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AIM: To compare the diagnostic test of integrated 2-[18F]-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.

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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.

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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.

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AIM: To investigate the predictive value of integrated 2-[18F]-fluoro-2-deoxy-d-glucose (18F-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 18F-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 18F-FDG PET/CT was 0.75 (95% confidence interval [CI]: 0.65-0.82) without heterogeneity (I2 = 47.2, p=0.08) and a pooled specificity of 0.73 (95% CI: 0.64-0.81) with heterogeneity (I2 = 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 18F-FDG PET/CT for the prediction of PD-L1 expression in solid tumours. At present, the literature regarding the use of 18F-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 18F-FDG PET/CT for prediction of PD-L1 expression in solid tumours.

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BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterised by involuntary muscle movements manifesting as motor and vocal tics. In the majority, tics are manageable without medication. Where tics cause discomfort or impair function, behavioural or pharmaceutical treatments may be considered. AIMS: To provide a meticulous examination of the quality of evidence for the current pharmacological treatments for TS. METHODS: PubMed and Google Scholar were searched to identify randomised, placebo-controlled trials (RCTs) of aripiprazole, risperidone, clonidine, guanfacine, haloperidol, pimozide, tiapride and sulpiride for the treatment of tics in children and adults with TS. Quality of reporting and risk of bias were assessed against the CONSORT checklist and Cochrane risk of bias criteria, respectively. RESULTS: Seventeen RCTs were identified. Response rates reached 88.6% for aripiprazole, 68.9% for clonidine, 62.5% for risperidone and 19% for guanfacine. Statistically significant improvements were reported for all medications compared to placebo in at least one study and for at least one measure of tic severity. Most studies predated the CONSORT and Cochrane criteria and did not score highly when assessed on these measures. CONCLUSIONS: There are relatively few placebo-controlled trials of commonly prescribed medications. Studies are often of poor quality and short duration. There is evidence for the efficacy of each medication, but no drug is clearly superior. Clonidine and guanfacine are better tolerated than antipsychotics, but less effective. There is too little evidence to determine whether adults respond differently from children.

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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 × 108  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.

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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.

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AIM: To investigate the diagnostic performance of 18F-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 18F-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 18F-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 18F-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 18F-fluciclovine PET/CT for management of PCa patients.

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scFv-BM3 is a single-chain variable fragment (scFv) against aflatoxin B1 (AFB1 ) 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 AFB1 , 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 AFB1 . 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 ß-sheet structure and adopted a proper conformation to bind AFB1 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 B1 (AFB1 ) (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 AFB1 . This study promotes the application of functional scFv-BM3 to the immunological detection of AFB1 in biotechnology fields.

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The use of calcium phosphate bone cement has been described to allow for retention of reduction. Therefore, we evaluated whether augmentation with resorbable calcium phosphate could improve fracture stability in osteoporotic hip fractures. The results showed that augmentation with calcium phosphate cement significantly improved the stability of intertrochanteric fractures. INTRODUCTION: The aim with this study was to measure whether augmentation with resorbable calcium phosphate cement could improve fracture stability in osteoporotic hip fractures. METHODS: We retrospectively reviewed 82 patients who underwent closed reduction and internal fixation with proximal femoral nail (PFN) for unstable intertrochanteric fractures between 2014 and 2017. In 42 of 82 patients, patients were treated with a PFN alone (group I). These patients were compared with 40 patients for whom the same device combined with calcium phosphate cement for augmentation was used (group II). Questionnaire surveys or telephone interviews were conducted and patients completed a self-report Harris hip score (HHS) and visual analog scale (VAS) scores. Radiographic outcomes including mean sliding distance of screw, femoral shortening, and varus collapse were compared. Postoperative complications were compared. RESULTS: Clinical outcomes at 6 months after surgery were equivalent in both groups. Screw sliding, femoral shortening, and varus collapse were all significantly reduced in the cemented group at the last follow-up (p < 0.001, p = 0.005, p < 0.001, respectively). A total of 9 (21%) complications occurred in group I. In contrast, 2 (5%) complications were seen in group II (p = 0.029). CONCLUSIONS: Augmentation with calcium phosphate cement significantly improved the stability of intertrochanteric fractures fixed with a PFN and reduced overall failure rates. We believe augmentation with resorbable calcium phosphate cement for osteoporotic hip fractures is a reasonable option in selected patients.

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AIMS: Tattooing and use of permanent makeup (PMU) has dramatically increased over the last decade, with a concomitant increase in ink-related infections. The aim of this study was to determine whether micro-organisms are present, and if so, the number and their identification in the commercial tattoo and PMU inks available in the United States. METHODS AND RESULTS: We surveyed 85 unopened tattoo and PMU inks, purchased from 13 companies. We incubated 100 µl of ink samples on trypticase soy agar plates for bacterial growth, 7H10 Middlebrook medium for mycobacterial growth, and Sabouraud dextrose medium for fungal growth. In total, 42 inks were contaminated with micro-organisms (49%). Thirty-three inks were contaminated with bacteria, 2 inks with fungi, and 7 inks had both bacterial and fungal growth. Mycobacteria were not detected in any of the examined tattoo and PMU inks. In 26 inks, microbial concentrations ranged between 101 and 103 CFU per ml, but higher counts (>103 CFU per ml) were recorded in 16 inks. We identified 83 bacteria by their 16S rDNA sequences, including 20 genera and 49 species. Strains of Bacillus spp. (53%) were dominant, followed by Lysinibacillus fusiformis (7%) and Pseudomonas aeruginosa (5%). Thirty-four (41%) possibly clinically relevant strains were identified, including P. aeruginosa, Dermacoccus barathri and Roseomonas mucosa, some of which have been previously reported to be associated with human skin infections. CONCLUSIONS: The results indicate that commercial tattoo and PMU inks on the US market surveyed in this study contain a wide range of micro-organisms, including pathogenic bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Microbial contaminants in tattoo and PMU inks are an emerging safety concern for public health. This study provides evidence that microbial contamination of tattoo and PMU inks available in the United States is more common than previously thought and highlights the importance of monitoring these products for potentially pathogenic micro-organisms.

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Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1f/f; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca2+/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1f/f; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.

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OBJECTIVES: The aim of the current study was to analyse the effects of posterior cruciate ligament (PCL) deficiency on forces of the posterolateral corner structure and on tibiofemoral (TF) and patellofemoral (PF) contact force under dynamic-loading conditions. METHODS: A subject-specific knee model was validated using a passive flexion experiment, electromyography data, muscle activation, and previous experimental studies. The simulation was performed on the musculoskeletal models with and without PCL deficiency using a novel force-dependent kinematics method under gait- and squat-loading conditions, followed by probabilistic analysis for material uncertain to be considered. RESULTS: Comparison of predicted passive flexion, posterior drawer kinematics and muscle activation with experimental measurements showed good agreement. Forces of the posterolateral corner structure, and TF and PF contact forces increased with PCL deficiency under gait- and squat-loading conditions. The rate of increase in PF contact force was the greatest during the squat-loading condition. The TF contact forces increased on both medial and lateral compartments during gait-loading conditions. However, during the squat-loading condition, the medial TF contact force tended to increase, while the lateral TF contact forces decreased. The posterolateral corner structure, which showed the greatest increase in force with deficiency of PCL under both gait- and squat-loading conditions, was the popliteus tendon (PT). CONCLUSION: PCL deficiency is a factor affecting the variability of force on the PT in dynamic-loading conditions, and it could lead to degeneration of the PF joint.Cite this article: K-T. Kang, Y-G. Koh, M. Jung, J-H. Nam, J. Son, Y.H. Lee, S-J. Kim, S-H. Kim. The effects of posterior cruciate ligament deficiency on posterolateral corner structures under gait- and squat-loading conditions: A computational knee model. Bone Joint Res 2017;6:31-42. DOI: 10.1302/2046-3758.61.BJR-2016-0184.R1.

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We analysed scaphoid deformity as a result of surgical treatment of scaphoid fracture nonunion and assessed the deformity associated with a dorsal intercalated segmental instability pattern of carpal malalignment. A total of 45 patients who were treated for scaphoid fracture nonunion were included in the study. The height-to-length ratio of the scaphoid was measured on computed tomographic images and used to assess scaphoid deformity. Carpal malalignment was quantified based on the radio-lunate angle. A correlation analysis between the height-to-length ratio and the radio-lunate angle was performed. Dorsal intercalated segmental instability was defined as a radio-lunate angle >15°, and a receiver operating curve analysis was used to calculate the cutoff height-to-length ratio that can be accompanied with dorsal intercalated segmental instability. Extension of the lunate increases in proportion to the flexion deformity of the scaphoid; dorsal intercalated segmental instability can occur if the height-to-length ratio of the scaphoid is >0.73. LEVEL OF EVIDENCE: IV.

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AIMS: The aim of the study was to develop a quantitative scoring system to predict whether a large-to-massive rotator cuff tear was arthroscopically reparable prior to surgery. PATIENTS AND METHODS: We conducted a retrospective review of the pre-operative MR imaging and surgical records of 87 patients (87 shoulders) who underwent arthroscopic repair of a large-to-massive rotator cuff tear. Patients were divided into two groups, based on the surgical outcome of the repair. Of the 87 patients, 53 underwent complete repair (Group I) and 34 an incomplete repair (Group II). Pre-operative MR images were reviewed to quantify several variables. Between-group differences were evaluated and multiple logistic regression analysis was used to calculate the predictive value of significant variables. The reparability index (RI) was constructed using the odds ratios of significant variables and a receiver operating characteristic curve analysis performed to identify the optimal RI cutoff to differentiate between the two groups. RESULTS: The following variables were identified as independent predictors of arthroscopic reparability: the size of the defect with medial-lateral diameter (cutoff, 4.2 cm) and anterior-posterior diameter (cutoff, 3.7cm); Patte's grade of muscle atrophy (cutoff, grade 3) and Goutallier grade of fatty degeneration (cutoff, grade 3). An RI cutoff value of 2.5 provided the highest differentiation between groups I and II, with an area under the curve of 0.964, and a sensitivity of 73.5% and specificity of 96.2%. CONCLUSION: The RI developed in our study may prove to be an efficient clinical scoring system to predict whether a large-to-massive rotator cuff tear is arthroscopically reparable. Cite this article: Bone Joint J 2016;98-B:1656-61.

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BACKGROUND: Organ donation after brain death is a major source for obtaining transplantable organs for patients with end-stage organ disease. However, the time from declaring brain death to organ procurement is often longer than expected. Analyzing factors that delay organ procurement may help to prevent damage to organs from marginal and unstable donors and aid in preparation for recipient operation. The aim of this study was to examine factors associated with the interval between the time of declaring brain death and organ procurement. METHODS: Medical records of patients who underwent organ procurement after brain death from February 2009 to April 2015 were retrospectively reviewed. RESULTS: Of the 77 patients which were scheduled to undergo organ procurement, 68 eventually underwent procurement of ≥1 organ. The average time interval from 1st exam for brain death to organ procurement decreased from 1,248 minutes in 2009 to 910 minutes in 2015. Although not statistically significant, during the 6-year period, the time interval decreased from 1,105 minutes to 1,075 minutes in the latter half of the period (P = .623). Organ procurement was extensively delayed most commonly owing to false negative electroencephalogram (EEG; 62.5%). CONCLUSIONS: With increasing experience in dealing with brain death donors, the time interval from declaring brain death to organ procurement decreased. We suggest that an EEG be performed during the initial stages of examination for brain death to prevent unnecessary preparation of recipient operation owing to a false EEG test.

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PURPOSE: The influence of human leukocyte antigen (HLA) mismatch on liver transplantation has been widely studied, but is still controversial. The aim of this large single-center study was to analyze the role of HLA compatibility between donor and recipient in the graft outcomes of living donor liver transplantation (LDLT). MATERIALS AND METHODS: A total of 925 recipients who had undergone LDLT between March 2001 and April 2012 were retrospectively analyzed. HLA typing was performed using a standard complement-dependent cytotoxicity technique. The degree and type of HLA-A, HLA-B, and HLA-DR mismatch were assessed. We also investigated the posttransplantation laboratory data, incidence of rejection, recurrence of hepatitis B virus (HBV), and graft survival as outcome parameters. RESULTS: The type of HLA-A, HLA-B, and HLA-DR mismatch had no effect on rejection episodes, whereas the beneficial effect of a much lower degree (0-2) of HLA mismatch was notable. Recipients with 2 HLA-B mismatches or recipients with a higher degree of mismatch were associated with elevated bilirubin level, a higher recurrence rate of HBV, and inferior graft survival. A complete mismatch of 2 at the DR locus also decreased graft survival in LDLT recipients. CONCLUSIONS: This study confirmed that the degree of HLA mismatch, as well as the locus-specific type of HLA mismatch, namely B and DR, play a major role in graft outcomes after LDLT. To obtain an improved graft outcome, HLA compatibility should be considered in the setting of LDLT, which provides sufficient time to select a more favorable donor-recipient combination.

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OBJECTIVES: The aim of this study was to explore the phenotypic differences underpinning obesity susceptibility or resistance based on the metabolic and transcriptional profiling of C57BL/6J mice fed a high-fat diet (HFD). METHODS: The mice were fed either a normal diet or HFD for 12 weeks. After 6 weeks, the mice on HFD were classified as either obesity-prone (OP) or obesity-resistant (OR) depending on the body weight gain. RESULTS: Lipid profiles from plasma and liver significantly improved in OR mice relative to the OP group. Energy expenditure was greater in OR mice than in OP mice, with a simultaneous decrease in body fat mass. Epididymal white adipose tissue (eWAT) and liver were enlarged in OP mice (with visible immune-cell infiltration), but these effects were attenuated in OR mice compared with OP mice. Overall glucose metabolism was enhanced in OR mice compared with OP mice, including homeostasis model assessment for insulin resistance, plasma glucose and insulin concentrations, glucokinase activity and hepatic glycogen. Plasma adipokines and proinflammatory cytokines were upregulated in OP mice, and these changes were attenuated in OR mice. Transcriptomic profiles of eWAT and liver revealed common and divergent patterns of transcriptional changes in OP and OR mice, and pointed to differential metabolic phenotypes of OP and OR mice. There were substantial differences between OP and OR mice in molecular pathways, including atherosclerosis signaling, sperm motility, cAMP-mediated signaling in eWAT; and fibrosis, agranulocyte adhesion and diapedesis, and atherosclerosis signaling in liver. CONCLUSIONS: Taken altogether, the results provide robust evidence of major divergence in the transcriptomes, phenotypes and metabolic processes between obesity susceptibility and obesity resistance in the HFD-fed C57BL/6J mice.

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Humanin is the first newly discovered peptide encoded in the mitochondrial genome in over three decades. It is the first member of a novel class of mitochondrial derived peptides. This small, 24 amino acid peptide was initially discovered to have neuroprotective effects and subsequent experiments have shown that it is beneficial in a diverse number of disease models including stroke, cardiovascular disease, and cancer. Over a decade ago, our lab found that humanin bound IGFBP-3 and more recent studies have found it to decrease circulating IGF-I levels. In turn, IGF-I also seems to regulate humanin levels and in this review, we cover the known interaction between humanin and IGF-I. Although the exact mechanism for how humanin and IGF-I regulate each other still needs to be elucidated, it is clear that humanin is a new player in IGF-I signaling.

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