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Tattooing and use of permanent makeup (PMU) have dramatically increased over the last decade, with a concomitant increase in ink-related infections. Studies have shown evidence that commercial tattoo and PMU inks are frequently contaminated with pathogenic microorganisms. Considering that tattoo inks are placed into the dermal layer of the skin where anaerobic bacteria can thrive and cause infections in low-oxygen environments, the prevalence of anaerobic and aerobic bacteria should be assessed in tattoo and PMU inks. In this study, we tested 75 tattoo and PMU inks using the analytical methods described in the FDA Bacteriological Analytical Manual Chapter 23 for the detection of both aerobic and anaerobic bacterial contamination, followed by 16S rRNA gene sequencing for microbial identification. Of 75 ink samples, we found 26 contaminated samples with 34 bacterial isolates taxonomically classified into 14 genera and 22 species. Among the 34 bacterial isolates, 19 were identified as possibly pathogenic bacterial strains. Two species, namely Cutibacterium acnes (four strains) and Staphylococcus epidermidis (two strains) were isolated under anaerobic conditions. Two possibly pathogenic bacterial strains, Staphylococcus saprophyticus and C. acnes , were isolated together from the same ink samples ( n = 2), indicating that tattoo and PMU inks can contain both aerobic ( S. saprophyticus ) and anaerobic bacteria ( C. acnes ). No significant association was found between sterility claims on the ink label and the absence of bacterial contamination. The results indicate that tattoo and PMU inks can also contain anaerobic bacteria., Importance: The rising popularity of tattooing and permanent makeup (PMU) has led to increased reports of ink-related infections. This study is the first to investigate the presence of both aerobic and anaerobic bacteria in commercial tattoo and PMU inks under aerobic and anaerobic conditions. Our findings reveal that unopened and sealed tattoo inks can harbor anaerobic bacteria, known to thrive in low-oxygen environments, such as the dermal layer of the skin, alongside aerobic bacteria. This suggests that contaminated tattoo inks could be a source of infection from both types of bacteria. The results emphasize the importance of monitoring these products for both aerobic and anaerobic bacteria, including possibly pathogenic microorganisms., Competing Interests: The authors declare no conflict of interest.

Background: Chronic cough (CC) is common in the general population of China, creating a difficult-to-ignore public health burden. However, there is a lack of research on the nationwide prevalence and disease burden of CC in the Chinese population. We aim to use an insurance claims database to assess the prevalence and the corresponding economic burden owing to CC in China., Methods: This was a retrospective observational study based on an administrative medical insurance database in 2015, 2016 and 2017, from nine cities in North, South, East, South-West, and North-West regions of China. The study population was Chinese adults (≥ 18 years old) who had been identified as CC patients. Descriptive data analyses were used in statistical analysis., Results: A total of 44,472, 55,565, and 56,439 patients with mean ages of 53.2 (16.3) years were identified as patients with CC in 2015, 2016, and 2017, respectively. Of these, 55.24% were women. In addition, 8.90%, 9.46%, and 8.37% of all patients in 2015, 2016, and 2017, who had applied for medical insurance, had CC, respectively, with a three-year average probability of 8.88%. The median number of outpatient visits within a calendar year was 27 per year due to any reason during the period of 2015-2017. The median medical cost of each patient per year increased from 935.30 USD to 1191.47 USD from 2015 to 2017., Conclusion: CC is common among medical insurance users, with a substantial utilization of medical resources, highlighting the huge burden of CC in China., (© 2024. Merck & Co., Inc., Rahway, NJ, USA and its affiliates & Fang Yi, Kefang Lai 2024.)

Aim: The aim of this study was to identify preoperative magnetic resonance imaging (MRI) findings that can predict the shunt responsiveness in idiopathic normal-pressure hydrocephalus (iNPH) patients and to investigate postoperative outcome and complications., Materials and Methods: A total of 192 patients with iNPH who underwent shunt at our hospital between 2000 and 2021 were included to investigate complications. Of these, after exclusion, 127 (1-month postoperative follow-up) and 77 (1-year postoperative follow-up) patients were evaluated. The preoperative MRI features (the presence of tightness of the high-convexity subarachnoid space, Sylvian fissure enlargement, Evans' index, and callosal angle) of the shunt-response and nonresponse groups were compared, and a systematic review was conducted to evaluate whether preoperative MRI findings could predict shunt response., Results: Postoperative complications within one month after surgery were observed in 6.8% (13/192), and the most common complication was hemorrhage. Changes in corpus callosum were observed in 4.2% (8/192). The shunt-response rates were 83.5% (106/127) in the 1-month follow-up group and 70.1% (54/77) in 1-year follow-up group. In the logistic regression analysis, only Evans' index measuring >0.4 had a significant negative relationship with shunt response at 1-month follow-up; however, no significant relationship was observed at 1-year follow-up. According to our systematic review, it is still controversial whether preoperative MRI findings could predict shunt response., Conclusion: Evans' index measure of >0.4 had a significant relationship with the shunt response in the 1-month follow-up group. In systematic reviews, there is ongoing debate about whether preoperative MRI findings can accurately predict responses to shunt surgery. Postoperative corpus callosal change was observed in 4.2% of iNPH patients., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Menopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women's health., Purpose: To investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women., Methods and Results: Untargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36:6, and PC ae C42:3 in plasma as well as PC aa 34:1, PC aa C34:3, PC aa C36:5, PC aa C32:1, PC aa C36:2, and sphingosine in muscle as top featured metabolites that differentiate the OVX mice from the sham-operated group. When circulating levels of AKG, arginine, and carnosine, which showed the most significant changes in OVX mice blood, were measured in postmenopausal women, higher plasma AKG levels were associated with lower bone mass, weak grip strength, poor physical performance, and increased frailty risk., Conclusions: Metabolomics- and ML-based methods identified the key metabolites of blood and muscle that were significantly changed after ovariectomy in mice, and the clinical implication of several metabolites was investigated by looking at their correlation with body composition and frailty-related parameters in postmenopausal women. These findings provide crucial context for understanding the diverse physiological alterations caused by estrogen deficiency in women., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Vibrio harveyi strain 22FBVib0145 was isolated from a diseased olive flounder farmed in Jeju, Korea. Here, we report the draft genome sequence of this strain. It is 6,238,277 bp in length with a G + C content of 44.8%., Competing Interests: The authors declare no conflict of interest.

Aim: To compare the diagnostic test of integrated 2-[ 18 F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG PET/CT) with that of magnetic resonance imaging (MRI) for the differentiation of malignant peripheral nerve sheath tumours (MPNSTs) in neurofibromatosis type 1 (NF1) patients., Materials and Methods: A systematic search was performed in PubMed and EMBASE (last updated in 30 November 2022). Studies investigating the performance of FDG PET/CT and MRI for differentiation of MPNSTs were eligible for inclusion. Only studies reporting a direct comparison between these imaging methods were considered to establish precise summary estimates in the same setting of patients., Results: The pooled estimate of sensitivity of FDG PET/CT was 0.99 and a pooled specificity of 0.53. The pooled estimate of sensitivity of MRI was 0.85 and a pooled specificity of 0.85., Conclusion: Analysis of the available studies indicated that FDG PET/CT and MRI had similar diagnostic performances for differentiation of MPNSTs in patients with NF1; however, either technique can be a complement to the other rather than being used singly., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: This study explored factors related to Korean adults' smoking patterns and also the reasons for using new types of tobacco products., Study Design: Cross-sectional survey., Methods: Data from the Korea National Health and Nutrition Examination Survey from 2013 to 2021 were used. The prevalence of the use of electronic cigarettes (e-cigarettes) or heated tobacco products (HTPs) alone or in combination with conventional cigarettes (CC) and the reasons for using new tobacco products are presented. Factors associated with using new types of tobacco products alone or in combination with CC compared to exclusive CC users were identified using multinomial logistic regression analysis., Results: The prevalence of current smoking was 25.54% in 2013 and 23.05% in 2021, with no significant change. The prevalence of CC decreased from 23.39% in 2013 to 15.77% in 2021. The prevalence of new tobacco use in combination with CC did not show a definite trend. The prevalence of exclusive use of new tobacco was <1% until 2018 and has rapidly increased thereafter. Of the HTPs users, 46.68% responded with 'no cigarette smell' as the main reason for HTPs use, followed by 'It seems less harmful than cigarette' (19.19%), and 'It seems to be helpful for quitting smoking' (15.04%). Of the e-cigarette users, 45.19% responded 'It seems to be helpful for quitting smoking' as the main reason for e-cigarette use, followed by 'It is less harmful than cigarettes' (19.98%). Compared to CC users, new tobacco users were younger, had a higher household income or education, and used more nutritional supplements., Conclusion: Regulations for newer tobacco products are more lenient than for traditional cigarettes, leading to misunderstandings, especially among women and young people. To increase awareness of the risks of these products, specific policies such as disclosure of ingredients, ban on online sales, and increase in consumption tax, are needed., (Copyright © 2023 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Aim: To verify the diagnostic performance of the loss of nigrosome-1 on susceptibility-weighted imaging (SWI) with compressed sensing-sensitivity encoding (CS-SENSE) and neuromelanin on neuromelanin-sensitive (NM) magnetic resonance imaging (MRI) for the diagnosis of Parkinson's disease (PD) and atypical Parkinsonism., Materials and Methods: A total of 195 patients who underwent MRI between October 2019 and February 2020, including SWI, with or without CS-SENSE, and NM-MRI, were reviewed retrospectively. Two neuroradiologists assessed the loss of nigrosome-1 on SWI and neuromelanin on the NM-MRI. The result of N-3-fluoropropyl-2-beta-carbomethoxy-3-beta-(4-iodophenyl) nortropane positron-emission tomography (PET) was set as the reference standard., Results: When CS-SENSE was applied for nigrosome-1 imaging on SWI, the non-diagnostic scan rate was lowered significantly from 19.3% (17/88) to 5.6% (6/107; p=0.004). Diagnosis of PD and atypical Parkinsonism based on the loss of nigrosome-1 on SWI and based on NM-MRI showed good diagnostic value (area under the curve [AUC] 0.821, 95% confidence interval [CI] = 0.755-0.875: AUC 0.832, 95% CI = 0.771-0.882, respectively) with a substantial inter-reader agreement (κ = 0.791 and 0.681, respectively). Combined SWI and neuromelanin had a similar discriminatory ability (AUC 0.830, 95% CI = 0.770-0.880). Similarly, the diagnosis of PD was excellent., Conclusions: CS-SENSE may add value to the diagnostic capability of nigrosome-1 on SWI to reduce the nondiagnostic scan rates. Furthermore, loss of nigrosome-1 on SWI or volume loss of neuromelanin on NM-MRI may be helpful for diagnosing PD., (Copyright © 2023. Published by Elsevier Ltd.)

Denosumab is an effective antiresorptive drug commonly prescribed for the treatment of osteoporosis. However, some patients do not respond well to denosumab treatment. The aim of this study was to evaluate the factors underlying treatment nonresponses to denosumab in elderly patients following hip fracture. This retrospective study included 130 patients treated with denosumab after osteoporotic hip fracture between March 2017 and March 2020. The patients were categorized as denosumab nonresponders if they had a T-score <-3 that persisted between dual-energy X-ray absorptiometry scans, a >3% decrease in bone mineral density (BMD), or an incident fracture on denosumab therapy. We examined the baseline characteristics associated with blunted BMD responses and compared the groups following denosumab treatment for 12 months. Of 130 patients with baseline data, 105 patients (80.8%) were considered responders. No difference in baseline vitamin D, calcium, BMI, age, gender, prior fracture history, or bisphosphonate use was observed between responders and nonresponders. A longer interval between denosumab injections was associated with suboptimal BMD response at both spine and total hip (p<0.001 and p=0.04, respectively). The overall L-BMD and H-BMD were significantly increased compared with pretreatment levels after denosumab treatment (5.7% and 2.5%, respectively). This study revealed that nonresponse was not strongly associated with certain baseline variables and it appears that the reponders and nonresponders were reasonably comparable in this study population. The results of our study highlight the importance of timely denosumab administration when using this drug for osteoporosis management. Physicians should keep these results in mind in clinical practice so that they can improve utilization of 6-month denosumab.

Aim: To evaluate the detection rate of magnetic resonance (MR) myelography without intrathecal gadolinium for cerebrospinal fluid (CSF) leakage in patients with newly diagnosed spontaneous intracranial hypotension (SIH) and to validate a published scoring system for predicting CSF leakage., Materials and Methods: This retrospective, observational, single-institution study included patients with newly diagnosed SIH between March 2015 and April 2021. Patients were included if they (a) had newly diagnosed SIH and (b) underwent initial brain MR imaging and preprocedural MR myelography with two- and three-dimensional turbo spin-echo sequences. Patients who underwent spine surgery or procedures including epidural injection and acupuncture were excluded. The detection rate was defined as the proportion of patients with a true-positive MR myelography result among all patients with confirmed CSF leakage. The interobserver agreement for the MR myelography results between two radiologists was analysed using weighted kappa statistics., Results: A total of 136 patients (mean age, 48 years; 70 women) with suspected SIH were included. Of these patients, 120 (88%, 120/136) were confirmed to have CSF leakage. Of the patients with confirmed CSF leakage, 90 (75%, 90/120) had epidural fluid collection. The detection rate of MR myelography for CSF leakage was 88% (105/120). The interobserver agreement between the two readers for detecting CSF leakage (κ = 0.76) or epidural fluid collection (κ = 0.76) on MR myelography was high. Among 24 patients with normal brain MR imaging results, 16 had CSF leakage (67%, 16/24)., Conclusions: Non-invasive MR myelography without intrathecal gadolinium should be considered to detect CSF leakage in patients with suspected SIH., (Copyright © 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Disinfection of shared spaces has become essential to minimize the spread of various diseases. An efficient disinfection device that can simultaneously inactivate airborne bacteria and surface-adhered bacteria in an enclosed space is required., Aim: An air-passable plasma filter (APF) was developed and applied to a chamber model to evaluate the efficacy of zone disinfection., Methods: The 60 L chamber consisted of a nebulizer, circulation fans, temperature and humidity monitors, an air-sampling port with a sealed gate, airborne bacteria-trapping media, and a built-in fan for evaluation. After spraying each bacterial strain (Escherichia coli, Staphylococcus epidermidis, and Mycobacterium smegmatis) as a bioaerosol, airborne and surface-attached bacteria were quantified simultaneously to evaluate the zone-disinfection effect of APF., Findings: The operation of APF in the 60 L chamber showed a complete zone-disinfection effect for E. coli (10 min), S. epidermidis (10 min), and M. smegmatis (60 min) present in the air and on the walls at various locations. The time required to completely disinfect each of the airborne bacteria and surface-attached bacteria within the same space was different., Conclusion: APF has the potential to exhibit significant germicidal effects on various micro-organisms and can be an effective alternative for disinfection of enclosed spaces., (Copyright © 2022 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Objectives: A multicenter randomized clinical trial in Hong Kong Accident and Emergency (A&E) departments concluded that intramuscular (IM) olanzapine is noninferior to haloperidol and midazolam, in terms of efficacy and safety, for the management of acutely agitated patients in A&E setting. Determining their comparative cost-effectiveness will further provide an economic perspective to inform the choice of sedative in this setting., Methods: This analysis used data from a randomized clinical trial conducted in Hong Kong A&E departments between December 2014 and September 2019. A within-trial cost-effectiveness analysis comparing the 3 sedatives was conducted, from the A&E perspective and a within-trial time horizon, using a decision-analytic model. Sensitivity analyses were also undertaken., Results: In the base-case analysis, median total management costs associated with IM midazolam, haloperidol, and olanzapine were Hong Kong dollar (HKD) 1958.9 (US dollar [USD] 251.1), HKD 2504.5 (USD 321.1), and HKD 2467.6 (USD 316.4), respectively. Agitation management labor cost was the main cost driver, whereas drug costs contributed the least. Midazolam dominated over haloperidol and olanzapine. Probabilistic sensitivity analyses supported that midazolam remains dominant > 95% of the time and revealed no clear difference in the cost-effectiveness of IM olanzapine versus haloperidol (incremental cost-effectiveness ratio 667.16; 95% confidence interval -770.89, 685.90)., Conclusions: IM midazolam is the dominant cost-effective treatment for the management of acute agitation in the A&E setting. IM olanzapine could be considered as an alternative to IM haloperidol given that there is no clear difference in cost-effectiveness, and their adverse effect profile should be considered when choosing between them., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Multisystem inflammatory syndrome in children (MIS-C) can occur in association with coronavirus disease 2019 (COVID-19). It is not easy to differentiate MIS-C from severe COVID-19 or Kawasaki disease based on symptoms. The aim of this study was to describe the clinical and laboratory characteristics of MIS-C., Patients and Methods: We searched PubMed/Medline for case series and reports of MIS-C published until June 20, 2020. From a total of nine articles involving 45 cases, various clinical and laboratory data were extracted. Each target case was evaluated by using different diagnostic criteria., Results: The average age at onset of MIS-C was 8.6 years. In 80% of cases, the age of patients ranged from 5 to 15 years. Fever (100%) and shock (82%) were the most common presenting symptoms. Sixty percent of cases met the diagnostic criteria for typical or atypical Kawasaki disease. Biomarkers indicative of inflammation, coagulopathy, or cardiac injury were characteristically elevated as follows: ferritin (mean: 1,061 ng/mL), CRP (217 mg/L), ESR (69 mm/hr), IL-6 (214.8 pg/mL), TNFα (63.4 pg/mL), D-dimer (3,220 ng/mL), PT (15.5 s), troponin I (1,006 ng/L), and BNP (12,150 pg/mL). Intravenous immunoglobulin was administered in all target cases, and inotropic agents were commonly used as well. No case of death was observed., Conclusions: This study demonstrated that MIS-C is a serious condition that presents with fever, rash, as well as cardiovascular and gastrointestinal symptoms. Although it is challenging to differentiate MIS-C from Kawasaki disease or severe COVID-19, initiation of appropriate treatments through early diagnosis is warranted.

Background and Purpose: Accurate radiologic prediction of cavernous sinus invasion by pituitary adenoma remains challenging. We aimed to assess whether 1-mm-slice-thickness MRI with deep learning-based reconstruction can better predict cavernous sinus invasion by pituitary adenoma preoperatively and to estimate the depth of invasion and degree of contact in relation to the carotid artery, compared with 3-mm-slice-thickness MRI., Materials and Methods: This single-institution, prospective study included 67 consecutive patients (mean age, 53 [SD, 12] years; 28 women), between January and August 2020, who underwent a combined contrast-enhanced T1-weighted imaging protocol of 1-mm-slice-thickness MRI + deep learning-based reconstruction and 3-mm-slice-thickness MRI. An expert neuroradiologist who was blinded to the imaging protocol determined cavernous sinus invasion using the modified Knosp classification on 1-mm-slice-thickness MRI + deep learning-based reconstruction and 3-mm-slice-thickness MRI, respectively. Reference standards were established by the consensus of radiologic, intraoperative, pathologic, and laboratory findings. The primary end point was the diagnostic performance of each imaging protocol, and the secondary end points included depth of invasion and degree of contact in relation to the carotid artery., Results: The diagnostic performance of 1-mm-slice-thickness MRI + deep learning-based reconstruction (area under the curve, 0.79; 95% CI, 0.69 - 0.89) in predicting cavernous sinus invasion by pituitary adenoma was higher than that of 3-mm-slice-thickness MRI (area under the curve, 0.61; 95% CI, 0.52-0.70; P  < .001). One-millimeter-slice-thickness MRI + deep learning-based reconstruction demonstrated greater depth of invasion by pituitary adenomas from the medial intercarotid line than 3-mm-slice-thickness MRI (4.07 versus 3.12 mm, P  < .001). A higher proportion of cases were in a greater degree of contact with the intracavernous ICA with 1-mm-slice-thickness MRI + deep learning-based reconstruction than with 3-mm-slice-thickness MRI (total encasement, 37.3% versus 13.4%, P  < .001; >270°, 38.8% versus 16.4%, P  < .001)., Conclusions: Compared with 3-mm-slice-thickness MRI, 1-mm-slice-thickness MRI + deep learning-based reconstruction showed a higher diagnostic performance in preoperatively predicting cavernous sinus invasion by pituitary adenomas and demonstrated a greater depth and degree of contact in relation to the carotid artery., (© 2022 by American Journal of Neuroradiology.)

Aim: To investigate the predictive value of integrated 2-[ 18 F]-fluoro-2-deoxy-d-glucose ( 18 F-FDG) positron-emission tomography/computed tomography (PET/CT) for the prediction of programmed death ligand 1 (PD-L1) expression in solid tumours via a systematic review and meta-analysis., Materials and Methods: The PubMed, Cochrane, and EMBASE databases, from the earliest available date of indexing through 31 October 2020, were searched for studies evaluating the diagnostic performance of 18 F-FDG PET/CT for prediction of PD-L1 expression in solid tumours other than lung cancer., Results: Across seven studies (473 patients), the pooled sensitivity for 18 F-FDG PET/CT was 0.75 (95% confidence interval [CI]: 0.65-0.82) without heterogeneity (I 2  = 47.2, p=0.08) and a pooled specificity of 0.73 (95% CI: 0.64-0.81) with heterogeneity (I 2  = 53.8, p=0.04). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 2.8 (95% CI: 2.1-3.7) and negative likelihood ratio (LR-) of 0.35 (95% CI: 0.26-0.47). The pooled diagnostic odds ratio (DOR) was 8 (95% CI: 5-13). Hierarchical summary receiver operating characteristic (ROC) curve and indicates that the area under the curve was 0.80 (95% CI: 0.77-0.84)., Conclusion: The current meta-analysis showed a moderate sensitivity and specificity of 18 F-FDG PET/CT for the prediction of PD-L1 expression in solid tumours. At present, the literature regarding the use of 18 F-FDG PET/CT for the prediction of PD-L1 expression in solid tumours still limited; thus, further large multicentre studies would be necessary to substantiate the diagnostic accuracy of 18 F-FDG PET/CT for prediction of PD-L1 expression in solid tumours., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Foreign bodies in the ear, nose and throat commonly necessitate emergency department visits., Method: This retrospective study was conducted on emergency department visits from January 2010 to December 2019 to determine characteristics and clinical prognoses of ENT patients. Patients were divided into three groups according to foreign-body entry route; patient characteristics and clinical findings were compared between groups., Results: Of 676 142 emergency department visits, 10 454 were because of ENT-related foreign bodies. The mean (± standard deviation) age of subjects was 24.0 (± 23.4) years, and 5176 patients were male (49.5 per cent). The most common entry route was the mouth (74.5 per cent). Most patients (97.1 per cent) were discharged after emergency treatment. Intensive care and in-hospital mortality occurred only in the mouth group., Conclusion: Clinical findings differ depending on foreign-body entry route. After emergency treatment, most patients were discharged; some cases presented serious complications.

We investigated the anti-obesity effect and the underlying mechanisms of action of human-derived Limosilactobacillus fermentum MG4231, MG4244, and their combination, in high-fat diet-induced obese mice. Administration of the Limosilactobacillus strains decreased body weight gain, liver and adipose tissue weight, and glucose tolerance. Serum levels of total cholesterol, low-density lipoprotein-cholesterol, and leptin were reduced, while adiponectin increased. The administration of Limosilactobacillus strains improved the histopathological features of liver tissue, such as hepatic atrophy and inflammatory penetration, and significantly reduced the content of triglyceride in the liver. Limosilactobacillus administration discovered a significant reduction in the size of the adipocytes in the epididymal tissue. Limosilactobacillus treatment significantly reduced the expression of important regulators in lipid metabolism, including peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, fatty acid synthase (FAS), adipocyte-protein 2, and lipoprotein lipase in the epididymal tissue. Also, Limosilactobacillus lowered sterol regulatory element-binding protein 1-c and FAS in the liver tissue. Such changes in the expression of these regulators in both liver and epididymis tissue were caused by Limosilactobacillus upregulating phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase. Therefore, we suggest that the use of the combination of L. fermentum MG4231 and MG4244, as probiotics could effectively inhibit adipogenesis and lipogenesis from preventing obesity.

Background: Disproportionately enlarged subarachnoid space hydrocephalus is a specific radiologic marker for idiopathic normal pressure hydrocephalus. However, controversy exists regarding the prognostic utility of disproportionately enlarged subarachnoid space hydrocephalus., Purpose: Our aim was to evaluate the prevalence of disproportionately enlarged subarachnoid space hydrocephalus in idiopathic normal pressure hydrocephalus and its predictive utility regarding prognosis in patients treated with ventriculoperitoneal shunt surgery., Data Sources: We used MEDLINE and EMBASE databases., Study Selection: We searched for studies that reported the prevalence or the diagnostic performance of disproportionately enlarged subarachnoid space hydrocephalus in predicting treatment response., Data Analysis: The pooled prevalence of disproportionately enlarged subarachnoid space hydrocephalus was obtained. Pooled sensitivity, specificity, and area under the curve of disproportionately enlarged subarachnoid space hydrocephalus to predict treatment response were obtained. Subgroup and sensitivity analyses were performed to explain heterogeneity among the studies., Data Synthesis: Ten articles with 812 patients were included. The pooled prevalence of disproportionately enlarged subarachnoid space hydrocephalus in idiopathic normal pressure hydrocephalus was 44% (95% CI, 34%-54%). The pooled prevalence of disproportionately enlarged subarachnoid space hydrocephalus was higher in the studies using the second edition of the Japanese Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus compared with the studies using the international guidelines without statistical significance (52% versus 43%, P = .38). The pooled sensitivity and specificity of disproportionately enlarged subarachnoid space hydrocephalus for prediction of treatment response were 59% (95% CI, 38%-77%) and 66% (95% CI, 57%-74%), respectively, with an area under the curve of 0.67 (95% CI, 0.63-0.71)., Limitations: The lack of an established method for assessing disproportionately enlarged subarachnoid space hydrocephalus using brain MR imaging served as an important cause of the heterogeneity., Conclusions: Our meta-analysis demonstrated a relatively low prevalence of disproportionately enlarged subarachnoid space hydrocephalus in idiopathic normal pressure hydrocephalus and a poor diagnostic performance for treatment response., (© 2021 by American Journal of Neuroradiology.)

Background: The present study examined whether mitochondrial DNA copy number (mtDNAcn) and telomere length - key markers of cellular aging - were altered in male and female participants with obsessive-compulsive disorder (OCD) compared to healthy controls. We also tested for associations between these alterations and OCD-related clinical features and inflammatory index., Methods: A total of 235 patients with OCD (38.7% female) and 234 healthy controls (41.5% female) were included. We quantified whole-blood mtDNAcn and leukocyte telomere length using quantitative polymerase chain reaction. We also calculated the neutrophil-to-lymphocyte ratio from complete blood cell counts., Results: Multivariate analysis of covariance showed that OCD status had a significant overall effect on cellular aging markers in men (Wilks λ = 0.889, F2,275 = 17.13, p < 0.001) and women (Wilks λ = 0.742, F2,182 = 31.61, p < 0.001) after controlling for age, body mass index and childhood trauma. In post-hoc comparisons, men with OCD had lower mtDNAcn than controls (p < 0.001), but we found no between-group difference for telomere length (p = 0.55). Women with OCD had a significantly lower mtDNAcn (p < 0.001) and shortened telomere length (p = 0.023) compared to controls. Moreover, the lower mtDNAcn shown in the OCD group was significantly correlated with an increase in systemic inflammation for both sexes, as measured by neutrophil-to-lymphocyte ratio., Limitations: The present cross-sectional design did not allow us to infer a causal relationship between OCD disease status and cellular aging markers., Conclusion: The present study is, to our knowledge, the first to demonstrate alterations in mtDNAcn and telomere shortening in OCD. These results suggest that aging-associated molecular mechanisms may be important in the pathophysiology of OCD., Competing Interests: None declared., (© 2021 CMA Joule Inc. or its licensors.)

Aim: This study was purposed to evaluate release of nickel and chromium ions and methyl methacrylate (MMA) monomers from functional appliances and their possible health effects., Materials and Methods: Study design: Twin-block appliances and Bionators were immersed in artificial saliva and kept in a thermal incubator. Control group was established as artificial saliva without appliances. Artificial saliva was analysed after 7 days, 30 days and 90 days. Inductively coupled plasma mass spectrometry and gas chromatography-mass spectrometry was used for detection of nickel and chromium ions and MMA monomers. MTT assays and cytokine array were performed., Statistics: One way ANOVA with Tukey test and Dunnett's T3 for post-hoc analysis was used for evaluation of time-dependent changes and independent t-test was used for evaluation of MTT assay results., Results: The results revealed that metal ions and MMA monomers are released from the appliances. Metal ion detection pattern was irregular and could not be analysed. Twin-block group showed significantly larger amount of MMA release. MTT assay revealed statistically significant but minimally reduced cellular activity on Bionator and twin-block groups compared to control groups. Cytokine array showed no or less inflammatory cytokine release on Bionator and twin-block groups., Conclusion: MMA monomer release was confirmed but the cytotoxic effect of functional appliance material release is minimal or negligible. General toxicity of the functional appliance from the MMA monomer release is likely to be minimal or negligible.

Background: Current treatment options for peripheral T-cell lymphomas (PTCLs) in the relapsed/refractory setting are limited and demonstrate modest response rates with rare achievement of complete response (CR)., Patients and Methods: This phase I/II study (NCT03052933) investigated the safety and efficacy of copanlisib, a phosphatidylinositol 3-kinase-α/-δ inhibitor, in combination with gemcitabine in 28 patients with relapsed/refractory PTCL. Patients received escalating doses of intravenous copanlisib on days 1, 8, and 15, administered concomitantly with fixed-dose gemcitabine (1000 mg/m 2 on days 1 and 8) in 28-day cycles., Results: Dose-limiting toxicity was not observed in the dose-escalation phase and 60 mg copanlisib was selected for phase II evaluation. Twenty-five patients were enrolled in phase II of the study. Frequent grade ≥3 adverse events (AEs) included transient hyperglycemia (57%), neutropenia (45%), thrombocytopenia, (37%), and transient hypertension (19%). However, AEs were manageable, and none were fatal. The overall response rate was 72% with a CR rate of 32%. Median duration of response was 8.2 months, progression-free survival was 6.9 months, and median overall survival was not reached. Combination treatment produced a greater CR rate in patients with angioimmunoblastic T-cell lymphoma than those with PTCL-not otherwise specified (55.6% versus 15.4%, respectively, P = 0.074) and progression-free survival was significantly longer (13.0 versus 5.1 months, respectively, P = 0.024). In an exploratory gene mutation analysis of 24 tumor samples, TSC2 mutation was present in 25% of patients and occurred exclusively in responders., Conclusion: The combination of copanlisib and gemcitabine is a safe and effective treatment option in relapsed/refractory PTCLs and represents an important new option for therapy in this rare group of patients., Competing Interests: Disclosure D-HY reports receipt of institutional research funding from Bayer HealthCare Pharmaceuticals, Inc. All remaining authors have declared no conflicts of interest., (Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Background: The safety and effectiveness of intramuscular olanzapine or haloperidol compared to midazolam as the initial pharmacological treatment for acute agitation in emergency departments (EDs) has not been evaluated., Methods: A pragmatic, randomised, double-blind, active-controlled trial was conducted from December 2014 to September 2019, in six Hong Kong EDs. Patients (aged 18-75 years) with undifferentiated acute agitation requiring parenteral sedation were randomised to 5 mg intramuscular midazolam ( n  = 56), olanzapine ( n  = 54), or haloperidol ( n  = 57). Primary outcomes were time to adequate sedation and proportion of patients who achieved adequate sedation at each follow-up interval. Sedation levels were measured on a 6-level validated scale (ClinicalTrials.gov Identifier: NCT02380118)., Findings: Of 206 patients randomised, 167 (mean age, 42 years; 98 [58·7%] male) were analysed. Median time to sedation for IM midazolam, olanzapine, and haloperidol was 8·5 (IQR 8·0), 11·5 (IQR 30·0), and 23·0 (IQR 21·0) min, respectively. At 60 min, similar proportions of patients were adequately sedated (98%, 87%, and 97%). There were statistically significant differences for time to sedation with midazolam compared to olanzapine ( p  = 0·03) and haloperidol ( p  = 0·002). Adverse event rates were similar across the three arms. Dystonia ( n  = 1) and cardiac arrest ( n  = 1) were reported in the haloperidol group., Interpretation: Midazolam resulted in faster sedation in patients with undifferentiated agitation in the emergency setting compared to olanzapine and haloperidol. Midazolam and olanzapine are preferred over haloperidol's slower time to sedation and potential for cardiovascular and extrapyramidal side effects., Funding: Research Grants Council, Hong Kong., Competing Interests: All authors declare that no other support has been received from any organisation for the submitted work; no other financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted study. Outside the submitted work, EWC has received honorarium from the Hospital Authority, research grants from Narcotics Division of the Security Bureau of HKSAR, National Health and Medical Research Council (NHMRC, Australia), National Natural Science Foundation of China (NSFC), Research Fund Secretariat of the Food and Health Bureau (HMRF, HKSAR), Research Grants Council (RGC, HKSAR), Wellcome Trust; Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, Pfizer, RGA and Takeda outside the submitted work.. KSJL reports personal fees from MSD China, outside the submitted work. ICKW received grants from the Research Grants Council (RGC, Hong Kong), Innovative Medicines Initiative (IMI), Shire, Janssen-Cilag, Eli-Lily, Pfizer, Bayer, European Union FP7 program. ICKW is a member of the National Institute for Health and Clinical Excellence (NICE) ADHD Guideline Group, the British Association for Psychopharmacology ADHD guideline group, and advisor to Shire., (© 2021 The Authors.)

Objectives: Uremic pruritus is common in patients with chronic kidney disease (CKD). The retention of uremic solutes is thought to be associated with uremic pruritus. Meanwhile, activation of protease-activated receptor-2 (PAR-2) has been suggested to play an important role in pruritus. The present study was performed to investigate the effects of uremic solutes on the expression of PAR-2 in the skin., Methods: Indoxyl sulfate (IS), p -cresol (PC), and uremic sera from CKD patients were used to stimulate PAR-2 expression in normal human epidermal keratinocytes (NHEKs). Also, NHEKs were additionally pretreated with soybean trypsin inhibitor to evaluate its inhibitory effect on PAR-2 expression. Patterns of cutaneous PAR-2 expression were investigated in skin samples from five CKD patients and CKD mice., Results: In NHEKs, IS, PC, and sera from CKD patients significantly induced PAR-2 mRNA and protein expression. Soybean trypsin inhibitor significantly decreased PAR-2 mRNA and protein expression in NHEKs treated with IS, PC, and CKD sera. NHEKs treated with IS and PC exhibited significant increases in protease activity. Skin from both CKD patients and mice exhibited marked upregulation of PAR-2 expression compared to control skin., Conclusions: Results from the present study suggest that uremic solutes either directly or indirectly affect PAR-2 expression in the skin of CKD subjects, potentially playing an important role in the pathogenesis of uremic pruritus.

Background and Purpose: Limited evidence has suggested that a deep learning automatic brain segmentation and classification method, based on T1-weighted brain MR images, can predict Alzheimer disease. Our aim was to develop and validate a deep learning-based automatic brain segmentation and classification algorithm for the diagnosis of Alzheimer disease using 3D T1-weighted brain MR images., Materials and Methods: A deep learning-based algorithm was developed using a dataset of T1-weighted brain MR images in consecutive patients with Alzheimer disease and mild cognitive impairment. We developed a 2-step algorithm using a convolutional neural network to perform brain parcellation followed by 3 classifier techniques including XGBoost for disease prediction. All classification experiments were performed using 5-fold cross-validation. The diagnostic performance of the XGBoost method was compared with logistic regression and a linear Support Vector Machine by calculating their areas under the curve for differentiating Alzheimer disease from mild cognitive impairment and mild cognitive impairment from healthy controls., Results: In a total of 4 datasets, 1099, 212, 711, and 705 eligible patients were included. Compared with the linear Support Vector Machine and logistic regression, XGBoost significantly improved the prediction of Alzheimer disease ( P  < .001). In terms of differentiating Alzheimer disease from mild cognitive impairment, the 3 algorithms resulted in areas under the curve of 0.758-0.825. XGBoost had a sensitivity of 68% and a specificity of 70%. In terms of differentiating mild cognitive impairment from the healthy control group, the 3 algorithms resulted in areas under the curve of 0.668-0.870. XGBoost had a sensitivity of 79% and a specificity of 80%., Conclusions: The deep learning-based automatic brain segmentation and classification algorithm allowed an accurate diagnosis of Alzheimer disease using T1-weighted brain MR images. The widespread availability of T1-weighted brain MR imaging suggests that this algorithm is a promising and widely applicable method for predicting Alzheimer disease., (© 2020 by American Journal of Neuroradiology.)

Background: Neuroleptic malignant syndrome (NMS) is a rare and acute adverse drug reaction associated with antipsychotic therapy. However, few data on the risk and epidemiology of NMS are available., Objectives: The aim of this study was to ascertain the incidence risk and all-cause mortality of NMS associated with antipsychotic use, and to assess the association of recent antipsychotic exposure and NMS., Methods: We did a population-based study using data from the Hong Kong Hospital Authority's Clinical Data Analysis and Reporting System database. Cases had a first diagnosis of NMS between 1 January 2004 and 30 November 2017. A case-crossover analysis was used to compare antipsychotic exposure 30 days before the diagnosis of NMS (index date) and a reference period 91-120 days before the index date. To adjust for potential time trends in antipsychotic exposure, we sampled from cases to match current cases and future cases, and further adjusted for select medications and acute medical conditions., Results: 297,647 patients were prescribed antipsychotics, and the incidence risk of NMS was 0.11%. Of the 336 cases included in the case-crossover analysis, 20 (6%) died within 30 days after the index date; only one case had NMS recorded as the primary cause of death. When compared with the reference period, cases were more frequently prescribed multiple antipsychotics (15.8% vs 26.8%; standardized mean difference [SMD] 0.27) and short-acting injectable antipsychotics (3.6% vs 13.7%; SMD 0.37) during the 30 days prior to the diagnosis of NMS. Odds ratios for antipsychotic exposure in the case-crossover, case-crossover adjusted for time trend, and case-crossover adjusted for time trend and potential confounders analysis were 8.00 (95% confidence interval 3.42-18.69), 5.88 (2.46-14.04), and 4.77 (1.95-11.66)., Conclusions: Our results suggest that recent use of antipsychotics is associated with NMS. Although a case-only design inherently controls for confounding by time-invariant factors, residual confounding by acute medical conditions with similar presentations to NMS cannot be fully excluded.

In a 2018 survey, U.S. Food and Drug Administration (FDA) identified microbial contamination in 42 (49%) of 85 unopened tattoo and permanent makeup (PMU) inks purchased from 13 manufacturers in the US between November 2015 and April 2016. To confirm the results of our previous survey, we evaluated the level of microbial contamination in an additional 27 samples from 10 manufacturers from September 2017 to December 2017, including 21 unopened tattoo and PMU inks which were selected based on our previous survey results and 6 ink diluents that were not previously analysed. Aerobic plate count and enrichment culture methods from the FDA's Bacteriological Analytical Manual revealed 11 (52%) out of 21 inks, from six manufacturers, were contaminated with micro-organisms, with contamination levels up to 3·6 × 10 8  CFU per gram, consistent with our previous survey results. We identified 25 bacterial strains belonging to nine genera and 19 species. Strains of Bacillus sp. (11 strains, 44%) were dominant, followed by Paenibacillus sp. (5 strains, 20%). Clinically relevant strains, such as Kocuria rhizophila and Oligella ureolytica, were also identified, as similar to the findings in our previous survey. No microbial contamination was detected in any of the six ink diluents., (© 2020 The Society for Applied Microbiology.)

Introduction: The affinity of hemoglobin for carbon monoxide (CO) is 250 times higher than that for oxygen. Therefore, exposure to CO leads to a reduction in oxygen delivery to tissues, resulting in cellular hypoxia and affects whole body. Hepatic dysfunction in critically ill patients is related to poor outcome, but few studies have been conducted on this subject that occurs after CO poisoning. This study aims to conduct a study of hepatic injury in CO-poisoned patients in emergency department (ED)., Methods: This retrospective observational study collected data from patients who were diagnosed with acute CO poisoning at the ED between June 2011 and May 2018 in local tertiary-care hospital (Wonju, Republic of Korea). The primary end point of this study was to describe the prevalence of hepatic injury in acute CO-poisoned patients. The secondary goals were to investigate the recovery trends of hepatic injury caused by acute CO poisoning and the relation to neurologic outcome and mortality., Results: Eight hundred ninety-four patients were enrolled in the final analysis, 128 cases (14.3%) had subclinical hepatic injury and 15 (1.6%) cases had hepatic injury. The relationship with mortality was not statistically significant. However, the hepatic injury group was higher incidence of intensive care unit admission and other complications. Patients in the hepatic injury group recovered through conservative management within 1 week of being admitted to the ED., Conclusions: While CO-induced hepatic injury is relatively uncommon, it can be associated with complications and poor neurologic outcome. However, CO-induced hepatic injury was not found to have a statistically significant effect on mortality rate.

Background and Purpose: Hearing loss (HL) is one of the most influential risk factors of dementia in older adults. However, its potential association with neurodegeneration is not well established. The association between HL and cortical thickness in cognitively normal older adults was evaluated., Methods: In all, 982 cognitively normal older adults (age ≥65 years) were identified from the Health Promotion Center at the Samsung Medical Center from September 2008 to December 2014. The participants underwent pure-tone audiometry and brain magnetic resonance imaging. HL was evaluated according to a four-frequency (0.5, 1, 2, 4 kHz) pure-tone average. Participants were divided into three groups according to pure-tone average (normal hearing ≤15 dB, minimal HL 16-25 dB, mild-to-severe HL >25 dB). Cortical thickness in the HL groups was compared with that of the normal hearing group., Results: In women, right ear HL was associated with cortical thinning: the minimal HL group showed cortical thinning in the left frontal and bilateral occipital areas and the mild-to-severe HL group showed cortical thinning in the bilateral frontal, right temporal and bilateral occipital areas compared to the normal hearing group. In men, there was no significant association between HL on either side and cortical thickness., Conclusion: In older women, right ear HL is associated with neurodegeneration even in a cognitively normal state. Therefore, managing HL especially in older women may be an effective strategy for dementia prevention., (© 2020 European Academy of Neurology.)

Transoral endoscopic thyroid surgery (TOET) is a new, minimally-invasive approach that does not result in a scar in the anterior neck. To prevent infection of the surgical site from oral cavity flora into the thyroidectomy area, postoperative antibiotics are generally given orally for 3-7 days. However, there is no clinical evidence to support this approach. This study was an open-label, randomised, controlled trial to evaluate the clinical usefulness of postoperative antibiotics given orally to patients having TOET. Patients were randomly assigned to receive amoxicillin-clavulanate 625mg orally three times a day for a week after operation (treated group) or no antibiotics (untreated group). Fifty patients - 25 treated and 25 untreated - were enrolled. Maximum body temperature, pulse rate, white blood cell count, and C-reactive protein concentrations did not differ between the two groups. Evaluation of the surgical site showed no significant differences between them. Seven patients in the treated group developed nausea, vomiting, and diarrhoea compared with none in the untreated group. The results suggest that postoperative oral antibiotics are not essential after TOET. Large-scale prospective series are required to confirm this finding., (Copyright © 2020 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Haloperidol remains a frequently prescribed first-generation antipsychotic. However, haloperidol-associated mortality risk by all causes, cardiovascular disease (CVD), and pneumonia compared with other antipsychotics is unknown., Objective: This study investigated the mortality risk associated with long-term haloperidol treatment versus that with other antipsychotics., Methods: We identified incident antipsychotic users from 2004 to 2014 in the Clinical Data Analysis and Reporting System (CDARS), a population-based clinical database managed by the Hong Kong Hospital Authority. We included patients who were aged ≥ 18 and received antipsychotics for any indication apart from terminal illnesses or management of acute behavioural disturbance. Patients on haloperidol and other antipsychotic agents (risperidone, quetiapine, olanzapine, chlorpromazine, aripiprazole, sulpiride, amisulpride, or trifluoperazine) were matched by propensity score. Hazard ratios (HRs) for all-cause mortality and death due to CVD and pneumonia were estimated with 95% confidence intervals (CIs) using a Cox proportional hazards model., Results: In total, 136,593 users of antipsychotics were included. During a mean follow-up of 3.2 years, the incidence of all-cause mortality ranged from 186.8/1000 person-years for haloperidol to 10.4/1000 person-years for trifluoperazine. The risk of all-cause mortality was lower with non-haloperidol antipsychotics than with haloperidol, with HRs ranging from 0.68 (95% CI 0.64-0.72 [chlorpromazine]) to 0.43 (95% CI 0.36-0.53 [trifluoperazine]). Risperidone, quetiapine, sulpiride, chlorpromazine, aripiprazole, and trifluoperazine were associated with a significantly lower risk of pneumonia-related mortality. A significantly lower risk of CVD mortality was observed for risperidone, sulpiride, chlorpromazine, and quetiapine., Conclusion: Haloperidol was associated with increased overall mortality when compared with other antipsychotics in long-term follow-up. Treatment with haloperidol should be carefully considered, especially in older patients and patients at risk of CVD or pneumonia, since the risk of death appears to be lower with non-haloperidol agents.

Background: Melatonin is widely available either on prescription for the treatment of sleep disorders or as an over-the-counter dietary supplement. Melatonin has also recently been licensed in the UK for the short-term treatment of jetlag. Little is known about the potential for adverse events (AEs), in particular AEs resulting from long-term use. Concern has been raised over the possible risks of exposure in certain populations including pre-adolescent children and patients with epilepsy or asthma., Objectives: The aim of this systematic review was to assess the evidence for AEs associated with short-term and longer-term melatonin treatment for sleep disorders., Methods: A literature search of the PubMed/Medline database and Google Scholar was conducted to identify randomised, placebo-controlled trials (RCTs) of exogenous melatonin administered for primary or secondary sleep disorders. Studies were included if they reported on both the types and frequencies of AEs. Studies of pre-term infants, studies of < 1 week in duration or involving single doses of melatonin and studies in languages other than English were excluded. Findings from open-label studies that raised concerns relating to AE reports in patients were also examined. Studies were assessed for quality of reporting against the Consolidated Standards of Reporting Trials (CONSORT) checklist and for risk of bias against the Cochrane Collaboration risk-of-bias criteria., Results: 37 RCTs met criteria for inclusion. Daily melatonin doses ranged from 0.15 mg to 12 mg. Subjects were monitored for up to 29 weeks, but most studies were of much shorter duration (4 weeks or less). The most frequently reported AEs were daytime sleepiness (1.66%), headache (0.74%), other sleep-related AEs (0.74%), dizziness (0.74%) and hypothermia (0.62%). Very few AEs considered to be serious or of clinical significance were reported. These included agitation, fatigue, mood swings, nightmares, skin irritation and palpitations. Most AEs either resolved spontaneously within a few days with no adjustment in melatonin, or immediately upon withdrawal of treatment. Melatonin was generally regarded as safe and well tolerated. Many studies predated publication of the CONSORT checklist and consequently did not conform closely to the guidelines. Similarly, only eight studies were judged 'good' overall with respect to the Cochrane risk-of-bias criteria. Of the remaining papers, 16 were considered 'fair' and 13 'poor' but publication of almost half of the papers preceded that of the earliest version of the guidelines., Conclusion: Few, generally mild to moderate, AEs were associated with exogenous melatonin. No AEs that were life threatening or of major clinical significance were identified. The scarcity of evidence from long-term RCTs, however, limits the conclusions regarding the safety of continuous melatonin therapy over extended periods. There are insufficient robust data to allow a meaningful appraisal of concerns that melatonin may result in more clinically significant adverse effects in potentially at-risk populations. Future studies should be designed to comply with appropriate quality standards for RCTs, which most past studies have not.

Aim: To investigate the diagnostic performance of 18 F-fluciclovine positron-emission tomography (PET) or combined PET and computed tomography (PET/CT) for diagnosis of primary cancer, preoperative lymph node (LN) staging, and detection of recurrent disease of prostate cancer (PCa) through a systematic review and meta-analysis., Materials and Methods: The PubMed and EMBASE databases were searched from the earliest available date of indexing through 31 December 2018, for studies evaluating the diagnostic performance of 18 F-fluciclovine PET or PET/CT for the management of PCa patients. The sensitivities, specificities, and positive and negative likelihood ratios (LR+ and LR-) across the studies were calculated and summary receiver operating characteristic curves were constructed., Results: Across 13 studies (563 patients), the pooled sensitivity for 18 F-fluciclovine PET or PET/CT for diagnosis of primary PCa was 0.87 (95% confidence interval [CI]: 0.77-0.93) and a pooled specificity of 0.84 (95% CI: 0.68-0.93). For LN staging, the pooled sensitivity was 0.56 (95% CI: 0.37-0.74) and a pooled specificity of 0.98 (95% CI: 0.88-1.00). For detection of recurrent disease, the pooled sensitivity was 0.79 (95% CI: 0.60-0.91) and a pooled specificity of 0.69 (95% CI: 0.59-0.77). In meta-regression analysis, no definite variable was the source of the study heterogeneity., Conclusion: The current meta-analysis showed the moderate sensitivity and specificity of 18 F-fluciclovine PET or PET/CT for the diagnosis of primary cancer, preoperative LN staging, and detection of recurrent PCa. Further large multicentre studies will be necessary to substantiate the diagnostic accuracy of 18 F-fluciclovine PET/CT for management of PCa patients., (Copyright © 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Metastatic breast cancer is an extremely complex disease with limited treatment options due to the lack of information about the major characteristics of metastatic disease. There is an urgent need, therefore, to understand the changes in cellular complexity and dynamics that occur during metastatic progression. In the current study, we analyzed the cellular and molecular differences between primary tumors and paired lung metastases using a syngeneic p53-null mammary tumor model of basal-like breast cancer. Distinct subpopulations driven by the Wnt- and/or STAT3 signaling pathways were detected in vivo using a lentiviral Wnt- and STAT3 signaling reporter system. A significant increase in the overlapping populations driven by both the Wnt- and STAT3 signaling pathways was observed in the lung metastases as compared to the primary tumors. Furthermore, the overlapping populations showed a higher metastatic potential relative to the other populations and pharmacological inhibition of both signaling pathways was shown to markedly reduce the metastatic lesions in established lung metastases. An analysis of the unique molecular features of the lung metastases revealed a significant association with immune response signatures. Specifically, Foxp3 gene expression was markedly increased and elevated levels of Foxp3 + Treg cells were detected in close proximity to lung metastases. Collectively, these studies illustrate the importance of analyzing intratumoral heterogeneity, changes in population dynamics, and the immune microenvironment during metastatic progression.

We present a case of an undifferentiated subtype of non-keratinizing squamous cell carcinoma (NK-SCC) with sarcomatoid features in the nasopharynx in a 69-year-old man who was difficult to diagnose due to spindle-shaped malignant cells. He was admitted because of a right nasal obstruction and right headache, and imaging revealed a heterogeneously enhanced irregularly shaped mass at the nasopharynx. Histopathologically, the tumour was partially organised, and the tumour cells were epithelioid or spindle-shaped. Initially, we erroneously diagnosed the tumour as an angiosarcoma owing to its false-negative immunoreaction for cytokeratins and a mistaken interpretation for CD31. After in situ hybridization for Epstein-Barr virus was positive, a consultation and additional immunostaining (including re-staining for cytokeratin with varying dilutions) were performed, and the diagnosis was revised to NK-SCC with sarcomatoid features. We believe that sarcomatoid features may be observed in nasopharyngeal carcinoma and in this case, immunostaining using various epithelial markers is necessary and careful attention should be paid to the interpretation of immunostaining.

Background: Alcohol and obesity synergise to increase the risk of liver-related mortality. We examined the influence of adiposity on clinical outcomes in alcoholic hepatitis (AH) and the underlying inflammatory crosstalk between adipose tissue (AT) and the liver., Methods: A cohort of 233 patients with AH from the UK and USA provided data to analyse the effects of obesity in AH. Body mass index was corrected for the severity of ascites, termed cBMI. Inflammatory and metabolic profiling was undertaken by proteome analysis of human serum samples. The effect of alcohol on adipose tissue and CXCL11 expression was studied in 3 T3-derived adipocytes and in mice using the high-fat diet-plus-binge ethanol model., Findings: Obesity was common amongst patients with AH, seen in 19% of individuals. Obesity (HR 2.22, 95%CI 1.1-4.3, p = .022) and underweight (HR 2.38, 1.00-5.6, p = .049) were independently associated with mortality at 3 months. Proteome analysis demonstrated multiple metabolic and inflammatory factors differentially expressed in obese AH verse lean AH, with CXCL11 being the most elevated factor in obese AH. In vitro analysis of cultured adipocytes and in vivo analysis of mouse models showed that alcohol induced CXCL11 expression in AT, but not in liver., Interpretation: Obesity is common in AH and associated with a greater than two-fold increase in short-term mortality. Obese AH is associated with a different inflammatory phenotype, with the greatest elevation in CXCL11. These data confirm that adiposity is clinically important in acute alcohol-related liver disease and illustrate the adipose-liver inflammatory axis in AH. FUND: This work was supported in part by an EASL Sheila Sherlock Physician Scientist Fellowship. The funder played no role in gathering or analysing data or writing the manuscript. This paper presents independent research supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care., (Copyright © 2019. Published by Elsevier B.V.)

The plasma n-3 fatty acid level was 26.2% lower in patients with osteoporotic hip fracture than in those with osteoarthritis. In all patients, n-3 fatty acid was positively associated with bone mineral density and inversely associated with tartrate-resistant acid phosphatase-5b level in bone marrow aspirates, reflecting the bone microenvironment., Introduction: Despite the potential beneficial role of n-3 fatty acid (FA) on bone metabolism, the specific mechanisms underlying these effects in humans remain unclear. Here, we assessed whether the plasma n-3 level, as an objective indicator of its status, is associated with osteoporosis-related phenotypes and bone-related markers in human bone marrow (BM) samples., Methods: This was a case-control and cross-sectional study conducted in a clinical unit. n-3 FA in the blood and bone biochemical markers in the BM aspirates were measured by gas chromatography/mass spectrometry and immunoassay, respectively. BM fluids were collected from 72 patients who underwent hip surgery because of either osteoporotic hip fracture (HF; n = 28) or osteoarthritis (n = 44)., Results: After adjusting for confounders, patients with HF had 26.2% lower plasma n-3 levels than those with osteoarthritis (P = 0.006), and each standard deviation increment in plasma n-3 was associated with a multivariate-adjusted odds ratio of 0.40 for osteoporotic HF (P = 0.010). In multivariate analyses including all patients, a higher plasma n-3 level was associated with higher bone mass at the lumbar spine (β = 0.615, P = 0.002) and total femur (β = 0.244, P = 0.045). Interestingly, the plasma n-3 level was inversely associated with the tartrate-resistant acid phosphatase-5b level (β = - 0.633, P = 0.023), but not with the bone-specific alkaline phosphatase level, in BM aspirates., Conclusions: These findings provide clinical evidence that n-3 FA is a potential inhibitor of osteoclastogenesis that favors human bone health.

Background: Adequate kidney donor management after donation is increasingly emphasized due to concerns of renal function impairment after nephrectomy with increasing life expectancy. In this study, the clinical impact of a protocolized kidney donor follow-up system by nephrologists was evaluated., Methods: A total of 427 living kidney donors underwent nephrectomy from January 2010 to December 2014 and were followed for at least 2 years at the Samsung Medical Center. Donors were followed-up by nephrologists after the establishment of a donor clinic with systemized protocols in January 2013. The primary outcomes were incidence of post-donation low estimated glomerular filtration rate (eGFR) and renal function adaptability. Secondary outcomes were changes in compliance and incidence of hyperuricemia and microalbuminuria., Results: The patients were divided into 2 groups according to the time of nephrectomy: the pre-donor clinic period (n = 182) and the donor clinic period (n = 172). Preoperative eGFR in patients in the pre-donor clinic period was higher than that in patients in the donor clinic period. After donation, poor renal adaptation was less frequent in the donor clinic period compared to the pre-donor clinic period. Low eGFR tended to be less common during the donor clinic period. Shorter mean outpatient clinic visit intervals with more visits within 6 months after donation and earlier detection of de novo hyperuricemia were found during the donor clinic period., Conclusion: A protocolized donor clinic run by nephrologists may improve post-nephrectomy renal outcomes and compliance and facilitate better management of potential risk factors of chronic kidney disease in donors., (Copyright © 2019 Elsevier Inc. All rights reserved.)

scFv-BM3 is a single-chain variable fragment (scFv) against aflatoxin B 1 (AFB 1 ) engineered by affinity maturation and site-directed mutagenesis, and thus has a 31-fold higher affinity than its wild-type. To apply scFv-BM3 to immunological detection of AFB 1 , periplasmic expression in Escherichia coli was attempted to produce a functional form of scFv-BM3. scFv-BM3 accumulated as inactive aggregates in the cells. However, it was found that scFv-BM3 secreted into the culture medium had binding activity to AFB 1 . Expression conditions for scFv-BM3 were further manipulated to enhance secretion into the culture medium. This extracellular secretion of functional scFv-BM3 was significantly improved by supplementation with Triton X-100 and optimization of expression conditions. The scFv-BM3 purified from the culture medium exhibited a typical antiparallel β-sheet structure and adopted a proper conformation to bind AFB 1 with high affinity and specificity in various biophysical and biochemical analyses. SIGNIFICANCE AND IMPACT OF THE STUDY: Single-chain variable fragments (scFvs) are recombinant antibodies that are difficult to produce as a functional form in Escherichia coli. This study demonstrates the production of functional scFvs against aflatoxin B 1 (AFB 1 ) (scFv-BM3) using Escherichia coli by extracellular secretion. While periplasmic expression of scFv-BM3 resulted in formation of inactive aggregates in E. coli, the scFv-BM3 secreted into the culture medium adopted a properly folded structure for specific binding to AFB 1 . This study promotes the application of functional scFv-BM3 to the immunological detection of AFB 1 in biotechnology fields., (© 2018 The Society for Applied Microbiology.)

The rate of mortality from dapsone poisoning is high because of the long absorption half-life of dapsone. This study aimed to evaluate the usefulness of the sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) scoring systems for the early prediction of mortality in patients with dapsone poisoning. This is a retrospective and observational study of consecutive patients diagnosed with dapsone poisoning. The SOFA and APACHE II scores were obtained within the first 24 h of admission. Patients were divided into survivor and non-survivor groups. In total, 106 patients were included. The SOFA scores of the survivor and non-survivor groups were 1 (0-8) and 4 (1-10), respectively ( p < 0.001). The APACHE II scores of the survivor and non-survivor groups were 9 (1-25) and 14 (3-23), respectively ( p < 0.001). Based on these scores and in-hospital mortality cases, the standardized mortality ratios for the APACHE II and SOFA were 1.00 (95% confidence interval (CI): 0.64-1.48) and 1.00 (95% CI: 0.64-1.49), respectively. In the model adjusted for clinically important variables and variables with significant differences between the survivor and non-survivor groups, the area under the curve of the SOFA (0.907; 95% CI: 0.834-0.955) was significantly higher than that of the APACHE II (0.793; 95% CI: 0.703-0.867) ( p = 0.008). The SOFA and APACHE II score systems had good discrimination and satisfactory calibration performance in patients with dapsone poisoning. However, the SOFA score was a more useful method in predicting mortality than the APACHE II score.

Background and Aims:: This study was designed to analyze the feasibility of laparoscopic right posterior sectionectomy compared to laparoscopic right hemihepatectomy in patients with hepatocellular carcinoma located in the posterior segments., Material and Methods:: The study included patients who underwent either laparoscopic right posterior sectionectomy or laparoscopic right hemihepatectomy for hepatocellular carcinoma located in segment 6 or 7 from January 2009 to December 2016 at Samsung Medical Center. After 1:1 propensity score matching, patient baseline characteristics and operative and postoperative outcomes were compared between the two groups. Disease-free survival and overall survival were compared using Kaplan-Meier log-rank test., Results:: Among 61 patients with laparoscopic right posterior sectionectomy and 37 patients with laparoscopic right hemihepatectomy, 30 patients from each group were analyzed after propensity score matching. After matching, baseline characteristics of the two groups were similar including tumor size (3.4 ± 1.2 cm in laparoscopic right posterior sectionectomy vs 3.7 ± 2.1 cm in laparoscopic right hemihepatectomy, P = 0.483); differences were significant before matching (3.1 ± 1.3 cm in laparoscopic right posterior sectionectomy vs 4.3 ± 2.7 cm in laparoscopic right hemihepatectomy, P = 0.035). No significant differences were observed in operative and postoperative data except for free margin size (1.04 ± 0.71 cm in laparoscopic right posterior sectionectomy vs 2.95 ± 1.75 cm in laparoscopic right hemihepatectomy, P < 0.001). Disease-free survival (5-year survival: 38.0% in laparoscopic right posterior sectionectomy vs 47.0% in laparoscopic right hemihepatectomy, P = 0.510) and overall survival (5-year survival: 92.7% in laparoscopic right posterior sectionectomy vs 89.6% in laparoscopic right hemihepatectomy, P = 0.593) did not differ between the groups based on Kaplan-Meier log-rank test., Conclusion:: For hepatocellular carcinoma in the posterior segments, laparoscopic right posterior sectionectomy was feasible compared to laparoscopic right hemihepatectomy when performed by experienced laparoscopic surgeons.

Background: Despite the increasing population of elderly individuals in Korea, there are no evidence-based geriatric nursing practice guidelines., Aim: This study aimed to identify and prioritize topics related to the development of evidence-based geriatric nursing practice guidelines in long-term care facilities in Korea., Methods: To identify potential topics, 89 nurses responded to a questionnaire on activities that require further evidence and/or standardization in the long-term care facility setting. To prioritize these topics, 14 geriatric nursing experts completed surveys to prioritize five categories., Results: The collected data included 240 clinical topics, which were classified into 41 subcategories and 18 main categories. According to topic prioritization by the geriatric nursing experts, the following were the most heavily weighted categories: fall prevention, position change and prevention of pressure ulcers., Conclusions: The development of standardized guidelines based on these results may help improve the quality of geriatric care and quality of life of older individuals. The small number of respondents may be a limitation of this study, and further study is needed to expand the population., Implications for Nursing and Health Policy: The development of evidence-based nursing guidelines based on the present findings will help improve the quality of nursing in long-term care facilities. Additionally, health policies and systems, such as introduction of a fee for nursing services for older individuals based on the evidence, are worth considering., (© 2018 International Council of Nurses.)

The presence of lipopolysaccharide (LPS) in blood induces an inflammatory response which leads to multiple organ dysfunction and numerous metabolic disorders. Uncontrolled, improper or late intervention may lead to tissue hypoxia, anaerobic glycolysis and a disturbance in the acid -base balance. The effects of LPS-induced toxemia on biological and immunological markers were well studied. However, parameters such as base excess, ions, and acid-base balance were not fully investigated. Therefore, the objective of this study was to examine these blood parameters collectively in LPS-induced inflammatory toxemia in rat's model. After induction of toxemia by injecting LPS at a rate of 5 mg/kg body weight intravenously, blood was collected from the tail vein of twenty rats and immediately analyzed. After 24 hours, the animals were sacrificed and the blood was collected from the caudal vena cava. The results revealed that the levels of pH, bicar- bonate, partial pressure of oxygen, oxygen saturation, Alveolar oxygen, hemoglobin, hematocrit, magnesium (Mg2+), and calcium (Ca2+) were significantly decreased. On the other side, the levels of Base excess blood, Base excess extracellular fluid, partial pressure of carbon dioxide, lactate, Ca2+/Mg2+, potassium, and chloride were significantly increased compared to those found pre toxemia induction. However, sodium level showed no significant change. In conclusion, Acute LPS-toxemia model disturbs acid-base balance, blood gases, and ions. These parameters can be used to monitor human and animal toxemic inflammatory response induced by bacterial LPS conditions to assist in the management of the diagnosed cases., (Copyright© by the Polish Academy of Sciences.)

Objectives: The long-term success of dental implants is established by literature. Although clinically well defined, the complex genetic pathways underlying osseointegration have not yet been fully elucidated. Furthermore, patients with osteopenia/osteoporosis are considered to present as higher risk for implant failure. Porous tantalum trabecular metal (PTTM), an open-cell porous biomaterial, is suggested to present enhanced biocompatibility and osteoconductivity. The goal of this study was to evaluate the expression patterns of a panel of genes closely associated with osteogenesis and wound healing in osteopenic patients receiving either traditional titanium (Ti) or PTTM cylinders to assess the pathway of genes activation in the early phases of osseointegration., Material and Methods: Implant cylinders made of Ti and PTTM were placed in osteopenic volunteers. At 2- and 4 weeks of healing, one Ti and one PTTM cylinder were removed from each subject for RT-PCR analysis using osteogenesis PCR array., Results: Compared to Ti, PTTM-associated bone displayed upregulation of bone matrix proteins, BMP/TGF tisuperfamily, soluble ligand and integrin receptors, growth factors, and collagen genes at one or both time points. Histologically, PTTM implants displayed more robust osteogenesis deposition and maturity when compared to Ti implants from the same patient., Conclusions: Our results indicate that PTTM properties could induce an earlier activation of genes associated with osteogenesis in osteopenic patients suggesting that PTTM implants may attenuate the relative risk of placing dental implants in this population., Competing Interests: Zimmer Biomet Dental (formerly Zimmer Dental Inc.) has no role in the writing or publication of this manuscript. Zimmer Biomet Dental supported experimental research.