GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans.

GLP-1 receptor agonists (GLP-1RAs) are effective anti-obesity drugs. However, the precise central mechanisms of GLP-1RAs remain elusive. We administered GLP-1RAs to obese patients and observed heightened sense of preingestive satiation. Analysis of human and mouse brain samples pinpointed GLP-1R neurons in the dorsomedial hypothalamus (DMH) as candidates for encoding preingestive satiation. Optogenetic manipulation of DMHGLP-1R neurons caused satiation. Calcium imaging demonstrated that these neurons are actively involved in encoding preingestive satiation. GLP-1RA administration increased the activity of DMHGLP-1R neurons selectively during eating behavior. We further identified an intricate interplay between DMHGLP-1R neurons and arcuate NPY/AgRP neurons (ARCNPY/AgRP), to regulate food intake. Our findings reveal a hypothalamic mechanism through which GLP-1RAs control preingestive satiation, offering novel neural targets for obesity and metabolic diseases.

Proteomic profiling of postmortem prefrontal cortex tissue of suicide completers.

Suicide is a leading cause of death worldwide, presenting a serious public health problem. We aimed to investigate the biological basis of suicide completion using proteomics on postmortem brain tissue. Thirty-six postmortem brain samples (23 suicide completers and 13 controls) were collected. We evaluated the proteomic profile in the prefrontal cortex (Broadmann area 9, 10) using tandem mass tag-based quantification with liquid chromatography-tandem mass spectrometry. Bioinformatics tools were used to elucidate the biological mechanisms related to suicide. Subgroup analysis was conducted to identify common differentially expressed proteins among clinically different groups. Of 9801 proteins identified, 295 were differentially expressed between groups. Suicide completion samples were mostly enriched in the endocannabinoid and apoptotic pathways (CAPNS1, CSNK2B, PTP4A2). Among the differentially expressed proteins, GSTT1 was identified as a potential biomarker among suicide completers with psychiatric disorders. Our findings suggest that the previously under-recognized endocannabinoid system and apoptotic processes are highly involved in suicide.

χ-separation: Magnetic susceptibility source separation toward iron and myelin mapping in the brain.

Obtaining a histological fingerprint from the in-vivo brain has been a long-standing target of magnetic resonance imaging (MRI). In particular, non-invasive imaging of iron and myelin, which are involved in normal brain functions and are histopathological hallmarks in neurodegenerative diseases, has practical utilities in neuroscience and medicine. Here, we propose a biophysical model that describes the individual contribution of paramagnetic (e.g., iron) and diamagnetic (e.g., myelin) susceptibility sources to the frequency shift and transverse relaxation of MRI signals. Using this model, we develop a method, χ-separation, that generates the voxel-wise distributions of the two sources. The method is validated using computer simulation and phantom experiments, and applied to ex-vivo and in-vivo brains. The results delineate the well-known histological features of iron and myelin in the specimen, healthy volunteers, and multiple sclerosis patients. This new technology may serve as a practical tool for exploring the microstructural information of the brain.

Optimizing tissue clearing and imaging methods for human brain tissue.

OBJECTIVES: To identify optimum sample conditions for human brains, we compared the clearing efficiency, antibody staining efficiency, and artifacts between fresh and cadaver samples. METHODS: Fresh and cadaver samples were cleared using X-CLARITY™. Clearing efficiency and artifact levels were calculated using ImageJ, and antibody staining efficiency was evaluated after confocal microscopy imaging. Three staining methods were compared: 4-day staining (4DS), 11-day staining (11DS), and 4-day staining with a commercial kit (4DS-C). The optimum staining method was then selected by evaluating staining time, depth, method complexity, contamination, and cost. RESULTS: Fresh samples outperformed cadaver samples in terms of the time and quality of clearing, artifacts, and 4',6-diamidino-2-phenylindole (DAPI) staining efficiency, but had a glial fibrillary acidic protein (GFAP) staining efficiency that was similar to that of cadaver samples. The penetration depth and DAPI staining improved in fresh samples as the incubation period lengthened. 4DS-C was the best method, with the deepest penetration. Human brain images containing blood vessels, cell nuclei, and astrocytes were visualized three-dimensionally. The chemical dye staining depth reached 800 µm and immunostaining depth exceeded 200 µm in 4 days. CONCLUSIONS: We present optimized sample preparation and staining protocols for the visualization of three-dimensional macrostructure in the human brain.

Fructose Promotes Leaky Gut, Endotoxemia, and Liver Fibrosis Through Ethanol-Inducible Cytochrome P450-2E1-Mediated Oxidative and Nitrative Stress.

Fructose intake is known to induce obesity, insulin resistance, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the effects of fructose drinking on gut leakiness, endotoxemia, and NAFLD and study the underlying mechanisms in rats, mice, and T84 colon cells. Levels of ileum junctional proteins, oxidative stress markers, and apoptosis-related proteins in rodents, T84 colonic cells, and human ileums were determined by immunoblotting, immunoprecipitation, and immunofluorescence analyses. Fructose drinking caused microbiome change, leaky gut, and hepatic inflammation/fibrosis with increased levels of nitroxidative stress marker proteins cytochrome P450-2E1 (CYP2E1), inducible nitric oxide synthase, and nitrated proteins in small intestine and liver of rodents. Fructose drinking significantly elevated plasma bacterial endotoxin levels, likely resulting from decreased levels of intestinal tight junction (TJ) proteins (zonula occludens 1, occludin, claudin-1, and claudin-4), adherent junction (AJ) proteins (ß-catenin and E-cadherin), and desmosome plakoglobin, along with α-tubulin, in wild-type rodents, but not in fructose-exposed Cyp2e1-null mice. Consistently, decreased intestinal TJ/AJ proteins and increased hepatic inflammation with fibrosis were observed in autopsied obese people compared to lean individuals. Furthermore, histological and biochemical analyses showed markedly elevated hepatic fibrosis marker proteins in fructose-exposed rats compared to controls. Immunoprecipitation followed by immunoblot analyses revealed that intestinal TJ proteins were nitrated and ubiquitinated, leading to their decreased levels in fructose-exposed rats. Conclusion: These results showed that fructose intake causes protein nitration of intestinal TJ and AJ proteins, resulting in increased gut leakiness, endotoxemia, and steatohepatitis with liver fibrosis, at least partly, through a CYP2E1-dependent manner.

Comparative analysis of the tonsillar microbiota in IgA nephropathy and other glomerular diseases.

Immunoglobulin A nephropathy (IgAN) involves repeated events of gross haematuria with concurrent upper airway infections. The mucosal immune system, especially the tonsil, is considered the initial site of inflammation, although the role of the tonsillar microbiota has not been established in IgAN. In this study, we compared the tonsillar microbiota of patients with IgAN (n = 21) and other glomerular diseases (n = 36) as well as, healthy controls (n = 23) from three medical centres in Korea. The microbiota was analysed from tonsil swabs using the Illumina MiSeq system based on 16S rRNA gene. Tonsillar bacterial diversity was higher in IgAN than in other glomerular diseases, although it did not differ from that of healthy controls. Principal coordinates analysis revealed differences between the tonsillar microbiota of IgAN and both healthy and disease controls. The proportions of Rahnella, Ruminococcus_g2, and Clostridium_g21 were significantly higher in patients with IgAN than in healthy controls (corrected p < 0.05). The relative abundances of several taxa were correlated with the estimated glomerular filtration rate, blood urea nitrogen, haemoglobin, and serum albumin levels. Based on our findings, tonsillar microbiota may be associated with clinical features and possible immunologic pathogenesis of IgAN.

Changes in Clinical and Legal Autopsy Rates in Korea from 2001 to 2015.

BACKGROUND: The autopsy is the medical examination of a deceased person that mainly provides information on the cause and manner of death. Two types are conducted in Korea: clinical and legal, depending on its purpose. Despite this procedure's importance, autopsy rates have been decreasing worldwide. The aim of this study was to determine the nationwide autopsy rate in Korea and compare it with that in other countries. METHODS: We collected data of autopsies performed between 2001 and 2015 by searching previously published literature on autopsy statistics and by requesting data from the relevant institutions. We calculated the autopsy rate by using mortality data from Statistics Korea; furthermore, we investigated the type of autopsy performed by institution as well as by geographical region. RESULTS: The total autopsy rate in Korea increased from 2.16% in 2001 to 2.60% in 2015. In terms of autopsy types, however, clinical autopsy rates decreased from 0.17% in 2001 to 0.03% in 2015, while legal autopsy rates increased from 1.99% to 2.57% during the same period. Moreover, the clinical autopsy rate tended to decrease throughout the period, while the legal autopsy rate fluctuated between 2001 and 2010 but steadily increased thereafter. CONCLUSION: The autopsy rate in Korea is lower compared to that of the advanced countries. These findings implicate the need for nationwide policy to promote both clinical and legal autopsy, which remain crucial parts of medical science and public health.

Association between telomere length and completed suicide observed in 71 suicide victims - Preliminary findings.

OBJECTIVE: Telomere length has emerged as a cumulative marker for lifestyle, psychosocial stress, and cytotoxic environments. We aimed to examine the possible association between leukocyte telomere length (LTL) and completed suicide. METHODS: This study included 71 suicide completers and 117 healthy controls for whom LTL was determined by the ratio of the telomere repeat copy number to the single-copy gene copy number (T/S ratio). We compared the LTL between the suicide completers and the healthy controls and estimated the odds ratio (OR) for suicide for each age group, applying a generalized estimating equation (GEE). RESULTS: LTL was significantly shortened in the suicide completers as compared with the controls, overall subjects, or within-age categories (≤29 and 30-49 years). Furthermore, a longer LTL was associated with significantly decreased odds of completed suicide for those aged ≤29 years and 30-49 years (OR = 0.11, 95% confidence interval [CI] 0.03-0.37, p < .001 for the ≤29-year age group; OR = 0.54, 95% CI 0.34-0.84, p = .006 for the 30- to 49-year age group). CONCLUSIONS: This study provides evidence regarding the relationship between shortened LTL and completed suicide, especially in those aged <50 years. Future research should further assess potential confounders and examine underlying mechanisms.

Retrospective Genetic Analysis of 200 Cases of Sudden Infant Death Syndrome and Its Relationship with Long QT Syndrome in Korea.

BACKGROUND: There has been a campaign by the National Education on Sleeping Habits and Living Environment, to reduce the incidence of sudden infant death syndrome (SIDS). However, more than 100 infants die suddenly and unexplainably before the age of 1 year in Korea. Long QT syndrome (LQTS), an inheritable cardiac disease, has been reported to likely be associated with up to 14% of SIDS cases. However, genetic studies of the association between SIDS and LQTS have not yet been conducted in Korea. METHODS: We conducted genetic analysis using genomic DNA extracted from paraffin-embedded tissue blocks from 200 SIDS cases autopsied between 2005 and 2013. We analyzed the following genetic mutations associated with LQTS, KCNQ1, SCN5A, KCNE1, KCNE2, KCNJ2, and CAV3. RESULTS: Of the 200 SIDS cases, 58% involved male infants (116 male and 84 female infants, respectively), the mean age was 140 days (median, 107 days; range, 24-270 days), and they were all of Asian-Korean ethnicity. SIDS IA category criteria comprised 45 cases (22.5%) while the rest were SIDS IB. Fifteen infants (7.5%) had R1193Q in SCN5A, of doubtful pathogenicity, and no pathogenic LQTS variants were observed. CONCLUSION: This genetic investigation of LQTS in SIDS showed a low diagnostic yield. These findings suggest that LQTS molecular autopsy could be cautiously conducted in selected cases with family involvement to improve the available genetic counseling information. Meanwhile, a national SIDS registry should be established to document and evaluate the genetic risk of SIDS in Korea.

Characteristics of sauna deaths in Korea in relation to different blood alcohol concentrations.

Although the benefits of sauna bathing have been demonstrated in epidemiological studies, sauna deaths have been reported. The aim of this study was to determine the demographic and forensic characteristics associated with different blood alcohol concentrations (BACs) in sauna deaths in Korea. In this retrospective analysis, data were collected from a nationwide pool in Korea between January 2008 and December 2015 to determine the role of alcohol intoxication in sauna deaths based on the subjects' BAC and to evaluate the demographic and forensic characteristics associated with different BACs. One hundred and three deaths were classified into 2 groups: the non-intoxication (NI) group (BAC,<0.08%; n = 27) and the intoxication (I) group (BAC,≥0.08%; n = 76). Demographic and forensic characteristics were compared between the groups using a multinomial logistic regression analysis. The proportions of decedents who were male (odds ratio: 17.4, 95.0% confidence interval: 3.8-79.8) and in a prone position at the scene of death (odds ratio: 11.3, 95.0% confidence interval: 2.1-60.1) were significantly higher (P < 0.001 and P < 0.05, retrospectively) in the I group than in the NI group. However, no significant differences were observed with respect to obesity, coronary artery narrowing, and liver pathology. Sauna deaths exhibited different characteristics according to BACs detected at autopsy. The differences in sauna deaths between the I and NI groups may have implications for the targeted prevention of sauna deaths associated with alcohol consumption.

Bath-related Deaths in Korea between 2008-2015.

BACKGROUND: The diagnostic criteria for bathtub drownings are not standardized, and the risk factors associated with bath-related deaths are unclear. METHODS: We analyzed a Korean nationwide database of bath-related deaths that occurred between January 2008 and December 2015. Eighty-four cases were enrolled after reviewing 31,123 autopsy records. RESULTS: The subjects' ages ranged from 18 to 91 years, with a mean age ± standard deviation of 61.3 ± 16.0 years. Bath-related deaths in the winter were approximately 4.6-fold greater than those in the summer. Of the 84 subjects, the primary cause of death in 57 (67.9%) was drowning in the bath; 24 (28.6%) drowned of other causes such as natural diseases, and 3 (3.6%) died of acute alcohol intoxication. We analyzed water-inhalation signs to establish criteria for bathtub drowning diagnosis. There were significantly higher incidences of hyperinflated lungs, water in the sphenoid sinus and stomach/duodenal contents, and Paltauf's spots (subpleural hemorrhage) in bathtub-drowned subjects compared to non-drowned individuals (P < 0.01). Multiple signs of water inhalation were significantly associated with bathtub drowning (P < 0.01). The two leading contributory causes of bath-related death were cardiovascular diseases and alcohol intoxication (binge drinking before bathing). CONCLUSION: The diagnosis of bath-related deaths could present considerable medico-legal problems; therefore, a comprehensive autopsy with a thorough scene investigation can clarify the cause of death in these situations. Preventive strategies for reducing such deaths should target alcohol drinking before bathing and long soaking times in bathtubs, especially among elderly individuals with preexisting cardiovascular diseases.

Apoptosis of enterocytes and nitration of junctional complex proteins promote alcohol-induced gut leakiness and liver injury.

BACKGROUND & AIMS: Binge alcohol exposure causes gut leakiness, contributing to increased endotoxemia and inflammatory liver injury, although the molecular mechanisms are still elusive. This study was aimed at investigating the roles of apoptosis of enterocytes and nitration followed by degradation of intestinal tight junction (TJ) and adherens junction (AJ) proteins in binge alcohol-induced gut leakiness. METHODS: The levels of intestinal (ileum) junctional complex proteins, oxidative stress markers and apoptosis-related proteins in rodents, T84 colonic cells and autopsied human ileums were determined by immunoblot, immunoprecipitation, immunofluorescence, and mass-spectral analyses. RESULTS: Binge alcohol exposure caused apoptosis of gut enterocytes with elevated serum endotoxin and liver injury. The levels of intestinal CYP2E1, iNOS, nitrated proteins and apoptosis-related marker proteins were significantly elevated in binge alcohol-exposed rodents. Differential, quantitative mass-spectral analyses of the TJ-enriched fractions of intestinal epithelial layers revealed that several TJ, AJ and desmosome proteins were decreased in binge alcohol-exposed rats compared to controls. Consistently, the levels of TJ proteins (claudin-1, claudin-4, occludin and zonula occludens-1), AJ proteins (ß-catenin and E-cadherin) and desmosome plakoglobin were very low in binge alcohol-exposed rats, wild-type mice, and autopsied human ileums but not in Cyp2e1-null mice. Additionally, pretreatment with specific inhibitors of CYP2E1 and iNOS prevented disorganization and/or degradation of TJ proteins in alcohol-exposed T84 colonic cells. Furthermore, immunoprecipitation followed by immunoblot confirmed that intestinal TJ and AJ proteins were nitrated and degraded via ubiquitin-dependent proteolysis, resulting in their decreased levels. CONCLUSIONS: These results demonstrated for the first time the critical roles of CYP2E1, apoptosis of enterocytes, and nitration followed by ubiquitin-dependent proteolytic degradation of the junctional complex proteins, in promoting binge alcohol-induced gut leakiness and endotoxemia, contributing to inflammatory liver disease. LAY SUMMARY: Binge alcohol exposure causes gut leakiness, contributing to increased endotoxemia and inflammatory liver injury. Our results demonstrated for the first time the critical roles of apoptosis of enterocytes and nitration followed by ubiquitin-dependent proteolytic degradation of the junctional complex proteins in promoting this gut leakiness and endotoxemia. These results provide insight into the molecular mechanisms of alcohol-induced inflammatory liver disease.

Characteristics of completed suicide in different blood alcohol concentrations in Korea.

AIMS: This study aimed to determine the role of acute alcohol use among suicide decedents based on their blood alcohol concentrations (BAC), and identify sociodemographic and clinical characteristics associated with the differences in BAC. METHODS: Data were collected from nationwide autopsies conducted between May 2015 and November 2015 in South Korea. A total of 683 suicide decedents were classified into three groups according to the BAC at the time of autopsy: no alcohol (NA) group (BAC<0.01%), no intoxication (NI) group (0.01≤BAC<0.08%), and intoxication (I) group (BAC≥0.08%). Sociodemographic data and clinical factors related to suicide among the three groups were analyzed using a multinomial logistic regression analysis. RESULTS: Among the suicide decedents (N=683), the NA group was 55.6% (N=380), NI group was 15.7% (N=107), and I group was 28.7% (N=196). History of suicide attempts (odds ratio [OR]: 1.798, 95% confidence interval [CI]: 1.073-3.012) and absence of medical illness (OR: 1.633, CI: 1.038-2.571) were higher in the I group compared to the NA group. Psychiatric and medical illness triggers of suicide were significantly lower in the I group than the NA group (OR: 0.325, CI: 0.118-0.892). Being male (OR: 2.494, CI: 1.363-4.565) and financial problems as triggers of suicide (OR: 3.234, CI: 1.636-6.393) were higher in the NI group than in the NA group. Being male and having financial problems were associated with no intoxication (0.01≤BAC<0.08%), whereas the history of suicide attempts and absence of medical and/or psychiatric illness were associated with acute alcohol intoxication (BAC≥0.08%) in the suicide decedents. CONCLUSIONS: Suicide decedents had different characteristics based on different BACs identified in the autopsy. The differences in acute alcohol intoxication and no intoxication in suicide decedents may have implications for the targeted prevention of suicides related to alcohol.

Mid-Term Results of Oxford Medial Unicompartmental Knee Arthroplasty in Young Asian Patients Less than 60 Years of Age: A Minimum 5-Year Follow-up.

PURPOSE: The purpose of this study was to evaluate the efficacy of unicompartmental knee arthroplasty (UKA) in young active Asian patients by analyzing clinical outcomes, complications and survival rates. MATERIALS AND METHODS: Eighty-two knees were evaluated with a minimum follow-up of 5 years after Oxford phase 3 UKA in patients less than 60 years of age at the time of surgery. Their mean age was 54.7 years (range, 44 to 59 years). The mean follow-up period was 8.9 years (range, 5.3 to 12 years). Kaplan-Meier survivorship analysis was used to estimate implant survival. RESULTS: Including 3 bearing dislocations, 1 medial tibial collapse and 1 lateral osteoarthritis, the total complication rate was 6.1% (5/82). Of the 3 cases of bearing dislocation, 2 cases were resolved by replacing with a thicker bearing and 1 case was converted to total knee arthroplasty (TKA) due to repeated dislocation. The two knees with a medial tibial collapse and a lateral osteoarthritis were converted to TKA. The 10-year cumulative survival rate using Kaplan-Meier survival method was 94.7% (95% confidence interval: 88.7%-100%). CONCLUSIONS: Oxford medial UKA was reliable and effective in young active Asian patients providing good clinical results and survival rate in the mid-term follow-up.

Impact of acute alcohol consumption on lethality of suicide methods.

BACKGROUND: The influence of acute alcohol consumption on the factors related to suicide remains understudied. Thus, the present study investigated the relationship between blood alcohol content (BAC) and the lethality of suicide methods. METHODS: Autopsy data on 315 South Korean suicide completers with a positive BAC were collected from a nationwide pool between May 2015 and November 2015, and the methods were dichotomised as suicide methods of low lethality (SMLL; drug/chemical overdose and sharp objects, n=67) and suicide methods of high lethality (SMHL; everything else, n=243). BAC at the time of autopsy and various suicide-related factors of these two groups were compared with logistic regression analyses. RESULTS: Compared to suicide completers with a BAC in the lowest range of 0.011-0.049%, suicide completers with a BAC in the range of 0.150-0.199% were more likely to use SMHL (odds ratio [OR]: 3.644, 95% confidence interval [CI]: 1.221-10.874). Additionally, the adoption of SMHL was significantly associated with the absence of a psychiatric illness (OR: 0.433, 95% CI: 0.222-0.843) and a younger age; the OR for high BAC among subjects in their 40s was 0.266 (95% CI: 0.083-0.856); in their 50s, 0.183 (95% CI: 0.055-0.615); and in their 60s, 0.057 (95% CI: 0.015-0.216). CONCLUSIONS: The relationship between BAC and suicide method lethality was represented by a bell-shaped pattern in which suicide methods of high lethality were more likely to be used by suicide completers with mid-range BAC levels. The increased impulsivity and impairments in particular executive functions, including planning and organization, associated with acute alcohol use may influence the selection of a particular suicide method based on its lethality.

Ossification of the Medial Clavicular Epiphysis on Chest Radiographs: Utility and Diagnostic Accuracy in Identifying Korean Adolescents and Young Adults under the Age of Majority.

The aim of our study was to evaluate the utility and diagnostic accuracy of the ossification grade of medial clavicular epiphysis on chest radiographs for identifying Korean adolescents and young adults under the age of majority. Overall, 1,151 patients (age, 16-30) without any systemic disease and who underwent chest radiography were included for ossification grading. Two radiologists independently classified the ossification of the medial clavicular epiphysis from chest radiographs into five grades. The age distribution and inter-observer agreement on the ossification grade were assessed. The diagnostic accuracy of the averaged ossification grades for determining whether the patient is under the age of majority was analyzed by using receiver operating characteristic (ROC) curves. Two separate inexperienced radiologists assessed the ossification grade in a subgroup of the patients after reviewing the detailed descriptions and image atlases developed for ossification grading. The median value of the ossification grades increased with increasing age (from 16 to 30 years), and the trend was best fitted by a quadratic function (R-square, 0.978). The inter-observer agreements on the ossification grade were 0.420 (right) and 0.404 (left). The area under the ROC curve (AUC) was 0.922 (95% CI, 0.902-0.942). The averaged ossification scores of 2.62 and 4.37 provided 95% specificity for a person < 19 years of age and a person ≥ 19 years of age, respectively. A preliminary assessment by inexperienced radiologists resulted in an AUC of 0.860 (95% CI, 0.740-0.981). The age of majority in Korean adolescents and young adults can be estimated using chest radiographs.

A Study of Core Humanistic Competency for Developing Humanism Education for Medical Students.

The authors conducted a survey on essential humanistic competency that medical students should have, and on teaching methods that will effectively develop such attributes. The participants consisted of 154 medical school professors, 589 medical students at Seoul National University College of Medicine, 228 parents, and 161 medical school and university hospital staff. They answered nine questions that the authors created. According to the results, all groups chose "morality and a sense of ethics," a "sense of accountability," "communication skills," and "empathic ability" were selected as essential qualities. According to the evaluation on the extent to which students possess each quality, participants believed students had a high "sense of accountability" and "morality," whereas they thought students had low "empathic ability," "communicate," or "collaborate with others". In terms of effective teaching methods, all sub-groups preferred extracurricular activities including small group activities, debates, and volunteer services. With regard to the speculated effect of humanism education and the awareness of the need for colleges to offer it, all sub-groups had a positive response. However the professors and students expressed a relatively passive stance on introducing humanism education as a credited course. Most participants responded that they preferred a grading method based on their rate of participation, not a relative evaluation. In order to reap more comprehensive and lasting effects of humanism education courses in medical school, it is necessary to conduct faculty training, and continuously strive to develop new teaching methods.

Peri-articular injections of local anaesthesia can replace patient-controlled analgesia after total knee arthroplasty: a randomised controlled study.

PURPOSE: In recent years, there has been an increasing interest in peri-articular injections (PAI) to control post-operative pain after total knee arthroplasty (TKA). Previous studies have evaluated the effect of PAI using multimodal analgaesic protocols, but the concomitant use of patient-controlled analgesia (PCA) may has masked the genuine effects of PAI. We investigated the efficacy of PAI compared with PCA and determined whether conventional PCA can be effectively replaced with PAI after TKA. METHODS: Eighty patients undergoing unilateral TKA were randomised into two groups. The PCA group consisted of patients who used PCA after surgery, while the PAI group included patients who did not use PCA post-operatively but were given PAI during surgery. We measured changes in visual analogue scale (VAS) scores, straight leg raising (SLR), range of motion (ROM) and consumption of antiemetics or analgaesics. RESULTS: Pain levels in the PAI group were significantly lower than in the PCA group during two weeks post-operatively (p < 0.05).; functional recovery in the SLR test showed no difference between groups (p > 0.05).; mean ROM showed no difference; (p > 0.05) and there was no difference in the number of patients who needed additional analgaesics. However, antiemetic use was significantly lower for the PAI group (p < 0.05). CONCLUSIONS: PAI offered improved pain control and minimal side effects compared with PCA. Thus, PAI can replace conventional PCA for controlling post-operative pain after TKA.

Genetic predisposition of donors affects the allograft outcome in kidney transplantation: Single-nucleotide polymorphism of aquaporin-11.

BACKGROUND: Aquaporin-11 (AQP11) is a novel member of the aquaporin family. Disruption of the murine Aqp11 gene causes severe proximal tubular injury and renal failure. The rs2276415 (G>A) single-nucleotide polymorphism in the human AQP11 gene results in glycine to serine substitution in a functionally important domain. In this study, the role of the genetic predispositions of AQP11 rs2276415 (G>A) on renal allograft outcomes was evaluated. METHODS: A total of 198 pairs of donors and recipients were enrolled in this study. Long-term graft survival was traced and clinical parameters that could have influenced graft outcome were collected through the electronic medical record system. RESULTS: The genotype distribution and allele frequency of rs2276415 polymorphism were not different between donors and recipients. Despite similar allele frequencies between donors and recipients, the minor allele rs2276415 (GA+AA) of AQP11 from the donors, but not from the recipients, had a harmful effect on the graft survival compared with the wild-type donor (GG; P=0.029). This association was significant after adjusting for several risk factors including age, sex, human leukocyte antigen mismatch, donor type, hypertension, and diabetes mellitus (P=0.032). CONCLUSION: A donor-derived, not recipient-derived, genetic AQP11 polymorphism has different effects on graft outcome. Thus, the genetic influence from donors should be carefully considered for proper management of allografts after kidney transplantation.

Errata to "Coronal Alignment of the Lower Limb and the Incidence of Constitutional Varus Knee in Korean Females".

[This corrects the article on p. 49 in vol. 27, PMID: 25750894.].