Generation of a lethal mouse model expressing human ACE2 and TMPRSS2 for SARS-CoV-2 infection and pathogenesis.

Mouse models expressing human ACE2 for coronavirus disease 2019 have been frequently used to understand its pathogenesis and develop therapeutic strategies against SARS-CoV-2. Given that human TMPRSS2 supports viral entry, replication, and pathogenesis, we established a double-transgenic mouse model expressing both human ACE2 and TMPRSS2 for SARS-CoV-2 infection. Co-overexpression of both genes increased viral infectivity in vitro and in vivo. Double-transgenic mice showed significant body weight loss, clinical disease symptoms, acute lung injury, lung inflammation, and lethality in response to viral infection, indicating that they were highly susceptible to SARS-CoV-2. Pretreatment with the TMPRSS2 inhibitor, nafamostat, effectively reduced virus-induced weight loss, viral replication, and mortality in the double-transgenic mice. Moreover, the susceptibility and differential pathogenesis of SARS-CoV-2 variants were demonstrated in this animal model. Together, our results demonstrate that double-transgenic mice could provide a highly susceptible mouse model for viral infection to understand SARS-CoV-2 pathogenesis and evaluate antiviral therapeutics against coronavirus disease 2019.

Clinical correlates of pareidolias and color discrimination deficits in idiopathic REM sleep behavior disorder and Parkinson's disease.

Visuoperceptual dysfunction is common in Parkinson's disease (PD) and is also reported in its prodromal phase, isolated REM sleep behavior disorder (iRBD). We aimed to investigate color discrimination ability and complex visual illusions known as pareidolias in patients with iRBD and PD compared to healthy controls, and their associating clinical factors. 46 iRBD, 43 PD, and 64 healthy controls performed the Farnsworth-Munsell 100 hue test and noise pareidolia tests. Any relationship between those two visual functions and associations with prodromal motor and non-motor manifestations were evaluated, including MDS-UPDRS part I to III, Cross-Cultural Smell Identification Test, sleep questionnaires, and comprehensive neuropsychological assessment. iRBD and PD patients both performed worse on the Farnsworth-Munsell 100 hue test and had greater number of pareidolias compared to healthy controls. No correlations were found between the extent of impaired color discrimination and pareidolia scores in either group. In iRBD patients, pareidolias were associated with frontal executive dysfunction, while impaired color discrimination was associated with visuospatial dysfunction, hyposmia, and higher MDS-UPDRS-III scores. Pareidolias in PD patients correlated with worse global cognition, whereas color discrimination deficits were associated with frontal executive dysfunction. Color discrimination deficits and pareidolias are frequent but does not correlate with each other from prodromal to clinically established stage of PD. The different pattern of clinical associates with the two visual symptoms suggests that evaluation of both color and pareidolias may aid in revealing the course of neurodegeneration in iRBD and PD patients.

Antimicrobial Resistance Profiles of Enterococcus faecium and Enterococcus faecalis Isolated from Healthy Dogs and Cats in South Korea.

Enterococcus spp. are typically found in the gastrointestinal tracts of humans and animals. However, they have the potential to produce opportunistic infections that can be transmitted to humans or other animals, along with acquired antibiotic resistance. In this study, we aimed to investigate the antimicrobial resistance profiles of Enterococcus faecium and Enterococcus faecalis isolates obtained from companion animal dogs and cats in Korea during 2020-2022. The resistance rates in E. faecalis towards most of the tested antimicrobials were relatively higher than those in E. faecium isolated from dogs and cats. We found relatively higher resistance rates to tetracycline (65.2% vs. 75.2%) and erythromycin (39.5% vs. 49.6%) in E. faecalis isolated from cats compared to those from dogs. However, in E. faecium, the resistance rates towards tetracycline (35.6% vs. 31.5%) and erythromycin (40.3% vs. 35.2%) were comparatively higher for dog isolates than cats. No or very few E. faecium and E. faecalis isolates were found to be resistant to daptomycin, florfenicol, tigecycline, and quinupristin/dalfopristin. Multidrug resistance (MDR) was higher in E. faecalis recovered from cats (44%) and dogs (33.9%) than in E. faecium isolated from cats (24.1%) and dogs (20.5%). Moreover, MDR patterns in E. faecalis isolates from dogs (27.2%) and cats (35.2%) were shown to encompass five or more antimicrobials. However, E. faecium isolates from dogs (at 13.4%) and cats (at 14.8%) were resistant to five or more antimicrobials. Taken together, the prevalence of antimicrobial-resistant enterococci in companion animals presents a potential public health concern.

First Experience of Single-Port Robotic Areolar Approach Thyroidectomy.

OBJECTIVES: Numerous minimally invasive thyroidectomy techniques have been developed and are actively utilized in hospitals around the globe. Herein, we describe a recently developed minimally invasive thyroidectomy technique that employs the da Vinci SP, and we present the preliminary clinical outcomes of single-port robotic areolar thyroidectomy (SPRA). METHODS: A 3-cm semi-circular incision on the right areola and a small 8-mm incision on the left areola were created. Using hydro-dissection and an advanced bipolar device, a subcutaneous skin flap was created, extending from the areola to the thyroid cartilage. The da Vinci SP was then inserted through the incision in the right areola. Between December 2022 and March 2023, 21 SPRA procedures were conducted. Patients' medical records and surgical videos were subsequently reviewed. RESULTS: Lobectomy was performed in 17 patients, isthmectomy in 2 patients, and total thyroidectomy in 2 patients. The mean flap time was 14.9±4.2 minutes and the console time was 62.4±17.1 minutes. The mean tumor size was 0.89± 0.65 cm and the number of retrieved lymph nodes was 3.94±3.98 (range, 0-12). There were no observed instances of vocal cord palsy or hypoparathyroidism. CONCLUSION: We successfully developed and performed the novel SPRA for the first time worldwide. Unlike other robotic surgery. METHODS: SPRA is less invasive and leaves no visible scars. This technique employs a sophisticated single-port robotic device. However, to assess the efficacy of this method, we need to analyze more cases and conduct comparative studies in the near future.

Glymphatic function assessment in Parkinson's disease using diffusion tensor image analysis along the perivascular space.

INTRODUCTION: Glymphatic dysfunction can contribute to α-synucleinopathies. We examined glymphatic function in idiopathic Parkinson's disease (PD) utilizing Diffusion Tensor Image Analysis aLong the Perivascular Space (DTI-ALPS). METHODS: This study enrolled consecutive patients diagnosed with de novo PD between June 2017 and March 2019 who underwent brain DTI with concurrent 123I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT) SPECT, and age- and sex-matched controls. From DTI-ALPS, the ALPS-index was calculated as a ratio of diffusivities along the x-axis in the region of neural fibers passing vertically to the diffusivities perpendicular to them, which reflected perivascular water motion at the lateral ventricular body level. The ALPS-index of the PD and control groups was compared using Student's t-test; its correlations with clinical scores for motor and cognition (UPDRS-III, MMSE, and MoCA) and striatal dopamine transporter uptake measured by 123I-FP-CIT specific binding ratios (SBRs) were examined using a correlation coefficient. RESULTS: In all, 54 patients in the de novo PD group (31 women, 23 men; mean age, 68.9 ± 9.4 years) and 54 in the control group (mean age, 69.0 ± 10.5 years) were included. The ALPS-index was lower in the PD group than in the controls (1.51 ± 0.22 versus 1.66 ± 0.20; P < 0.001). In the PD group, the ALPS-index negatively correlated with the UPDRS-III score (r = -0.526), and positively correlated with the MMSE (r = 0.377) and MoCA scores (r = 0.382) (all, P < 0.05). No correlation was observed between the ALPS-index and striatal 123I-FP-CIT SBRs (P > 0.05). CONCLUSIONS: DTI-ALPS can reveal glymphatic dysfunction in patients with PD, whose severity correlated with motor and cognitive dysfunction, but not striatal dopamine transporter uptake.

Prevalence and Characterization of Extended-Spectrum ß-Lactamase-Producing Escherichia coli Isolated from Dogs and Cats in South Korea.

Overall, 836 Escherichia coli isolates (695 isolates from dogs and 141 from cats) were recovered from the diarrhea, skin/ear, urine, and genitals of dogs and cats between 2018 and 2019. Cefovecin and enrofloxacin resistance were noted in 17.1% and 21.2% of E. coli isolates, respectively. The cefovecin and enrofloxacin resistance rates were higher in dog isolates (18.1% and 22.9%) compared with the rates in cat isolates (12.1%, 12.8%). Interestingly, resistance to both antimicrobials was noted in 10.8% (90/836) of the isolates, predominantly in isolates from dogs. blaCTX-M-14, blaCTX-M-15, and blaCMY-2 were the most frequent extended-spectrum ß-lactamase/plasmid-mediated AmpC ß-lactamase (ESBL/AmpC)- gene types. The co-existence of blaCTX-M andblaCMY-2 was noted in six E. coli isolates from dogs. Sequencing analysis demonstrated that S83L and D87N in gyrA and S80I in parC were the most frequent point mutations in the quinolone resistance-determining regions of the cefovecin and enrofloxacin-resistant isolates. A total of 11 isolates from dogs carried the plasmid-mediated quinolone resistance genes (six aac(6')-Ib-cr, four qnrS, and one qnrB), while only two cat isolates carried the qnrS gene. Multilocus sequence typing of the cefovecin and enrofloxacin-resistant isolates revealed that sequence type (ST)131 E. coli carrying blaCTX-M-14 and blaCTX-M-15 genes and ST405 E. coli carrying blaCMY-2 gene were predominant among the isolated E. coli strains. The majority of the ESBL/AmpC-producing isolates displayed diverse pulsed-field gel electrophoresis profiles. This study demonstrated that third-generation cephalosporin- and fluoroquinolone-resistant E. coli were widely distributed in companion animals. The detection of the pandemic ST131 clone carrying blaCTX-M-14/15 in companion animals presented a public health threat.

Effects of Iron on Efficacy of Photodynamic Therapy Using Photolon in a Mouse Model of CT26 Colon Cancer.

BACKGROUND: Photodynamic therapy (PDT) -a minimally invasive anti-cancer therapy-is undergoing experimental studies to increase its anti-cancer effects. This study investigated the influence of iron on the anti-cancer effects of PDT. METHODS: PDT was performed in a cancer-bearing mouse model, which was created by using a murine colon carcinoma (CT26) cell line after administration of Photolon and iron. Tumor volume and the results of TdT-mediated dUTP-biotin nick end labeling (TUNEL), 8-OHdG, and TBARS assays were used to measure anti-cancer effect. RESULTS: On day 14, tumor volume had increased by 49% in the PDT group and decreased by 72% in the iron+PDT group. The percentage of TUNEL-positive cells in tumor tissues was 45% in the PDT group and 69% in the iron+PDT group, suggesting that the proportion of TUNEL-positive cells had increased in the iron+PDT group. The 8-OHdG content in tumor tissues was 33% higher in the iron+PDT group than in the PDT group. The TBARS content in tumor tissues was 46% higher in the iron+PDT group than in the PDT group. CONCLUSIONS: Iron enhances the anti-cancer effect of PDT using Photolon, most likely by increasing oxidative damage.

Antimicrobial Resistance Profiles and Molecular Characteristics of Extended-Spectrum ß-Lactamase-Producing Escherichia coli Isolated from Healthy Cattle and Pigs in Korea.

Antimicrobial-resistant bacteria isolated from food animals pose a major health threat to the public on this planet. This study aimed to determine the susceptibility profiles of Escherichia coli isolated from cattle and pig fecal samples and investigate the molecular characteristics of extended-spectrum ß-lactamase (ESBL)-producing E. coli using gene identification, conjugation, and Southern blot approach. Overall 293 E. coli were recovered from cattle (120 isolates) and pigs (173 isolates) in 7 provinces of Korea during 2017-2018. Ampicillin, chloramphenicol, streptomycin, and sulfisoxazole resistance rates were the highest in pigs' isolates (>60%, p ≤ 0.001) compared to that in cattle (3-39%). Multidrug resistance (MDR) was higher in pig isolates (73%) than in cattle (31%), and the MDR profile usually includes streptomycin, sulfisoxazole, and tetracycline. Resistance to critically important antimicrobials such as ceftiofur, colistin, and ciprofloxacin was higher in weaners than those from finishers in pigs. The qnrS gene was detected in 13% of the pig isolates. Eight isolates from pigs and one isolate from cattle were identified as ESBL-producers and ESBL genes belonged to blaCTX-M-55 (n = 4), blaCTX-M-14 (n = 3), and blaCTX-M-65 (n = 2). Notably, the blaCTX-M-65 and qnrS1 genes were found to be carried together in an identical plasmid (IncHI2) in two isolates from finisher pigs. The blaCTX-M-carrying isolates belonged to phylogenetic groups B1 (n = 4), B2 (n = 2), A (n = 2), and D (n = 1). The blaCTX-M genes and non-ß-lactam resistance traits were transferred to the E. coli J53 recipient from seven blaCTX-M-positive strains isolated from pigs. The blaCTX-M genes belonged to the IncI1α, IncFII, and IncHI2 plasmids and are also associated with the ISEcp1, IS26, IS903, and orf477 elements. These findings suggested the possibility of blaCTX-M-carrying E. coli transmission to humans through direct contact with cattle and pigs or contamination of food products.

Antibiotic Resistance Profiles and Molecular Characteristics of blaCTX-M-15-Carrying Salmonella enterica Serovar Enteritidis Isolates from Healthy and Diseased Chickens in Korea.

Extended-spectrum ß-lactamase (ESBL)-producing Salmonella enterica serovar Enteritidis has emerged as a public health concern. The main objectives of this study were therefore to determine the antimicrobial susceptibility profiles of Salmonella Enteritidis and to investigate the molecular characteristics of identified ESBL-producing isolates. In the study, 237 Salmonella Enteritidis isolates (232 isolates from chickens, 4 from cattle, and 1 from a pig) were recovered from carcasses and fecal samples of healthy and diseased food animals between 2010 and 2017. Ceftiofur resistance was noted only in chicken isolates (43%, 102/237), with the highest in healthy chickens and their carcasses (48.3%, 83/172) compared with that in diseased chickens (31.7%, 19/60). All of the ceftiofur-resistant isolates exhibited resistance to multiple antimicrobials. Indeed, a relatively higher percentage of ceftiofur-resistant isolates demonstrated resistance to the tested aminoglycosides and tetracycline compared with the ceftiofur-susceptible strains. In this study, blaCTX-M-15 was the only ESBL gene detected in all of the ceftiofur-resistant isolates. The blaCTX-M-15-carrying isolates belonged to 11 different pulsotypes. The blaCTX-M-15 gene was transferred from 20.6% (21/102) of the blaCTX-M-15-harboring isolates to a recipient Escherichia coli J53. The coexistence of IncHI2/ST2 and IncFIIs/ST1 plasmids was noted in the majority (81.8%, 18/22) of the transconjugants. E. coli J53 transconjugants carrying blaCTX-M-15 gene showed distinct genetic environments, predominantly ISEcp1-blaCTX-M-15-orf477 (15/21, 71.4%). This study demonstrated that healthy chickens and their carcasses act as reservoirs of blaCTX-M-15-carrying Salmonella Enteritidis that can potentially be transmitted to humans.

Movement Disorders Associated With Cerebral Artery Stenosis: A Nationwide Study.

Background: Studies of secondary movement disorder (MD) caused by cerebrovascular diseases have primarily focused on post-stroke MD. However, MD can also result from cerebral artery stenosis (CAS) without clinical manifestations of stroke. In this study, we aimed to investigate the clinical characteristics of MD associated with CAS. Materials and Methods: A nationwide multicenter retrospective analysis was performed based on the data from patients with CAS-associated MDs from 16 MD specialized clinics in South Korea, available between January 1999 and September 2019. CAS was defined as the >50% luminal stenosis of the major cerebral arteries. The association between MD and CAS was determined by MD specialists using pre-defined clinical criteria. The collected clinical information included baseline demographics, features of MD, characteristics of CAS, treatment, and MD outcomes. Statistical analyses were performed to identify factors associated with the MD outcomes. Results: The data from a total of 81 patients with CAS-associated MD were analyzed. The mean age of MD onset was 60.5 ± 19.7 years. Chorea was the most common MD (57%), followed by tremor/limb-shaking, myoclonus, and dystonia. Atherosclerosis was the most common etiology of CAS (78%), with the remaining cases attributed to moyamoya disease (MMD). Relative to patients with atherosclerosis, those with MMD developed MD at a younger age (p < 0.001) and had a more chronic mode of onset (p = 0.001) and less acute ischemic lesion (p = 0.021). Eight patients who underwent surgical treatment for CAS showed positive outcomes. Patients with acute MD onset had a better outcome than those with subacute-to-chronic MD onset (p = 0.008). Conclusions: This study highlights the spectrum of CAS-associated with MD across the country. A progressive, age-dependent functional neuronal modulation in the basal ganglia due to CAS may underlie this condition.

Bacterial Prevalence in Skin, Urine, Diarrheal Stool, and Respiratory Samples from Dogs.

The emergence of bacterial infections in companion animals is a growing concern as humans can also be infected through the transmission of pathogenic bacteria. Because there have been few studies conducted on companion animals, the extent and significance of prevalence in veterinary practices remain unknown. This is the first nationwide surveillance report aimed at elucidating the prevalence pattern and associated infections of isolated bacteria from dogs in Korea. Bacterial isolates were collected from seven different laboratories participating in the Korean Veterinary Antimicrobial Resistance Monitoring System from 2018 to 2019. The samples were obtained from the diarrheal stool, skin/ear, urine, and respiratory samples of veterinary hospital-visited dogs. Isolation and identification of bacterial species was carried out using a bacterial culture approach and then confirmed with matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF) and polymerase chain reaction (PCR). Out of 3135 isolates in dogs, 1085, 1761, 171, and 118 were extracted from diarrheal stool, skin/ear, urine, and respiratory samples, respectively. The overall prevalence of bacteria was higher among two age groups (1-5 and 6-10 years) with a 66.5 percent prevalence. This study showed that Escherichia coli was the most prevalent species among isolated bacterial species of diarrheal and urine origin, whereas Staphylococcus pseudintermedius was the most prevalent among skin and respiratory sample isolates. The data on the prevalence of bacteria for each dog specimen could provide basic information to estimate the extent of bacterial infection and antimicrobial resistance development and to guide veterinarians in therapeutic decisions in clinical practices throughout Korea.

Prevalence of Bacterial Species in Skin, Urine, Diarrheal Stool, and Respiratory Samples in Cats.

Bacterial infections are a significant cause of illness and death in different animals. However, these bacterial infections could be a source of human disease or illness if these pathogenic bacteria are present in companion animals. This study aimed to investigate the prevalence of pathogenic bacteria associated with different site infections in cats in the Republic of Korea. For this purpose, samples were collected from the skin/ear, urine, respiratory, and diarrheal stool origins of cats obtained between 2018 and 2019 from seven different laboratories and centers participating in the Korean Veterinary Antimicrobial Resistance Monitoring System. These samples were subjected to analysis for the identification and isolation of associated bacterial species using a bacterial culture approach. A total of 609 isolates were identified in four different cat samples. Among them, 267, 184, 57, and 101 were extracted from diarrheal stool, skin, urine, and respiratory samples, respectively. The findings of this study showed that Escherichia coli was the most prevalent species among isolated bacterial species of diarrheal stool and urine origin. Staphylococcus felis and Pasteurella multocida were most prevalent in the skin and respiratory tract, respectively. However, there was no significant difference in bacterial distribution among the different age groups in all samples. This is the first nationwide surveillance report that associates bacterial prevalence with their site of origin and helps in the prevention of bacterial infections in cats. Moreover, the pattern of bacterial prevalence could provide sufficient guidance for the selection of empirical antimicrobial therapy against infections in cats.

Antimicrobial Resistance in Escherichia coli Isolates from Healthy Food Animals in South Korea, 2010-2020.

Antimicrobial-resistant bacteria in food animals pose a major public health threat worldwide. In this study, we aimed to assess the antimicrobial resistance profiles and resistance trends of commensal Escherichia coli isolated from the feces of healthy cattle, pigs, and chickens in South Korea during 2010 and 2020. A total of 7237 E. coli isolates (2733 cattle, 2542 pig, and 1962 chicken isolates) were tested for susceptibility towards 12 antimicrobials. About 48%, 90%, and 97% of cattle, pig, and chicken isolates, respectively, were resistant to one or more antimicrobial agents. Cattle isolates presented low resistance (<15%) to most of the tested antimicrobials. In contrast, chicken and pig isolates demonstrated a relatively high (>45%) resistance rate to ampicillin, chloramphenicol, streptomycin, and tetracycline. We observed high ciprofloxacin and nalidixic acid resistance rates in chicken (76.1% and 88.6%, respectively), isolates in pig (12.7% and 26.7%, respectively) and cattle (2.7% and 8.2%, respectively) isolates. Notably, a very small proportion of isolates (<5%) from cattle, chickens, and pigs demonstrated resistance to amoxicillin/clavulanic acid, cefoxitin, and colistin. We identified ceftiofur resistance in a small proportion of chicken (8.8%), pig (3.7%), and cattle (0.7%) isolates. We noted an increasing but fluctuating trend of ampicillin, amoxicillin/clavulanic acid, ceftiofur, cefoxitin, chloramphenicol, ciprofloxacin, and streptomycin resistance in pig isolates. Similarly, the ampicillin, ceftiofur, and chloramphenicol resistance rates were increased but fluctuated through time in chicken isolates. Overall, 56% of the isolates showed multidrug-resistant (MDR). The proportion of MDR isolates was low in cattle (17.1%); however, this proportion was high in chickens (87.1%) and pigs (73.7%). Most of the resistance patterns included streptomycin and tetracycline in pigs and cattle, and ciprofloxacin and nalidixic acid in chickens. In conclusion, this study showed high resistance of commensal E. coli isolated from major food animals in Korea to commonly used antimicrobials including critically important antimicrobials. These bacteria could not only be a resistance reservoir but also could have potential to spread this resistance through gene transfer to pathogenic bacteria. Thus, the high prevalence of antimicrobial resistance in food animals highlights the urgent need for measures to restrict and ensure the prudent use of antimicrobials in Korea.

Community Transmission of SARS-CoV-2 Omicron Variant, South Korea, 2021.

In South Korea, a November 2021 outbreak caused by severe acute respiratory syndrome coronavirus 2 Omicron variant originated from 1 person with an imported case and spread to households, kindergartens, workplaces, restaurants, and hospitals, resulting in 11 clusters within 3 weeks. An epidemiologic curve indicated rapid community transmission of the Omicron variant.

Data-driven subtype classification of patients with early-stage multiple system atrophy.

INTRODUCTION: Patients with multiple system atrophy (MSA) are conventionally identified as having MSA-P (prominent parkinsonism) or MSA-C (prominent cerebellar ataxia) based on their predominant motor manifestations. The objective of the present study was to conduct latent class analysis (LCA) of various motor and nonmotor symptoms in early MSA to characterize data-driven subgroups. METHODS: Sixty-one probable or possible MSA patients with disease durations of 3 years or less were included prospectively. LCAs were performed to identify similar clinical subgroups giving even weights to a wide range of MSA motor and nonmotor features. We ran latent models of up to 6 class solutions; the overall model fit was evaluated based on the parsimony of the derived classes, the fit indices, and clinical interpretability. RESULTS: The LCA outcome supported categorization of at least three subgroups of patients with early MSA: the largest class 1, labeled "moderate parkinsonism + extensive dysautonomia", included approximately half of our study patients and showed marked autonomic dysfunction with a burden of parkinsonism. The two other classes, class 2 "predominant parkinsonism + limited dysautonomia" and class 3 "predominant cerebellar symptoms + limited dysautonomia", showed marked core motor features (parkinsonism or cerebellar symptoms) with generally mild dysautonomia. CONCLUSIONS: To our knowledge, this is the first data-driven identification of disease subtypes covering various symptom constellations in early MSA (<3 years from motor symptom onset). The present LCA result did not replicate the conventional motor classification and supported the heterogeneity within MSA-P and MSA-C subtypes.

Enhancing the Effect of Placental Extract on the Regeneration of Crush Injured Facial Nerve.

There is a scarcity of experimental studies on peripheral nerve regeneration using placental extract (PE). This study aimed to investigate the effects of topical PE application on recovery after crush injury to the rat facial nerve using functional, electrophysiological, and morphological evaluations. The viability of the RSC96 Schwann cells treated with PE (0.5~4 mg/ml) increased significantly. Immunoblot test revealed that PE application enhanced the migration of RSC96 cells. Quantitative polymerase chain reaction demonstrated that PE increased the expression of neurotropic genes. The recovery from vibrissa fibrillation in the PE-treated group was superior to that in the control group. The threshold of action potential was also significantly lower in the PE group. Histopathological examination showed that crushed facial nerves treated with PE exhibited larger axons. The surrounding myelin sheaths were more distinct and thicker in the PE-treated group. Hence, PE may be considered a topical therapeutic agent for treating traumatic facial nerve paralysis.

Placebo response in degenerative cerebellar ataxias: a descriptive review of randomized, placebo-controlled trials.

Placebo response in degenerative cerebellar ataxias (CAs) has never been studied despite the large number of randomized controlled trials (RCTs) that have been conducted. In this descriptive review, we aimed to examine the placebo response in patients with CAs. We performed a literature search on PubMed for RCTs on CAs that were published from 1977 to January 2020 and collected data on the changes from the baseline to the endpoint on various objective ataxia-associated clinical rating scales. We reviewed 56 clinical trials, finally including 35 parallel-group studies and excluding 21 cross-over studies. The included studies were categorized as follows: (1) studies showing significant improvements in one or more ataxia scales in the placebo groups (n = 3); (2) studies reporting individual placebo responders with improvements in one or more ataxia scales in the placebo groups (n = 5)-the overall proportion of placebo responders was 31.9%; (3) studies showing mean changes in the direction of improvement in at least one ataxia scale in the placebo groups, though not statistically significant (n = 19); (4) studies showing no placebo response in any of the ataxia scales in the placebo groups (n = 4); (5) studies where data on the placebo groups were unavailable (n = 9). This review demonstrated the placebo response in patients with CAs on various objective ataxia scales. Our study emphasizes that the placebo response should be considered when designing, analyzing, and interpreting clinical trials and in clinical practice in CA patients.