The timing of intravenous antibiotics and clinical outcomes of Mycobacterium abscessus complex lung diseases.

BACKGROUND: The importance of early intravenous (IV) antibiotic use for Mycobacterium abscessus complex lung diseases (MABC-LD) treatment remains unknown. METHODS: A retrospective multi-centre observational study was conducted in Taiwan. Patients who were diagnosed with and received treatment for MABC-LD from January 2007 to April 2021 were included. Treatment outcome was defined as modified microbiological cure of MABC-LD.RESULTS: Of the 89 enrolled patients, 34 (38.2%) received IV antibiotics as part of the treatment regimen. The median time to IV initiation was 1 day (IQR 1???49); 24 (70.6%) of these patients received IV agents within 4 weeks, defined as early-use. Forty-two (47.2%) patients achieved modified microbiological cure. In the multivariable logistic analysis, early IV antibiotic use was an independent factor associated with modified microbiological cure (aOR 5.32, 95% CI 1.66???17.00), whereas high radiological score (aOR 0.86, 95% CI 0.73???1.00) demonstrated negative association.CONCLUSIONS: In the present study, early use of effective IV antibiotic was prescribed in a low percentage (27%) for MABC-LD. By contrast, early IV antibiotic use was correlated with higher microbiological cure than were late or non-use. Future larger and prospective studies are needed to validate the association.

Familial risk for endometriosis and its interaction with smoking, age at menarche and body mass index: a population-based cohort study among siblings.

OBJECTIVE: To quantify familial risk of endometriosis among full siblings and examine interactions between family history and smoking, age at menarche or body mass index (BMI). DESIGN, SETTING AND POPULATION: Population-based nationwide cohort study. METHODS: Using data from the Korean National Health Insurance and Screening Programme databases on kinship, healthcare utilisation, lifestyle and anthropometrics, we identified 2 109 288 women with full siblings and their environmental risk factors from 2002 to 2018. Familial risks were estimated using Cox proportional-hazards models, represented as incidence risk ratios (IRR) with 95% CI. Interaction between family history and smoking, age at menarche or BMI were assessed on an additive scale. MAIN OUTCOME MEASURES: IRR of endometriosis among women with and without affected siblings. RESULTS: From 19 195 women with affected siblings, 1126 developed endometriosis with an incidence of 35.45/10 000 person-years. Familial risk of endometriosis with versus without affected siblings was increased to IRR 2.75 (95% CI 2.25-3.36), and the highest risk was with affected twins (IRR 6.98; 95% CI 4.19-11.62). Women with both a family history and either smoking, early menarche or low BMI had a significantly higher risk of endometriosis compared with the general population and can be regarded as a high-risk group, the IRRs were 4.28 (95% CI 2.43-7.55), 3.47 (95% CI 2.82-4.26) and 3.09 (95% CI 2.68-3.56), respectively. Substantial effect modification of the associations was noted by smoking and early menarche, as their combined risk with family history exceeded the sum of their individual risks, which was also statistically significant. CONCLUSION: Genetic factors are the primary contributor to the familial aggregation of endometriosis. Significant gene-environment interaction exists between family history and smoking or early menarche. TWEETABLE ABSTRACT: Significant gene-environment interaction exists between family history of endometriosis and smoking or early menarche.

Assessment of the efficacy of intra-articular platelet rich plasma treatment in an ACLT experimental model by dynamic contrast enhancement MRI of knee subchondral bone marrow and MRI T2∗ measurement of articular cartilage.

OBJECTIVE: The vascularization of subchondral bone plays a significant role in the progression of knee osteoarthritis (OA). Treatment with platelet-rich plasma (PRP) has positive effects on cartilage lesions. However, PRP's efficacy for subchondral bone marrow lesions and the relationship of these lesions to cartilage are still undiscovered. Therefore, our aims were first to longitudinally investigate the change in subchondral flow by dynamic contrast enhanced MRI and degeneration of cartilage by MRI T2∗ in an anterior cruciate transection rodent (ACLT) model, and second to examine changes in parameters after intra-articular PRP injection. DESIGN: A 32-week investigation in 18 rats allocated to sham-control, ACLT with normal saline injection (ACLT + NS), and ACLT with PRP injection groups ended with histological evaluation. Another rat was used as a donor of allogenic PRP. RESULTS: Compared to the sham-control group, the ACLT + NS group had higher subchondral blood volume A (0.051, 95% confidence interval: 0.009, 0.092) and lower venous washout kel (-0.030: -0.055, -0.005) from week 4; lower permeability kep from week 18 (-0.954: -1.339, -0.569); higher cartilage T2∗ values (1.803: 1.504, 2.102) reflecting collagen loss beginning at week 10. For the PRP treatment group, subchondral bone marrow A and cartilage T2∗ decreased from week 10. Histological results confirmed and were correlated with the MRI findings. CONCLUSION: Subchondral hyper-perfusion plays a vital role in the pathogenesis of OA and was associated with cartilage degeneration. The efficacy of PRP can be observed from reduced perfusion and MRI T2∗ values.

An easy way to secure catheter in position during marsupialization procedure.

Marsupialization is the conservative treatment for cystic lesion in children. This technique requires maintaining the patency between the cyst and oral cavity to allow spontaneous healing of cystic lesion. There have been various fixation methods for securing the patency. However, the previous fixation methods have limitation of being invasive and inability to retain catheter firmly during the treatment. In this technical note, we adopted a novel and easy fixation method to obtain firm stability of catheter without damage to intraoral tissues during marsupialization technique.

Association of serum ferritin levels with non-alcoholic fatty liver disease in postmenopausal women.

OBJECTIVE: This study aimed to investigate the association between serum ferritin levels and the presence of non-alcoholic fatty liver disease (NAFLD) in postmenopausal women. METHODS: Two hundred and forty-one postmenopausal women who participated in a heath examination program were enrolled in the present study. Serum ferritin tertiles were categorized as follows: T1, ≤46.4 ng/ml; T2, 46.5-76.1 ng/ml; and T3, ≥76.2 ng/ml. The odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD were calculated after adjusting for confounding variables across serum ferritin tertiles using multiple logistic regression analysis. RESULTS: The overall prevalence of NAFLD was 41.4% and was significantly increased in accordance with the serum ferritin tertiles as follows: 30.0% for T1, 40.7% for T2, and 54.3% for T3, respectively. As compared with the lowest tertile, the OR (95% CI) for NAFLD in the highest tertile was 2.69 (1.16-5.28) after adjusting for age, body mass index, regular exercise, mean arterial pressure, fasting plasma glucose, triglyceride, high-density lipoprotein cholesterol, alanine aminotransferase, and leukocyte count. CONCLUSION: The serum ferritin level was positively and independently associated with NAFLD in postmenopausal women and could be a useful additional measure in assessing the risk of NAFLD in postmenopausal women.

Direct bilirubin is associated with low-density lipoprotein subfractions and particle size in overweight and centrally obese women.

BACKGROUND AND AIMS: Bilirubin has antioxidant and anti-inflammatory properties; serum bilirubin levels have been known to be inversely associated with cardiovascular disease. However, the effects of different bilirubin subtypes on cardiometabolic traits are unknown. In this study, we aimed to determine whether direct bilirubin is more strongly correlated with small, dense low-density lipoprotein (sdLDL) compared to other bilirubin subtypes. We also investigated which LDL subfractions exhibited the highest correlation with direct bilirubin. METHODS AND RESULTS: A total of 288 overweight and centrally obese women were included in this study. The Pearson correlation and Steiger's Z test were used to compare the correlation coefficients between bilirubin subtypes and lipoproteins. Multiple linear regression analyses were used to evaluate the independent association between direct bilirubin and mean LDL particle size. Only direct bilirubin levels were significantly associated with the sdLDL subfraction and mean LDL particle size. Mean LDL particle size exhibited a significantly stronger correlation with direct bilirubin than sdLDL, percent sdLDL, and the sdLDL:large LDL ratio. Regression analysis showed that direct bilirubin was significantly associated with mean LDL particle size, according to both the stepwise method (ß = 11.445, P value = 0.002) and the enter method (ß = 11.655, P value = 0.002). CONCLUSIONS: Direct bilirubin is more strongly correlated with the sdLDL subfraction compared with total and indirect bilirubin, and is independently associated with mean LDL particle size in overweight and centrally obese women.

Repeated measurement of fractional exhaled nitric oxide is not essential for asthma screening

Background: Older guidelines recommend that fractional exhaled nitric oxide (FeNO) should be checked more than twice during the same session to confirm an asthma diagnosis. Recent studies show the excellent reproducibility of FeNO measurements. Objective: We aimed to determine whether repeated FeNO measurements during the same session are necessary for asthma screening. Methods: We retrospectively reviewed the electronic medical records of adult outpatients who visited the respiratory medicine department for diagnosis of asthma and assessed FeNO measurements obtained from June 2016 to July 2017. Results: Of the 132 patients enrolled, 79 (59.8%) were diagnosed with asthma. Repeated FeNO measurements taken during the same session showed high reproducibility (intraclass correlation coefficient >0.9; P<.001) and a strong correlation (Pearson coefficient >0.9; P<.001), although reproducibility and correlation were slightly weaker in patients with low FeNO values. The value of repeated measurement was not significant; however, the second FeNO measurement was significantly higher than the first measurement in patients with the worst and best lung function. The predictive power of the first measurement of FeNO (sensitivity, 80.5%; specificity, 85.1%) was not inferior to the second (sensitivity, 76.6%; specificity 85.1%). The same was true of the geometric mean of the two. Conclusion: Repeated FeNO measurement during the same session is not essential for asthma screening in cases where the first acceptable FeNO measurement is performed using the proper method

Introducción: Aunque las guías más antiguas recomiendan que el óxido nítrico exhalado (FeNO) se determine más de dos veces en la misma sesión para el diagnóstico de asma, algunos estudios recientes han demostrado la excelente reproducibilidad de las mediciones de FeNO. Objetivo: Nuestro objetivo fue determinar si las mediciones repetidas de FeNO durante la misma sesión son necesarias para el cribado del asma. Métodos: Revisamos retrospectivamente los registros médicos electrónicos de pacientes adultos ambulatorios que visitaron el departamento de neumología para confirmar un diagnóstico de asma durante los meses de junio de 2016 a julio de 2017, y se evaluaron las mediciones de FeNO obtenidas. Resultados: De un total de 132 pacientes estudiados, 79 pacientes (59,8%) fueron diagnosticados con asma. Las mediciones repetidas de FeNO tomadas durante la misma sesión mostraron una alta reproducibilidad (coeficiente de correlación intraclase> 0,9; p <0,001) y una fuerte correlación (coeficiente de Pearson> 0,9; p <0,001); sin embargo, la reproducibilidad y la correlación fueron ligeramente más débiles en sujetos con valores bajos de FeNO. El valor de la medición repetida no fue significativamente diferente entre sí en general; sin embargo, la segunda medición de FeNO fue significativamente más alta que la primera medición en sujetos con valores de la función pulmonar más bajos y más altos. El poder predictivo de FeNO para el diagnóstico de asma medido la primera vez (sensibilidad, 80,5%; especificidad, 85,1%) no fue inferior al medido la segunda vez (sensibilidad, 76,6%; especificidad 85,1%) o la media geométrica uniforme de los dos. Conclusión: La medición repetida de FeNO durante la misma sesión no es esencial para el cribado del asma en los casos en que la primera medición de FeNO es aceptable y se realiza con el método adecuado

Cognitive decision strategies adopted by consumers in reminder difference tests: Influence of the authenticity test.

Discrimination tests are used in food companies to quantify small differences between products. Within the diversity of methods available, some are quicker to conduct, whereas others are more sensitive or statistically powerful. One class of methods includes the reminder tasks in which the reference product is given before tasting the actual test stimuli. During the task, such a 'reminder' can be compared directly to each test stimulus, or alternatively, only serve to prime the memory of the judge without being taken into account in decision-making. Previous research with trained judges provided evidence for the latter process while research with untrained consumers has provided some evidence for the former process. Two studies were conducted with untrained consumers using the A Not-AR and 2-AFCR reminder tasks. Objectives were to determine the decision strategies used in, and the relative sensitivity of the tasks. In addition, the use of an "authenticity test" was explored to see if this has a positive effect on test performance. In the first study, mayonnaise and ice tea with small stimulus differences (d'<1) were used in A Not-AR and 2-AFCR. Results were compared to those from A Not-A and 2-AFC tasks, with and without an authenticity test. It was difficult to draw clear conclusions on the decision strategy used, though the use of an authenticity test increased the sensitivity for these small differences, as it improved the performance of 6 out of 8 tests. In the second study, ice teas with larger stimulus differences (at two levels) were tested using the A Not-AR and 2-AFCR tasks, in comparison to the same-different task. The results showed that consumers use the less optimal strategies and that the authenticity test decreases performance, which is contradictory to the results of the first study. It seems that for very small stimulus differences the authenticity test can improve performance, but with larger differences the authenticity test decreases performance; it seems to confuse the judges.

Increased sputum levels of thymus and activation-regulated chemokine in children with asthma not eosinophilic bronchitis

BACKGROUND: Thymus and activation-regulated chemokine (TARC), a member of the CC chemokine family, plays a crucial role in Th2-specific inflammation. We aimed to determine the concentration of sputum TARC in children with asthma and eosinophilic bronchitis (EB) and its relation with eosinophilic inflammation, pulmonary function, and bronchial hyper-responsiveness. METHODS: In total, 90 children with asthma, 38 with EB, and 45 control subjects were enrolled. TARC levels were measured in sputum supernatants using an ELISA. We performed pulmonary function tests and measured exhaled fractional nitric oxide, eosinophil counts in blood, and sputum and serum levels of total IgE in all children. RESULTS: Sputum TARC levels were significantly higher in children with asthma than in either children with EB (p = 0.004) or the control subjects (p = 0.014). Among patients with asthma, sputum TARC concentration was higher in children with sputum eosinophilia than in those without sputum eosinophilia (p = 0.035). Sputum TARC levels positively correlated with eosinophil counts in sputum, serum total IgE levels, exhaled fractional nitric, and the bronchodilator response. Negative significant correlations were found between sputum TARC and FEV1/FVC (the ratio of forced expiratory volume in one second and forced expiratory vital capacity) or PC20 (the provocative concentration of methacholine causing a 20% decrease in the FEV1). CONCLUSION: Elevated TARC levels in sputum were detected in children with asthma but not in children with EB. Sputum TARC could be a supportive marker for discrimination of asthma from EB in children showing characteristics of eosinophilic airway inflammation

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Immunologic regulatory effects of human umbilical cord blood-derived mesenchymal stem cells in a murine ovalbumin asthma model.

BACKGROUND: Mesenchymal stem cells (MSCs) have multiple immunomodulatory properties and hold therapeutic potential for inflammatory diseases. However, the therapeutic and immunologic effects of human umbilical cord blood-derived MSCs (huMSCs) remain largely unexamined for asthma. OBJECTIVE: This study was to investigate the immunomodulatory properties of huMSCs in an ovalbumin (OVA)-induced murine asthma model. METHODS: Mice were injected intraperitoneally with OVA and an aluminium hydroxide adjuvant. huMSCs were administered via the tail vein (5×105 cells/100 uL) to female BALB/c mice prior to the initial OVA challenge. The effects of huMSCs were assessed by investigating airway hyperresponsiveness, histological changes, inflammatory cell numbers, serum allergen-specific antibodies, cytokine production in spleen, lung tissue, and bronchoalveolar lavage (BAL) fluid as well as expansion of regulatory T cells. RESULTS: Administration of huMSCs significantly reduced methacholine bronchial hyperresponsiveness and eosinophil counts in BAL cells. Similarly, there was a significant decrease in serum OVA-specific IgE and IgG1 levels along with Th2 cytokine production (IL-4, IL-5, and IL-13) in the lung and spleen tissues, whereas increased percentage of regulatory T cells was observed after treatment with huMSCs. CONCLUSIONS: Our results suggest that huMSC treatment reduces OVA-induced allergic inflammation, which could be mediated by regulatory T cells.

Evaluation of the bristle end-rounding patterns of children's toothbrushes using scanning electron microscopy and stereomicroscopy.

OBJECTIVES: The aim of this study was to evaluate the proportions of end-rounded bristles via observations of the end patterns of various children's toothbrushes with scanning electron microscopy (SEM) and stereomicroscopy. METHODS: Ten different brands of children's toothbrushes were chosen, and tufts from each toothbrush were used. The prepared bristle specimens were observed on SEM and stereomicroscopic images and classified as acceptable (A1-A3) and non-acceptable (N1-N5) according to the modified classification. Then, the proportions of end-rounded bristles were calculated. RESULTS: Analyses of the 10 toothbrushes revealed that the proportions of acceptable end-rounded bristles ranged from 1.4% to 20.2% on SEM and from 0.0% to 18.0% on stereomicroscopic examinations. Additionally, some toothbrushes had labels that indicated bristle end-rounding, but the proportions of end-rounded bristles were low. CONCLUSIONS: The types and percentages of bristle ends of children's toothbrushes marketed in Korea were various, but the amount of acceptable end-rounded bristles was low. The result, that even toothbrushes labelled as end-rounded had potential to harm oral tissue, demonstrates that quality control for rounding bristle ends as well as the labelling for end-rounded bristles is needed.

Cartilage MRI T2∗ relaxation time and perfusion changes of the knee in a 5/6 nephrectomy rat model of chronic kidney disease.

OBJECTIVE: Chronic kidney disease (CKD) is characterized by metabolic disturbances in calcium and phosphorus homeostasis as kidney function declines. Alterations in blood perfusion in bone resulting from arteriosclerosis of bone vessels may relate to the progression of CKD. Herein, change in dynamic contrast enhanced (DCE) MRI parameters (A: amplitude, kel: elimination constant, and kep: permeability rate constant) and MRI T2∗ relaxation time of the knee cartilage were measured in a rodent nephrectomy model in order to (1) examine the relationship of peripheral blood perfusion to CKD and (2) demonstrate the feasibility of using DCE-MRI parameters and MRI T2∗ as imaging biomarkers to monitor disease progression. DESIGN: Two groups of male Sprague-Dawley rats received either (1) no intervention or (2) 5/6 nephrectomy. RESULTS: We found that the CKD group (compared with the control group) had lower A and kel values and similar kep value in the lateral and medial articular cartilages beginning at 12 weeks (P < 0.05); statistically significantly higher T2∗ values in the lateral and medial articular cartilages beginning at 18 weeks (P < 0.05); statistically significantly decreased inner luminal diameter of the popliteal artery, and altered structure of the lateral and medial articular cartilages (P < 0.05). CONCLUSION: Perfusion deficiency and CKD may be related. DCE parameters and MRI T2∗ could serve as imaging biomarkers of cartilage degeneration in CKD progression.

Identifying fibromyalgia subgroups using cluster analysis: Relationships with clinical variables.

BACKGROUND: Patients with fibromyalgia (FM) exhibit significant clinical heterogeneity, in terms of physical, social and psychological functions, as well as therapeutic responses. Here, we examined FM patients in terms of pain, physical, social and psychological variables to identify clinical subgroups that may be predictive of treatment patterns. METHODS: A total of 313 FM patients were interviewed using a structured questionnaire that included sociodemographic data, current or past FM symptoms and current use of relevant medications. A K-means cluster analysis was conducted using variables reflecting tender points, the Fibromyalgia Impact Questionnaire, Beck Depression Inventory, State-Trait Anxiety Inventor and Social Support Scale. RESULTS: Four distinct clusters were identified in these patients. Group 1 was characterized by high pain levels, severe physical and mental impairment and low social support. Group 2 had moderate pain and physical impairment, mild mental impairment and moderate social support. Group 3 had moderate pain, low physical and moderate mental impairment and low social support. Group 4 had low pain levels, nearly normal physical and mental function and high social support. Group 1 was more often a current or past smoker, more likely to have a variety of symptoms, including swelling, cognitive dysfunction, dizziness, syncope, oesophageal dysmotility, dyspepsia, irritable bladder, vulvodynia and restless leg syndrome. CONCLUSIONS: We identified four subgroups of FM patients based on pain, physical, social and psychological function. These subgroups had different clinical symptoms and medication profiles, suggesting that FM may be better managed using a more comprehensive assessment of an individual patient's symptoms. SIGNIFICANCE: FM patients can be clustered into four distinct subgroups based on clinically measurable variables - pain, physical involvement, psychological function and social support. These subgroups had different clinical symptoms and medication profiles.

Protein stability changes of the novel p.Arg180Cys mutant A glycosyltransferase resulted in a weak A phenotype.

A novel A subgroup allele (c.538C>T p.Arg180Cys) showing weak A phenotype was found in a 30-year-old Korean woman with ABO discrepancy. Using 3D structural analysis, protein stability prediction and flow cytometric analysis of ABO antigen expression on HeLa cells transfected with plasmids containing the p.Arg180Cys mutant, we found that the Arg180 residue in the loop region of the A glycosyltransferases (GTA) structure plays significant role in stabilizing its closed conformation, which is required for substrate binding and catalysis study.

Comparison of the oral microbiome of siblings using next-generation sequencing: a pilot study.

OBJECTIVE: The purpose of this study was to compare the oral microbiome of siblings with and without dental caries using next-generation sequencing. MATERIALS AND METHODS: To investigate the oral microbiome composition, 14 young siblings, seven with caries and seven without, were enrolled from seven sibling-pair families. Supragingival plaque samples were collected from the cervicobuccal area of posterior teeth. All samples were analyzed by pyrosequencing, based on the 16S rRNA gene hypervariable regions, V1-V4. RESULTS: The organisms identified belonged to 65 genera. Fifty-two genera were identified in the subjects with caries and 58 in those without; 45 genera were shared by both groups. In the Shannon index, the caries group showed lower bacterial diversity than the caries-free group and the difference was significant (Wilcoxon signed-rank test, P < 0.05). Additionally, similarities between siblings were evident in analyses based on weighted UniFrac distances (P < 0.05). CONCLUSIONS: In this study, the diversity of the microbiome was reduced in subjects with dental caries, while similarity between siblings seemed to be retained.

The Introduction of Human Heme Oxygenase-1 and Soluble Tumor Necrosis Factor-α Receptor Type I With Human IgG1 Fc in Porcine Islets Prolongs Islet Xenograft Survival in Humanized Mice.

Apoptosis during engraftment and inflammation induce poor islet xenograft survival. We aimed to determine whether overexpression of human heme oxygenase-1 (HO-1) or soluble tumor necrosis factor-α receptor type I with human IgG1 Fc (sTNF-αR-Fc) in porcine islets could improve islet xenograft survival. Adult porcine islets were transduced with adenovirus containing human HO-1, sTNF-αR-Fc, sTNF-αR-Fc/HO-1 or green fluorescent protein (control). Humanized mice were generated by injecting human cord blood-derived CD34(+) stem cells into NOD-scid-IL-2Rγ(null) mice. Both HO-1 and sTNF-αR-Fc reduced islet apoptosis under in vitro hypoxia or cytokine stimuli and suppressed RANTES induction without compromising insulin secretion. Introduction of either gene into islets prolonged islet xenograft survival in pig-to-humanized mice transplantation. The sTNF-αR-Fc/HO-1 group showed the best glucose tolerance. Target genes were successfully expressed in islet xenografts. Perigraft infiltration of macrophages and T cells was suppressed with decreased expression of RANTES, tumor necrosis factor-α and IL-6 in treatment groups; however, frequency of pig-specific interferon-γ-producing T cells was not decreased, and humoral response was not significant in any group. Early apoptosis of islet cells was suppressed in the treatment groups. In conclusion, overexpression of HO-1 or sTNF-αR-Fc in porcine islets improved islet xenograft survival by suppressing both apoptosis and inflammation. HO-1 or sTNF-αR-Fc transgenic pigs have potential for islet xenotransplantation.

Disulfanyl peptide decreases melanin synthesis via receptor-mediated ERK activation and the subsequent downregulation of MITF and tyrosinase.

OBJECTIVE: Bioactive peptides are commonly used in cosmeceutical purpose. This study was performed to search for an effective and short hypopigmenting peptide using normal human melanocytes as a screening model. A peptide that exhibits multitarget activities will be a promising peptide. METHODS: Depigmenting effects were tested in normal human melanocytes. One peptide was selected, and signalling mechanism was investigated by Western blotting and immunofluorescent microscopic examination. RESULTS: A novel hypopigmenting peptide (dSHP) has been found to inhibit the production of melanin. This peptide significantly decreases tyrosinase activity but was not effective in a direct in vitro assay. It also induces the prolonged activation of ERK, and subsequently downregulates the levels of MITF. PD98059 abolished the dSHP-induced downregulation of MITF. These findings indicate that the dSHP-induced activation of ERK contributes to a reduced melanin synthesis via the downregulation of MITF. Fluorescent microscopic studies were consistent with such findings. Pertussis toxin reverses the downregulation of MITF, which means that the receptor-mediated ERK activation is involved. Moreover, it was also found that downregulation of MITF was clearly inhibited by lysosomal inhibitor (chloroquine). CONCLUSION: Novel tetrapeptide dSHP reduces the melanin synthesis by a receptor-mediated pathway. Furthermore, dSHP works by ERK activation and key transcription factor MITF degradation. Thus, it may be a good candidate as an effective hypopigmenting cosmetic agent.

Abnormal perfusion in patellofemoral subchondral bone marrow in the rat anterior cruciate ligament transection model of post-traumatic osteoarthritis: a dynamic contrast-enhanced magnetic resonance imaging study.

OBJECTIVE: Although anterior cruciate ligament (ACL) injury is a well-recognized risk factor for developing knee post-traumatic osteoarthritis (PTOA), the process in the patellofemoral (PF) joint after ACL injury is still under-researched. Our aim was to investigate the perfusion changes in PF subchondral bone marrow in the rat ACL transection (ACLX) model of PTOA using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). DESIGN: Eighteen male Sprague Dawley rats were randomly separated into three groups (n = 6 each group): a normal control group and groups receiving ACLX and sham-surgery, respectively, in the right knee. Perfusion parameters in the patellar and femoral subchondral bone marrows of all rats were measured on DCE-MRI at 0, 4, 8, and 16 weeks after respective treatment. After the last MRI at week 16, the rats were sacrificed and their right knees were harvested for histologic examination. In addition, to observe the long-term histologic change in PF joints, 9 additional rats (n = 3 in each group) were included and sacrificed at week 32 for histologic examination. RESULTS: In the ACLX group vs the sham and control groups, the perfusion parameters were significantly changed in both patellar and femoral subchondral bone marrows at week 16. Histologic examination revealed cartilage defects in ACLX rats at 32 weeks after surgery. CONCLUSIONS: These data point to a possible functional relationship between subchondral bone marrow perfusion abnormalities and cartilage breakdown in PTOA. Moreover, the perfusion parameters derived from DCE-MRI can potentially serve as biomarkers of early OA.

Neuraxial block and postoperative epidural analgesia: effects on outcomes in the POISE-2 trial†.

BACKGROUND: We assessed associations between intraoperative neuraxial block and postoperative epidural analgesia, and a composite primary outcome of death or non-fatal myocardial infarction, at 30 days post-randomization in POISE-2 Trial subjects. METHODS: 10 010 high-risk noncardiac surgical patients were randomized aspirin or placebo and clonidine or placebo. Neuraxial block was defined as intraoperative spinal anaesthesia, or thoracic or lumbar epidural anaesthesia. Postoperative epidural analgesia was defined as postoperative epidural local anaesthetic and/or opioid administration. We used logistic regression with weighting using estimated propensity scores. RESULTS: Neuraxial block was not associated with the primary outcome [7.5% vs 6.5%; odds ratio (OR), 0.89; 95% CI (confidence interval), 0.73-1.08; P=0.24], death (1.0% vs 1.4%; OR, 0.84; 95% CI, 0.53-1.35; P=0.48), myocardial infarction (6.9% vs 5.5%; OR, 0.91; 95% CI, 0.74-1.12; P=0.36) or stroke (0.3% vs 0.4%; OR, 1.05; 95% CI, 0.44-2.49; P=0.91). Neuraxial block was associated with less clinically important hypotension (39% vs 46%; OR, 0.90; 95% CI, 0.81-1.00; P=0.04). Postoperative epidural analgesia was not associated with the primary outcome (11.8% vs 6.2%; OR, 1.48; 95% CI, 0.89-2.48; P=0.13), death (1.3% vs 0.8%; OR, 0.84; 95% CI, 0.35-1.99; P=0.68], myocardial infarction (11.0% vs 5.7%; OR, 1.53; 95% CI, 0.90-2.61; P=0.11], stroke (0.4% vs 0.4%; OR, 0.65; 95% CI, 0.18-2.32; P=0.50] or clinically important hypotension (63% vs 36%; OR, 1.40; 95% CI, 0.95-2.09; P=0.09). CONCLUSIONS: Neuraxial block and postoperative epidural analgesia were not associated with adverse cardiovascular outcomes among POISE-2 subjects.