The role of CDKN2A/B deletions in pediatric acute lymphoblastic leukemia

The CDKN2A/B genes in the 9p21 chromosomal region are frequently involved in human cancer, including pediatric acute lymphoblastic leukemia (ALL). These genes encode 3 proteins that belong to the RB1 and TP53 pathways and act as tumor suppressors by regulating the G1/S checkpoint of the cell cycle. The prognostic value of deletions in the CDKN2A/B locus in ALL is controversial in part due to the limitations of the methodologies used. Further studies with advanced technologies are needed for elucidation. Future studies would also highlight whether CDK4/CDK6 selective inhibitors might be useful therapies for children with these genetic aberrations.     

The Spoke-Hub-and-Node Model of Integrated Heart Failure Care

Heart failure (HF) is a significant public health concern. Specialized HF clinics provide the optimal environment to address the complex needs of these patients and improve outcomes. The current and growing population of patients with HF outstrips the ability of these clinics to deliver care. Integrated care is defined as health services that are managed and delivered so that people receive a seamless continuum of health promotion, disease prevention, diagnosis, treatment, disease management, rehabilitation, and palliative care services. This approach requires coordination across different levels and sites of care within and beyond the health sector, according to changing patient needs throughout their lives. The spoke-hub-and-node (SHN) model represents an organization of care that works collaboratively with the primary care sector and is highly integrated with community-based multidisciplinary teams of health care professionals and specialty care. The purpose of this article is to analyze the requirements for successful implementation of SHN models. We consider the respective roles of HF clinics, HF nurse specialists, pharmacists, palliative care teams, telemonitoring, and solo practitioners. We also discuss levels of care delivery and the importance of patient stratification and patient flow. The SHN approach has the potential to build on and improve the chronic care model (CCM) to deliver centralized services to preserve high-quality patient-centred care at affordable costs.     

Japanese orthopaedic association cervical myelopathy evaluation questionnaire (JOACMEQ): Part 5. Determination of responsiveness

Background

In 1999, the Japanese Orthopaedic Association decided to develop a new Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). The final version of the JOACMEQ, comprising 24 questions and five domains (cervical spine function (CF); upper extremity function (UF); lower extremity function (LF); bladder function (BF); and quality of life (QOL)), was established after three nationwide investigations. The fourth investigation, reported in this paper, was performed to confirm the responsiveness of the questionnaire.

Protein-Losing Enteropathy Following Fontan Palliation

Protein-losing enteropathy (PLE) is a chronic condition involving multiple organ systems that may develop any time following Fontan completion. The pathogenesis of PLE is complex and multifactorial. Chronic venous hypertension, low cardiac output, and abnormal lymphatics may all play a role in the pathogenesis of PLE. Common signs and symptoms include chronic diarrhea, abdominal pain, and ascites. Diagnosis is based on the presence of signs and symptoms in addition to hypoalbuminemia and elevated stool alpha 1 antitrypsin. Early identification and a comprehensive approach to evaluation and treatment are important, as they may affect survival. The initial evaluation should include cardiac catheterization for hemodynamic assessment. Although an evidence base for treatment is lacking, various medical, interventional, and surgical approaches have been described with variable degrees of success. Commonly used therapies include nutritional support, diuretics, subcutaneous unfractionated heparin, budesonide, and sildenafil. Limited data exist for Fontan conversion or takedown. Assessment for heart transplantation should be considered. PLE mortality is high—approximately 50%—but may be mitigated by aggressive investigation and management. The evolving understanding of the role of lymphatics in the pathophysiology of PLE and the emerging role of interventional lymphatic procedures may further improve outcomes in this patient population.     

中文版颈部结局评分评估颈痛患者反应度的研究

目的探讨中文版颈部结局评分（NOOS-C）的反应度，为颈痛患者干预效果的评估提供可靠工具。方法对 NOOS 量表进行跨文化调适形成 NOOS-C。以 2016 年 9 月—2017 年 5 月收治并符合纳入标准的 80 例颈痛患者作为研究对象，干预前后使用 NOOS-C 和中文版颈椎功能障碍指数（NDI-C）进行评估，其中 71 例患者完成问卷调查。采用配对t 检验比较干预前后 NOOS-C 各维度评分及总分差异。计算 NOOS-C、NDI-C 评分干预前后差值（变化值），并基于变化值计算效应大小（effect size，ES）、标准化反应均数（standardized response mean，SRM），分析量表内部反应度。干预前后 NOOS-C、NDI-C 评分行 Spearman 相关分析，分析量表外部反应度。 结果干预前后 NOOS-C 评分中除活动评分比较差异无统计学意义（P>0.05）外，症状、睡眠障碍、日常活动和疼痛、日常生活参与度和总分比较，差异均有统计学意义（P<0.05）。NDI-C 指数变化值为–12.11%±17.45%、ES 为 0.77、SRM 为 0.69；NOOS-C 分别为（13.74±17.22）分、0.83、0.80。相关性分析显示，NOOS-C 与 NDI-C 干预前后均成负相关（r=–0.914，P=0.000； r=–0.872，P=0.000）。 结论NOOS-C 具有良好的反应度。     

骨性Ⅲ类错（牙合）畸形患者双颌手术前后面部软组织变化的三维研究

目的探讨骨性 Ⅲ 类错（牙合）畸形患者双颌手术前后面部软组织变化规律。方法选择 2016 年 8 月—2017 年 4 月，接受上颌骨 LeFortⅠ型截骨前徙+下颌骨矢状劈开截骨后退术治疗的 30 例骨性Ⅲ类错（牙合）畸形患者为研究对象。其中，男 11 例，女 19 例；年龄 18～35 岁，平均 22.6 岁。于术前 2 周内任一时间点及术后 6 个月行全头颅 CT 扫描和面部软组织三维面像扫描，采用 Artec Studio11.0、CMF Proplan3.0 软件建立三维面像模型，分析手术前后面部软组织变化区域，测量面部各区域软组织解剖标志点，并比较手术前后差异。结果双颌手术后面部软组织变化区域为上颌鼻旁至下颌颏下区域，两侧不超过外眦垂线界限。手术前后比较，水平方向左右侧鼻翼基点以及左右侧颊点发生显著变化（P<0.05）。矢状方向鼻下点、鼻尖点、左右鼻翼基点、上唇缘点显著前移（P<0.05），左右口角点、下唇缘点、颏唇沟中点、颏前点、颏下点显著后退（P<0.05）。垂直方向上唇缘点、双侧口角点、下唇缘点、左右侧颊点、左右侧内眦点显著下降（P<0.05），颏下点显著上抬（P<0.05）。术后鼻小柱显著变短、上唇变长、鼻翼基底变宽（P<0.05）。 结论骨性 Ⅲ 类错（牙合）畸形患者双颌手术后面部整体变短且更饱满，面部软组织变化范围下颌大于上颌，提示手术设计时需考虑患者术后面型变化。     

[6]-Shogaol,a dietary phenolic compound,induces oxidative stress mediated mitochondrial dependant apoptosis through activation of proapoptotic factors in Hep-2 cells

Ginger (Zingiber officinale) is a well-known herb used in ethnomedicine. [6]-shogaol, a phenolic nature is a major constituent of ginger. In this study, we investigated the anticancer activity of [6]-shogaol in Laryngeal cancer (Hep-2) cells. We demonstrated the effects of [6]-shogaol on the cell growth and apoptosis in Hep-2 cells were analyzed by the generation of reactive oxygen species (ROS), the level of mitochondrial membrane potential (ΔYm), DNA damage and apoptotic morphological changes were analyzed by AO/EtBr, AO and Hoechst staining. Further, apoptotic protein expressions were analyzed by western blot analysis. Our results indicated that [6]-shogaol induces apoptosis as evidenced by loss of cell viability, enhanced ROS, lipid peroxidation results in altered mitochondrial membrane potential, increased DNA damage in Hep-2 cells. Further, the prooxidant role of [6]-shogaol inhibit Bcl-2 expression with the simultaneous up-regulation of Bax, Cytochrome c, Caspase-9 and -3 protein expressions were observed in Hep-2 cells. Thus, [6]-shogaol induces apoptosis in Hep-2 cells through inducing oxidative damage and modulate apoptotic marker expressions. Therefore, [6]-shogaol might be used as a therapeutic agent for the treatment of laryngeal cancer.     

IL6Rα function in myeloid cells modulates the inflammatory response during irritant contact dermatitis

Irritant contact dermatitis (ICD) is characterized by epidermal hyperplasia, infiltration of leucocytes into lesional skin and inflammatory cytokine release. The cellular infiltrate during ICD comprises primarily cells of the myeloid lineage. Our group has previously shown that the cytokine IL‐6 confers a protective effect to lesional skin during ICD. How IL‐6Rα function in myeloid cells is involved in the inflammatory response during ICD is, however, unknown. In the present study, utilizing a chemical model of ICD, it is shown that mice with a myeloid‐specific knockout of the IL‐6Rα (IL‐6Rα^Δmyeloid) display an exaggerated inflammatory response to benzalkonium chloride (BKC) and Jet propellant‐8 (JP8) fuel, two well‐characterized irritants relative to littermate control. Results from immunohistochemical and flow cytometric analyses revealed that IL‐6Rα^Δmyeloid mouse skin displayed increased epidermal hyperplasia and inflammatory monocyte influx into lesional skin but lower numbers of resident macrophages relative to littermate controls after irritant exposure. Multiplex immunoassay revealed significantly higher levels of pro‐inflammatory cytokines IL‐1α and TNF‐α, but reduced expression of chemokine proteins including CCL2‐5, CCL7, CCL11, CXCL1 and CXCL10 in IL‐6Rα^Δmyeloid mouse skin relative to littermate control following irritant exposure. These results highlight a previously unknown role of IL‐6Rα function in myeloid cells in modulating the inflammatory response and myeloid population dynamics during ICD.