Blood neurofilament light chain as a surrogate marker for dystonia.

BACKGROUND AND PURPOSE: Dystonia is a heterogeneous movement disorder, and it remains unclear whether neurodegeneration is involved. Neurofilament light chain (NfL) is a biosignature of neurodegeneration. We aimed to investigate whether plasma NfL levels were elevated and associated with disease severity in patients with dystonia. METHOD: We enrolled 231 unrelated dystonia patients (isolated dystonia n = 203; combined dystonia n = 28) and 54 healthy controls from movement disorder clinics. Clinical severity was evaluated using the Fahn Marsden Dystonia Rating Scale, the Unified Dystonia Rating Scale, and the Global Dystonia Rating Scale. Blood NfL levels were measured by single-molecule array. RESULTS: Plasma NfL levels were significantly higher in those with generalized dystonia compared to those with focal dystonia (20.1 ± 8.8 vs. 11.7 ± 7.2 pg/mL; p = 0.01) or controls (p < 0.01), while the level was comparable between the focal dystonia group and controls (p = 0.08). Furthermore, the dystonia combined with parkinsonism group had higher NfL levels than the isolated dystonia group (17.4 ± 6.2 vs. 13.5 ± 7.5 pg/mL; p = 0.04). Notably, whole-exome sequencing was performed in 79 patients and two patients were identified as having likely pathogenic variants: one had a heterozygous c.122G>A (p.R41H) variant in THAP1 (DYT6) and the other carried a c.1825G>A (p.D609N) substitution in ATP1A3 (DYT12). No significant correlation was found between plasma NfL levels and dystonia rating scores. CONCLUSION: Plasma NfL levels are elevated in patients with generalized dystonia and dystonia combined with parkinsonism, suggesting that neurodegeneration is involved in the disease process of this subgroup of patients.

Gut microenvironmental changes as a potential trigger in Parkinson's disease through the gut-brain axis.

Parkinson's disease (PD) is the second most common neurodegenerative disease attributed to the synergistic effects of genetic risk and environmental stimuli. Although PD is characterized by motor dysfunction resulting from intraneuronal alpha-synuclein accumulations, termed Lewy bodies, and dopaminergic neuronal degeneration in the substantia nigra, multiple systems are involved in the disease process, resulting in heterogenous clinical presentation and progression. Genetic predisposition to PD regarding aberrant immune responses, abnormal protein aggregation, autophagolysosomal impairment, and mitochondrial dysfunction leads to vulnerable neurons that are sensitive to environmental triggers and, together, result in neuronal degeneration. Neuropathology studies have shown that, at least in some patients, Lewy bodies start from the enteric nervous system and then spread to the central dopaminergic neurons through the gut-brain axis, suggesting the contribution of an altered gut microenvironment in the pathogenesis of PD. A plethora of evidence has revealed different gut microbiomes and gut metabolites in patients with PD compared to unaffected controls. Chronic gut inflammation and impaired intestinal barrier integrity have been observed in human PD patients and mouse models of PD. These observations led to the hypothesis that an altered gut microenvironment is a potential trigger of the PD process in a genetically susceptible host. In this review, we will discuss the complex interplay between genetic factors and gut microenvironmental changes contributing to PD pathogenesis.

Comparative Outcomes of Robotic Radical Prostatectomy in Patients with Locally Advanced Prostate Cancer.

The effectiveness of radical prostatectomy alone for locally advanced prostate cancer is controversial owing to an increased complication rate and treatment-related morbidity. With technical advances and refinements in surgical techniques, robotic-assisted radical prostatectomy (RARP) has improved the outcomes of patients with locally advanced prostate cancer. RARP therefore plays a role in the treatment of locally advanced prostate cancer. In this study, we enrolled a total of 76 patients with pathologic stage pT3a, pT3b, pT4, or pN1. All patients were followed from surgery to June 2022, and their characteristics, perioperative outcomes, complications, adjuvant therapies and outcomes were analyzed. The median age of the patients was 69 years, and the initial PSA level was 20.5 (IQR 10.8-31.6) ng/mL. The median operative time was 205 (IQR 182-241) minutes. Sixty-six patients (86.8%) regained continence within 1 year, and the continence rate within 3 years of follow-up was 90.8% (69 patients). The overall survival rate was 100%. Twenty-two patients had BCR, of whom 13 received salvage androgen deprivation therapy (ADT), 2 received salvage external beam radiation therapy (EBRT) alone, and 7 received combined ADT and EBRT. No patient had disease progression to castration-resistant prostate cancer during a median 36 months of follow-up after salvage therapy. Our results suggest that RARP can also decrease tumor burden and allow for accurate and precise pathological staging with the need for subsequent treatment. Therefore, we recommend that RARP represents a well-standardized, safe, and oncologically effective option for patients with locally advanced prostate cancer.

Similar outcomes between vitamin K and non-vitamin K antagonist oral anticoagulants associated intracerebral hemorrhage.

BACKGROUND: The application of non-vitamin K antagonist oral anticoagulant (NOAC) reduces the risk of intracerebral hemorrhage (ICH) in comparison with vitamin K antagonist (VKA). However, the features and outcomes of NOAC-associated ICH are still unclear, especially for Asian populations. METHODS: We retrospectively analyzed 49 consecutive patients who had spontaneous ICH while using NOAC or VKA. We compared the clinical characteristics, ICH volume, 7-day and 3-month mortality, and functional outcomes at discharge and 3 months post-stroke using the modified Rankin Scale (mRS) between NOAC- and VKA-associated ICH. The clinical features, ICH volume, ICH location, and/or treatment methods were statistically adjusted. RESULTS: Among the 49 ICH patients, 15 (30.6%) were using NOAC and 34 (69.4%) were taking VKA. There were no significant differences in the initial ICH volume between groups (mean volume 34.2 ± 43.8 vs. 59.4 ± 46.5 mL, p = 0.061). The percentage of early mortality (within 7 days post-ICH) was significantly lower in the NOAC group (13.3% vs. 44.1%; p = 0.047), but the 3-month mortality was similar (33.3% vs. 47.1%; p = 0.294). The functional outcome was equally poor in both groups at discharge (p = 0.670) and 3 months post-ICH (mean mRS score 4.7 ± 1.3 vs. 4.6 ± 1.7, p = 0.766). CONCLUSION: There were no significant differences in initial ICH volume, 90-day mortality, or functional outcomes between NOAC and VKA-associated ICH in Asians.

Clinical, radiological, and genetic characteristics in patients with Huntington's disease in a Taiwanese cohort.

Characteristics of Huntington's disease (HD) differ among various ethnicities. Few studies have explored the relationship between phenotypes and genotypes of HD in Asians. We evaluated the relationship between integrated clinical and imaging phenotypes and genotypes in a Taiwanese HD cohort, enrolling 123 HD patients genetically diagnosed between August 1994 and February 2019. The clinical presentations and brain magnetic resonance imaging characteristics were analyzed from 67 patients and examined the correlation with genetic findings. Chorea was the most common initial manifestation (66.1%), especially in patients with late-onset disease (onset age > 60 years old), followed by psychiatric symptoms (25%) and cognitive impairment (14.3%). Compared to patients with adult-onset HD, the prevalence of parkinsonism was significantly higher in juvenile-onset HD patients (onset age < 20 years old, p = .007). Disease burden, which was measured by CAG repeats and age, was significantly associated with atrophy in caudate nucleus (p = .004), followed by putamen (p = .029), nucleus accumbens (p = .002), thalamus (p = .003), and total cortical volume (p = .001) after correcting for total intracranial volume. Our findings, that provided the first series of Taiwanese HD patients, delineated the clinical, radiological, and genetic characteristics in Asian HD patients.

Isolated Basilar Artery Dissection with Ischemic Stroke: Report of 4 Cases.

PURPOSE: Isolated basilar artery dissection (BAD) is a rare cause of ischemic stroke. Since the clinical presentations and imaging findings could be non-specific and subtle, the diagnosis may be difficult. Here, we presented four cases of isolated BAD with acute ischemic stroke. CASE REPORT: Four patients (age, 22 to 57 years) experienced acute onset of hemiparesis and/or vertigo with half of them having initial headache. Acute infarct was noted at pons or thalamus. Three cases needed more than one imaging modality or serial follow-up imaging to confirm a diagnosis of isolated BAD. Vascular tapering and/or false lumen restrictive to basilar artery were the commonest imaging findings. Three of our patients received anticoagulant without recurrent infarct or hemorrhagic complication. All of the patients had good functional outcome with modified Ranking scale scoring 1. CONCLUSION: Isolated BAD may cause variable clinical manifestations and the outcome can be favorable. Application of different and advanced imaging studies with serial image follow-up are useful to confirm the diagnosis.

Scrotal Pain after Varicocelectomy: A Narrative Review.

Varicocele is a frequently encountered urological disorder, which has a prevalence rate of 8 to 15% among healthy men. However, the incidence is higher in male patients with primary or secondary infertility, with up to 35 to 80% of varicocele cases occurring in this population. The clinical manifestations of varicocele typically include the presence of an asymptomatic mass that feels like a "bag of worms", chronic scrotal pain, and infertility. Most patients with varicocele only undergo varicocelectomy after conservative treatments have failed. Unfortunately, some patients may still experience persistent scrotal pain due to a recurrence of varicocele, the development of hydrocele, neuralgia, referred pain, ureteral lesions, or nutcracker syndrome. Therefore, clinicians should consider these conditions as potential causes of postoperative scrotal pain, and take measures to address them. Several factors can assist in predicting surgical outcomes for patients with varicocele. Clinicians should consider these factors when deciding whether to perform surgery and what type of surgical intervention to use. By doing so, they can increase the likelihood of a successful surgical outcome and minimize the risk of complications such as postoperative scrotal pain.

A Case Report of Intratesticular Hematoma in a Patient with Reiter's Syndrome.

We present a case of a 28-year-old male patient with a spontaneous intratesticular hematoma. He had no history of trauma but experienced sudden onset of painful swelling in his right testis. Initially, testicular malignancy was suspected. The tumor marker of testis, including alfa-fetoprotein, lactic dehydrogenase, and ß-human chorionic gonadotropin, was within normal range. The patient had been diagnosed with Reiter's syndrome at the age of 20 and had been treated with sulfasalazine, non-steroidal anti-inflammatory drugs, and acetaminophen for eight years. Various imaging techniques before operation planning, including ultrasonography and computed tomography, revealed a hematoma that accounted for 32% of the testicular volume. During the waiting period before the operation, the patient was diagnosed with a hematoma and avoided a possible diagnosis of malignancy. Follow-up imaging with computed tomography and magnetic resonance imaging confirmed the presence of an intratesticular hematoma that had decreased in size. Since no other related factor contributed to this hematoma, and considering the possible hematological side effects of sulfasalazine, we suggest that this may be a rare side effect of sulfasalazine. Although the patient's testis was preserved, further fertility should be observed because animal studies have reported that testicular hematoma may cause fertility changes if the initial volume occupied is over 30% of the testis.

Interaction between cerebral small vessel disease, blood pressure, and remote ischemic lesions in acute spontaneous intracerebral hemorrhage.

BACKGROUND: Acute blood pressure (BP) reduction is the first-line treatment for acute spontaneous intracerebral hemorrhage (ICH); however, recent research suggests that intensive BP reduction along with cerebral small vessel disease (cSVD) is a risk factor for remote DWI lesions (RDWILs). We aimed to delineate the interplay between cSVD and BP reduction therapy on the risk of RDWILs. METHODS: We enrolled 303 patients who underwent brain magnetic resonance imaging within 7 days after acute spontaneous ICH. RDWILs were categorized as occurring in borderzone (BZ) or non-BZ areas. We examined the effect of cSVD, acute BP reduction, and their interaction on RDWILs. RESULTS: RDWILs were observed in 34 (11%) patients (59.8 ± 10.3-years-old, 24% male). RDWILs were associated with a larger acute weighted average mean arterial pressure (MAP) reduction in the initial 24 h after ICH onset and a higher total cerebral microbleed (CMB) count. Intensive MAP changes (odds ratio (OR) per 10 mmHg 1.76, 95% confidence interval (CI) 1.03-3.20), total CMBs burden (OR per 10 CMBs 1.21, 95% CI 1.08-1.39), and presence of lobar CMBs (OR 7.33, 95% CI 1.59-55.6) were risk factors for RDWILs at BZ, but not at non-BZ. Furthermore, a significant interaction was observed between lobar CMBs and MAP reduction on increased risk of RDWILs at BZ (p = 0.030). CONCLUSION: cSVD modulates the effect of acute BP reduction on the risk of RDWILs. Patients with extensive microangiopathy have a higher risk of developing cerebral ischemic changes in BZ during unstable hemodynamic status.

Plasma metabolites of aromatic amino acids associate with clinical severity and gut microbiota of Parkinson's disease.

Gut microbial proteolytic metabolism has been reportedly altered in Parkinson's disease (PD). However, the circulating aromatic amino acids (AAA) described in PD are inconsistent. Here we aimed to investigate plasma AAA profiles in a large cohort of PD patients, and examine their correlations with clinical severity and gut microbiota changes. We enrolled 500 participants including 250 PD patients and 250 neurologically normal controls. Plasma metabolites were measured using liquid chromatography mass spectrometry. Faecal samples were newly collected from 154 PD patients for microbiota shotgun metagenomic sequencing combined with data derived from 96 PD patients reported before. Data were collected regarding diet, medications, and motor and non-motor symptoms of PD. Compared to controls, PD patients had higher plasma AAA levels, including phenylacetylglutamine (PAGln), p-cresol sulfate (Pcs), p-cresol glucuronide (Pcg), and indoxyl sulfate (IS). Multivariable linear regression analyses, with adjustment for age, sex, and medications, revealed that the plasma levels of PAGln (coefficient 4.49, 95% CI 0.40-8.58, P = 0.032) and Pcg (coefficient 1.79, 95% CI 0.07-3.52, P = 0.042) positively correlated with motor symptom severity but not cognitive function. After correcting for abovementioned potential confounders, these AAA metabolites were also associated with the occurrence of constipation in PD patients (all P < 0.05). Furthermore, plasma levels of AAA metabolites were correlated with the abundance of specific gut microbiota species, including Bacteroides sp. CF01-10NS, Bacteroides vulgatus, and Clostridium sp. AF50-3. In conclusion, elevated plasma AAA metabolite levels correlated with disease characteristics in PD, suggesting that upregulated proteolytic metabolism may contribute to the pathophysiology of PD.

Emodin, a Natural Anthraquinone, Increases Uric Acid Excretion in Rats with Potassium Oxonate-Induced Hyperuricemia.

The treatment of hyperuricemia and gout is mostly based on lowering serum uric acid levels using drugs, such as allopurinol, or increasing urinary excretion of uric acid. However, some patients still experience adverse reactions to allopurinol and turn to Chinese medicine as an alternative. Therefore, it is crucial to design a preclinical study to obtain more convincing data on the treatment of hyperuricemia and gout with Chinese medicine. This study aimed to explore the therapeutic effect of emodin, a Chinese herbal extract, in a rat model of hyperuricemia and gout. In this study, we used 36 Sprague-Dawley rats, which were randomly divided into six groups for experimentation. Hyperuricemia was induced in rats by intraperitoneal injections of potassium oxonate. The efficacy of emodin in reducing serum uric acid levels was demonstrated by comparing the positive control group with groups treated with three different concentrations of emodin. The inflammatory profiles, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α levels, were unaffected by emodin treatment. In the experimental results, it was observed that the serum uric acid concentration in the vehicle control group was 1.80 ± 1.14, while the concentrations in the moderate and high concentration emodin groups were 1.18 ± 0.23 and 1.12 ± 0.57, resulting in no significant difference in uric acid concentration between these treatment groups and the control group, indicating that emodin has a therapeutic effect on hyperuricemia. The increase in the fractional excretion of uric acid (FEUA) demonstrated that emodin promoted urinary uric acid excretion without significantly affecting the inflammatory profile. Thus, emodin reduced the serum uric acid concentration to achieve effective treatment of hyperuricemia and gout by increasing urinary excretion. These results were supported by the measured serum uric acid and FEUA levels. Our data have potential implications for the treatment of gout and other types of hyperuricemia in clinical practice.

Elevated α-synuclein and NfL levels in tear fluids and decreased retinal microvascular densities in patients with Parkinson's disease.

The pathognomonic hallmark of Parkinson's disease (PD), α-synuclein, has been observed in the retina of PD patients. We investigated whether biomarkers in the tears and retinal microvascular changes associate with PD risk and progression. This prospective study enrolled 49 PD patients and 45 age-matched healthy controls. The α-synuclein and neurofilament light chain (NfL) levels were measured using an electrochemiluminescence immunoassay. Retinal vessel density was assessed using optical coherence tomography angiography (OCT-A). The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Mini-Mental State Examination score were used to assess motor and cognitive progression. The α-synuclein and NfL levels in the tears were higher in PD patients than in controls (α-synuclein: 55.49 ± 8.12 pg/mL vs. 31.71 ± 3.25 pg/mL, P = 0.009; NfL: 2.89 ± 0.52 pg/mL vs. 1.47 ± 0.23 pg/mL, P = 0.02). The vessel densities in the deep plexus of central macula and the radial peripapillary capillary layer of disc region were lower in PD patients with moderate-stage compared with early-stage PD (P < 0.05). The accuracy of predicting PD occurrence using age and sex alone (area under the curve [AUC] 0.612) was significantly improved by adding α-synuclein and NfL levels and retinal vascular densities (AUC 0.752, P = 0.001). After a mean follow-up of 1.5 ± 0.3 years, the accuracy of predicting motor or cognitive progression using age, sex, and baseline motor severity as a basic model was increased by incorporating retinal microvascular and biofluid markers as a full model (P = 0.001). Our results showed that retinal microvascular densities combined with α-synuclein and NfL levels in tears are associated with risk and progression of PD.

Prostate Cancer after Percutaneous Arterial Embolization of the Prostate: A Case Report.

We report a patient with prostate cancer found 2 years after percutaneous arterial embolization (PAE) of the prostate with a rapid increase in prostate specific antigen (PSA) 3 months later, even though the initial result was low. He did not consult a urologist during or after PAE until acute urinary retention developed. The clinical stage was cT2cN1M1b with Gleason grade 5 + 5 = 10. An increase in PSA a short interval after PAE may suggest the presence of prostate cancer. We suggest that patients undergoing PAE should consult a urologist, and that PSA levels should be checked every 3 months in the first year after PSA.

Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: Short-chain fatty acids (SCFAs) are gut microbial metabolites that promote the disease process in a rodent model of Parkinson disease (PD), but fecal levels of SCFAs in patients with PD are reduced. Simultaneous assessments of fecal and plasma SCFA levels, and their interrelationships with the PD disease process, are scarce. We aimed to compare fecal and plasma levels of different SCFA subtypes in patients with PD and healthy controls to delineate their interrelations and link to gut microbiota changes and clinical severity of PD. METHODS: A cohort of 96 patients with PD and 85 controls were recruited from National Taiwan University Hospital. Fecal and plasma concentrations of SCFAs were measured using chromatography and mass spectrometry. Gut microbiota was analyzed using metagenomic shotgun sequencing. Body mass index and medical comorbidities were evaluated and dietary information was obtained using a food frequency questionnaire. To assess motor and cognitive impairment, we used the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Mini-Mental Status Examination (MMSE). RESULTS: Compared with controls, patients with PD had lower fecal but higher plasma concentrations of acetate, propionate, and butyrate. After adjustment for age, sex, disease duration, and anti-PD medication dosage, MDS-UPDRS part III motor scores correlated with reduced fecal levels of acetate (ρ = -0.37, p = 0.012), propionate (ρ = -0.32, p = 0.036), and butyrate (ρ = -0.40, p = 0.004) and with increased plasma propionate concentrations (ρ = 0.26, p = 0.042) in patients with PD. MMSE scores negatively correlated with plasma levels of butyrate (ρ = -0.09, p = 0.027) and valerate (ρ = -0.032, p = 0.033) after adjustment for confounders. SCFAs-producing gut bacteria correlated positively with fecal levels of SCFAs in healthy controls but revealed no association in patients with PD. In the PD patient group, the abundance of proinflammatory microbes, such as Clostridiales bacterium NK3B98 and Ruminococcus sp AM07-15, significantly correlated with decreased fecal levels and increased plasma levels of SCFAs, especially propionic acid. DISCUSSION: Reductions in fecal SCFAs but increased plasma SCFAs were observed in patients with PD and corelated to specific gut microbiota changes and the clinical severity of PD. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that gut metabolite SCFAs distinguish between patients with PD and controls and are associated with disease severity in patients with PD.

Alteration of Gut Microbial Metabolites in the Systemic Circulation of Patients with Parkinson's Disease.

BACKGROUND: Emerging evidence suggests that gut dysbiosis contributes to Parkinson's disease (PD) by signaling through microbial metabolites. Hippuric acid (HA), indole derivatives, and secondary bile acids are among the most common gut metabolites. OBJECTIVE: To examine the relationship of systemic concentrations of these microbial metabolites associated with changes of gut microbiota, PD status, and severity of PD. METHODS: We enrolled 56 patients with PD and 43 age- and sex-matched healthy participants. Motor and cognitive severity were assessed with Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III motor score and the Mini-Mental State Examination (MMSE), respectively. Plasma concentrations of targeted gut metabolites were measured with liquid chromatography-tandem mass spectrometry. Gut microbiota was analyzed with shotgun metagenomic sequencing. RESULTS: Compared with controls, PD patients had significantly higher plasma levels of HA, indole-3-propionic acid (IPA), deoxycholic acid (DCA), and glycodeoxycholic acid (GDCA). After adjustment for age and sex in a multivariate logistic regression analysis, plasma levels of HA (odds ratio [OR] 3.21, p < 0.001), IPA (OR 2.59, p = 0.031), and GDCA (OR 2.82, p = 0.036) were associated with positive PD status. Concentrations of these gut metabolites did not correlate with MDS-UPDRS part III score or MMSE after adjustment for confounders. Microbial metabolite levels were associated with the relative abundance of pro-inflammatory gut bacteria. CONCLUSION: Aberrant gut microbial metabolites of HA, indole derivatives and secondary bile acids associated with specific gut microbiota changes were observed in patients with PD.

Astragalus membranaceus Extract Prevents Calcium Oxalate Crystallization and Extends Lifespan in a Drosophila Urolithiasis Model.

Approximately 1 in 20 people develops kidney stones at some point in their life. Although the surgical removal of stones is common, the recurrence rate remains high and it is therefore important to prevent the occurrence of kidney stones. We chose Astragalus membranaceus (AM), which is a traditional Chinese medicine, to study the prevention of urolithiasis using a Drosophila model based on our previous screening of traditional Chinese herbs. Wild-type Drosophila melanogaster Canton-S adult fruit flies were used in this study. Ethylene glycol (EG, 0.5%) was added to food as a lithogenic agent. The positive control agent (2% potassium citrate (K-citrate)) was then compared with AM (2, 8, and 16 mg/mL). After 21 days, the fruit flies were sacrificed under carbon dioxide narcotization, and the Malpighian tubules were dissected, removed, and processed for polarized light microscopy examination to observe calcium oxalate (CaOx) crystallization. Then, the ex vivo dissolution of crystals in the Malpighian tubules was compared between K-citrate and AM. Survival analysis of the EG, K-citrate, and AM groups was also performed. Both 2% K-citrate and AM (16 mg/mL) significantly inhibited EG-induced CaOx crystal formation. Mean lifespan was significantly reduced by the administration of EG, and the results were significantly reversed in the AM (8 and 16 mg/mL) groups. However, AM extract did not directly dissolve CaOx crystals in Drosophila Malpighian tubules ex vivo. In conclusion, AM extract decreased the ratio of CaOx crystallization in the Malpighian tubules and significantly ameliorated EG-induced reduction of lifespan. AM prevented CaOx crystal formation in the Drosophila model.

Plasma Lipopolysaccharide-Binding Protein Reflects Risk and Progression of Parkinson's Disease.

BACKGROUND: Lipopolysaccharide-binding protein (LBP) presents bacterial endotoxin, lipopolysaccharides, to cellular surface pattern receptors for immune responses in the gut-brain axis of Parkinson's disease (PD). OBJECTIVE: We investigated whether plasma LBP levels were associated with PD severity and progression. METHODS: This study included 397 participants (248 PD patients and 149 controls). We measured participants' plasma levels of LBP and pro-inflammatory cytokines, including TNF-α, IL-6, andIL-17A. PD patients underwent motor and cognition evaluations at baseline and at a mean follow-up interval of 4.7±2.3 years. We assessed the progression of motor and cognition symptoms based on changes in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III motor score and Mini-Mental State Examination (MMSE) score, respectively. RESULTS: Plasma LBP levels were lower in PD patients than controls (9.08±2.91 vs. 10.10±3.00µg/ml, p < 0.01). A multiple logistic regression model with adjustment for age, sex, and plasma cytokine levels revealed that reduced plasma LBP levels were associated with increased PD risk (odds ratio 0.816, [95% CI 0.717-0.929], p = 0.002). Among PD patients, LBP levels were correlated with MDS-UPDRS part III motor score after adjustment for confounders (coefficient = 0.636, p = 0.017), but not with MMSE score. Adjusted Cox regression analysis showed that higher plasma LBP levels associated with faster motor progression (adjusted hazard ratio 1.084 [95% CI 1.011-1.163], p = 0.024) during follow-up. CONCLUSION: Our results demonstrated that plasma LBP levels reflect risk, motor symptom severity and progression in patients with PD.

Lack of PTRHD1 mutation in patients with young-onset and familial Parkinson's disease in a Taiwanese population.

Mutations in the peptidyl-tRNA hydrolase domain containing 1 (PTRHD1) gene have been recently identified in consanguineous Iranian and African families with juvenile parkinsonism and intellectual disability. However, the pathogenicity of PTRHD1 mutations in the disease and their role in young-onset Parkinson's disease (PD) remains unclear. We aimed to investigate PTRHD1 mutations in a Taiwanese cohort with young-onset and familial PD. We enrolled 464 participants, including 178 probands from PD pedigrees without known PD-causative gene mutations and 286 patients with young-onset PD (age of onset <50 years). All exons and exon-intron boundary junctions of PTRHD1 were analyzed by Sanger sequencing. We did not find any pathogenic coding variants or previously reported mutations, suggesting that PTRHD1 mutations are rare in young-onset and familial PD in our population.

Review of Animal Models to Study Urinary Bladder Function.

The urinary bladder (UB) serves as a storage and elimination organ for urine. UB dysfunction can cause multiple symptoms of failure to store urine or empty the bladder, e.g., incontinence, frequent urination, and urinary retention. Treatment of these symptoms requires knowledge on bladder function, which involves physiology, pathology, and even psychology. There is no ideal animal model for the study of UB function to understand and treat associated disorders, as the complexity in humans differs from that of other species. However, several animal models are available to study a variety of other bladder disorders. Such models include animals from rodents to nonhuman primates, such as mice, rats, rabbits, felines, canines, pigs, and mini pigs. For incontinence, vaginal distention might mimic birth trauma and can be measured based on leak point pressure. Using peripheral and central models, inflammation, bladder outlet obstruction, and genetic models facilitated the study of overactive bladder. However, the larger the animal model, the more difficult the study is, due to the associated animal ethics issues, laboratory facility, and budget. This review aims at facilitating adapted animal models to study bladder function according to facility, priority, and disease.