Severe Clinical Symptoms Research Articles

(NZW × BXSB) F1 male mice: An unusual, severe and fatal mouse model of lupus erythematosus.

BackgroundSystemic lupus erythematosus (SLE) is a chronic autoimmune/inflammatory disease. The heterogeneity and complexity of clinical presentation has made it challenging to study or treat this syndrome. The (NZW×BXSB) F1 lupus-prone male mouse model of this disease is potentially useful to study mechanism and treatment modalities, but there is a lack of information about this model’s characterization and disease progression. Therefore, the aim was to examine this lupus model’s physical/clinical disease presentation and its immunological status.Materials and methodsClinical and physical status were observed in 8- and 16-week-old male and female (± 1 week) (NZW/LacJ x BXSB/MpJ) F1 mice (n = 8 per group). Young males (8 ± 1 week) without disease and female (16 ± 1 week) mice served as controls. Physical changes, quantitative values of autoantibodies, and blood cell parameters were determined. Necropsy and post-mortem histopathology were also performed.ResultsWith aging (≥ 12 weeks), significant increases in severe abdominal distension/swelling, inability to walk, paleness of paws and significant weight increase were observed compared to controls (p < 0.05). The necropsy examination showed abdominal distension associated with serous effusion and histological examination identified severe edema and multi-organ abnormalities (spleen, lymph nodes, and kidney). Significant increases in anti-double-stranded DNA antibody (anti-dsDNA) was seen in old/sick compared to female (p = 0.0002) or young male (p = 0.0036) mice. Old mice developed immune thrombocytopenia compared to female (p = 0.0056) and young male (p = 0.0007) mice. Anti-platelet was detectable in old, sick mice. The mortality rate increased with aging; more than 35% of male mice died during this study between the ages of 13-18 weeks.ConclusionWe found that the (NZW/LacJ x BXSB/MpJ) F1 male mice spontaneously exhibit, over varying lengths of time, extremely severe and fatal clinical disease symptoms. This model may be too severe to be helpful in investigating SLE and testing potential treatment modalities.

A multicenter cross-sectional study of quality of life and nonsurgical treatment in patients with knee osteoarthritis

Objective: To explore the influencing factors of health-related quality of life (HRQoL) in patients with knee osteoarthritis, and to analyze the non-surgical treatment of knee osteoarthritis. Methods: Demographic variables, treatment modalities, imaging data, and 12-item short form health survey (SF-12) scores of patients with knee osteoarthritis in orthopedic outpatient departments of five hospitals in Beijing from December 2017 to November 2018 were collected to analyze influencing factors of HRQoL and non-surgical treatment. Results: A total of 2 034 patients were included. There were 530 males (26.1%) and 1 504 females (73.9%), with a mean age of (59.17±10.22) years. In terms of physical quality of life, female patients with knee osteoarthritis had lower physical components summary (PCS) compared with male patients (β=-0.521, P=0.036); patients aged ≥64 years had lower PCS than those aged<55 years (β=-0.636, P=0.026). Patients with an education of more than 12 years had higher PCS than those with less than 10 years (β=1.063, P<0.001). Compared to patients with mild clinical symptoms, the PCS of patients with moderate clinical symptoms was lower (β=-0.860, P=0.002), while the PCS of those with severe clinical symptoms was much lower (β=-1.126, P<0.001). Patients treated with combination therapy had higher PCS than untreated patients (β=0.731, P=0.005). In terms of mental quality of life, compared to patients engaged in sedentary work, the mental components summary (MCS) of patients engaged in mild manual labor jobs was lower (β=-0.712, P=0.015); Compared to patients with a Charson comorbidity index of 0, patients with a Charlson comorbidity index ≥ 2 had lower MCS (β=-1.183, P=0.007). In the past 12 months, 648 (31.9%), 143 (7.0%), 406 (20.0%), 680 (33.4%), 343 (16.9%), 681 (33.5%), 170 (8.4%) patients had used non-steroid anti-inflammatory drugs (NSAIDs), acetaminophen, glucosamine/chondroitin formulations, physical therapy, articular cavity puncture injection, traditional Chinese medicine treatment and exercise therapy, respectively. Total of 451 patients (22.2%) received monotherapy and 889 patients (43.7%) received combination therapy. Conclusions: The major non-surgical treatment methods for patients with knee osteoarthritis in Beijing are NSAIDs, physiotherapy and traditional Chinese medicine. Combination therapy is used more frequently than monotherapy. Physical quality of life is related to gender, age, education, severity of symptoms and treatment, while mental quality of life is related to occupational labor and comorbidities.

Does potential antibody-dependent enhancement occur during SARS-CoV-2 infection after natural infection or vaccination? A meta-analysis

Coronavirus disease 2019 (COVID-19) continues to constitute an international public health emergency. Vaccination is a prospective approach to control this pandemic. However, apprehension about the safety of vaccines is a major obstacle to vaccination. Amongst health professionals, one evident concern is the risk of antibody-dependent enhancement (ADE), which may increase the severity of COVID-19. To explore whether ADE occurs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and increase confidence in the safety of vaccination, we conducted a meta-analysis to investigate the relationship between post-immune infection and disease severity from a population perspective. Databases, including PubMed, EMBASE, Chinese National Knowledge Infrastructure, SinoMed, Scopus, Science Direct, and Cochrane Library, were searched for articles on SARS-CoV-2 reinfection published until 25 October 2021. The papers were reviewed for methodological quality, and a random effects model was used to analyse the results. Heterogeneity was assessed using the I2 statistic. Publication bias was evaluated using a funnel plot and Egger’s test. Eleven studies were included in the final meta-analysis. The pooled results indicated that initial infection and vaccination were protective factors against severe COVID-19 during post-immune infection (OR = 0.55, 95%CI = 0.31–0.98). A subgroup (post-immune infection after natural infection or vaccination) analysis showed similar results. Primary SARS-CoV-2 infection and vaccination provide adequate protection against severe clinical symptoms after post-immune infection. This finding demonstrates that SARS-CoV-2 may not trigger ADE at the population level.

Separation of Immune Cell Subpopulations in Peripheral Blood Samples from Children with Infectious Mononucleosis.

Infectious mononucleosis (IM) is an acute syndrome mostly associated with primary Epstein-Barr virus (EBV) infection. The main clinical symptoms include irregular fever, lymphadenopathy, and significantly increased lymphocytes in peripheral blood. The pathogenic mechanism of IM is still unclear; there is no effective treatment method for it, with mainly symptomatic therapies being available. The main question in EBV immunobiology is why only a small subset of infected individuals shows severe clinical symptoms and even develop EBV-associated malignancies, whilemost individuals are asymptomatic for life with the virus. B cells are first involved in IM because EBV receptors are presented on their surface. Natural killer (NK) cells are cytotoxic innate lymphocytes that are important for killing EBV-infected cells. The proportion of CD4+ T cells decreases while that of CD8+ T cells expands dramatically during acute EBV infection, and the persistence of CD8+ T cells is important for lifelong control of IM. Those immune cells play important roles in IM, and their functions need to be identified separately. For this purpose, monocytes are separated first from peripheral blood mononuclear cells (PBMCs) of IM individuals using CD14 microbeads, a column, and a magnetic separator. The remaining PBMCs are stained with peridinin-chlorophyll-protein (PerCP)/Cyanine 5.5 anti-CD3, allophycocyanin (APC)/Cyanine 7 anti-CD4, phycoerythrin (PE) anti-CD8, fluorescein isothiocyanate (FITC) anti-CD19, APC anti-CD56, and APC anti-CD16 antibodies to sort CD4+ T cells, CD8+ T cells, B cells, and NK cells using a flow cytometer. Furthermore, transcriptome sequencing of five subpopulations was performed to explore their functions and pathogenic mechanisms in IM.

Presence of Varicella Zoster Virus DNA in Saliva May Be Associated with the Severity of Ramsay Hunt Syndrome.

Background: The relationship between varicella zoster virus (VZV) collected from saliva and Ramsay Hunt syndrome (RHS) remains unclear. Therefore, this study aimed to investigate whether VZV DNA in saliva alters the clinical symptoms and prognosis of RHS. Methods: To measure the severity of clinical symptoms of 100 RHS patients, the initial House–Brackmann (HB) grade and associated symptoms were evaluated. The final HB grade at the end of treatment was measured to determine the prognosis. Electroneurography (ENoG) was performed on four facial muscles, including the frontalis, oculi, nasalis, and oris. Results: Salivary VZV DNA was isolated from 72 patients with RHS. The VZV DNA-positive group was 34.023 times more likely to have severe initial HB grade than the control group (95% CI, 3.21–359.68; p = 0.003). There were no significant differences in final HB grade. All ENoG values of the VZV DNA-positive group were significantly higher than those of the control group (frontalis, p = 0.003; oculi, p = 0.001; nasalis, p < 0.001; oris, p = 0.037). Conclusions: RHS patients with salivary VZV DNA have more severe clinical symptoms than the control group. There were no differences in prognosis and associated symptoms. A VZV DNA test using saliva samples of patients with RHS can evaluate the clinical symptoms and provide early confirmation of VZV infection, enabling timely treatment in a non-invasive way.

Growth advantage of corrected hepatocytes in a juvenile model of methylmalonic acidemia following liver directed adeno-associated viral mediated nuclease-free genome editing.

Methylmalonic acidemia (MMA) is a rare and severe inherited metabolic disease typically caused by mutations of the methylmalonyl-CoA mutase (MMUT) gene. Despite medical management, patients with MMA experience frequent episodes of metabolic instability, severe morbidity, and early mortality. In several preclinical studies, systemic gene therapy has demonstrated impressive improvement in biochemical and clinical phenotypes of MMA murine models. One approach uses a promoterless adeno-associated viral (AAV) vector that relies upon homologous recombination to achieve site-specific in vivo gene addition of MMUT into the last coding exon of albumin (Alb), generating a fused Alb-MMUT transcript after successful editing. We have previously demonstrated that nuclease-free AAV mediated Alb editing could effectively treat MMA mice in the neonatal period and noted that hepatocytes had a growth advantage after correction. Here, we use a transgenic knock-out mouse model of MMA that recapitulates severe clinical and biochemical symptoms to assess the benefits of Alb editing in juvenile animals. As was first noted in the neonatal gene therapy studies, we observe that gene edited hepatocytes in the MMA mice treated as juveniles exhibit a growth advantage, which allows them to repopulate the liver slowly but dramatically by 8-10 months post treatment, and subsequently manifest a biochemical and enzymatic response. In conclusion, our results suggest that the benefit of AAV mediated nuclease-free gene editing of the Alb locus to treat MMA could potentially be therapeutic for older patients.

Risk Factors for Legal Blindness in 77 Japanese Patients with Endogenous Endophthalmitis: A Multicenter Cohort Study from J-CREST

ABSTRACT Purpose We investigated potential predictive factors for visual prognosis in Japanese patients with endogenous endophthalmitis. Design Retrospective observational multicenter cohort study. Methods We examined the characteristics of 77 Japanese patients with endogenous endophthalmitis and performed statistical analyses of these real-world data. The primary endpoint was the identification of factors associated with visual prognosis. We examined differences between patients in the better vision and legal blindness groups at 12 weeks after treatment initiation. Results The five risk factors for visual impairment at 12 weeks after treatment initiation were presence of pressure injuries, severe clinical symptoms (presence of eye pain and ciliary injection), pathogen identification, and poor best-corrected visual acuity at baseline. Staphylococcus aureus and fungus were associated with a better visual impairment outcome. Conclusions Endogenous endophthalmitis remains a severe ocular infection; however, it can be managed with rapid treatments, as well as other advances in medical knowledge and technology.

Expert consensus for diagnosis and treatment of cervical spondylotic myelopathy with the integrated traditional Chinese and western medicine

Cervical spondylotic myelopathy (CSM) is the most serious subtype, which is characterized by severe clinical symptoms, a high disability rate, and poor prognosis. Traditional Chinese medicine and Western medicine have their own advantages in the diagnosis and treatment of CSM at different stages. In order to further standardize the clinical diagnosis and treatment of CSM and improve the clinical efficacy, based on previous experience and evidence-based medicine, after repeated discussions by the national expert group, the expert consensus on the diagnosis and treatment of integrated traditional Chinese and Western medicine was compiled. This consensus comprehensively introduces the definition, etiology, pathogenesis, diagnosis treatment principles, integrated traditional Chinese and Western medicine treatment, postoperative rehabilitation and nursing care of cervical spondylotic myelopathy, so as to provide reference for clinicians.

New coronavirus infection in a child at the age of 2 years 4 months with acute lymphoblastic leukemia (fatal case)

Children get sick less often than adults with a new coronavirus infection (in the Russian Federation, they account for 7.6% of registered cases of COVID-19), with less severe clinical symptoms, they require hospitalization less often, their disease is milder. The frequency of severe and extremely severe cases of COVID-19 in children does not exceed 1%. A clinical case of the course of COVID-19 in a child aged 2 years 4 months is presented. with acute lymphoblastic leukemia. A feature of the presented case is the development of an extremely severe new coronavirus infection in a child with secondary immunodeficiency caused by a long-term course of malignant, treatment-resistant of acute lymphoblastic leukemia. Slow, within 3 months, the development of the infectious process with long-term preservation of normal indicators of the function of the respiratory system led to the formation of viral-bacterial pneumonia with the development of respiratory distress syndrome. Despite the modern complex of therapeutic measures, severe comorbidity led to the development of DIC and multiple organ failure, which was the direct cause of the childs death. A possible therapy strategy is discussed in a patient with severe comorbidity against the background of secondary immunodeficiency and long-term persistence of SARS-CoV-2 in the presence of IgG antibodies to SARS-CoV-2 in the blood. For the first time, data on morphological changes in the lungs with a long course of COVID-19 (more than 100 days) in a young child are presented.

Investigation of Polymorphisms of ACEII Gene in People With Coronavirus With Severe and Mild Symptoms or Asymptomatic

Introduction: Angiotensin-converting enzyme 2 (ACE2) is the central receptor of coronavirus disease 2019 (COVID-19) in host cells. Genetic polymorphisms in the ACE2 gene may promote cardiovascular disease and systemic inflammatory injury in a patient affected by COVID-19. Thus, the genetic background may account for the substantial inter-individual diversity in illness susceptibility or severity. Our study was conducted to find a significant relationship between ACE2 rs4646142 and rs2285666 polymorphisms and susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: In this study, we randomly selected 230 samples, including 76 patients with severe clinical symptoms and 154 patients with mild clinical symptoms (the positive case of COVID-19 was confirmed by real-time reverse transcriptase polymerase chain reaction [RT-PCR] assay). Then, we performed DNA extraction and investigated the polymorphisms of rs2285666 and rs4646142 by RFLP-PCR method with TaqI and Alu1 restriction enzymes. Results: The study population included 107 men and 123 women, and the mean (±SD) age of the participants was 42.66±10.2. First, the levels of IgM and IgG were examined, and a significant association was observed in the level of IgM between the two groups of COVID-19 patients with mild and severe symptoms, as opposed to IgG. Meanwhile, no significant difference was observed between ACE2 rs4646142 and rs2285666 polymorphisms and the severity of COVID-19. Conclusion: To better understand the genetic variations in people’s susceptibility to COVID-19, this study was designed to evaluate the association between various ACE2 polymorphisms and the infection risk of SARS-CoV-2. However, no statistical difference was discovered.

One-year investigation of nut allergy cases in children referred to the allergy clinic of the children's medical center

Background: The prevalence of allergy to tree nuts is spreading worldwide. Allergy to tree nuts causes more severe clinical symptoms and anaphylaxis attacks are more likely. The present study was conducted in order to investigate the cases of tree nut allergy among children referred to the allergy clinic of the Children's Medical Center in a period of one year (from the beginning of 2018 to its end). Methods: There were 1920 children with a history of atopic disease (asthma, allergic rhinitis, atopic dermatitis, chronic urticaria) with a history of type I allergic reactions. Eighty seven patients with skin, digestive, respiratory symptoms or anaphylaxis after consuming tree nuts were included in the study. A skin test was performed for most of these people, and in some cases, the serum specific IgE level against the desired nuts was requested, and after confirming the positive history of allergy by the mentioned tests, a questionnaire containing 26 questions was completed by the parents to complete the information. Findings: The prevalence of allergy to tree nuts in the studied population was 4.5%. Allergy to almonds is at the top with a frequency of 62.1%. Totally, 55.2% of the patients were males.

A case report on leptospirosis with pseudohepatorenal syndrome

The spirochete Leptospira interrogans causes leptospirosis, a zoonosis. There are numerous clinical symptoms of leptospirosis. Clinical manifestations might range from a subclinical infection with a mild fever to severe clinical symptoms with jaundice and renal failure. Here, a case of leptospirosis with acute renal failure, thrombocytopenia, and hyperbilirubinemia is presented. A 51-year-old man presented with fever, body aches, muscle aches, colored urine, and jaundice for 2 days. On serology report, L. interrogans AB IGM-CARD was weekly positive. In the Renal function test, urea and creatinine values were high as well as the liver function test was abnormal. The patient was given 1 g of ceftriaxone intravenously and 100 mg of doxycycline orally. Hepatorenal treatment was supportive and the outcome was positive. It may have been overlooked when the diagnosis of leptospirosis was confirmed.

COVID-19 Symptoms and Deaths among Healthcare Workers, United States.

We evaluated whether demographics and COVID-19 symptoms predicted COVID-19 deaths among healthcare workers (HCWs) in the United States by comparing COVID-19 deaths in HCWs with 3 control groups (HCW nondeaths, non-HCW deaths, and non-HCW nondeaths) using a case–control design. We obtained patient-level data of 33 variables reported during January 1, 2020–October 12, 2021, in all US states. We used logistic regression analysis while controlling for confounders. We found that persons who were >50 years of age, male, Black, or Asian experienced significantly more deaths than matched controls. In addition, HCWs who died had higher risks for the most severe clinical indicators. We also found that the most indicative symptoms were preexisting medical conditions, shortness of breath, fever, cough, and gastrointestinal symptoms. In summary, minority, male, and older HCWs had greater risk for COVID-19 death. Severe clinical indicators and specific symptoms may predict COVID-19–related deaths among HCWs.

Advances in Diagnosis and Treatment of Leptomeningeal Metastasis of Lung Cancer

脑膜转移癌（leptomeningeal metastases, LM）是晚期肺癌中进展迅速、预后差的常见并发症。脑膜转移癌临床诊断率低，治疗手段有限，疗效差，自然生存时间短。脑脊液细胞学作为诊断脑膜转移癌的金标准，但是目前临床症状及影像学阳性的患者脑脊液首次细胞病理学阳性诊断率一般不超过50%，导致脑膜转移癌患者的诊断延迟、治疗延误。随着驱动基因阳性肺癌靶向治疗、驱动基因阴性肺癌免疫治疗的进展，肺癌患者生存期延长，但是脑膜转移癌发病率逐年增加，如何提高诊断率、寻找有效的治疗手段是目前临床研究的热点。本文就肺癌脑膜转移癌诊断及治疗研究进展予以综述。

A Retrospective Study of the Clinical Characteristics of Japanese Encephalitis in Adults.

This study aimed to explore the diagnostic points and treatment modes of the clinical characteristics of Japanese encephalitis (JE) in the middle-aged and elderly population. Six patients aged 47-72 who were diagnosed with JE at the Beijing Chaoyang Hospital Affiliated with the Capital Medical University between August 2018 and September 2019 were enrolled in the study. Their clinical manifestations, biochemical indicators, imaging data, diagnostic methods, and the evolution and outcomes of the treatments they underwent were retrospectively analyzed. (1) All six patients had severe clinical symptoms and poor prognoses that were more likely to be associated with other systemic diseases. (2) Lesions were most commonly distributed in the thalamus, basal ganglia, and midbrain. The appearance of hyperintensity in the corpus callosum, hippocampus, and subcortical white matter was more specific. The hyperperfusion metabolism in the lesion area in head computed tomography perfusion imaging indicated the state of inflammatory activity in the lesion. In cranial magnetic resonance imaging (MRI), T2 and fluid-attenuated inversion recovery (FLAIR) were more sensitive. (3) After a patient has been systematically treated in the intensive care unit (ICU), the patient gradually recovered and the level of consciousness improved (p < 0.05). In brain MRI-especially T2 and FLAIR-intracranial infection is often accompanied by abnormal signals in the thalamus, midbrain, hippocampus, and white matter hyperintensity (WMH), which is highly suggestive of JE. The positive detection of anti-JE virus immunoglobulin M antibodies in a patient's serum and/or cerebrospinal fluid can confirm the diagnosis of JE, and comprehensive ICU treatment (hormones combined with anti-inflammatory, antiviral, and mild hypothermic cerebral protection therapies) can improve the survival rate.

Antibiogram, Haemolysis and Biofilm Properties of Escherichia coli from Bovine Mastitis

Background: Escherichia coli cause mammary gland inflammation in dairy cows with striking local and sometimes severe systemic clinical symptoms. This disease affects many high producing cows in dairy herds and may cause several cases of death per year in the most severe cases. The present study was planned to evaluate the antibiogram and virulence factors of the isolated bacteria responsible for mastitis. Methods: In this study, 300 milk samples were collected and subjected to identify clinical mastitis (based on clinical symptoms) and sub clinical mastitis (using California mastitis test). E. coli was isolated and identified from mastitis positive samples and further tested for antibiogram and virulence factors such as haemolysis, biofilm formation and fimH and pap genes presence. Result: Out of 300 milk samples collected, 121 (40.33%) were positive for mastitis. E. coli was isolated from only 30 (24.79%) out of 121 mastitis positive samples. On Serotyping for somatic antigen, 13 E. coli isolates belonged to somatic serogroup O83, 2 to O157 and one each to O8, O20, O49, O119, O128 and O145. The highest sensitivity of E. coli isolates was recorded for ciprofloxacin, followed by gentamicin, tetracycline, nitrofurantoin, chloramphenicol, amikacin, cefixime, trimethoprim, ampicillin/sulbactam, ceftriaxone, cefoperazone, cefotaxime, kanamycin, cefotaxime/clavulanic acid and amoxycillin in the decreasing order. Multidrug resistance (MDR) was recorded in 96.66% of isolates. Out of 30 E. coli isolates, 46.66% were haemolytic and 40.0% positive for Congo red dye binding. Biofilm production was shown by 76.66% isolates. Molecular characterization revealed presence of fimH gene in 9 isolates, but pap gene was not detected in any of the strain. It may be concluded that E. coli is an emerging environmental mastitogen in cows and isolation of MDR strains with virulence factors is of serious concern.

The role of connective tissue biopolymers in the pathogenesis of dog bronchopneunmonia and cat brochnial asthma

The aim: to analyze the pathogenetic role of connective tissue biopolymers in canine pneumonia and feline asthma.&#x0D; Materials and methods. The study was conducted by analyzing the sources of scientific literature: PubMed, Elsevier, electronic resources of the National Library, named after V.I. Vernadsky and the results of our own scientific and clinical experience.&#x0D; Results. Studies on the pathogenetic justification of the role of biochemical indicators of the connective tissue in the diagnosis and treatment of diseases of the respiratory system of dogs and cats were conducted. This is due to the need to expand knowledge about the peculiarities of the course, to determine the leading pathogenetic links of the most common pathologies –bronchopneumonia and bronchial asthma, which are found in clinical veterinary practice.&#x0D; Conclusions. In bronchopneumonia of dogs on the background of severe clinical symptoms (cough, fever, wheezing in the lungs), radiological signs (inhomogeneous compaction of the lung tissue, lack of clear contours of the bronchi), anemic syndrome, general and neutrophilic leukocytosis, lymphocytopenia, hypoalbuminemia, dysproteinemia (increased concentration of α2- and β-globulins in the blood serum), hypercholesterolemia, hyper-β-lipoproteinemia, hyperfermentemia (increased activity of AST and alkaline phosphatase,) there is an increase in serum glycoproteins and chondroitin sulfates, sialic acids, total glycosaminoglycans (GAG) due to the chondroitin-4-sulfate fraction; urinary excretion of oxyproline and uronic acids increases. Disorders of connective tissue metabolism in dogs with bronchopneumonia are caused by an acute inflammatory process in the lungs with the development of pulmonary fibrosis.&#x0D; Bronchial asthma in cats is manifested by intermittent cough, shortness of breath, hypochromic normocytic anemia, leukocytosis, eosinophilia and lymphocytopenia, increased serum activity of AST and alkaline phosphatase, haptoglobin content, glial acid concentration sulfate; urinary excretion of oxyproline and uronic acids increases. Connective tissue disorders in cats with bronchial asthma are caused by increased mucus excretion with a high content of GAG, as well as chronic inflammation of the bronchial mucosa and their fibrosis

Simulating the progression of brain structural alterations in Parkinson’s disease

Considering brain structural alterations as neurodegenerative consequences of Parkinson's disease (PD), we sought to infer the progression of PD via the ordering of brain structural alterations from cross-sectional MRI observations. Having measured cortical thinning in gray matter (GM) regions and disintegrity in white matter (WM) regions as MRI markers of structural alterations for 130 patients with PD (69 ± 10 years, 72 men), stochastic simulation based on the probabilistic relationship between the brain regions was conducted to infer the ordering of structural alterations across all brain regions and the staging of structural alterations according to changes in clinical status. The ordering of structural alterations represented WM disintegrity tending to occur earlier than cortical thinning. The staging of structural alterations indicated structural alterations happening mostly before major disease complications such as postural instability and dementia. Later disease states predicted by the sequence of structural alterations were significantly related to more severe clinical symptoms. The relevance of the ordering of brain structural alterations to the severity of clinical symptoms suggests the clinical feasibility of predicting PD progression states.

Low serum uric acid levels are associated with incidence and severity in trigeminal neuralgia.

Uric acid is a natural antioxidant, and low levels of uric acid have been reported to be a potential risk factor in the development of nervous system diseases. Herein, we investigated whether uric acid levels play a role in trigeminal neuralgia (TN). We conducted a cohort study to compare the serum uric acid levels of patients with TN and healthy controls. We also analyzed the impact of uric acid levels on the risk of TN and symptom severity. In comparison to control participants (n = 133), uric acid levels were remarkably decreased in patients with TN (n = 181). Uric acid (OR = 0.989; 95% CI 0.986-0.993; P < 0.001) was also determined as a protective factor against TN based on multivariate logistic regression models. Furthermore, nonlinear relationships between serum uric acid levels and TN incidence rate and between that and the Barrow Neurological Institute (BNI) grading were observed. Our study is the first to show a relationship between serum uric acid levels and TN. Specifically, low serum uric acid levels were associated with an increased risk of TN and more severe clinical symptoms. We expect that these findings will provide new insights into the prevention and treatment of TN.

Detection of Japanese Encephalitis Virus RNA in Host-Questing Ticks in Japan, 2019-2020.

Japanese encephalitis virus (JEV), a mosquito-borne virus, causes severe clinical symptoms in humans in the Asian-Pacific region, where it circulates in a primary transmission cycle among Culex tritaeniorhynchus mosquitoes, domestic swine (Sus scrofa domesticus), and wading birds. We report here an anomalous result that mosquito-borne JEV was detected in unfed host-questing ticks collected from the field in Japan. JEV genomic RNA was detected in four pools of Haemaphysalis flava nymphs collected in November and December 2019, and March 2020, when Cx. tritaeniorhynchus adults were not presumed to be active. Moreover, JEV antigenomic RNA was detected in some JEV-positive tick samples, suggesting virus replication in ticks. However, taken together with no infectious virus isolated, the possibility that the antigenomic RNA was derived from the undigested bloodmeal source in ticks cannot be ruled out. Thus, the role of the ticks as a natural reservoir for JEV remains to be confirmed.