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Patients with maxillomandibular disharmony may present with a flat to concave midface. The effects of orthognathic surgery concomitant with midface fat grafting on facial appearance and midface volumetric and positional change have not formally been assessed to date. The authors' approach for synchronous orthognathic surgery and fat grafting is described and evaluated. Adult female patients (n = 20) who underwent synchronous two-jaw orthognathic surgery and cheek-specific fat grafting (1.9 ± 0.6 cm3 per side) for correction of skeletal class III deformity and anteromedial cheek deficiency were prospectively included. Preoperative and postoperative photographs were appraised by 42 blinded raters using facial appearance scales for beauty, attractiveness, and pleasantness parameters. The three-dimensional midface soft-tissue volume change and postoperative cheek mass position were computed. Facial imaging data from gender-, ethnic-, and facial pattern-matched adult patients (n = 20) who underwent isolated two-jaw orthognathic surgery (n = 20) were included for comparison. The three-dimensional facial norms database-derived cheek mass position information (2.19 ± 1.31mm) was also adopted for analysis. Patients treated with the synchronous procedure had significantly (p0.001) increased facial appearance-related perception change for beauty (2.9 ± 1.6), attractiveness (2.8 ± 1.8), and pleasantness (3.0 ± 1.5) parameters, three-dimensional midface volume change (1.8 ± 0.5 cm3), and postoperative cheek mass position (2.16 ± 0.47 mm) in comparison with those treated with the isolated procedure (2.0 ± 1.5, 1.9 ± 1.6, 2.3 ± 1.6, 0.6 ± 0.2 cm3, and 1.84 ± 0.43 mm, respectively). Healthy female individuals had similar and larger cheek mass position than patients treated with synchronous (p0.05) and isolated (p0.001) procedures, respectively. Synchronous orthognathic surgery and check-specific fat grafting resulted in superior enhancement of facial appearance and midface volume and position compared with isolated orthognathic surgery.Therapeutic, III.

This study traced intravenously administered induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSC) and assessed the impact of iPSC-MSC on preserving renal function in SD rat after 5/6 nephrectomy. The results of in vitro study showed that FeraTrack™Direct contrast particles (ie intracellular magnetic labelling) in the iPSC-MSC (ie iPS-MSCSPIONs ) were clearly identified by Prussian blue stain. Adult-male SD rats (n = 40) were categorized into group 1 (SC), group 2 [SC + iPS-MSCSPIONs (1.0 × 106 cells)/intravenous administration post-day-14 CKD procedure], group 3 (CKD), group 4 [CKD + iPS-MSCSPIONs (0.5 × 106 cells)] and group 5 [CKD + iPS-MSCSPIONs (1.0 × 106 cells)]. By day-15 after CKD induction, abdominal MRI demonstrated that iPS-MSCSPIONs were only in the CKD parenchyma of groups 4 and 5. By day 60, the creatinine level/ratio of urine protein to urine creatinine/kidney injury score (by haematoxylin and eosin stain)/fibrotic area (Masson's trichrome stain)/IF microscopic finding of kidney injury molecule-1 expression was lowest in groups 1 and 2, highest in group 3, and significantly higher in group 4 than in group 5, whereas IF microscopic findings of podocyte components (ZO-1/synaptopodin) and protein levels of anti-apoptosis ((Bad/Bcl-xL/Bcl-2) exhibited an opposite pattern to creatinine level among the five groups (all P < .0001). The protein expressions of cell-proliferation signals (PI3K/p-Akt/m-TOR, p-ERK1/2, FOXO1/GSK3β/p90RSK), apoptotic/DNA-damage (Bax/caspases8-10/cytosolic-mitochondria) and inflammatory (TNF-α/TNFR1/TRAF2/NF-κB) biomarkers displayed an identical pattern to creatinine level among the five groups (all P < .0001). The iPS-MSCSPIONs that were identified only in CKD parenchyma effectively protected the kidney against CKD injury.

Background/Purpose: The Bonebridge (BB) is a newly designed transcutaneous bone conduction hearing implant. We describe, for the first time, simultaneous BB implantation and different surgical techniques of auricular reconstruction for microtia patients with aural atresia/stenosis. Methods: Ten patients with unilateral or bilateral microtia underwent BB implantation combined simultaneously with either total auricular reconstruction using bespoke hand-carved Medpor framework or second stage auricular projection using autologous costal cartilage framework. Auditory aided and unaided sound fields were evaluated using (1) a pure-tone average (PTA4), (2) a speech reception threshold (SRT), and (3) a Speech Discrimination Score (SDS) at a sound level of 65 dB SPL. Results: All patients and their families were satisfied with the aesthetic outcome of their constructed ears with no requests for further revision. No major complications were encountered. One patient developed minor partial skin graft epidermolysis that healed uneventfully, and another patient had a three month period of auditory acclimatization to the BB device that resolved. Postoperatively, the mean aided PTA4 decreased by 35.35 dB, while the SRT was 54.5 dB HL unaided and 28 dB HL with use of a BB sound processor. The SDS increased by 16.4%–65 dB SPL. Conclusion: Simultaneous BB implantation during either total auricular reconstruction or framework projection for microtia patients who have aural atresia/stenosis is feasible and safe. This approach reduces operative stages, thereby minimizing schooling/occupational disruption and time to total microtia reconstruction and auditory rehabilitation. Keywords: Microtia reconstruction, Transcutaneous bone conduction hearing implant, Medpor, Autologous costal cartilage, Combined approach

Background Lower blepharoplasty is a common cosmetic operation that relies on minimal postoperative scarring, but Asian patients are at higher risk than Caucasians for hypertrophic and/or widened scars. Botulinum toxin type A (BTX) injections are widely employed to alleviate dynamic facial rhytids and also can improve scar quality by reducing scar tension. The authors assessed whether simultaneous transcutaneous lower blepharoplasty and BTX injections could improve subciliary scar quality. Objectives The objective of this study was to assess whether simultaneous transcutaneous lower blepharoplasty and BTX injections could improve subciliary scar quality. Methods This is a prospective, randomized, vehicle-controlled, double-blinded clinical trial. Between May 2015 and May 2018, 40 adults who underwent bilateral transcutaneous lower blepharoplasties were randomized to receive BTX (n = 20) or vehicle (normal saline; n = 20) injections into the lateral orbicularis oculi muscle immediately after wound closure. Vancouver Scar Scale, Visual Analogue Scale, and photographic scar width measurements at 3 reference points were recorded at the final clinical follow-up. Results Thirty-seven patients completed the trial. Vancouver Scar Scale and Visual Analogue Scale scores in the experimental and vehicle control groups were similar, but scar widths in the experimental group at all measured points were significantly narrower than in the vehicle control group (P < 0.001, P = 0.027, and P < 0.001 at each measured point, respectively). Conclusions Transcutaneous lower blepharoplasty scars in Asians can be significantly narrowed by simultaneous BTX injections without additional complications. Level of Evidence 4

This study tested the hypothesis that uremic-toxic substances play a crucial role in enhancing left-common carotid artery (LCCA) stenosis after balloon-denudation of LCCA endothelium (BDLCCAE), and that the adventitial layer plays a complementary role in worsening LCCA stenosis. In vitro results showed the protein expressions of inflammation (IL-1β/TNF-α/IL-6), apoptosis (mitochondrial-Bax/cleaved-caspase-3/cleaved-PARP) and autophagy (beclin/Atg5/LC3B-II to LC3B-I ratio) as well as protein (NOX-1/NOX-2/p22phox/oxidized-protein), total cellular (H2DCFDA) and mitochondrial (Mitosox) levels of oxidative stress were significantly increased in p-Cresol-treated umbilical vein endothelial cells (HUVECs) as compared with control, whereas angiogenesis capacity (i.e., Matrigel-assay for HUVECs) exhibited an opposite pattern to inflammation between the two groups (all P < 0.001). Animals (n = 60) were categorized into group 1 (sham-operated control), group 2 (BDLCCAE), group 3 [BDLCCAE + ESRD patient’s serum (1 cc/injection into deprived CA adventitia)], group 4 [BDLCCAE + ESRD patient’s serum (1 cc/injection from peri-adventitia)], and group 5 [BDLCCAE + ESRD patient’s serum (2 cc/by intravenous injection at days 1/3/7/10/14 after BDLCCADE)] and LCCA was harvested by day-21 after BDLCCAE procedure. Nitric-oxide release from LCCA and the LCCA cross-section area significantly and progressively reduced, whereas intimal and medial layers of LCCA significantly and progressively increased from groups 1 to 5 (all P < 0.001). The cellular expressions of inflammation (CD14+) and DNA-damage biomarker (γ-H2AX+) were significantly and progressively increased, whereas endothelial surface markers (CXCR4/vWF+) were significantly and progressively reduced from groups 1 to 5 (all P < 0.0001). Uremic toxins played an essential role in LCCA remodeling and obstruction. LCCA adventitia facilitated the initiation and propagation of LCCA proliferative obstruction.

This study tested the hypothesis that early implantation of mitochondria (Mito) into left myocardium could effectively protect heart against doxorubicin/12 mg/kg-induced dilated cardiomyopathy (DCM) in rat. Adult-male SD rats (n = 18) were equally categorized into group 1 (sham control), group 2 (DCM) and group 3 [DCM + Mito (500 μg/rat intramyocardial injection by day-21 after DCM induction)] and euthanized by day 60. In vitro studies showed that exogenously-transferred Mito was abundantly identified in H9C2 cells. The q-PCR showed significant increase in relative number of mitDNA in Mito-transferred H9C2 cells than in control group (P

Background: This study tested the hypothesis that combined hyperbaric oxygen (HBO) and autologous adipose-derived mesenchymal stem cell (ADMSC) therapy was superior to either alone at protecting renal function in rodents after acute ischemia-reperfusion (IR) injury. Methods and results: Adult-male SD rats (n = 40) were equally categorized: group 1 (sham-operated control); group 2 (IR + 50 μg medium intra-renal artery administration); group 3 [IR + HBO (at 1.5 h and days 1 and 2 after IR)]; group 4 [IR + ADMSC (2.0×10(6) cells/5.0×10(5)/per each renal artery and 1.0×10(6) by intravenous injection at 1.5 h after IR]; and group 5 (IR + HBO-ADMSC). By 72 hr after IR, the circulating levels of BUN/creatinine and ratio of urine protein/creatinine were significantly highest in group 2, lowest in group 1, significantly increased in group 5 than in groups 3 and 4, but not different between latter two groups, whereas the circulating levels of EPCs and soluble-angiogenesis biomarkers (SDF-1α/HIF-1α) exhibited an opposite pattern to BUN/creatinine among the five groups (all P

This study tested the hypothesis that combined adipose-derived mesenchymal stem cell (ADMSC) and low-energy extracorporeal shock wave (ECSW) therapy could protect brain from brain death (BD)-induced injury. Adult male Sprague Dawley rats were categorized into group 1 (sham control), group 2 (BD), group 3 (BD + ECSW [0.15 mJ/mm2/300 impulses] applied to the skull surface 3 hours after BD induction), group 4 (BD + ADMSC [1.2 × 106 cell] by intravenous injection 3 hours after BD induction) and group 5 (BD + ECSW + ADMSC). By 6 hours after BD induction, circulating/spleen levels of immune cells (CD3/CD4+, CD8/CD4+, Treg+) and circulating levels of inflammatory cells (MPO/Ly6G/CD11a/b) and soluble mediators (TNF-α/IL-6) were lowest in group 1 and significantly progressively reduced from groups 2 to 5 (all p < 0.0001). Brain protein expressions of inflammatory (TNF-α/NF-κB/MMP-9/IL-1β), apoptotic (caspase-3/PARP/mitochondrial-BAX), oxidative stress/DNA-damage (NOX-1/NOX-2/oxidized protein/γ-H2AX) biomarkers exhibited an identical pattern, whereas anti-oxidant (SIRT1/SIRT3) and mitochondrial-integrity (mitochondrial-cytochrome-C) biomarkers exhibited an opposite pattern to inflammatory biomarkers among the 5 groups (all p < 0.0001). The cellular expressions of inflammatory/brain-edema (F4/80/CD14+/GFAP/AQP4) biomarkers exhibited an identical pattern to inflammation among the 5 groups (all p < 0.0001). In conclusion, ECSW-ADMSC therapy is superior to either alone for attenuating brain from BD-induced damage.

Cleft lip and palate is the most common congenital craniofacial anomaly. Up to 60% of these patients will benefit from cleft orthognathic surgery, which consists primarily of maxillary advancement and mandibular setback to address midface retrusion and relative mandibular protrusion, respectively. It is believed that maxillary advancement can enlarge the airway whilst mandibular setback can reduce the airway, but this has not previously been quantified for cleft patients undergoing orthognathic surgery. This unique longitudinal prospective study of 18 patients was conducted between April 2013 and July 2016. No significant changes occurred by six months postoperatively in body mass index, apnoea-hypopnoea index or lowest oxygen saturation (LSAT). There was a mean increase of 0.73 cm3 in velopharyngeal volume, a mean decrease of 0.79 cm3 in oropharyngeal volume, an improvement in snoring index, and no statistically significant change in hypopharyngeal volume. In conclusion, cleft orthognathic surgery that produced anterior advancement of the maxilla, setback of the mandible and clockwise rotation of the maxillo-mandibular complex resulted in increased velopharyngeal, decreased oropharyngeal and unchanged hypopharyngeal airways, and improved snoring, but did not significantly alter objective sleep-related breathing function.

// Fan-Yen Lee 1, * , Kuan-Hung Chen 2, * , Christopher Glenn Wallace 3 , Pei-Hsun Sung 4 , Jiunn-Jye Sheu 1 , Sheng-Ying Chung 4 , Yung-Lung Chen 4 , Hung-I Lu 1 , Sheung-Fat Ko 5 , Cheuk-Kwan Sun 6 , Hsin-Ju Chiang 7 , Hsueh-Wen Chang 8 , Mel S. Lee 9, ** and Hon-Kan Yip 4, 10, 11, 12, 13, ** 1 Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 3 Department of Plastic Surgery, Royal Devon & Exeter Hospital, Exeter, United Kingdom 4 Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 6 Department of Emergency Medicine, E-Da Hospital, I-Shou University School of Medicine for International Students, Kaohsiung, Taiwan 7 Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 8 Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 9 Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 10 Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 11 Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 12 Department of Nursing, Asia University, Taichung, Taiwan 13 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan * These authors have contributed equally to this work ** These authors have contributed equally to this work senior co-authors Correspondence to: Hon-Kan Yip, email: han.gung@msa.hinet.net Keywords: acute respiratory distress syndrome, sepsis syndrome, inflammatory and immune reactions, xenogeneic mesenchymal stem cell, mortality Received: January 10, 2017 Accepted: April 03, 2017 Published: April 21, 2017 ABSTRACT This study tested the hypothesis that xenogeneic human umbilical cord-derived mesenchymal stem cell (HUCDMSC) therapy would improve survival rates in rats with acute respiratory distress-syndrome (ARDS, induction by 48 h inhalation of 100% oxygen) and sepsis-syndrome (SS, induction by cecal-ligation and puncture) (ARDS-SS). Adult-male Sprague-Dawley rats were categorized into group 1 (sham-controls), group 2 (ARDS-SS), group 3 [ARDS-SS+HUCDMSC (1.2 ×10 6 cells administered 1 h after SS-induction)], and group 4 [ARDS-SS+HUCDMSC (1.2 ×10 6 cells administered 24 h after SS-induction)]. The mortality rate was higher in groups 2 and 4 than in groups 1 and 3 (all p

We tested the hypothesis that arteriosclerosis-augmented aortic pulse wave velocity (PWV) and -impaired vasorelaxation were attenuated by rosuvastatin (Rosu) and propylthiouracil (PTU) therapy.Thirty-two New Zealand rabbits were equally divided into group 1 (sham-control), group 2 [high-cholesterol-diet (HCD) for 8weeks], group 3 [HCD-Rosu (20mg/kg/day administration after 4-week HFD for 4weeks)], and group 4 [HCD-PTU (0.1% PTU in drinking water), the treatment course as group 3]. KCl-induced vasoconstriction of carotid artery (CA) was significantly higher in group 2 than in other groups (all p0.01), but showed no differences among groups 1, 3 and 4, whereas acetylcholine-induced vasorelaxation exhibited an opposite pattern of KCl-induced vasoconstriction among the four groups (p0.001). Basic nitric-oxide release from endothelial cells of CA was highest in group 1, lowest in group 2, but showed no difference between groups 3 and 4 (all p0.001). PWV value was highest in group 2, lowest in group 1, and significantly higher in group 4 than in group 3 (all p0.001). Serum levels of total-cholesterol, LDL and TG showed an identical pattern to PWV (all p0.001), whereas the levels of free T4, sugar, and body weight did not differ among the four groups (all p0.4). Aortic inflammatory biomarkers in cellular (CD68+/IL-1β+/CD14+) and protein (TNF-α/NF-κB/IL-1β/MMP-9/MCP-1/ICAM-1/PDGF) levels, and aortic oxidative-stress biomarkers in cellular (8-OHdG) and protein (NOX-1/NOX-2/oxidized protein) levels showed an identical pattern to PWV among the four groups (all p0.001).Rosu-PTU therapy ameliorated aortic stiffness and inflammation/oxidative-stress, and improved endothelial-cell function after HCD challenge in rabbit.

This study traced intravenously administered induced pluripotent stem cell (iPSC)‐derived mesenchymal stem cells (MSC) and assessed the impact of iPSC‐MSC on preserving renal function in SD rat after 5/6 nephrectomy. The results of in vitro study showed that FeraTrack™Direct contrast particles (ie intracellular magnetic labelling) in the iPSC‐MSC (ie iPS‐MSCSPIONs) were clearly identified by Prussian blue stain. Adult‐male SD rats (n = 40) were categorized into group 1 (SC), group 2 [SC + iPS‐MSCSPIONs (1.0 × 106cells)/intravenous administration post‐day‐14 CKD procedure], group 3 (CKD), group 4 [CKD + iPS‐MSCSPIONs (0.5 × 106cells)] and group 5 [CKD + iPS‐MSCSPIONs (1.0 × 106cells)]. By day‐15 after CKD induction, abdominal MRI demonstrated that iPS‐MSCSPIONs were only in the CKD parenchyma of groups 4 and 5. By day 60, the creatinine level/ratio of urine protein to urine creatinine/kidney injury score (by haematoxylin and eosin stain)/fibrotic area (Masson's trichrome stain)/IF microscopic finding of kidney injury molecule‐1 expression was lowest in groups 1 and 2, highest in group 3, and significantly higher in group 4 than in group 5, whereas IF microscopic findings of podocyte components (ZO‐1/synaptopodin) and protein levels of anti‐apoptosis ((Bad/Bcl‐xL/Bcl‐2) exhibited an opposite pattern to creatinine level among the five groups (all P

Background: This study tested the hypothesis that intramuscular injections of erythropoietin (EPO) and endothelial progenitor cells (EPC) to critical limb ischemia (CLI; primary treatment site) could also improve heart function in rat after acute myocardial infarction (AMI; remote ischemic organ). Method: Adult-male SD rats (n = 40) were equally categorized into group 1 (sham-operated control), group 2 (CLI-AMI), group 3 [CLI-AMI + EPO (10 mg/kg)], group 4 [CLI-AMI + EPCs (1.2 × 106)] and group 5 (CLI-AMI + EPCs + EPO). Results: By day 21 (end of study period), 2-D echo and Laser doppler showed that left-ventricular injection fraction (LVEF) and the ratio of ischemic to normal blood flow were highest in group 1, lowest in group 2, significantly higher in group 5 than in groups 3 and 4, but not different in the latter two groups (all p

This study tested the hypothesis that combined hyperbaric oxygen (HBO) and melatonin (Mel) was superior to either one for protecting the brain functional and parenchymal integrity from acute ischemic stroke (IS) injury. Adult-male Sprague-Dawley rats were divided into groups 1 (sham-operated control), 2 (IS), 3 (IS + HBO), 4 (IS + Mel), and 5 (IS + HBO-Mel). By day 28 after IS, the brain infarct area (BIA) was lowest in group 1, highest in group 2, significantly higher in groups 3 and 4 than in group 5, but not different between groups 3 and 4. The neurological function at day 7, 14, and 28 exhibited an opposite pattern to BIA among the 5 groups. The protein expressions of inflammatory (IL-1β/IL-6/iNOS/TNF-α/p-NF-κB), apoptotic (cleaved-caspase3/cleaved-PARP/mitochondrial Bax), mitochondrial/DNA-damaged (cytochrome-C/γ-H2AX), oxidative stress (NOX-1/NOX-2), and autophagy (i.e. ratio of CL3B-II/CL3B-I) biomarkers displayed an identical pattern of BIA among 5 groups. Cellular expressions of inflammation (F4/80+/GFAP+) and DNA-damaged biomarker (γ-H2AX+) exhibited an identical pattern, whereas the integrities of myelin sheath/neuron (MPB+/NeuN+), endothelial cell (CD31+/vWF+), and number of small vessels exhibited an opposite pattern of BIA among the 5 groups. Combined HBO-Mel therapy offered an additional benefit in protecting the brain against IS injury.

Cleft lip and/or cleft palate are the most common congenital craniofacial anomalies. Philtral ridge morphology is an important aesthetic component of unilateral cleft lip (UCL) repair. To this end, we have developed two techniques of philtral ridge reconstruction: (1) asymmetric mattress muscle sutures, and (2) overlapping mattress muscle sutures. The objective of this retrospective cohort study was to compare their outcomes in UCL repairs. Group I patients (n=30) underwent UCL repair before August 2003, including philtral ridge reconstruction by asymmetric mattress muscle sutures. Group II patients (n=30) underwent UCL repair after August 2003, including philtral ridge reconstruction by overlapping mattress muscle sutures. Philtral morphology was evaluated by ultrasonographic and three-dimensional photographic measurements, examining cleft side philtral projection and philtral ridge symmetry. These demonstrated that group II patients had better philtral column symmetry and projection on the cleft side when compared to group I. Overlapping mattress muscle sutures produced better philtral morphology in UCL repairs than asymmetric mattress muscle sutures.

This study tested the impact of single dose and two doses of endothelial progenitor cells (EPCs) and EPCs-derived condition medium (CM) on protecting the left-ventricular myocardium (LVM) from acute ischemia-reperfusion (IR) injury. In vitro study showed EPCs and CM had comparably higher capacity for enhancement of angiogenesis as compared with the controls (all P < .001). Adult-male SD rats ( n = 36) were equally categorized into groups 1 (sham-operated control), 2 (IR+vehicle), 3 [IR+EPCs/1.2 × 106/intravenous administration at 3 h after IR procedure), 4 (IR+EPCs/1.2 × 106/at 3 h/24 h after IR), 5 (IR+CM/3.0cc/intravenous administration at 3 h after IR), 6 (IR+EPCs/3.0cc/at 3h/24 h after IR), and euthanized by day 3 after IR. The left-ventricular-ejection-fraction, protein and cellular expressions of endothelial-cell markers (CD31/vWF), small vessel number and protein expression of mitochondrial (mitochondrial-cytochrome-C) integrity were highest in group 1, lowest in group 2, significantly higher in group 4 than in groups 3/5/6 and significantly higher in groups 3/6 than in group 5 but they showed no differences in groups3/6, whereas the protein expressions of apoptotic (cleaved-caspase 3/cleaved-PARP), fibrotic (Smad3/TGF-ß), mitochondrial-damaged (cytosolic-cytochrome-C), heart-failed/pressure-overload (BNP), oxidative-stress (p47phox/NOX-1/NOX-2/oxidized protein), and autophagic (LCB3-II/LCB3-I) biomarkers and fibrotic/collagen-deposition areas exhibited an opposite pattern to endothelial-cell markers (all P < .0001). The protein expressions of angiogenesis (VEGF/SDF-1α/CXCR4/HIF-1α) were lowest in group 1, highest in group 4, significantly higher in groups 3/6 than in groups 2/5, significantly higher in group 5 than in group 2, but they showed no difference between groups 3/6 (all P < .0001). These results demonstrate that two consecutive doses of EPC/CM were superior to just one at protecting LVM against IR injury.

// Kuan-Hung Chen 1,8,* , Chih-Hung Chen 2,* , Christopher Glenn Wallace 3 , Chun-Man Yuen 4 , Gour-Shenq Kao 5 , Yi-Ling Chen 5 , Pei-Lin Shao 6 , Yung-Lung Chen 5 , Han-Tan Chai 5 , Kun-Chen Lin 1 , Chu-Feng Liu 7 , Hsueh-Wen Chang 8 , Mel S. Lee 9 and Hon-Kan Yip 5,6,10,11,12 1 Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Department of Internal Medicine, Division of General Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 3 Department of Plastic Surgery, University Hospital of South Manchester, Manchester, UK 4 Department of Surgery, Division of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Department of Internal Medicine, Division of Cardiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 6 Department of Nursing, Asia University, Taichung, Taiwan 7 Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 8 Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 9 Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 10 Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 11 Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 12 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan * These authors have contributed equally to this work Correspondence to: Hon-Kan Yip, email: // Keywords : xenogenic adipose-derived mesenchymal stem cell, exosomes, ischemic stroke, brain infarct size, neurological function, Pathology Section Received : August 15, 2016 Accepted : October 14, 2016 Published : October 25, 2016 Abstract We tested the hypothesis that combined xenogenic (from mini-pig) adipose-derived mesenchymal stem cell (ADMSC) and ADMSC-derived exosome therapy could reduce brain-infarct zone (BIZ) and enhance neurological recovery in rat after acute ischemic stroke (AIS) induced by 50-min left middle cerebral artery occlusion. Adult-male Sprague-Dawley rats ( n = 60) were divided equally into group 1 (sham-control), group 2 (AIS), group 3 [AIS-ADMSC ( 1 . 2 × 10 6 cells)], group 4 [AIS-exosome ( 100 &#x 3 bc;g)], and group 5 (AIS-exosome-ADMSC). All therapies were provided intravenously at 3h after AIS procedure. BIZ determined by histopathology (by day-60) and brain MRI (by day-28) were highest in group 2, lowest in group 1, higher in groups 3 and 4 than in group 5, but they showed no difference between groups 3 and 4 (all p < 0.0001). By day-28, sensorimotor functional results exhibited an opposite pattern to BIZ among the five groups ( p < 0.005). Protein expressions of inflammatory (inducible nitric oxide synthase/tumor necrosis factor-α/nuclear factor-κB/interleukin-1β/matrix metalloproteinase-9/plasminogen activator inhibitor-1/RANTES), oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (caspase-3/ Poly-ADP-ribose polymerase), and fibrotic (Smad3/transforming growth factor-β) biomarkers, and cellular expressions of brain-damaged (γ-H2AX+/ XRCC1-CD90+/p53BP1-CD90+), inflammatory (CD11+/CD68+/glial fibrillary acid protein+) and brain-edema (aquaporin-4+) markers showed a similar pattern of BIZ among the groups (all n < 0.0001). In conclusion, xenogenic ADMSC/ADMSC-derived exosome therapy was safe and offered the additional benefit of reducing BIZ and improving neurological function in rat AIS.

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in plastic and reconstructive surgery. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. Adult mesenchymal stem cells appear to be an ideal stem cell population for practical regenerative medicine. Among these cells, adipose-derived stem cells (ADSC) have the potential to differentiate the mesenchymal, ectodermal and endodermal lineages and are easy to harvest. Additionally, adipose tissue yields a high number of ADSC per volume of tissue. Based on this background knowledge, the purpose of this review is to summarise and describe the proliferation and differentiation capacities of ADSC together with current preclinical data regarding the use of ADSC as regenerative tools in plastic and reconstructive surgery.

Botulinum neurotoxin A (BoNT-A) is a minimally invasive and technically straightforward treatment of masseter muscle (MM) volume reduction and facial contouring, but the literature on its long-term effect on MM volume remains unclear.This study aimed to assess quantitatively for progressive volume changes of lower facial contour after 3 BoNT-A injections in patients with bilateral MM hypertrophy causing square facial morphology using 3-dimensional computed tomographic scans.Ten female patients with square facial morphology due to bilateral MM hypertrophy were recruited to, and 6 completed, this clinical study. Each received 24 U of BoNT-A into the inferior portion of each MM on both sides, repeated 6 monthly to complete 3 treatments. Masseter muscle volume changes were assessed using 3-dimensional computed tomography at pretreatment (before injections) and posttreatment (1 year after the third injection).Mean MM volume significantly reduced from 26.39 ± 4.18 cm before treatment to 23.26 ± 4.31 cm 1 year after treatment (P = 0.002).Three consecutive 6-monthly BoNT-A injections into the MMs reduced their volume by 12% when assessed 1 year after completion of treatment.

We tested the hypothesis that adipose-derived fresh stromal vascular fraction (SVF) is non-inferior to conventional adipose-derived mesenchymal stem cell (ADMSC) therapy for improving left-ventricular ejection fraction (LVEF) in rat after acute myocardial infarction (AMI). Male-adult SD rats (n = 48) were categorized into group 1 (sham control), AMI, AMI + ADMSCs (1.2 × 10(6)) cells] and AMI + SVF (1.2 × 10(6)) cells]. Flow cytometric and qPCR analyses showed that the expressions of surface biomarkers for endothelial progenitor cells, and cardiac-stem cells were significantly higher in the SVF population than in the ADMSC population, whereas MSCs showed a reversed pattern between these two groups (all P < 0.001). By day-42 after AMI, LVEF was highest in SC, lowest in AMI, and significantly higher in AMI + SVF than in AMI + ADMSCs (P < 0.0001). Protein expression indicating angiogenesis, anti-inflammatory/anti-apoptotic, mitochondrial/bioenergy-integrity and antifibrotic biomarkers showed an identical pattern, whereas protein expressions for inflammatory, apoptotic and pressure-overload/heart failure biomarkers exhibited an opposite pattern to LVEF among the four groups (all P < 0.001). Histopathology displayed that LV infarction/fibrotic area/collagen-deposition areas, cellular expressions of DNA-damage, and inflammatory biomarkers exhibited an opposite pattern, whereas cellular expressions of endothelial/gap-junction biomarkers showed an identical pattern to LVEF among the four groups (all P < 0.0001). Cellular expression of angiogenesis biomarkers significantly and progressively increased from groups 1 to 4 (all P < 0.0001). In conclusion, SVF may be better than ADMSC at improving LVEF in rat after AMI.

This study tested the hypothesis that early administration of empagliflozin (Empa), an inhibitor of glucose recycling in renal tubules, could preserve heart function in cardiorenal syndrome (CRS) in rat. Chronic kidney disease (CKD) was caused by 5/6 subtotal nephrectomy and dilated cardiomyopathy (DCM) by doxorubicin (DOX) treatment. In vitro results showed that protein expressions of cleaved-caspase3 and autophagy activity at 24 h/48 h in NRK-52P cells were significantly upregulated by para-Creso treatment; these were significantly downregulated by Empa treatment. Flow cytometric analysis showed that annexin-V (i.e., early/late apoptosis) in NRK-52P cells expressed an identical pattern to cleaved-caspase3 between the two groups (all p

Upper lip scars are at risk of hypertrophy. Our center therefore uses microporous tape and silicone sheeting for postoperative scar care following cleft lip repair. However, some babies have previously ingested their silicone sheeting, which has the potential for respiratory compromise or gastrointestinal obstruction. Self-dry silicone gel is reportedly also effective for preventing hypertrophic scars. Hence, we sought to test whether silicone gel, which cannot be ingested whole, might be non-inferior to silicone sheeting for controlling against upper lip scar hypertrophy. This was a mixed prospective and retrospective case-controlled clinical trial involving patients undergoing unilateral cleft lip repair, 29 of whom received standard postoperative silicone sheeting (control group) and another 33 age-matched consecutive patients who received self-dry silicone instead. The Vancouver scar scale, visual analogue scale and photographically assessed scar width assessments were the same in both groups at six months after surgery. In conclusion, silicone gel appears to be non-inferior to silicone sheeting for postoperative care of upper lip scars as judged by scar quality at six months, but silicone sheeting has the safety disadvantage that it can be swallowed whole by babies. It is thus recommended that silicone gel be used for upper lip scar management in babies.

This study tested whether inducible pluripotent stem cell (iPSC)-derived mesenchymal stem cell (MSC) therapy could effectively protect kidney from acute ischemia (1 h) - reperfusion (5 day) injury (IRI). Male-adult SD-rats (n = 24) were equally categorized into groups 1 (sham-control), 2 [sham-control + iPSC-MSC (1.2 × 106 cells/rat)], 3 (IR only) and 4 (IR + iPSC-MSC). Blood urine nitrogen/creatinine levels and ratio of urine protein to creatinine, kidney weight and expressions of inflammation (TNF-α/NF-κB), oxidative-stress (NOX-1/NOX-2/oxidized protein) and apoptosis (mitochondrial-Bax/cleaved caspase-3/PARP) were significantly higher in group 3 than in groups 1, 2 and 4 and significantly higher in group 4 than in groups 1 and 2 (all P

Limited information is currently available concerning HLA class I antigen abnormalities in sarcomatoid hepatocellular carcinoma (sHCC). Here, we have analyzed the growth characteristics and HLA class I antigen status of four sHCC cell lines (sHCC29, sHCC63, sHCC74, and SAR-HCV); the first three were newly established in this study. Among the four, sHCC29 showed the highest growth rate in vitro and tumorigenicity in NOD-SCID mice. Unlike sHCC74 and SAR-HCV, both sHCC29 and sHCC63 had no detectable surface HLA class I antigen expression, alongside undetected intracellular β2-microglobulin (β2m) and marked HLA class I heavy chain and selective antigen-processing machinery (APM) component downregulation. The loss of β2m in sHCC29 and sHCC63 was caused by a >49 kb deletion across the B2M locus, while their downregulation of APM components was transcriptional, reversible by IFN-γ only in several components. β2m was also undetected in the primary HCC lesions of the patients involved, indicating its in vivo relevance. We report for the first time HLA class I antigen loss with underlying B2M gene deficiency and APM defects in 50% (2 of 4) of the sHCC cell lines tested. These findings may have implications for a proper design of T cell immunotherapy for the treatment of sHCC patients.

This study tested the hypothesis that extracorporeal shock wave- (ECSW-) assisted adipose-derived stromal vascular fraction (SVF) therapy could preserve left ventricular ejection fraction (LVEF) and inhibit LV remodeling in a rat after acute myocardial infarction (AMI). Adult male SD rats were categorized into group 1 (sham control), group 2 (AMI induced by left coronary artery ligation), group 3 [AMI + ECSW (280 impulses at 0.1 mJ/mm2, applied to the chest wall at 3 h, days 3 and 7 after AMI), group 4 [AMI + SVF (1.2 × 106) implanted into the infarct area at 3 h after AMI], and group 5 (AMI + ECSW-SVF). In vitro, SVF protected H9C2 cells against menadione-induced mitochondrial damage and increased fluorescent intensity of mitochondria in nuclei (p<0.01). By day 42 after AMI, LVEF was highest in group 1, lowest in group 2, significantly higher in group 5 than in groups 3 and 4, and similar between the latter two groups (all p<0.0001). LV remodeling and infarcted, fibrotic, and collagen deposition areas as well as apoptotic nuclei exhibited an opposite pattern to LVEF among the groups (all p<0.0001). Protein expressions of CD31/vWF/eNOS/PGC-1α/α-MHC/mitochondrial cytochrome C exhibited an identical pattern, whilst protein expressions of MMP-9/TNF-α/IL-1β/NF-κB/caspase-3/PARP/Samd3/TGF-β/NOX-1/NOX-2/oxidized protein/β-MHC/BNP exhibited an opposite pattern to LVEF among five groups (all p<0.0001). Cellular expressions of CXCR4/SDF-1α/Sca-1/c-Kit significantly and progressively increased from groups 1 to 5 (all p<0.0001). Cellular expression of γ-H2AX/CD68 displayed an opposite pattern to LVEF among the five groups (all p<0.0001). In conclusion, ECSW-SVF therapy effectively preserved LVEF and inhibited LV remodeling in rat AMI.

Objective: This study tested the hypothesis that allogenic adipose-derived mesenchymal stem cell (ADMS) and extracorporeal shock wave (ECSW) therapy could attenuate brain death (BD)-induced remote cardiac organ damage in rat. Methods: Adult-male SD rats (n=30) were equally divided into group 1 (sham control); group 2 (BD); group 3 [BD + ECSW (0.15 mJ/mm2/300 impulses applied to skull surface 3 h after BD induction)]; group 4 [BD + ADMSC (1.2 x 106 cell) by intravenous injection 3 h after BD induction]; and group 5 (BD-ECSW-ADMSC). Animals were sacrificed by 6 h after BD induction and the heart specimens harvested. Results: ELISA analysis showed that the circulating level of inflammation (IL-6/MPO/TNF-α) was lowest in group 1, highest in group 2, significantly lower in groups 5 than in groups 3 and 4, and significantly lower in group 4 than in group 3 (all p

This study tested the hypothesis that shock wave therapy (SW) enhances mitochondrial uptake into the lung epithelial and parenchymal cells to attenuate lung injury from acute respiratory distress syndrome (ARDS). ARDS was induced in rats through continuous inhalation of 100% oxygen for 48 h, while SW entailed application 0.15 mJ/mm2for 200 impulses at 6 Hz per left/right lung field. In vitro and ex vivo studies showed that SW enhances mitochondrial uptake into lung epithelial and parenchyma cells (allp<0.001). Flow cytometry demonstrated that albumin levels and numbers of inflammatory cells (Ly6G+/CD14+/CD68+/CD11b/c+) in bronchoalveolar lavage fluid were the highest in untreated ARDS, were progressively reduced across SW, Mito, and SW + Mito (allp<0.0001), and were the lowest in sham controls. The same profile was also seen for fibrosis/collagen deposition, levels of biomarkers of oxidative stress (NOX-1/NOX-2/oxidized protein), inflammation (MMP-9/TNF-α/NF-κB/IL-1β/ICAM-1), apoptosis (cleaved caspase 3/PARP), fibrosis (Smad3/TGF-β), mitochondrial damage (cytosolic cytochrome c) (allp<0.0001), and DNA damage (γ-H2AX+), and numbers of parenchymal inflammatory cells (CD11+/CD14+/CD40L+/F4/80+) (p<0.0001). These results suggest that SW-assisted Mito therapy effectively protects the lung parenchyma from ARDS-induced injury.

We tested the hypothesis that transfusion of autologous peripheral blood-derived endothelial progenitor cells (PBDEPC) via the internal carotid artery could reduce brain-infarct zone (BIZ) and neurological deficit in rats following acute ischemic stroke (IS) induced by 50-min left middle cerebral artery occlusion.Adult male Sprague-Dawley rats (n=60) were equally divided into group 1 [sham control (SC)], group 2 [SC-PBDEPC (5.7 × 10(6)/kg)], group 3 (IS), group 4 [IS-low-dose PBDEPC (1.7 × 10(6)/kg)], group 5 [IS-high-dose PBDEPC (5.7×10(6)/kg)]. Groups 2 to 5 received G-CSF (35 μg/kg subcutaneously) for 4 days before drawing blood for PBDEPC culture.By day 90, BIZ determined by histopathology (area) and brain MRI (volume) were highest in group 3, lowest in groups 1 and 2, higher in group 4 than in group 5 (all p0.0001), and not significantly different between groups 1 and 2. Sensorimotor functional results exhibited an opposite pattern of BIZ among groups 3 to 5 (p0.005). Angiogenesis biomarkers (SDF-1α, CXCR4, VEGF, angiopoietin-1) significantly increased progressively from groups 1 and 2 to group 5 (all p0.0001). Oxidative-stress (NOX-1, NOX-2, oxidized protein), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), inflammatory (MMP-9, TNF-α, AQP-4, GFAP, iNOS), and brain-damaged (cytosolic cytochrome-C) biomarkers showed an identical pattern, whereas anti-inflammatory (Bcl-2), mitochondrial preservation (mitochondrial cytochrome-C, PGC-1α), and endothelial function (CD31+, vWF+, eNOS) biomarkers, and vessel density showed an opposite pattern of BIZ among these five groups (all p0.001).Higher-dose was superior to lower-dose EPC treatment for reducing BIZ and improving neurological functional outcome.

This study tested the hypothesis that combination therapy using extracorporeal shock wave (ECSW)-melatonin (Mel) was superior to either alone at ameliorating neuropathic pain (NP). NP was induced by chronic constriction injury (CCI) to the left sciatic nerve in rats. Animals were categorized into sham control (group 1), CCI only (group 2), CCI-ECSW (group 3), CCI-Mel (group 4) and CCI-ECSW-Mel (group 5). By days 2 and 8 after CCI, the mechanical paw withdrawal threshold (MPWT)/thermal paw withdrawal latency (TPWL) were highest in group 2, lowest in group 1, significantly lower in group 5 than in groups 3 and 4 (all p

This study tested the hypothesis that SS31 therapy could effectively protect the heart against transverse aortic constriction (TAC)-induced hypertrophic cardiomyopathy (HCM) damage. Adult-male B6 mice (n=36) were equally divided into sham-operated control (group 1), TAC only (group 2) and TAC+SS31 (group) (2.0 mg/kg/day by intra-peritoneal administration from day 28 after TAC induction) and euthanized by day 60. In vitro results showed that SS31 markedly suppressed angiotensin-II induced protein expressions of BNP/β-MHC, ATM, p-P38 and P53 and ATP damage in H9C2 cells, and protein expression of pro-collagen-I/CTGF in fibroblasts (all P

This study tested the hypothesis that combined therapy with exendin-4 (Ex4) and autologous adipose-derived mesenchymal stem cells (ADMSCs) was superior to either alone for protecting renal function against acute kidney ischemia-reperfusion (IR; 40-min ischemia/27-h reperfusion) injury when complicated by sepsis syndrome (SS; by cecal-ligation-puncture). Adult-male Sprague-Dawley rats (n=40) were equally divided into group 1 (sham-control), group 2 (IR-SS), group 3 (IR-SS + Ex4, 10 μg/kg subcutaneously 30 min after reperfusion and daily for 3 days), group 4 [IR-SS + ADMSC (1.2 × 106)], and group 5 (IR-SS + Ex4 + ADMSC). The circulating levels of BUN and creatinine and the ratio of urine protein to creatinine were highest in group 2, lowest in group 1, significantly higher in groups 3 and 4 than group 5, and significantly higher in group 3 than in group 4 (all P

We analyzed the effects of acute ischemia-reperfusion (KIR) injury on the status of kidney function and architecture in dipeptidyl peptidase4-difficient (DPP4D) rats and the effect of remote small bowel ischemia-reperfusion (BIR) preconditioning. DPP4-deficient (DPP4D) and normal Fischer344 (F344) rats were divided into 6 groups: (1) sham-F344, (2) sham-DPP4D, (3) KIR-F344 (4) KIR-DPP4D, (5) DPP4D-KIR-extendin-9-39 and (6) BIR-KIR-F344. Blood creatinine and urea nitrogen levels and the urinary protein-to-creatinine ratio was higher in KIR-F344 rats than BIR-KIR-F344 or KIR-DPP4D rats 72 h after acute KIR. Conversely, the circulating glucagon-like peptide 1 (GLP-1) levels were higher in BIR-KIR-F344 and KIR-DPP4D than KIR-F344 rats after acute KIR. KIR-F344 rats showed greater inflammation, oxidative stress, apoptosis, DNA damage and kidney injury than other rat groups. Damage to the kidney architecture in KIR-F344 rats was greater than in BIR-KIR-F344 or KIR-DPP4D rats. Expression of antioxidant proteins and GLP-1 receptor was higher in kidneys from KIR-DPP4D and BIR-KIR-F344 than KIR-F344 rats, which suggests better intrinsic responses. We therefore suggest that elevated circulating GLP-1 levels due to DPP4 deficiency and BIR preconditioning protect kidney function and architecture during acute IR injury.

The purpose of this study was to evaluate progressive changes in surgical techniques and results, aiming for improved nasal shape in primary bilateral cleft rhinoplasty.This is an institutional review board-approved retrospective study. Ninety-one consecutive patients with bilateral complete cleft lip underwent primary cheiloplasty with four different techniques of nasal reconstruction from 1992 to 2007 as follows: group I, primary rhinoplasty alone; group II, nasoalveolar molding alone; group III, nasoalveolar molding plus primary rhinoplasty; group IV, nasoalveolar molding plus primary rhinoplasty with overcorrection; and group V, patients without cleft lip. The surgical results were analyzed using photographic records obtained at age 3 years. Four measurements and one angle measurement were obtained. A panel assessment was obtained to grade the appearance of the surgical results.The results are expressed in order from groups I through V. The nostril height-to-width ratio was 0.49, 0.59, 0.62, 0.78, and 0.82, respectively. The nasal tip height-to-nasal width ratio was 0.29, 0.39, 0.49, 0.57, and 0.60. The columella height-to-nasal width ratio was 0.11, 0.18, 0.22, 0.27, and 0.28. The dome-to-columella ratio was 1.88, 1.25, 1.26, 1.14, and 1.10. The nostril area ratio was 1.2, 1.17, 1.13, 1.11, and 1.07. The nasolabial angle was 144.95, 143.98, 121.98, 120.99, and 100.88. Finally, group IV had the best panel assessment.The results revealed that group IV had the best overall result. Presurgical nasoalveolar molding followed by primary rhinoplasty with overcorrection resulted in a nasal appearance that was closer to the patients without cleft lip.

Osseointegrated dental implants in double-barrel, or single-barrel and then vertically distracted, fibula osteoseptocutaneous free flaps can achieve segmental mandibular reconstruction, dental rehabilitation, and premorbid facial height. However, it remains unknown which configuration provides better osseointegration outcomes.Between 2003 and 2009, all patients who underwent segmental mandibular defect reconstruction using vertical distraction osteogenesis of single-barrel fibula with secondary osseointegration (group A, 10 patients and 35 osseointegrated dental implants) or double-barrel fibula with primary osseointegration (group B, 13 patients and 36 osseointegrated dental implants) were evaluated prospectively for crown-implant ratios, mesial/distal marginal bone losses, and complications. In group B, 18 osseointegrated dental implants were surrounded by palatal mucosal grafts; the other retained fibula skin paddles.Palatal mucosal grafts in group B improved mesial (p0.001) and distal (p0.001) marginal bone losses. Mesial marginal bone loss of group B with palatal mucosal grafts was better than that of group A (p0.05), despite higher crown-implant ratios in group A (p0.01). Mesial (p0.01) and distal (p0.05) marginal bone losses of group A were better than that of group B osseointegrated dental implants without palatal mucosal grafts. Complications in group A were common and complex, unlike group B. All patients completed dental rehabilitation.Osseointegration was adequate to complete dental rehabilitation in group B without palatal mucosal grafts, but was significantly better in group A, and significantly best in group B with palatal mucosal grafts. Given the complexity and frequency of complications in group A, the authors recommend the double-barrel configuration with osseointegrated dental implants for segmental mandibular defect reconstruction. Palatal mucosal grafts have a definite advantage.Therapeutic, III.

Background Upper lip wounds that lie perpendicular to the relaxed skin tension lines are subjected to repetitive dynamic tension caused by the orbicularis oris muscle and are susceptible to unsatisfactory scarring. Methods In this double-blind, randomized, vehicle-controlled, prospective trial, 60 consecutive patients with unilateral cleft lip undergoing primary cheiloplasties between August of 2011 and June of 2012 were randomized to receive botulinum toxin type A or vehicle injections into the subjacent orbicularis oris muscle immediately after wound closure. Scars were assessed after 6 months using the Vancouver Scar Scale, photographic visual analogue scale, and photographic scar width measurements. Results Fifty-nine patients completed the trial. Measurements of scar widths at two defined points revealed significantly better visual analogue scale scores and narrower scars in the experimental group. However, Vancouver Scar Scale assessments were similar between groups. Conclusions Botulinum toxin injections into the subjacent orbicularis oris muscle produced better appearing and narrower cheiloplasty scars, but provided no additional benefits in terms of scar pigmentation, vascularity, pliability, or height. Clinical question/level of evidence Therapeutic, II.

This study tested the hypothesis that exposure to ambient fine particulate matter (PM2.5) pollution increased susceptibility of rat lung to damage from acute ischemia-reperfusion (IR) injury that was reversed by melatonin (Mel) treatment. Male-adult SD rats (n = 30) were categorized into group 1 (normal control), group 2 (PM2.5 only), group 3 (IR only at day 8 after PM2.5 exposure), group 4 (PM2.5 + IR) and group 5 (PM2.5 + IR + Mel), and all animals were sacrificed by day 10 after PM2.5 exposure. Oxygen saturation (%) was significantly higher in group 1 than in other groups and significantly lower in group 4 than in groups 2, 3 and 5 but it did not differ among the latter three groups (p

This study tested the hypothesis that combined therapy with melatonin (Mel) and exendin-4 (Ex4) would be superior to either therapy alone for preventing the deterioration of renal function in cardiorenal syndrome (CRS). Male adult Sprague Dawley rats (n = 48) were randomly and equally divided into sham-control (SC), chronic kidney disease (CKD; induced by 5/6 nephrectomy), CRS (CKD + dilated cardiomyopathy, DCM; induced by doxorubicin 7 mg/kg i.p. every 5 days, 4 doses), CRS-Mel (20 mg/kg/day), CRS-Ex4 (10 µg/kg/day) and CRS-Mel-Ex4. They were euthanized by day 60 after CRS induction. By day 60, plasma creatinine level, urine protein/creatinine ratio and kidney injury histopathology score were highest in CRS, lowest in SC, and progressively decreased from CKD, CRS-Mel, CRS-Ex4 to CRS-Mel-Ex4 (all P