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BACKGROUND Unilateral pulmonary hemorrhage is typically reported in young and healthy men with upper respiratory tract obstruction during anesthesia in special situations. Negative pressure in the lungs is created, resulting in negative pressure pulmonary edema (NPPE). CASE SUMMARY A 78-year-old male patient diagnosed with spinal stenosis was admitted to receive a unilateral laminectomy with bilateral decompression. The patient had been diagnosed with hypertension four years earlier and asthma more than 70 years earlier. We experienced a unilateral alveolar hemorrhage associated with NPPE that occurred in a longstanding asthma patient who bit the intubated endotracheal tube for a short period during posture change at the end of surgery. Because diffuse alveolar hemorrhage accompanied by NPPE was caused in this case by airway obstruction in an older patient with asthma without known risk factors, anesthesiologists should be careful not to induce airway irritation during anesthesia awakening in asthma patients. CONCLUSION Because diffuse alveolar hemorrhage accompanied by NPPE can occur, anesthesiologists should take care not to induce airway irritation.

With an increase in the number of individuals opting for illegal abortion, the use of counterfeit abortion medicines is increasing throughout the black market. In the present study, a rapid and simultaneous liquid chromatography–tandem mass spectrometry method for detecting abortion-inducing drugs in counterfeit medicines was developed. The parameters used for validating the method using tablet-, powder- and capsule-type matrix-blank samples were limit of detection (0.10–5.00 ng/mL), limit of quantitation (0.31–15.00 ng/mL), linearity (r2 > 0.998), recovery of spiked matrix-blank samples (83.1–114.5%), intraday and interday accuracy (86.4–113.5%) and precision (≤ 9.7% RSD) and stability (≤ 13.3% RSD). Seized tablet-type drugs, advertised for their abortion-inducing activity, were analysed using an established method and were observed to be adulterated with mifepristone and misoprostol in a concentration of 0.02–293.80 mg/g, which can pose a risk to public health. This study demonstrates the successful application of a fast and reliable screening method for detecting illegal abortion-inducing drugs.

Background: Complex regional pain syndrome is a disease characterized by chronic pain caused by tissue damage and worsens over time. The quality of randomized controlled trials on complex regional pain syndrome is low due to the rarity of the disease and difficulty in designing studies. Therefore, we evaluated the completeness of evidence by assessing the quality. Methods: We searched articles that were published between 1998 and 2017. The quality was assessed using the Jadad scale, van Tulder scale, and the Cochrane collaboration risk of bias tool.Results: A total of 72 articles on complex regional pain syndrome have been published. Only 31 articles were found to have a low risk of bias according to the Cochrane Collaboration. On the Jadad and van Tulder scale, 52 and 58 articles, respectively, were assessed as high quality. Only a few trials described the randomization method adequately and presented allocation concealment correctly. We also found that research trials with funding statements had higher Jadad scales than unfunded (P = 0.03). Furthermore, articles that described the sample size were of significantly higher quality (P < 0.01) than those that did not. Conclusions: There was no observed improvement in quality over time. In particular, the performance rate of the allocation concealment for the analyzed papers was low. In addition, we found that the number of high-quality articles increased when institutional review board approval was granted and funding provided. For the future, we recommend that researchers focus their efforts on conducting high-quality studies.

Recent studies have revealed that protein arginine methyltransferases (PRMTs) are responsible for diverse neurodegenerative diseases. However, their pathophysiological role in dopaminergic neuronal death in Parkinson's disease (PD) has not been evaluated. In this study, we demonstrated that 1-Methyl-4-phenylpyridinium iodide (MPP+), rotenone and paraquat, which cause dopaminergic neuronal cell death, increased PRMT1 expression in dopaminergic cell line. Dopaminergic neuronal cell death was increased by PRMT1 overexpression. MPP+-induced cell death was attenuated by PRMT1 knockdown. Poly (ADP-ribose) polymerase-1 (PARP1) expression and activity, poly-ADP-ribosylation (PARylation), were elevated by MPP+. Moreover, we found that PRMT1 positively regulates nuclear translocation of apoptosis-inducing factor (AIF). Elevated PRMT1 expression was observed in the substantia nigra pars compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-injected mice. Furthermore, MPTP-induced dopaminergic neuronal death was reduced in PRMT1 haploinsufficient (prmt1+/-) mice. These data suggest that PRMT1 is implicated in PARP1/AIF-mediated dopaminergic neuronal cell death, which might be involved in the pathology of PD. Therefore, our results propose PRMT1 as a new target to develop a potential treatment of PD.

The development of treatment for neurodegenerative diseases (NDs) such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis is facing medical challenges due to the increasingly aging population. However, some pharmaceutical companies have ceased the development of therapeutics for NDs, and no new treatments for NDs have been established during the last decade. The relationship between ND pathogenesis and risk factors has not been completely elucidated. Herein, we review the potential involvement of transient receptor potential (TRP) channels in NDs, where oxidative stress and disrupted Ca2+ homeostasis consequently lead to neuronal apoptosis. Reactive oxygen species (ROS) -sensitive TRP channels can be key risk factors as polymodal sensors, since progressive late onset with secondary pathological damage after initial toxic insult is one of the typical characteristics of NDs. Recent evidence indicates that the dysregulation of TRP channels is a missing link between disruption of Ca2+ homeostasis and neuronal loss in NDs. In this review, we discuss the latest findings regarding TRP channels to provide insights into the research and quests for alternative therapeutic candidates for NDs. As the structures of TRP channels have recently been revealed by cryo-electron microscopy, it is necessary to develop new TRP channel antagonists and reevaluate existing drugs.

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by cognitive dysfunction and memory loss as the main symptoms. The deposition of amyloid beta (Aβ) and tau hyperphosphorylation are hallmarks of AD and are major therapeutic targets. However, the exact etiology has not yet been fully elucidated; thus, no drug that cures the disease has been approved. JBPOS0101 is a phenyl carbamate compound that has been tested as a drug for epileptic diseases. In our previous study, we showed that JBPOS0101 attenuated the accumulation of Aβ as well as the deficits in learning and memory in the 5xFAD mouse model. Here, we tested the dose effect (70 or 35 mg/kg) of JBPOS0101 on the memory defect and pathological markers and further investigated the underlying mechanisms in 5xFAD mice. In the behavior tests, JBPOS0101 treatment ameliorated deficits in learning and memory. Moreover, JBPOS0101 attenuated Aβ accumulation and tau phosphorylation. The elevated phosphorylation levels of the active GSK3β form (GSK3β-y216) in 5xFAD, which are responsible for tau phosphorylation, decreased in the JBPOS0101-treated groups. Furthermore, the elevation of reactive astrocytes and microglia in 5xFAD mice was attenuated in JBPOS0101-treated groups. These data suggest that JBPOS0101 may be a new drug candidate to lessen amyloid- and tau-related pathology by regulating glial cells.

Background and objectiveDespite the awareness of the important roles of physical activity (PA), the majority of cancer survivors fail to meet PA guidelines due to a lack of access to facilities or motivation. The purpose of this study is to examine the effectiveness of lifestyle intervention in prostate cancer (PC) patients receiving androgen deprivation therapy (ADT). Material and methodsA total of 23 PC patients (aged 75.26 ± 6.9 years) receiving ADT at least 3 months were randomized into an intervention group (n=12) and a control group (n=11). The intervention group received lifestyle intervention in the form of education program. Levels of PA, body composition, physical function, disease-specific quality of life (QoL), and fatigue were assessed before and after the 12-week intervention. ResultsThe intervention group showed improvements in the level of PA (step count: p=0.028, moderate to vig-orous PA: p=0.013) compared with the control group. Thigh circumference (p=0.002), physical function (grip strength: p=0.034; knee extensor: p=0.004, up and go: p=0.001; 2-min step: p=0.001), QoL (p

PURPOSE To assess the quality of randomized controlled trials (RCTs) on varicocele published from 1979 to 2017. MATERIALS AND METHODS We searched for original RCT on varicocele published between 1979 and 2017. Jadad scale, van Tulder scale, and Cochrane Collaboration Risk of Bias Tool were used to analyze RCT quality over time. Effects on RCT quality including funding source, Institutional Review Board (IRB) approval, and intervention were assessed. Treatment parameters of varicocele were also analyzed. RESULTS Blinding and allocation concealment were described in 25.9% and 9.4% of RCT, respectively. Both tended to increase and a sharp dip in allocation concealment was observed in 2010-2017. Jadad scores increased steadily from 1979 to 2017 (1.28±0.59 to 2.19±1.10, p

Alzheimer's disease (AD) is a major neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) in the brain. Defects in Aβ clearance or the interference of Aβ homeostasis could result in Aβ aggregation. JBPOS0101 has been studied for its antiepileptic activity. It showed a neuroprotective effect and prevented memory deficits in lithium-pilocarpine-induced status epilepticus rats. In this study, we tested the effect of JBPOS0101 in an AD model. We showed that JBPOS0101 attenuated the accumulation of Aβ in 5XFAD mouse brains. Moreover, the treatment of JBPOS0101 rescued the deficits in learning and memory in 5XFAD mice. These data suggest that JBPOS0101 could be a potential therapeutic drug candidate for AD.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline and dementia with no effective treatment. Here, we investigated a novel compound from oats named avenanthramide-C (Avn-C), on AD-related memory impairment and behavioral deficits in transgenic mouse models. Acute hippocampal slices of wild-type or AD transgenic mice were treated with Avn-C in the presence or absence of oligomeric Aβ42. LTP analyses and immunoblotting were performed to assess the effect of Avn-C on Aβ-induced memory impairment. To further investigate the effect of Avn-C on impaired memory and Aβ pathology, two different AD transgenic mice (Tg2576 and 5XFAD) models were orally treated with either Avn-C or vehicle for 2 weeks. They were then assessed for the effect of the treatment on neuropathologies and behavioral impairments. Avn-C reversed impaired LTP in both ex vivo- and in vivo-treated AD mice hippocampus. Oral administration (6 mg/kg per day) for 2 weeks in AD mice leads to improved recognition and spatial memory, reduced caspase-3 cleavage, reversed neuroinflammation, and to accelerated glycogen synthase kinase-3β (pS9GSK-3β) and interleukin (IL-10) levels. Avn-C exerts its beneficial effects by binding to α1A adrenergic receptors to stimulate adenosine monophosphate-activated kinase (AMPK). All of the beneficial effects of Avn-C on LTP retrieval could be blocked by prazosin hydrochloride, a specific inhibitor of α1A adrenergic receptors. Our findings provide evidence, for the first time, that oats’ Avn-C reverses the AD-related memory and behavioral impairments, and establish it as a potential candidate for Alzheimer’s disease drug development.

Protein S-palmitoylation, the covalent lipid modification of the side chain of Cys residues with the 16‑carbon fatty acid palmitate, is the most common acylation, and it enhances the membrane stability of ion channels. This post-translational modification (PTM) determines a functional mechanism of ion channel life cycle from maturation and membrane trafficking to localization. Especially, neurodevelopment is regulated by balancing the level of synaptic protein palmitoylation/depalmitoylation. Recently, we revealed the pathological role of the transient receptor potential canonical type 5 (TRPC5) channel in striatal neuronal loss during Huntington's disease (HD), which is abnormally activated by oxidative stress. Here, we report a mechanism of TRPC5 palmitoylation at a conserved cysteine residue, that is critical for intrinsic channel activity. Furthermore, we identified the therapeutic effect of TRPC5 depalmitoylation by enhancing the TRPC5 membrane instability on HD striatal cells in order to lower TRPC5 toxicity. Collectively, these findings suggest that controlling S-palmitoylation of the TRPC5 channel as a potential risk factor can modulate TRPC5 channel expression and activity, providing new insights into a therapeutic strategy for neurodegenerative diseases.

δ-Catenin is abundant in the brain and affects its synaptic plasticity. Furthermore, loss of δ-catenin is related to the deficits of learning and memory, mental retardation (cri-du-chat syndrome), and autism. A few studies about δ-catenin deficiency mice were performed. However, the effect of δ-catenin overexpression in the brain has not been investigated as yet. Therefore we generated a δ-catenin overexpressing mouse model. To generate a transgenic mouse model overexpressing δ-catenin in the brain, δ-catenin plasmid having a Thy-1 promotor was microinjected in C57BL/6 mice. Our results showed δ-catenin transgenic mice expressed higher levels of N-cadherin, β-catenin, and p120-catenin than did wild type mice. Furthermore, δ-catenin transgenic mice exhibited better object recognition, better sociability, and lower anxiety than wild type mice. However, both mice groups showed a similar pattern in locomotion tests. Although δ-catenin transgenic mice show similar locomotion, they show improved sociability and reduced anxiety. These characteristics are opposite to the symptoms of autism or mental retardation, which are caused when δ-catenin is deficient. These results suggest that δ-catenin may alleviate symptoms of autism, Alzheimer's disease and mental retardation.

Open-wedge high tibial osteotomy (HTO) cannot always accurately correct limb alignment, resulting in under- or over-correction. This study assessed the relationship between soft tissue laxity of the knee joint and alignment correction in open-wedge HTO. This prospective study involved 85 patients (86 knees) undergoing open-wedge HTO for primary medial osteoarthritis. The mechanical axis (MA), weight-bearing line (WBL) ratio, and joint line convergence angle (JLCA) were measured on radiographs preoperatively and after 6 months, and the differences between the pre- and post-surgery values were calculated. Post-operative WBL ratios of 57–67 % were classified as acceptable correction. WBL ratios 67 % were classified as under- and over-corrections, respectively. Preoperative JLCA correlated positively with differences in MA (r = 0.358, P = 0.001) and WBL ratio (P = 0.003). Difference in JLCA showed a stronger correlation than preoperative JLCA with differences in MA (P

Purpose In anatomical single-bundle (SB) anterior cruciate ligament (ACL) reconstruction, the traditional transtibial approach can limit anatomical placement of the femoral tunnel. Surgical Technique We present a novel three-point freehand technique that allows for anatomic SB ACL reconstruction with the transtibial technique. Materials and Methods Between January 2012 and December 2012, 55 ACL reconstructions were performed using the three-point freehand technique. All the patients were followed for a minimum of 12 months post-operatively. Clinical evaluation was done using the Lysholm score and International Knee Documentation Committee (IKDC) grade. All patients were analyzed by 3-dimensional computed tomography (3D CT) at 1 week after surgery. Results The mean Lysholm score improved from 68.2±12.7 points preoperatively to 89.2±8.2 points at final follow-up. At final follow-up, the IKDC grade was normal in 42 patients and nearly normal in 13 patients. None of the patients had a positive pivot shift test, anterior drawer test and Lachman test at final follow-up. The anatomical position of the femoral tunnel was confirmed on 3D CT scans. Conclusions The three-point freehand technique for SB transtibial ACL reconstruction is a simple, anatomic technique showing good clinical results.

Background The aims of alveolar bone grafting are closure of the fistula, stabilization of the maxillary arch, support for the roots of the teeth adjacent to the cleft on each side. We observed nostril base augmentation in patients with alveolar clefts after alveolar bone grafting. The purpose of this study was to evaluate the nostril base augmentation effect of secondary alveolar bone grafting in patients with unilateral alveolar cleft. Methods Records of 15 children with alveolar clefts who underwent secondary alveolar bone grafting with autogenous iliac cancellous bone between March of 2011 and May of 2012 were reviewed. Preoperative and postoperative worm's-eye view photographs and reconstructed three-dimensional computed tomography (CT) scans were used for photogrammetry. The depression of the nostril base and thickness of the philtrum on the cleft side were measured in comparison to the normal side. The depression of the cleft side pyriform aperture was measured in comparison to the normal side on reconstructed three-dimensional CT. Results Significant changes were seen in the nostril base (P=0.005), the philtrum length (P=0.013), and the angle (P=0.006). The CT measurements showed significant changes in the pyriform aperture (P Conclusions An alveolar bone graft not only fills the gap in the alveolar process but also augments the nostril base after surgery. In this study, only an alveolar bone graft was performed to prevent bias from other procedures. Nostril base augmentation can be achieved by performing alveolar bone grafts in children, in whom invasive methods are not advised.

International audience; Inhibition of mitochondrial complex I activity is hypothesized to be one of the major mechanisms responsible for dopaminergic neuron death in Parkinson's disease. However, loss of complex I activity by systemic deletion of the Ndufs4 gene, one of the subunits comprising complex I, does not cause dopaminergic neuron death in culture. Here, we generated mice with conditional Ndufs4 knockout in dopaminergic neurons (Ndufs4 conditional knockout mice [cKO]) to examine the effect of complex I inhibition on dopaminergic neuron function and survival during aging and on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in vivo. Ndufs4 cKO mice did not show enhanced dopaminergic neuron loss in the substantia nigra pars compacta or dopamine-dependent motor deficits over the 24-month life span. These mice were just as susceptible to MPTP as control mice. However, compared with control mice, Ndufs4 cKO mice exhibited an age-dependent reduction of dopamine in the striatum and increased alpha-synuclein phosphorylation in dopaminergic neurons of the substantia nigra pars compacta. We also used an inducible Ndufs4 knockout mouse strain (Ndufs4 inducible knockout) in which Ndufs4 is conditionally deleted in all cells in adult to examine the effect of adult onset, complex I inhibition on MPTP sensitivity of dopaminergic neurons. The Ndufs4 inducible knockout mice exhibited similar sensitivity to MPTP as control littermates. These data suggest that mitochondrial complex I inhibition in dopaminergic neurons does contribute to dopamine loss and the development of alpha- synuclein pathology. However, it is not sufficient to cause cell-autonomous dopaminergic neuron death during the normal life span of mice. Furthermore, mitochondrial complex I inhibition does not underlie MPTP toxicity in vivo in either cell autonomous or nonautonomous manner. These results provide strong evidence that inhibition of mitochondrial complex I activity is not sufficient to cause dopaminergic neuron death during aging nor does it contribute to dopamine neuron toxicity in the MPTP model of Parkinson's disease. These findings suggest the existence of alternative mechanisms of dopaminergic neuron death independent of mitochondrial complex I inhibition.

Purpose To compare the clinical outcomes between medial soft-tissue surgery and medial patellofemoral ligament (MPFL) reconstruction for recurrent patellar dislocation without any evident predisposing factors. Methods A literature search was performed on the established medical databases MEDLINE, EMBASE, and the Cochrane register. The inclusion criteria were as follows: English-language papers for recurrent patellar dislocation without any evident predisposing factors, clinical trial(s) with clear description of surgical technique, adult subjects, medial soft-tissue surgery or MPFL reconstruction without combined surgery, and a follow-up longer than 2 years. The methodological quality of all articles was assessed by 2 authors according to the Coleman methodology score. Results Thirteen studies (mean Coleman methodology score value, 74.1; standard deviation, 11.5) were included in the analysis. Five studies reported the outcomes of patients undergoing medial soft-tissue surgery, compared with 7 studies reporting MPFL reconstruction. Overall, 109 patients underwent medial soft-tissue surgery with a minimum 2-years follow-up, compared with 308 patients of MPFL reconstruction. There was one direct comparative study between medial soft-tissue surgery and MPFL reconstruction. Of the patients who received medial soft-tissue surgery, 0 to 9.7% experienced redislocation, compared with 0 to 10.7% of the MPFL reconstruction group. The ranges of differences in Kujala scores were 23.6 to 31.7 points in patients who underwent medial soft-tissue surgery and 23.11 to 38.8 points in patients who underwent MPFL reconstruction. The ranges of postoperative congruence angles were −14.4° to 8.2° for medial soft-tissue surgery and −7.7° to −5.2° for MPFL reconstruction. The ranges of postoperative lateral patellofemoral angles were 7.9° to 9.4° for medial soft-tissue surgery and 5° to 5.3° for MPFL reconstruction. Conclusions All studies on medial soft-tissue surgery and MPFL reconstruction for recurrent patellar dislocation without predisposing factors showed satisfactory outcomes despite the use of numerous surgical techniques, graft types, and follow-up periods. Level of Evidence Level IV, Systematic Review.

Objectives : Korea faces a number of challenges to meet demands in the area of geriatric professional medicine in a country with a rapidly ageing population. We evaluated the satisfaction and feasibility of the current education certification for geriatric physicians. Methods : Geriatric physicians who were deemed qualified by the Korean Geriatrics Society during the period of 2001 to 2005 (n=2,200) were asked to complete structured questionnaires sent to them by mail about their satisfaction of and need for certificates of education, as well as their opinions on their geriatric specialty training. A total of 419 physicians responded. Descriptive analysis and hierarchical regression were performed to rate the respondents' satisfaction, the characteristics of the need for clarity and utility in education certification, and the characteristics of their patients. Results : Although most respondents were satisfied with their education certification, those who had more elderly patients, aged 65 or older, and those who had more cognitively impaired patients, rated their education as significantly lower than did other physicians. Both groups expressed the need for more the comprehensive care and assessment concerning of their education. Multiple regression analysis indicated that satisfaction with geriatric physician qualification was associated with a physician's age, specialty, and percentage of elderly patients. Conclusions : This study suggests that the current system of education certification is limited in terms of feasibility and physician satisfaction.