Nox4-SH3YL1 complex is involved in diabetic nephropathy.

Nox4-derived H2O2 generation plays an important role in the pathogenesis of chronic kidney diseases (CKDs) such as diabetic nephropathy (DN). Here, we showed that SH3 domain-containing Ysc84-like 1 (SH3YL1), a Nox4 cytosolic activator, regulated DN. Streptozotocin (STZ)-induced type Ⅰ diabetic models in SH3YL1 whole-body knockout (KO) mice and podocyte-specific SH3YL1 conditional KO (Nphs2-Cre/SH3YL1fl/fl) mice were established to investigate the function of SH3YL1 in DN. The expression of fibrosis markers and inflammatory cytokines, the generation of oxidative stress, and the loss of podocytes were suppressed in diabetic SH3YL1 KO and Nphs2-Cre/SH3YL1fl/fl mice, compared to diabetic control mice. To extrapolate the observations derived from diabetic mice to clinical implication, we measured the protein level of SH3YL1 in patients DN. In fact, the SH3YL1 level was increased in patients DN. Overall, the SH3YL1-Nox4 complex was identified to play an important role in renal inflammation and fibrosis, resulting in the development of DN.

High water intake induces primary cilium elongation in renal tubular cells.

Background: The primary cilium protrudes from the cell surface and functions as a mechanosensor. Recently, we found that water intake restriction shortens the primary cilia of renal tubular cells, and a blockage of the shortening disturbs the ability of the kidneys to concentrate urine. Here, we investigate whether high water intake (HWI) alters primary cilia length, and if so, what is its underlying mechanism and its role on kidney urine production. Methods: Experimental mice were given free access to normal water (normal water intake) or 3% sucrose-containing water for HWI for 2 days. Some mice were administered with U0126 (10 mg/kg body weight), an inhibitor of MEK kinase, from 2 days before HWI, daily. The primary cilium length and urine amount and osmolality were investigated. Results: HWI-induced diluted urine production and primary cilium elongation in renal tubular cells. HWI increased the expression of α-tubulin acetyltransferase 1 (αTAT1), leading to the acetylation of α-tubulins, a core protein of the primary cilia. HWI also increased phosphorylated ERK1/2 (p-ERK1/2) and exocyst complex component 5 (EXOC5) expression in the kidneys. U0126 blocked HWI-induced increases in αTAT1, p-ERK1/2, and EXOC5 expression. U0126 inhibited HWI-induced α-tubulin acetylation, primary cilium elongation, urine amount increase, and urine osmolality decrease. Conclusion: These results show that increased water intake elongates the primary cilia via ERK1/2 activation and that ERK inhibition prevents primary cilium elongation and diluted urine production. These data suggest that the elongation of primary cilium length is associated with the production of diluted urine.

Shortening of primary cilia length is associated with urine concentration in the kidneys.

BACKGROUND: The primary cilium, a microtubule-based cellular organelle present in certain kidney cells, functions as a mechano-sensor to monitor fluid flow in addition to various other biological functions. In kidneys, the primary cilia protrude into the tubular lumen and are directly exposed to pro-urine flow and components. However, their effects on urine concentration remain to be defined. Here, we investigated the association between primary cilia and urine concentration. METHODS: Mice either had free access to water (normal water intake, NWI) or were not allowed access to water (water deprivation, WD). Some mice received tubastatin, an inhibitor of histone deacetylase 6 (HDAC6), which regulates the acetylation of α-tubulin, a core protein of microtubules. RESULTS: WD decreased urine output and increased urine osmolality, concomitant with apical plasma membrane localization of aquaporin 2 (AQP2) in the kidney. After WD, compared with after NWI, the lengths of primary cilia in renal tubular epithelial cells were shortened and HDAC6 activity increased. WD induced deacetylation of α-tubulin without altering α-tubulin levels in the kidney. Tubastatin prevented the shortening of cilia through increasing HDAC6 activity and consequently increasing acetylated α-tubulin expression. Furthermore, tubastatin prevented the WD-induced reduction of urine output, urine osmolality increase, and apical plasma membrane localization of AQP2. CONCLUSIONS: WD shortens primary cilia length through HDAC6 activation and α-tubulin deacetylation, while HDAC6 inhibition blocks the WD-induced changes in cilia length and urine output. This suggests that cilia length alterations are involved, at least in part, in the regulation of body water balance and urine concentration.

The Concordance of Alveolar Bone Deficiency with Severity of Lip Deformity in Microform Cleft Lip.

Background: We assessed the anthropometric measurements of bone defects in microform cleft lip. Methods: The external phenotypes of the nose and upper lip, and alveolar bone defects in microform cleft lip were measured anthropometrically using multimodal tools and clinical photographs. The height and thickness of the alveolar bone, paranasal hypoplasia, and alveolar volume were measured on CT. Results: Our study included 23 patients with unilateral microform cleft lip. The mean age of the patients was 13.84 ± 12.35 years (range: 1.25−50 years). Alveolar height (C1), thickness (C2), and paranasal hypoplasia (C3) were evaluated on 3D CT scans. The mean differences in C1, C2, and C3 between the cleft and normal sides were 5.52 ± 3.76 mm (p < 0.0001), 1.96 ± 2.8 mm (p < 0.0001), and 5.57 ± 9.72 mm (p < 0.0001), respectively. There was bony deficiency at the cleft side of the alveolar bone and paranasal area. In volumetric analysis, the means of the normal and cleft-side alveolar bone volumes were 6579 ± 2200 mm3 and 6528 ± 2255 mm3, respectively. The mean difference in alveolar bone volume between the cleft and normal sides was 51.05 ± 521 mm3 (p < 0.0001). C1 was positively correlated with lip height (F2; correlation coefficient (r) = 0.564, p = 0.0051) and dry vermilion thickness (F3; r = −0.543, p = 0.0074). The linear regression test revealed significant correlations between C1 and F2 (r2 = 0.318, p = 0.0051), and F3 (r2 = 0.295, p = 0.0074). However, there was no correlation between alveolar height and nasal anthropometric measurements. Conclusions: Alveolar bone deficiency was concordant with the severity of soft tissue in microform cleft lip.

An Evaluation of Muscle Repair Techniques: Implications in Musculoskeletal Healing and Corollaries in Oral-Facial Clefting.

We performed an animal study to identify the techniques associated with the best muscle healing outcomes in cleft lip/palate surgery. The right triceps of thirty adult male Sprague-Dawley rats were cut and repaired by three different suture techniques: simple (n = 10), overlapping (n = 10), and splitting sutures (n = 10). Muscle tissues were isolated from 5 rats per group 1 and 8 weeks postoperation. The inflammatory response and muscle fiber healing were evaluated by hematoxylin and eosin (H&E) staining, Western blotting, immunohistochemistry for TNF-α and IL-1ß, and immunofluorescence for laminin and MyoD. Grip strength (N/100 g) and spatial gait symmetry were evaluated before surgery and 1, 2, 4 and 8 weeks postoperation. Eight weeks postoperation, grip force per weight was significantly higher in the simple suture (median, 3.49; IQR, 3.28-3.66) and overlapping groups (median, 3.3; IQR, 3.17-3.47) than the splitting group (median, 2.91; IQR, 2.76-3.05). There was no significant difference in range of motion between groups. The simple group exhibited significant remission of inflammation by H&E staining and lower expression of TNF-α and IL-1ß than the other groups by Western blotting and immunohistochemistry. Immunofluorescence revealed stronger expression of MyoD and weaker expression of laminin in the splitting group than in the other groups at week 8, indicating prolonged inflammation and healing followed by poor muscle fiber remodeling. Simple and overlapping sutures demonstrated similar functional healing, although greater inflammation and failure to maintain a thicker muscle belly were observed in the overlapping suture group compared with the simple suture group. Therefore, reconstruction of the philtral column with overlapping sutures alone may result in limited long-term fullness, and additional procedures may be needed.

Coordinating Global Multi-Site Studies of Military-Relevant Traumatic Brain Injury: Opportunities, Challenges, and Harmonization Guidelines.

Traumatic brain injury (TBI) is common among military personnel and the civilian population and is often followed by a heterogeneous array of clinical, cognitive, behavioral, mood, and neuroimaging changes. Unlike many neurological disorders that have a characteristic abnormal central neurologic area(s) of abnormality pathognomonic to the disorder, a sufficient head impact may cause focal, multifocal, diffuse or combination of injury to the brain. This inconsistent presentation makes it difficult to establish or validate biological and imaging markers that could help improve diagnostic and prognostic accuracy in this patient population. The purpose of this manuscript is to describe both the challenges and opportunities when conducting military-relevant TBI research and introduce the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Military Brain Injury working group. ENIGMA is a worldwide consortium focused on improving replicability and analytical power through data sharing and collaboration. In this paper, we discuss challenges affecting efforts to aggregate data in this patient group. In addition, we highlight how "big data" approaches might be used to understand better the role that each of these variables might play in the imaging and functional phenotypes of TBI in Service member and Veteran populations, and how data may be used to examine important military specific issues such as return to duty, the late effects of combat-related injury, and alteration of the natural aging processes.

Anthropometric Changes in the Upper Lip Between the Standing Position in the Clinic and Supine Position on the Operative Table in Secondary Cleft Lip Nasal Deformities.

BACKGROUND: We evaluated changes in lip height and length by position in cleft lip nasal deformity patients who underwent treatment with Millard technique. METHODS: A retrospective review of the medical records and an anthropometric analysis of photographs were performed in 209 cases of cleft lip nasal deformity. In the photogrammetric analysis, the lip height and length were calculated with respect to the intercanthal width. To evaluate the change in the difference between the cleft- and noncleft-side measurements between the standing and supine positions, the difference between the cleft- and noncleft-side measurements (Δnc-c) was calculated. We identified which patients and surgical factors affected the difference between the cleft- and noncleft-side measurements between the standing and supine positions (Δst-sp). RESULTS: From a total of 120 cases, cases with missing medical charts and clinical photographs were excluded, and 89 cases were included in this study. The discrepancy between the cleft-side lip height and noncleft-side lip height was significantly different between the standing and supine positions (P = 0.007). According to the univariate regression analysis, Δst-sp (sbal-cphi) had a significant positive correlation with body mass index (P = 0.044). In the final multiple linear regression analysis, body mass index had a significant positive correlation with Δst-sp (sbal-cphi, P = 0.044). CONCLUSION: In our results, the difference in vertical lip height is easy to underestimate in the supine position during surgery. Therefore, surgeons should verify lip height with the patient in the sitting or standing position during the operation to avoid undercorrecting lips with short heights.

Cognitive Training Reorganizes Network Modularity in Traumatic Brain Injury.

Background. Graph-theoretic approaches are increasingly popular for identifying the patterns of disrupted neural systems after traumatic brain injury (TBI). However, the patterns of neuroplasticity in brain organization after cognitive training in TBI are less well understood. Objective. We identified the patterns of training-induced neuroplasticity of the whole-brain network in TBI, using resting-state functional connectivity and graph theory. Methods. A total of 64 civilians and veterans with TBI were randomized into either a strategy-based cognitive training group (n = 33) or a knowledge-based training group (active control group; n = 31) for 8 weeks. The participants experienced mild to severe TBI without focal damage and persistent cognitive dysfunctions. A subset of participants complained of subclinical but residual psychiatric symptoms. We acquired their resting-state functional magnetic resonance imaging before training, immediately posttraining, and 3 months posttraining. From participants' resting-state networks, we obtained the modularity, participation coefficient, within-module connectivity, global efficiency, and local efficiency over multiple network densities. We next performed longitudinal analyses on those measures corrected for multiple comparisons across network densities using false discovery rate (FDR). Results. Relative to the knowledge-based training group, the strategy-based cognitive training group had reduced modularity and increased participation coefficient, global efficiency, and local efficiency over time (Pnodal < .05; qFDR < 0.05). Brain behavior analysis revealed that the participation coefficient and global efficiency within the strategy-based cognitive training group correlated with trail-making scores in the context of training (Pnodal < .05; qFDR < 0.05). Conclusions. Cognitive training reorganized modular networks in TBI over the whole brain. Graph-theoretic approaches may be useful in identifying a potential brain-based marker of training efficacy in TBI.

Correlation between the inframammary fold and sixth rib: Application to breast reconstruction.

The inframammary fold (IMF) is an essential aesthetic element that influences the outcome of breast surgery. In this study, we introduced a new method for finding the IMF based on retrospective analysis of chest computed tomography (CT) scans of women's breasts. Sagittal sections of 80 female chest CTs were analyzed. Sagittal sections of 80 female chest CTs were analyzed by a single plastic surgeon. The distances between the fifth, sixth, and seventh ribs and the IMF were measured using Photoshop, and the location of the IMF was statistically analyzed according to age and height using paired t tests and Pearson's correlation test. As determined by our new method, the average distance between the IMF and the sixth rib was 5.33 mm, which was less than that between the IMF and any other rib. The IMF was closest to the sixth rib in all age groups (P < 0.001), and all IMFs were located between 39.5 mm superior and 24 mm inferior to the sixth rib. The sixth rib, one of the most visible reference structures in women's surface anatomy, is the "sentinel rib" for the IMF and the most predictive indicator of the location of the IMF. Knowing the original anatomic location of the IMF will enable better outcomes during breast surgery. Clin. Anat. 33:165-172, 2020. © 2019 Wiley Periodicals, Inc.

Associating Psychotic Symptoms with Altered Brain Anatomy in Psychotic Disorders Using Multidimensional Item Response Theory Models.

Reduced cortical thickness has been demonstrated in psychotic disorders, but its relationship to clinical symptoms has not been established. We aimed to identify the regions throughout neocortex where clinical psychosis manifestations correlate with cortical thickness. Rather than perform a traditional correlation analysis using total scores on psychiatric rating scales, we applied multidimensional item response theory to identify a profile of psychotic symptoms that was related to a region where cortical thickness was reduced. This analysis was performed using a large population of probands with psychotic disorders (N = 865), their family members (N = 678) and healthy volunteers (N = 347), from the 5-site Bipolar-Schizophrenia Network for Intermediate Phenotypes. Regional cortical thickness from structural magnetic resonance scans was measured using FreeSurfer; individual symptoms were rated using the Positive and Negative Syndrome Scale, Montgomery-Asberg Depression Rating Scale, and Young Mania Rating Scale. A cluster of cortical regions whose thickness was inversely related to severity of psychosis symptoms was identified. The regions turned out to be located contiguously in a large region of heteromodal association cortex including temporal, parietal and frontal lobe regions, suggesting a cluster of contiguous neocortical regions important to psychosis expression. When we tested the relationship between reduced cortical surface area and high psychotic symptoms we found no linked regions describing a related cortical set.

Septal Integration Graft, a Modified Direct Type of Septal Extension Graft for the Treatment of Unilateral Cleft Lip Nose Deformity: An Anthropometric Analysis.

BACKGROUND: The purpose of this study was to evaluate the cosmetic outcomes and stability of septal integration grafts (SIGs), a modified direct type of septal extension graft, in patients with cleft lip nose deformity. METHODS: Seventy-three patients underwent SIGs between January 2002 and July 2017. The exclusion criteria were patients who lacked clinical photographs preoperatively or postoperatively. We reviewed data regarding the patient demographics, combined procedures, and complications as well as preoperative and postoperative clinical photography. Eleven measurement items were evaluated from basal and right lateral views with photogrammetry and 3-dimensional anthropometry using standardized clinical photographic techniques. RESULTS: Sixty-one patients were analyzed in this study. Twelve patients were excluded owing to a lack of postoperative photographs. The mean ± SD follow-up period was 26.70 ± 29.43 months (range, 6-134 months). Compared with the preoperative value, the nasal tip projection index, height of nose index, and nostril axis inclination significantly improved. The columellar length (Rt-Lt) index significantly decreased, which implied improved columellar deviation. Complications included hematoma (n = 1), wound dehiscence (n = 1), tearing of septal mucosa (n = 3), and silicone implant deviation (n = 2). CONCLUSIONS: We used SIGs to correct nasal deformity in patients with cleft lip nose deformity. The SIG can minimize the amount of the graft used for septal extension and can effectively correct nasal tip and columella deformities.

Executive function training in chronic traumatic brain injury patients: study protocol.

BACKGROUND: Some individuals who sustain traumatic brain injuries (TBIs) continue to experience significant cognitive impairments chronically (months to years post injury). Many tests of executive function are insensitive to these executive function impairments, as such impairments may only appear during complex daily life conditions. Daily life often requires us to divide our attention and focus on abstract goals. In the current study, we compare the effects of two 1-month electronic cognitive rehabilitation programs for individuals with chronic TBI. The active program (Expedition: Strategic Advantage) focuses on improving goal-directed executive functions including working memory, planning, long-term memory, and inhibitory control by challenging participants to accomplish life-like cognitive simulations. The challenge level of the simulations increases in accordance with participant achievement. The control intervention (Expedition: Informational Advantage) is identical to the active program; however, the cognitive demand level is capped, preventing participants from advancing beyond a set level. We will evaluate these interventions with a military veteran TBI population. METHODS/DESIGN: One hundred individuals will be enrolled in this double-blinded clinical trial (all participants and testers are blinded to condition). Each individual will be randomly assigned to one of two interventions. The primary anticipated outcomes are improvement of daily life cognitive function skills and daily life functions. These are measured by a daily life performance task, which tests cognitive skills, and a survey that evaluates daily life functions. Secondary outcomes are also predicted to include improvements in working memory, attention, planning, and inhibitory control as measured by a neuropsychological test battery. Lastly, neuroimaging measures will be used to evaluate changes in brain networks supporting cognition pre and post intervention. DISCUSSION: We will test whether electronically delivered cognitive rehabilitation aimed at improving daily life functional skills will provide cognitive and daily life functional improvements for individuals in the chronic phase of TBI recovery (greater than 3 months post injury). We aim to better understand the cognitive processes involved in recovery and the characteristics of individuals most likely to benefit. This study will also address the potential to observe generalizability or to transfer from a software-based cognitive training tool toward daily life improvement. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03704116 . Retrospectively registered on 12 Oct 2018.

The influence of oxytocin and vasopressin on men's judgments of social dominance and trustworthiness: An fMRI study of neutral faces.

Cues signaling trust and dominance are crucial for social life. Previous studies on the effects of oxytocin (OT) nasal sprays on trustworthiness evaluations have been inconsistent and its influence on dominance is unknown. Vasopressin (AVP) may also influence social cue perception, but even fewer investigations have evaluated this possibility. We evaluated the effects of intranasal OT and AVP compared to placebo control during three double-blinded functional magnetic resonance imaging sessions. Twenty males received a pseudo-randomized order of nasal spray conditions and rated the trustworthiness and dominance of neutral faces. OT increased facial dominance ratings compared to placebo. Neuroimaging results revealed an inverse relationship between brain activation and face ratings for OT compared to placebo in regions involved in processing emotional expressions. Specifically, the right superior temporal gyrus was attenuated as ratings increased and the left precuneus selectively diminished with increasing dominance ratings. Additionally, OT increased functional connectivity between frontoparietal regions and the right amygdala for faces rated as highly dominant, but OT increased connectivity between the fusiform gyrus, hippocampus, and bilateral ventral tegmental area (VTA) for faces perceived as highly trustworthy. Overall, OT increased the perception of dominance but did not influence trustworthiness judgments. However, we observed regional neural effects for OT that differed between judgments of trustworthiness and dominance. AVP attenuated left temporoparietal junction activity as face ratings increased, a result consistent with AVP influencing mentalization. AVP also led to increased left amygdala and right VTA connectivity with the putamen, which is consistent with cue-driven, habitual responses.

Atg7-dependent canonical autophagy regulates the degradation of aquaporin 2 in prolonged hypokalemia.

Prolonged hypokalemia induces a decrease of urinary concentrating ability via down-regulation of aquaporin 2 (AQP2); however, the precise mechanisms remain unknown. To investigate the role of autophagy in the degradation of AQP2, we generated the principal cell-specific Atg7 deletion (Atg7Δpc) mice. In hypokalemic Atg7-floxed (Atg7f/f) mice, huge irregular shaped LC3-positive autophagic vacuoles accumulated mainly in inner medullary collecting duct (IMCD) cells. Total- and pS261-AQP2 were redistributed from apical and subapical domains into these vacuoles, which were not co-localized with RAB9. However, in the IMCD cells of hypokalemic Atg7Δpc mice, these canonical autophagic vacuoles were markedly reduced, whereas numerous small regular shaped LC3-negative/RAB9-positive non-canonical autophagic vacuoles were observed along with diffusely distributed total- and pS261-AQP2 in the cytoplasm. The immunoreactivity of pS256-AQP2 in the apical membrane of IMCD cells was markedly decreased, and no redistribution was observed in both hypokalemic Atg7f/f and Atg7Δpc mice. These findings suggest that AQP2 down regulation in hypokalemia was induced by reduced phosphorylation of AQP2, resulting in a reduction of apical plasma labeling of pS256-AQP2 and degradation of total- and pS261-AQP2 via an LC3/ATG7-dependent canonical autophagy pathway.

Altered Redox State Modulates Endothelial KCa2.3 and KCa3.1 Levels in Normal Pregnancy and Preeclampsia.

AIMS: Altered redox state has been related to the development of normal pregnancy (NP) and preeclampsia (PE). Endothelial KCa2.3 and KCa3.1 (KCas) play an important role in vasodilation, and KCas levels are affected by oxidative stress. We investigated the mechanisms of oxidative stress-mediated KCas expression modulation during NP and PE. RESULTS: Human uterine microvascular endothelial cells were incubated in serum from normal nonpregnant women (n = 13) and women with NP (n = 24) or PE (n = 15), or in vascular endothelial growth factor (VEGF), oxidized low-density lipoprotein (ox-LDL), progesterone, or estradiol-17ß (E2)-containing medium for 24 h. NP serum elevated H2O2 levels via reducing catalase and glutathione peroxidase 1 levels, thereby enhancing KCas levels via a H2O2/fyn/extracellular signal-regulated kinase (ERK)-mediated pathway. VEGF enhanced H2O2 and KCas levels and KCa3.1 currents. KCas were upregulated and KCas activation-induced endothelium-dependent relaxation (EDR) was augmented in vessels from pregnant mice and rats. Whereas PE serum, ox-LDL, progesterone, or soluble fms-like tyrosine kinase 1 (sFlt-1) elevated superoxide levels via elevating NADPH oxidase 2 (NOX2) and NOX4 levels and reducing superoxide dismutase (SOD) 1 levels, thereby downregulating KCas. sFlt-1 inhibited EDR. PE serum- or progesterone-induced alterations in levels of KCas were reversed by polyethylene glycol-SOD, NOX inhibition, or E2. Innovation and Conclusions: This is the first study of how endothelial KCas levels are modulated during NP and PE. KCas were upregulated by soluble serum factors such as VEGF via H2O2 generation in NP, and were downregulated by serum factors such as progesterone and ox-LDL via superoxide generation in PE, which may contribute to hemodynamic adaptations in NP or to the development of PE.

Subsegmental Osteotomy Technique With Distraction Osteogenesis for Natural Frontal Contouring in Metopic Synostosis.

Vectoring issues occur due to the dynamics of unidirectional procedure that is selected. To circumvent such difficulties, we have devised subsegmental osteotomy with distraction. In our technique, frontal bone flap was divided into 4 segments that were linked to each other by suturing wires in an 8-year-old patient with trigonocephaly. Subsegmental osteotomy and wiring of bone flap enabled us to slide bone in a more curvilinear manner and achieve natural contour. Distraction was initiated on postoperative day 7 at the rate of 1 mm/d for 20-mm gain. At the 9-year follow-up, the patient showed improved head shape and intellectual status.

Fragmentation of kidney epithelial cell primary cilia occurs by cisplatin and these cilia fragments are excreted into the urine.

The primary cilium, which protrudes from the cell surface, is associated with the pathogenesis of various diseases, including acute kidney injury (AKI). Primary cilium length dynamically changes during the progression of diseases. However, its relevance in disease and the underlying mechanism are largely unknown. In this study, we investigated the role of primary cilia in AKI induced by cisplatin, an effective anticancer drug, and the underlying mechanisms. In addition, we evaluated the usefulness of length alteration and deciliation of primary cilia into the urine for the diagnosis of AKI. Cisplatin induced shortening, elongation, and normalization of the primary cilia in kidney epithelial cells over time. During shortening, primary cilia fragments and ciliary proteins were excreted into the urine. During deciliation, cell proliferation and the expression of cyclin-dependent kinase inhibitor and proliferating cell nuclear antigen were not significantly changed. Shortening and deciliation of primary cilia were observed before significant increases in plasma creatinine and blood urea nitrogen concentration occurred. Pretreatment with Mito-Tempo, a mitochondria-targeted antioxidant, prevented cisplatin-induced primary cilium shortening and inhibited the increases in superoxide formation, lipid peroxidation, blood urea nitrogen, and tissue damage. In contrast, isocitrate dehydrogenase 2 (Idh2) gene deletion, which results in defect of the NADPH-associated mitochondrial antioxidant system, exacerbated cisplatin-induced changes in mice. Taken together, our findings demonstrate that cisplatin induces deciliation into the urine and antioxidant treatment prevents this deciliation, renal dysfunction, and tissue damage after cisplatin injection. These results suggest that cisplatin-induced AKI is associated with primary cilia and urine primary cilia proteins might be a non-invasive biomarker of kidney injury.

Oxytocin Receptor Polymorphism Decreases Midline Neural Activations to Social Stimuli in Anorexia Nervosa.

Oxytocin is a neurotransmitter related to both feeding and social behavior; anorexia nervosa is a psychiatric illness defined by reduced food intake, weight loss, and problems in social perceptions. Oxytocin receptor single nucleotide polymorphisms rs2254298 or rs53576 and neural responses to social stimuli were evaluated in adult women with or recovered from anorexia nervosa using functional magnetic resonance imaging. Carriers of the A allele for OXTR rs2254298 (2 AA and 10 AG) showed significantly reduced activation of portions of the posterior cingulate cortex and medial prefrontal cortex for social stimuli as well as greater negative connectivity between the posterior cingulate and the occipital lobe relative to the GG subjects for rs2254298. Differences in the other OXTR SNP, rs53576, did not result in detectable neural differences in either whole brain or region of interest analyses. Development of a mechanistic, biological model of how social behavior is impacted by mental illness requires linking genes to functional brain activations in disease. This pilot study suggests that in anorexia nervosa, differences related to OXTR SNP rs2254298 may alter neural responses to social stimuli and disrupt the engagement and disengagement of the default mode network.

Neuroplasticity of cognitive control networks following cognitive training for chronic traumatic brain injury.

Cognitive control is the ability to coordinate thoughts and actions to achieve goals. Cognitive control impairments are one of the most persistent and devastating sequalae of traumatic brain injuries (TBI). There have been efforts to improve cognitive control in individuals with post-acute TBI. Several studies have reported changes in neuropsychological measures suggesting the efficacy of cognitive training in improving cognitive control. Yet, the neural substrates of improved cognitive control after training remains poorly understood. In the current study, we identified neural plasticity induced by cognitive control training for TBI using resting-state functional connectivity (rsFC). Fifty-six individuals with chronic mild TBI (9 years post-injury on average) were randomized into either a strategy-based cognitive training group (N = 26) or a knowledge-based training group (active control condition; N = 30) for 8 weeks. We acquired a total of 109 resting-state functional magnetic resonance imaging from 45 individuals before training, immediately post-training, and 3 months post-training. Relative to the controls, the strategy-based cognitive training group showed monotonic increases in connectivity in two cognitive control networks (i.e., cingulo-opercular and fronto-parietal networks) across time points in multiple brain regions (pvoxel < 0.001, pcluster < 0.05). Analyses of brain-behavior relationships revealed that fronto-parietal network connectivity over three time points within the strategy-based cognitive training group was positively associated with the trail making scores (pvoxel < 0.001, pcluster < 0.05). These findings suggest that training-induced neuroplasticity continues through chronic phases of TBI and that rsFC can serve as a neuroimaging biomarker of evaluating the efficacy of cognitive training for TBI.

Personal technique for definite repair of complete unilateral cleft lip: modified Millard technique.

BACKGROUND: Millard's rotation-advancement repair, which is used by many surgeons, can make a natural philtral column, but most surgeons use a modification of the rotation-advancement flap. The purpose of this article is to introduce a modification utilized by the authors and to provide detailed surgical procedure. METHODS: We retrospectively reviewed 82 patients' medical records and presented surgical technique and outcomes. The main features of the authors' strategy are emphasizing horizontal length of the lip, orbicularis oris muscle duplication for improving the definition of the philtral column, overcorrection of domal portion than the non-cleft side in order to compensate for the recurrence during growth. Two judges rated two times the appearance of the patients' nose and lip using Asher-McDade aesthetic index. Intra- and interobserver reliabilities were determined using Cohen's kappa statistics. RESULTS: All patients recovered eventually after surgery; however, two patients have a minor complications (wound infection in one patient, wound disruption due to trauma in the other patient). The improvement of the aesthetic results can be achieved with this modified Millard technique. Total mean scores of the Asher-McDade index was 2.08, fair to good appearance. The intraobserver reliabilities were substantial to almost perfect agreement and the interobserver reliabilities were moderate to almost perfect agreement. CONCLUSION: We modified Millard method for repair of complete unilateral cleft lip. The surgical outcomes were favorable in long-term follow-up. We hope our technique will serve as a guide for those new to the procedure.