS positivity in biopsy specimens between patients and controls (9.1% [2/22] vs 18.2% [4/22]; p = 0.664). INTERPRETATION: Our results demonstrate that AS accumulation identified via pAS IHC of GI biopsies is unreliable due to its low positive rates and poor concordance with surgical specimens, and that future studies investigating AS accumulation in the GI tract should target the stomach, rather than the colon or rectum.