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We herein report a 61-year-old woman who was genetically diagnosed with spinocerebellar ataxia type 31 whose symptoms were modified by anti-amino terminal of alpha-enolase (NAE) antibodies, known as a biomarker of Hashimoto's encephalopathy (HE), and ultimately responded to immunotherapy. The relative titers of anti-NAE antibodies increased when her cerebellar ataxia showed acute deterioration and decreased after immunotherapy. This is the first report of cerebellar ataxia associated with genetic spinocerebellar ataxia with concomitant cerebellar type HE. Physicians should be mindful of measuring anti-NAE antibodies to prevent overlooking patients with genetic spinocerebellar ataxia with treatable simultaneous ataxic diseases.

RNA in extracellular vesicles (EVs) are uptaken by cells, where they regulate fundamental cellular functions. EV-derived mRNA in recipient cells can be translated. However, it is still elusive whether “naked nonvesicular extracellular mRNA” (nex-mRNA) that are not packed in EVs can be uptaken by cells and, if so, whether they have any functions in recipient cells. Here, we show the entrance of nex-mRNA in the nucleus, where they exert a translation-independent function. Human nex-interleukin-1β (IL1β)-mRNA outside cells proved to be captured by RNA-binding zinc finger CCCH domain containing protein 12D (ZC3H12D)-expressing human natural killer (NK) cells. ZC3H12D recruited to the cell membrane binds to the 3′-untranslated region of nex-IL1β-mRNA and transports it to the nucleus. The nex-IL1β-mRNA in the NK cell nucleus upregulates antiapoptotic gene expression, migration activity, and interferon-γ production, leading to the killing of cancer cells and antimetastasis in mice. These results implicate the diverse actions of mRNA., Nonvesicular extracellular RNA (nex-RNA) that are not packed in extracellular vesicles is detected outside the cell, but it is poorly understood. Here the authors report that nex-RNA is captured by a zinc finger protein and transported to the nucleus to enhance antimetastatic characters of the cell.

Coronavirus disease (COVID-19) causes neurological symptoms in a high percentage of patients and is associated with various types of encephalitides and encephalopathies, which are etiologically classified into (a)direct infection of the central nervous system with severe acute respiratory syndrome coronavirus 2 and resultant meningoencephalitis (this is a rare presentation), (b)COVID-19-induced cytokine storms, which trigger endothelial cell injury, blood-brain barrier disruption, and microangiopathy and consequent encephalopathy and, (c)autoimmune encephalitis secondary to para- or post-infectious mechanisms that play a key role during the acute or post-COVID-19 phase. Notably, some patients present with neurological symptoms as the first manifestation. Radiologically characteristic encephalitides and encephalopathies, such as acute necrotizing encephalopathy, acute disseminated encephalomyelitis, posterior reversible encephalopathy syndrome, and clinically mild encephalitis/encephalopathy with a reversible splenial lesion are also complicated by COVID-19. Further investigations and appropriate treatments are warranted in patients with COVID-19, who develop new neurological symptoms.

Neuropathy with anti-myelin-associated glycoprotein (MAG) antibodies commonly demonstrates distal-dominant prolongation of nerve conduction. However, recent electrophysiological studies have shown that distal motor demyelination is not always a distinct feature. We aimed to elucidate whether the longitudinal progression of nerve impairment occurs in a distal-dominant manner. Seven patients with neuropathy with anti-MAG antibodies were enrolled. Sequential nerve conduction studies revealed nerve conduction reduction only at the wrist segment in the median nerve of the patients, but not in the ulnar nerve. Median nerve entrapment at the wrist may play a role in longitudinal disease progression in neuropathy with anti-MAG antibodies.

The business world is changing due to the occupational climate and a large proportion of business executives that are bound to retire in the nearest future leading to an anticipated great loss of knowledge and performance. The paper seeks to evaluate job performance by considering the effect of mentoring on employee performance in the Nigerian service sector. Research focuses on finding out the level at which exposure, counseling, and role modelling affect employee performance in the Nigerian service sector.

Background The current guideline lacks evidence for creating individualized surveillance strategies for upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). Objective To create a novel risk model and to simulate individualized surveillance duration that dynamically illustrates the changing risk relationship of UTUC-related death and non-UTUC death, considering the impact of cigarette smoking. Design, setting, and participants This multicenter cohort study comprised 714 pTa-T4N0M0 UTUC patients, with a median follow-up duration of 65 mo. There were 279 (39.1%) nonsmokers, 260 (36.4%) current smokers, and 175 (24.5%) ex-smokers. Intervention All patients underwent RNU. Outcome measurements and statistical analysis The risks of UTUC death and non-UTUC death over time were estimated using parametric models for time to failure with Weibull distributions. Age-specific, stage-specific, and smoking status-specific surveillance durations were simulated based upon Weibull estimates. Results and limitations The hazard rate (HR) of non-UTUC death gradually increased over time in all age groups regardless of the smoking status, whereas that of UTUC-related death decreased markedly according to the pathological T (pT) stage and was affected by the smoking status. Among current smokers, the baseline HR of UTUC-related death in pT3/4 was higher than that of pT ≤2 and remained high even 10 yr after RNU. Among heavy smokers, the HR of UTUC-related death in all pT stages was highest at baseline and remained high after RNU, compared with nonsmokers, current smokers, or ex-smokers. We simulated specific time points when the risk of non-UTUC death was greater than that of UTUC-related death. Among patients ≥80 yr of with pT3N0M0, the risk of non-UTUC death was greater than that of UTUC-related death 1 yr after RNU in nonsmokers, but 7 yr for heavy smokers. Conclusions Our result revealed that smokers bear a long-term risk burden of UTUC-related death more than the risk of non-UTUC death. For UTUC smokers, longer-term surveillance duration is recommended even in elderly stage. Patient summary In the present study, we evaluated the risk transition of upper tract urothelial carcinoma (UTUC)-related death and non-cancer-related death over time. We found that smoking weighed a huge impact upon UTUC-related death compared with death from other cause, and therefore, we created a more individualized surveillance duration model.

Background The novel coronavirus disease (COVID-19) has been recognized as a global threat, and several studies are being conducted using various mathematical models to predict the probable evolution of this epidemic, which are subject to potential bias. In this study, we aimed to assess and compare the impact of lockdown among the Punjab, Delhi, and Gujarat states of India using the Auto Regressive Integrated Moving Average (ARIMA) model by comparing forecasted COVID-19 data with real-time data. Methods We analyzed the COVID-19 data of Indian states from the index case until May 17, 2020. Auto Regressive Integrated Moving Average (1,1,3) (0,0,0) model was used to forecast the possible cumulative cases until May 17, from data up to May 3, and compared with real-time data. Recovery rate, case-fatality rate, and test per millions of states were collated. Results The trend of cumulative cases in Punjab was moving downward below the forecasted lower confidence limit (R-2 = 0.9799), whereas the cumulative case trend of Delhi was moving along the forecasted upper confidence limit with the forecasted data until May 3 (R-2 = 0.9971) and the trend of cumulative cases was below the forecasted upper confidence limit (R-2 = 0.9992) in Gujarat. Conclusions In Gujarat and Delhi, the lockdown was not effective in controlling the rise in COVID-19 cases even after the 56th day of lockdown, whereas the Punjab state succeeded in preventing havoc of COVID-19. In lieu of lockdown, using facemasks and improving ventilation in closed workspace settings, crowded spaces, and close-contact settings are more pragmatic than keeping away from others in India.

Background Intravenous (IV) infusions of volatile anesthetics in lipid emulsion may increase blood lipid concentration, potentially altering the anesthetic agent's blood solubility and blood-gas partition coefficient (BGPC). We examined the influence of a low-lipid concentration 20% sevoflurane emulsion on BGPC, and the anesthetic potency of this emulsion using dogs. Methods We compared BGPC and anesthetic characteristics in 6 dogs between the IV anesthesia of emulsion and the sevoflurane inhalation anesthesia in a randomized crossover substudy. Minimum alveolar concentrations (MACs) were determined by tail-clamp stimulation by using the up-and-down method. Blood sevoflurane concentration and partial pressure were measured by gas chromatography; end-tidal sevoflurane concentration was measured using a gas monitor. The primary outcome was BGPC at the end of IV anesthesia and inhalation anesthesia. Secondary outcomes were time to loss/recovery of palpebral reflex, finish intubation and awakening, MAC, blood concentration/partial pressure at MAC and awakening, correlation between blood partial pressure and gas monitor, and the safety of emulsions. Results BGPC showed no difference between IV and inhaled anesthesia (0.859 [0.850-0.887] vs 0.813 [0.791-0.901]; P = .313). Induction and emergence from anesthesia were more rapid in IV anesthesia of emulsion than inhalation anesthesia. MAC of emulsion (1.33% [1.11-1.45]) was lower than that of inhalation (2.40% [2.33-2.48]; P = .031), although there was no significant difference in blood concentration. End-tidal sevoflurane concentration could be estimated using gas monitor during IV anesthesia of emulsion. No major complications were observed. Conclusions IV anesthesia with emulsion did not increase the BGCP significantly compared to inhalation anesthesia. It was suggested that the anesthetic potency of this emulsion may be equal to or more than that of inhalation.

The study investigated the wound healing potential of leaf extract of Terminalia avicenniodes in vivo models of Wistar rats. The antimicrobial potential of the plant extract was first determined against a panel of pathogens associated with wound infection using agar-well dilution method. Thirty healthy male Wistar rats weighing 180±2.8 g were anaesthetized, incision and excision wound were made on the animal aseptically. The wounds were aseptically infected with standardized inoculums of Staphylococcus aureus and Pseudomonas aeruginosa respectively. Two concentrations of the ointment incorporated with the plant extract were prepared (TaEAF 0.35 mg/kg and 0.175 mg/kg) and applied on incised and excised wound for 10 and 22 days respectively. The rate of wound contraction, period of epithelization and histology of the healed tissue antioxidant enzymes, free radicals and connective tissue markers were estimated in excision wound model. There was increased wound breaking strength in TaEAF 0.35 mg/kg treated group (p ˂ 0.001), wound contraction rate (98%) and early epithelization period were observed in both S. aureus and P. aeruginosa infected wounds as against the control group. Also, reduction in free radicals and stimulation of antioxidant enzymes as well as connective tissue markers were observed. Histological evidence of restoration of adnexa and fibrosis within the dermis in the treated grouped animals justified wound healing potential of T. avicennioides.

ObjectiveTo clinically diagnose MM2-cortical (MM2C) and MM2-thalamic (MM2T)-type sporadic Creutzfeldt-Jakob disease (sCJD) at early stage with high sensitivity and specificity.MethodsWe reviewed the results of Creutzfeldt-Jakob disease Surveillance Study in Japan between April 1999 and September 2019, which included 254 patients with pathologically confirmed prion diseases, including 9 with MM2C-type sCJD (MM2C-sCJD) and 10 with MM2T-type sCJD (MM2T-sCJD), and 607 with non-prion diseases.ResultsAccording to the conventional criteria of sCJD, 4 of 9 patients with MM2C- and 7 of 10 patients with MM2T-sCJD could not be diagnosed with probable sCJD until their death. Compared with other types of sCJD, patients with MM2C-sCJD showed slower progression of the disease and cortical distribution of hyperintensity lesions on diffusion-weighted images of brain MRI. Patients with MM2T-sCJD also showed relatively slow progression and negative results for most of currently established investigations for diagnosis of sCJD. To clinically diagnose MM2C-sCJD, we propose the new criteria; diagnostic sensitivity and specificity to distinguish ‘probable’ MM2C-sCJD from other subtypes of sCJD, genetic or acquired prion diseases and non-prion disease controls were 77.8% and 98.5%, respectively. As for MM2T-sCJD, clinical and laboratory features are not characterised enough to develop its diagnostic criteria.ConclusionsMM2C-sCJD can be diagnosed at earlier stage using the new criteria with high sensitivity and specificity, although it is still difficult to diagnose MM2T-sCJD clinically.

Background The importance of advance care planning (ACP) has been recognized in the palliative care of patients with heart failure. It is necessary for dissemination of ACP to characterize the perceptions of physicians and nurses towards ACP and to promote mutual understanding. The aim of this study is to investigate the perceptions of physicians and nurses concerning ACP for patients with heart failure. Methods We conducted a self-administered questionnaire survey with physicians and nurses who belonged to the 427 certified institutions for implantable cardioverter defibrillator (ICD) and/or cardiac resynchronization therapy (CRT) in Japan. The self-administered questionnaire was originally designed based on the guidelines on palliative care or ACP and previous studies on the barriers of ACP. We asked the participants the recognition about condition/timing to implement ACP, Content of care to be implemented in ACP, and barriers against implementing ACP. A Mann-Whitney U test was performed and r value was calculated an effect size (ES) in order to evaluate the characteristic perceptions among physicians and nurses. Results Valid responses were obtained from 163 physicians (38.2%) and 208 nurses (48.7%). Regarding the condition/timing, nurses tended to recognize that ACP should be implemented from earlier clinical stages than physicians. Regarding the contents of ACP, both physicians and nurses placed emphasis in assessing the patient's perception of disease progression. The biggest difference was found in the item "Ask patient about what has been important in life so far"; 78.6% of physicians but 94.2% of nurses chose "it must/should be implemented" (Cohen's r=0.31). Regarding the barriers, both physicians and nurses recognized the difficulty in prognosis prediction. The biggest differences were found in the items "Medical staff does not know how to implement ACP for patients and their families" (45.6% of physicians and 70.4% of nurses chose "strongly agree/agree", r=0.27), and "There is disagreement regarding care goals among team members of different professions" (18.5% in physicians and 43.3% in nurses, r=0.27). Conclusions It is suggested that discussions and further studies are necessary concerning the condition/ timing of implementing ACP from early stages, specific manuals/protocols and recommendation on rolesharing within a multidisciplinary team.

Background At present, one out of six couples is infertile, and in 50% of cases, infertility is attributed to male infertility factors. Genetic abnormalities are found in 10%‐20% of patients showing severe spermatogenesis disorders, including non‐obstructive azoospermia. Methods Literatures covering the relationship between male infertility and genetic disorders or chromosomal abnormalities were studied and summarized. Main findings (Results) Genetic disorders, including Klinefelter syndrome, balanced reciprocal translocation, Robertsonian translocation, structural abnormalities in Y chromosome, XX male, azoospermic factor (AZF) deletions, and congenital bilateral absence of vas deferens were summarized and discussed from a practical point of view. Among them, understanding on AZF deletions significantly changed owing to advanced elucidation of their pathogenesis. Due to its technical progress, AZF deletion test can reveal their delicate variations and predict the condition of spermatogenesis. Thirty‐nine candidate genes possibly responsible for azoospermia have been identified in the last 10 years owing to the advances in genome sequencing technologies. Conclusion Genetic testing for chromosomes and AZF deletions should be examined in cases of severe oligozoospermia and azoospermia. Genetic counseling should be offered before and after genetic testing.

The COVID-19 lockdown has had a marked effect on citizen science projects, such as the Southern African Bird Atlas Project, SABAP2. With their mobility severely constrained, most citizen scientists...

To prospectively clarify whether endoscopic contact laser vaporization of the prostate (CVP) can be safely performed even in patients undergoing antithrombotic therapy.Fifty-five patients treated with CVP were enrolled. Patients were assigned to: (i) the antithrombotic therapy group (n = 21, 38%); or (ii) control group without antithrombotic therapy (n = 34, 62%). All patients in the antithrombotic therapy group continued all antithrombotic agents during the perioperative period and thereafter.No difference was noted in patient background between the two groups. In primary endpoints, decreases in the postoperative hemoglobin level were remarkable in the antithrombotic therapy group, while no serious effects were noted in either group. The control and antithrombotic therapy groups did not show a significant difference in the occurrence of catheter obstruction due to blood clots or serious hematuria following catheter removal. During follow-up, transurethral coagulation for hemostasis was needed only in the antithrombotic therapy group, with a frequency of transurethral coagulation of up to 14%. In secondary endpoints, no difference in the occurrence of perioperative or late-onset complications after surgery was noted between the two groups. Finally, no difference was noted in improvements in the International Prostate Symptom Score (IPSS), IPSS quality of life score, overactive bladder symptom score, maximum flow rate, or post-voiding residual urine volume between the two groups throughout the follow-up period.CVP can be performed safely and effectively in patients undergoing continuous antithrombotic therapy. However, the possibility of secondary bleeding after discharge in a subset of patients, such as those undergoing antithrombotic therapy, may be noted.

Different treatment strategies can have varying effects on disability and whole brain volume in patients with multiple sclerosis (MS). However, the association between regional brain volume and treatment efficacy is currently unclear. Our objective was to determine whether whole brain volume, as well as the regional volume of cortical and subcortical grey matter, differ with the administration of high-efficacy therapy (HET) versus low-efficacy therapy (LET).We evaluated clinical data and change in regional brain volume in 44 patients with relapse-onset MS, who underwent HET (n = 19) or LET (n = 25). Regional brain volume was determined with three-dimensional T1-weighted magnetic resonance imaging using FreeSurfer. The association between volume change and treatment type was assessed via generalised linear mixed models (GLMMs).During the observation period (2.0 ± 0.16 years), the proportion of patients with a "no evidence of disease activity-3″ status was significantly greater in those who underwent HET versus LET (p = 0.012). HET was positively associated with volume changes in the cortex (β = 0.64, p = 0.0499), left (β = 0.98, p = 0.0033) and right (β = 0.77, p = 0.019) caudate and right putamen (β = 0.87, p = 0.0077), after adjusting for age, sex, and MS severity scores in the GLMMs. Further correction for multiple comparisons by false discovery rate revealed that HET was consistently associated with the volume changes of the left caudate (p = 0.049) and right putamen (p = 0.049).HET can improve the mid-term prognosis of Japanese patients with relapse-onset MS by reducing disease activity and regional brain volume loss.