CARD9-mediated macrophage responses and collagen fiber capsule formation caused by textured-type breast implants.

BACKGROUND: An increasing number of women are undergoing breast implantation for cosmetic purposes and for reconstructive purposes after breast excision. The surface morphology of the breast implant is one of the key factors associated with the induction of capsule contraction. The effect of surface morphology on the inflammatory response following implant insertion remains unclear, however. This study conducted comparative analyses to determine the effect of the textured and smooth surface morphology of silicone sheets. METHODS: Each type of silicone sheet was inserted into the subcutaneous pocket below the panniculus carnosus in C57BL/6 mice and mice with genetic disruption of CARD9, Dectin-1, Dectin-2, or Mincle. We also analyzed the collagen fiber capsule thickness, histological findings, and macrophage inflammatory response, including TGF-ß synthesis. RESULTS: We found that textured surface morphology contributed to the formation of collagen fiber capsules and the accumulation of fibroblasts and myofibroblasts, and was accompanied by the accumulation of TGF-ß-expressing macrophages and foreign-body giant cells. CARD9 deficiency attenuated collagen fiber capsule formation, macrophage responses, and TGF-ß synthesis, although the responsible C-type lectin receptors (CLRs) remain to be clarified. CONCLUSIONS: These results suggest that CARD9 may have a strong impact on silicone sheet insertion through the regulation of macrophage responses.

Topical Administration of Heat-Killed Enterococcus faecalis Strain KH2 Promotes Re-Epithelialization and Granulation Tissue Formation during Skin Wound-Healing.

Lactic acid bacteria (LAB) are known to have beneficial effects on immune responses when they are orally administered as bacterial products. Although the beneficial effects of LAB have been reported for the genera Lactobacillus and Lactococcus, little has been uncovered on the effects of the genus Enterococcus on skin wound-healing. In this study, we aimed to clarify the effect of heat-killed Enterococcus faecalis KH2 (heat-killed KH2) strain on the wound-healing process and to evaluate the therapeutic potential in chronic skin wounds. We analyzed percent wound closure, re-epithelialization, and granulation area, and cytokine and growth factor production. We found that heat-killed KH2 contributed to the acceleration of re-epithelialization and the formation of granulation tissue by inducing tumor necrosis factor-α, interleukin-6, basic fibroblast growth factor, transforming growth factor (TGF)-ß1, and vascular endothelial growth factor production. In addition, heat-killed KH2 also improved wound closure, which was accompanied by the increased production of TGF-ß1 in diabetic mice. Topical administration of heat-killed KH2 might have therapeutic potential for the treatment of chronic skin wounds in diabetes mellitus. In the present study, we concluded that heat-killed KH2 promoted skin wound-healing through the formation of granulation tissues and the production of inflammatory cytokines and growth factors.

Contribution of Invariant Natural Killer T Cells to the Clearance of Pseudomonas aeruginosa from Skin Wounds.

Chronic infections are considered one of the most severe problems in skin wounds, and bacteria are present in over 90% of chronic wounds. Pseudomonas aeruginosa is frequently isolated from chronic wounds and is thought to be a cause of delayed wound healing. Invariant natural killer T (iNKT) cells, unique lymphocytes with a potent regulatory ability in various inflammatory responses, accelerate the wound healing process. In the present study, we investigated the contribution of iNKT cells in the host defense against P. aeruginosa inoculation at the wound sites. We analyzed the re-epithelialization, bacterial load, accumulation of leukocytes, and production of cytokines and antimicrobial peptides. In iNKT cell-deficient (Jα18KO) mice, re-epithelialization was significantly decreased, and the number of live colonies was significantly increased, when compared with those in wild-type (WT) mice on day 7. IL-17A, and IL-22 production was significantly lower in Jα18KO mice than in WT mice on day 5. Furthermore, the administration of α-galactosylceramide (α-GalCer), a specific activator of iNKT cells, led to enhanced host protection, as shown by reduced bacterial load, and to increased production of IL-22, IL-23, and S100A9 compared that of with WT mice. These results suggest that iNKT cells promote P. aeruginosa clearance during skin wound healing.

Impact of CAD/CAM mandibular reconstruction on chewing and swallowing function after surgery for locally advanced oral cancer: A retrospective study of 50 cases.

OBJECTIVE: Computer-aided design and computer-aided manufacturing (CAD/CAM) techniques are increasingly applied to mandibular reconstruction, but the superiority of this method in oral food intake has not been well established. Considering the extent of mandibular defects, this retrospective study was aimed to clarify the impact of CAD/CAM mandibular reconstruction on chewing and swallowing function after surgery for locally advanced oral cancer. MATERIALS AND METHODS: We performed a retrospective review of 50 patients who had undergone segmental mandibulectomy with free flap reconstruction for locally advanced oral cancer. The patients' Functional Oral Intake Scale scores were measured at 3 months after surgery, and possible contributing factors including CAD/CAM mandibular reconstruction and the extent of mandibular defects for oral food intake were subjected to univariate analysis and multivariate logistic regression analysis. RESULTS: Multivariate logistic regression analysis showed that CAD/CAM mandibular reconstruction was independently associated with good oral intake, whereas both anterior or extensive mandibular resection and glossectomy were also independently associated with poor oral intake after surgery. CONCLUSION: The present study showed the positive impact of CAD/CAM mandibular reconstruction on chewing and swallowing function after surgery for locally advanced oral cancer for the first time.

Distinct Roles for Dectin-1 and Dectin-2 in Skin Wound Healing and Neutrophilic Inflammatory Responses.

C-type lectin receptors recognize microbial polysaccharides. The C-type lectin receptors such as dendritic cell-associated C-type lectin (Dectin)-1 and Dectin-2, which are triggered by ß-glucan and α-mannan, respectively, contribute to upregulation of the inflammatory response. Recently, we demonstrated that activation of the Dectin-2 signal delayed wound healing; in previous studies, triggering the Dectin-1 signal promoted this response. However, the precise roles of these C-type lectin receptors in skin wound healing remain unclear. This study was conducted to determine the roles of Dectin-1 and Dectin-2 in skin wound healing, with a particular focus on the kinetics of neutrophilic inflammatory response. Full-thickness wounds were created on the backs of C57BL/6 mice, and the effects of Dectin-1 or Dectin-2 deficiency and those of ß-glucan or α-mannan administration were examined. We also analyzed wound closure, histological findings, and neutrophilic inflammatory response, including neutrophil extracellular trap formation at the wound sites. We found that Dectin-1 contributed to the acceleration of wound healing by inducing early-phase neutrophil accumulation, whereas Dectin-2 was involved in prolonged neutrophilic responses and neutrophil extracellular trap formation, leading to delayed wound healing. Dectin-2 deficiency also improved collagen deposition and TGF-ß1 expression. These results suggest that Dectin-1 and Dectin-2 have different roles in wound healing through their different effects on the neutrophilic response.

Congenital Lateral Palatal Synechia Associated With Cleft Palate: A Case Report With Long-Term Follow-Up and Review of the Literature.

Lateral palatal synechiae are rare congenital adhesions running from the free borders of the cleft palate to the lateral parts of the tongue or the oral cavity floor, typically found in cleft palate lateral synechiae syndrome. We present a case of congenital lateral palatal synechia associated with a cleft palate that we treated and followed up for 10 years. We present the long-term prognosis. We also discuss variations in intraoral synechiae associated with cleft palate and the etiology of lateral palatal synechiae through a literature review.

Defying hard-to-heal wounds with an early antibiofilm intervention strategy: 'wound hygiene'.

Biofilm has been implicated as a barrier to wound healing and it is widely accepted that the majority of wounds not following a normal healing trajectory contain biofilm. Therefore, strategies that inform and engage clinicians to reduce biofilm and optimise the wound tissue environment to enable wound progression are of interest to wound care providers. In March 2019, an advisory board was convened where experts considered the barriers and opportunities to drive a broader adoption of a biofilm-based approach to wound care. Poor clarity and articulation of wound terminology were identified as likely barriers to clinical adoption of rigorous and proactive microbial decontamination that is supportive of wound healing advancement. A transition to an intuitive term such as 'wound hygiene' was proposed to communicate a comprehensive wound decontamination plan with an associated message of expected habitual routine. 'Wound hygiene', is a relatable concept that supports meticulous wound practice that addresses barriers to wound healing, such as biofilm, while aligning with antimicrobial stewardship programmes.

Defect of Interferon γ Leads to Impaired Wound Healing through Prolonged Neutrophilic Inflammatory Response and Enhanced MMP-2 Activation.

Interferon (IFN)-γ is mainly secreted by CD4+ T helper 1 (Th1), natural killer (NK) and NKT cells after skin injury. Although IFN-γ is well known regarding its inhibitory effects on collagen synthesis by fibroblasts in vitro, information is limited regarding its role in wound healing in vivo. In the present study, we analyzed how the defect of IFN-γ affects wound healing. Full-thickness wounds were created on the backs of wild type (WT) C57BL/6 and IFN-γ-deficient (KO) mice. We analyzed the percent wound closure, wound breaking strength, accumulation of leukocytes, and expression levels of COL1A1, COL3A1, and matrix metalloproteinases (MMPs). IFN-γKO mice exhibited significant attenuation in wound closure on Day 10 and wound breaking strength on Day 14 after wound creation, characteristics that are associated with prolonged neutrophil accumulation. Expression levels of COL1A1 and COL3A1 mRNA were lower in IFN-γKO than in WT mice, whereas expression levels of MMP-2 (gelatinase) mRNA were significantly greater in IFN-γKO than in WT mice. Moreover, under neutropenic conditions created with anti-Gr-1 monoclonal antibodies, wound closure in IFN-γKO mice was recovered through low MMP-2 expression levels. These results suggest that IFN-γ may be involved in the proliferation and maturation stages of wound healing through the regulation of neutrophilic inflammatory responses.

Diabetes care providers' manual for disaster diabetes care.

To ensure that experiences and lessons learned from the unprecedented 2011 Great East Japan Earthquake are used to improve future disaster planning, the Japan Diabetes Society (JDS) launched the "Research and Survey Committee for Establishing Disaster Diabetes Care Systems Based on Relevant Findings from the Great East Japan Earthquake" under the supervision of the Chairman of the JDS. The Committee conducted a questionnaire survey among patients with diabetes, physicians, disaster medical assistance teams (DMATs), nurses, pharmacists, and nutritionists in disaster areas about the events they saw happening, the situations they found difficult to handle, and the needs that they felt required to be met during the 2011 Great East Japan Earthquake. A total of 3,481 completed questionnaires were received. Based on these and other experiences and lessons reported following the 2011 Great East Japan Earthquake and the 2004 Niigata-Chuetsu Earthquakes, the current "Manual for Disaster Diabetes Care" has been developed by the members of the Committee and other invited authors from relevant specialties. To our knowledge, the current Manual is the world's first to focus on emergency diabetes care, with this digest English version translated from the Japanese original. It is sincerely hoped that patients with diabetes and healthcare providers around the world will find this manual helpful in promoting disaster preparedness and implementing disaster relief.

Diabetes Care Providers' Manual for Disaster Diabetes Care.

To ensure that experiences and lessons learned from the unprecedented 2011 Great East Japan Earthquake are used to improve future disaster planning, the Japan Diabetes Society (JDS) launched the "Research and Survey Committee for Establishing Disaster Diabetes Care Systems Based on Relevant Findings from the Great East Japan Earthquake" under the supervision of the Chairman of the JDS. The Committee conducted a questionnaire survey among patients with diabetes, physicians, disaster medical assistance teams (DMATs), nurses, pharmacists, and nutritionists in disaster areas about the events they saw happening, the situations they found difficult to handle, and the needs that they felt required to be met during the 2011 Great East Japan Earthquake. A total of 3,481 completed questionnaires were received. Based on these and other experiences and lessons reported following the 2011 Great East Japan Earthquake and the 2004 Niigata-Chuetsu Earthquakes, the current "Manual for Disaster Diabetes Care" has been developed by the members of the Committee and other invited authors from relevant specialties. To our knowledge, the current Manual is the world's first to focus on emergency diabetes care, with this digest English version translated from the Japanese original. It is sincerely hoped that patients with diabetes and healthcare providers around the world will find this manual helpful in promoting disaster preparedness and implementing disaster relief.

The Birth Prevalence of Cleft Lip and/or Cleft Palate After the 2011 Tohoku Earthquake and Tsunami.

OBJECTIVE: This study examined whether the 2011 Tohoku earthquake and tsunami affected the birth prevalence of cleft lip and/or cleft palate (CL/P) in Miyagi Prefecture, where the earthquake and tsunami caused severe damage. DESIGN: This was a retrospective cohort study. SETTING: The study was conducted at university and children's hospitals in Miyagi Prefecture. PARTICIPANTS: The annual and monthly numbers of infants born with CL/P were obtained from medical records. The affected period of birth was defined as 1 year from December 1, 2011, to November 30, 2012. The control period was 5 years from January 1, 2006, to December 31, 2010. The annual and monthly numbers of births in Miyagi Prefecture were obtained using e-Stat, which is a portal for Japanese government statistics. MAIN OUTCOME MEASURES: Main outcome measures were birth prevalence of CL/P during the control and affected periods. RESULTS: There were no significant differences between the control and affected periods in the prevalence (per 10 000 live births) of cleft lip with or without palate (13.8 vs 16.7; P = .342), isolated cleft palate (5.2 vs 3.2; P = .267), or overall CL/P (19.0 vs 19.9; P = .799). CONCLUSIONS: We did not observe that the 2011 Tohoku earthquake and tsunami affected the birth prevalence of CL/P in Miyagi Prefecture, even though it severely impacted human health in the area.

Mental Development and Surgical Prognosis of Pai Syndrome: A Case Report and Review of the Literature.

Pai syndrome is a rare congenital disorder, and there are few reports about the long-term prognosis of mental development and surgical results. Here, we report a patient with Pai syndrome who was followed up from birth up to the age of 8 years. Additionally, we review 32 articles and discuss the long-term prognosis of Pai syndrome. In our case, an intracranial lipoma grew a little, but neither epilepsy nor intellectual disabilities occurred. However, she showed attention-deficit/hyperactivity disorder. Furthermore, her nasal airway was gradually obstructed by a residual intranasal polyp.

Dectin-2-Mediated Signaling Leads to Delayed Skin Wound Healing through Enhanced Neutrophilic Inflammatory Response and Neutrophil Extracellular Trap Formation.

Dendritic cell-associated C-type lectin-2 (i.e., dectin-2) recognizes fungal polysaccharides, including α-mannan. Dectin-2-mediated recognition of fungi, such as Candida albicans, leads to NF-κB activation, which induces production of inflammatory cytokines. However, the role of dectin-2 in skin wound healing remains unclear. In this study, we sought to determine how dectin-2 deficiency and the administration of α-mannan affected the wound healing process. Full-thickness wounds were created on the backs of wild type C57BL/6 and dectin-2-deficient mice. We analyzed wound closure, histological findings, and re-epithelialization. We also examined the neutrophilic inflammatory responses and neutrophil extracellular trap (NET)-osis at the wound sites after administration of α-mannan. The percent wound closure and re-epithelialization was significantly accelerated in dectin-2-knockout mice compared with wild-type mice on days 3 and 5 after wounding. In contrast, administration of α-mannan delayed wound closure in wild-type mice, and these responses were canceled in dectin-2-knockout mice. Furthermore, mice administered α-mannan, neutrophil infiltration was prolonged, and the expression of citrullinated histone, an indicator of NETosis, at the wound sites was accelerated. Administration of a neutrophil elastase inhibitor significantly improved the delayed wound healing caused by α-mannan. These results suggest that dectin-2 may have a deep impact on the skin wound healing process through regulation of neutrophilic responses.

Reliability of Ultrasound-Guided One-Point Fixation for Zygomaticomaxillary Complex Fractures.

This study aimed to analyze the precision and postoperative stability of ultrasound guided 1-point fixation on the zygomaticomaxillary buttress for the treatment of zygomaticomaxillary complex (ZMC) fractures. The authors analyzed 24 consecutive patients who underwent ultrasound-guided 1-point fixation for ZMC fractures without separation of the fracture at the frontal process of the zygomatic bone. The authors used titanium plates in the first 6 cases, and biodegradable plates in the remaining 18 cases. The authors obtained computed tomography images preoperatively, and again the first day after surgery (T1) and 6 months after the surgery (T2). The authors calculated vertical change (VC) and horizontal change (HC) of the zygoma on computed tomography. Precision was evaluated with T1 images. Stability was evaluated from T1 to T2, and titanium and biodegradable plates were compared. From T1 images, the mean VC and HC was 0.22° (range, 1.60°-1.08°) and 0.33° (range, 1.86°-1.03°), respectively. From T1 to T2, the mean VC and HC was 0.08° and 0.28°, respectively. Comparing the types of plates, the mean HC in the biodegradable plate group was 0.39°, which was significantly greater than that in the titanium plate group (mean -0.10°). However, as the degree of change was relatively small, this did not pose any clinical problems. Our findings suggest that ultrasound-guided 1-point fixation on the zygomaticomaxillary buttress provides accurate reduction on ZMC fractures without the separation of the frontal process of the zygomatic bone fracture. Sufficient stability was obtained, even with the use of biodegradable plates.

Loss of protein phosphatase 6 in mouse keratinocytes enhances K-rasG12D -driven tumor promotion.

Here, we address the function of protein phosphatase 6 (PP6) loss on K-ras-initiated tumorigenesis in keratinocytes. To do so, we developed tamoxifen-inducible double mutant (K-rasG12D -expressing and Ppp6c-deficient) mice in which K-rasG12D expression is driven by the cytokeratin 14 (K14) promoter. Doubly-mutant mice showed early onset tumor formation in lips, nipples, external genitalia, anus and palms, and had to be killed by 3 weeks after induction by tamoxifen, while comparably-treated K-rasG12D -expressing mice did not. H&E-staining of lip tumors before euthanasia revealed that all were papillomas, some containing focal squamous cell carcinomas. Immunohistochemical analysis of lips of doubly-mutant vs K-rasG12D mice revealed that cell proliferation and cell size increased approximately 2-fold relative to K-rasG12D -expressing mutants, and epidermal thickness of lip tissue greatly increased relative to that seen in K-rasG12D -only mice. Moreover, AKT phosphorylation increased in K-rasG12D -expressing/Ppp6c-deficient cells, as did phosphorylation of the downstream effectors 4EBP1, S6 and GSK3, suggesting that protein synthesis and survival signals are enhanced in lip tissues of doubly-mutant mice. Finally, increased numbers of K14-positive cells were present in the suprabasal layer of doubly-mutant mice, indicating abnormal keratinocyte differentiation, and γH2AX-positive cells accumulated, indicating perturbed DNA repair. Taken together, Ppp6c deficiency enhances K-rasG12D -dependent tumor promotion.

Initial organ distribution and biological safety of Mg2+ released from a Mg alloy implant.

Magnesium (Mg) alloys are considered promising materials for biodegradable medical devices; however, the initial effects and distribution of released Mg2+ ions following implantation are unclear. This is addressed in the present study, using two types of Mg alloys implanted into rats. An in vitro immersion test was first carried out to quantify Mg2+ ions released from the alloys at early stages. Based on these data, we performed an in vivo experiment in which large amounts of alloys were subcutaneously implanted into the backs of rats for 1, 5, 10, and 25 h. Mg2+ accumulation in organs was measured by inductively coupled plasma mass spectrometry. In vivo, blood and urine Mg2+ concentrations were higher in rats receiving the implants than in controls after 1 h; however, the levels were within clinically accepted guidelines. The Mg2+ concentration in bone was significantly higher in the 25 h implanted group than in the other groups. Our results suggest that homeostasis is maintained by urinary excretion and bone accumulation of released Mg2+ ions in response to sudden changes in Mg2+ ion concentration in the body fluid in a large number of Mg alloy implants at the early stages.

Nasopharyngoscopic Analyses through Anterior Maxillary Distraction Osteogenesis for Adolescent Patients With Cleft Palate.

Anterior maxillary distraction osteogenesis (AMDO) is a novel technique for correcting hypoplastic maxilla by sagittal expansion of the maxilla. Recent reports suggest that AMDO does not have an effect on fragile velopharyngeal function in patients with cleft palate. Furthermore, no studies have evaluated the impact of AMDO on velopharyngeal function.We adopted AMDO to correct severe hypoplastic maxilla in adolescent patients with cleft palate and evaluated its impact on velopharyngeal space and function in 8 patients aged 12 to 21 years who underwent AMDO from 2006 to 2014. All the patients had received treatment for cleft palate; however, they still exhibited marginal velopharyngeal insufficiency. The mean activation of the distractor was 10.9 ±â€Š0.9 mm.We determined changes in velopharyngeal closure ratio and closure pattern via nasopharyngoscopy. Additionally, skeletal changes were evaluated using lateral cephalograms.The mean horizontal advancement in the cephalogram obtained 1 year after the distraction was +6.4 mm. Nasopharyngoscopic examination revealed that no deterioration of velopharyngeal gap had occurred after AMDO in all 8 patients. The velopharyngeal closure pattern changed from coronal to circular in 1 patient.Our results indicate that AMDO achieved correction of hypoplastic maxilla without deterioration in velopharyngeal gap and function. Therefore, AMDO is an effective and optimal approach for correcting hypoplastic maxilla especially in patients with fragile velopharyngeal function, such as those with cleft palate.

Invariant NKT cells promote skin wound healing by preventing a prolonged neutrophilic inflammatory response.

The wound-healing process consists of the inflammation, proliferation, and remodeling phases. In chronic wounds, the inflammation phase is prolonged with persistent neutrophil infiltration. The inflammatory response is critically regulated by cytokines and chemokines that are secreted from various immune cells. Recently, we showed that skin wound healing was delayed and the healing process was impaired under conditions lacking invariant natural killer T (iNKT) cells, an innate immune lymphocyte with potent immuno-regulatory activity. In the present study, we investigated the effect of iNKT cell deficiency on the neutrophilic inflammatory response during the wound healing process. Neutrophil infiltration was prolonged in wound tissue in mice genetically lacking iNKT cells (Jα18KO mice) than in wild-type (WT) control mice on days 1 and 3 after wounding. MIP-2, KC, and IL-17A were produced at a significantly higher level in Jα18KO mice than in WT mice. In addition, neutrophil apoptosis was significantly reduced in the wound tissue in Jα18KO mice than in WT mice. Treatment with anti-IL-17A mAb, anti-Gr-1 mAb, or neutrophil elastase inhibitor reversed the impaired wound healing in Jα18KO mice. These results suggest that iNKT cells may promote the wound healing process through preventing the prolonged inflammatory response mediated by neutrophils.

Consensus guidelines for the identification and treatment of biofilms in chronic nonhealing wounds.

BACKGROUND: Despite a growing consensus that biofilms contribute to a delay in the healing of chronic wounds, conflicting evidence pertaining to their identification and management can lead to uncertainty regarding treatment. This, in part, has been driven by reliance on in vitro data or animal models, which may not directly correlate to clinical evidence on the importance of biofilms. Limited data presented in human studies have further contributed to the uncertainty. Guidelines for care of chronic wounds with a focus on biofilms are needed to help aid the identification and management of biofilms, providing a clinical focus to support clinicians in improving patient care through evidence-based medicine. METHODS: A Global Wound Biofilm Expert Panel, comprising 10 clinicians and researchers with expertise in laboratory and clinical aspects of biofilms, was identified and convened. A modified Delphi process, based on published scientific data and expert opinion, was used to develop consensus statements that could help identify and treat biofilms as part of the management of chronic nonhealing wounds. Using an electronic survey, panel members rated their agreement with statements about biofilm identification and treatment, and the management of chronic nonhealing wounds. Final consensus statements were agreed on in a face-to-face meeting. RESULTS: Participants reached consensus on 61 statements in the following topic areas: understanding biofilms and the problems they cause clinicians; current diagnostic options; clinical indicators of biofilms; future options for diagnostic tests; treatment strategies; mechanical debridement; topical antiseptics; screening antibiofilm agents; and levels of evidence when choosing antibiofilm treatments. CONCLUSION: This consensus document attempts to clarify misunderstandings about the role of biofilms in clinical practice, and provides a basis for clinicians to recognize biofilms in chronic nonhealing wounds and manage patients optimally. A new paradigm for wound care, based on a stepped-down treatment approach, was derived from the consensus statements.