Ciliary IFT88 Protects Coordinated Adolescent Growth Plate Ossification From Disruptive Physiological Mechanical Forces

Compared with our understanding of endochondral ossification, much less is known about the coordinated arrest of growth defined by the narrowing and fusion of the cartilaginous growth plate. Throughout the musculoskeletal system, appropriate cell and tissue responses to mechanical force delineate morphogenesis and ensure lifelong health. It remains unclear how mechanical cues are integrated into many biological programs, including those coordinating the ossification of the adolescent growth plate at the cessation of growth. Primary cilia are microtubule-based organelles tuning a range of cell activities, including signaling cascades activated or modulated by extracellular biophysical cues. Cilia have been proposed to directly facilitate cell mechanotransduction. To explore the influence of primary cilia in the mouse adolescent limb, we conditionally targeted the ciliary gene Intraflagellar transport protein 88 (Ift88^fl/fl) in the juvenile and adolescent skeleton using a cartilage-specific, inducible Cre (AggrecanCreER^T2 Ift88^fl/fl). Deletion of IFT88 in cartilage, which reduced ciliation in the growth plate, disrupted chondrocyte differentiation, cartilage resorption, and mineralization. These effects were largely restricted to peripheral tibial regions beneath the load-bearing compartments of the knee. These regions were typified by an enlarged population of hypertrophic chondrocytes. Although normal patterns of hedgehog signaling were maintained, targeting IFT88 inhibited hypertrophic chondrocyte VEGF expression and downstream vascular recruitment, osteoclastic activity, and the replacement of cartilage with bone. In control mice, increases to physiological loading also impair ossification in the peripheral growth plate, mimicking the effects of IFT88 deletion. Limb immobilization inhibited changes to VEGF expression and epiphyseal morphology in Ift88cKO mice, indicating the effects of depletion of IFT88 in the adolescent growth plate are mechano-dependent. We propose that during this pivotal phase in adolescent skeletal maturation, ciliary IFT88 protects uniform, coordinated ossification of the growth plate from an otherwise disruptive heterogeneity of physiological mechanical forces. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Efficacy of short‐course lansoprazole with clarithromycin and amoxicillin in the eradication of Helicobacter pylori in South‐East Asian patients: 5‐day t.d.s. versus 7‐day b.d. treatment regimens

OBJECTIVE : To determine and compare the efficacy of 5‐day t.d.s and 7‐day b.d. treatment regimens comprising lansoprazole, clarithromycin and amoxicillin in the eradication of Helicobacter pylori. METHODS : Patients with unequivocal evidence of H. pylori infection based on histology and rapid urease tests of both antrum and corpus biopsies were recruited for the study. The study was a randomized, investigator‐blind, comparative study. Patients received either 500 mg clarithromycin t.d.s. and 500 mg amoxicillin t.d.s. for 5 days (LAC5) or 500 mg clarithromycin b.d. and 500 mg amoxicillin b.d. for 7 days (LAC7) together with 30 mg lansoprazole (both groups) daily for either 5 or 7 days, depending on the treatment group. Patients were assessed for the successful eradication of H. pylori, defined as the absence of bacteria based on histology and urease tests on both antral and corporeal biopsies, carried out at least 4 weeks after completion of the therapy. RESULTS : One hundred and eight patients were recruited for the study. In the LAC5 treatment group, four patients failed to return for follow up and in the LAC7 group, two failed to return for follow up and two were not compliant with medications. Eradication rates based on an intention‐to‐treat analysis were: 46/54 for LAC5 (85.2%; 95% CI = 72.9–93.4) and 47/54 for LAC7 (87.0%; 95% CI = 75.1–94.6). Based on a per protocol analysis, the rates were: 46/50 for LAC5 (92.0%; 95% CI = 80.8–97.8) and 47/50 for LAC7 (94.0%; 95% CI = 83.5–98.7). Both treatment regimens were convenient for patients and except for two patients in the LAC7 group, all patients reported taking 100% of all prescribed medications. The side‐effects encountered were uniformly mild and no patient discontinued treatment because of intolerance to medications. The most common side‐effects were altered taste (LAC5 64.7%; LAC7 78.8%). Diarrhea, nausea and anorexia were reported in a minority of patients. CONCLUSIONS : Both the LAC5 t.d.s. and the LAC7 b.d. treatment regimens were well tolerated by patients and were highly effective in the eradication of H. pylori.     

Depressive symptoms in relation to periodontal health in a Jordanian sample

Abstract:  Objectives : This cross-sectional study examines the relationship of depression symptoms to periodontal diseases and decayed (D), missing (M) and filled teeth (FT) in a sample of the Jordanian population. Methods : Subjects escorting dental patients attending two dental hospitals in North Jordan were included. Each subject received full periodontal examination, including probing pocket depth (PPD), clinical attachment level (CAL), gingival index (GI) and plaque index (PI). The numbers of M, D and F teeth were also recorded. The Zung Self-rating Depression Scale was used to determine susceptibility to depression. Results : The frequency of high susceptibility to depression among periodontitis-free subjects and those with periodontitis was found to be 48% and 50% respectively. There was no statistically significant association between susceptibility to depression symptoms and periodontal parameters, including PPD, CAL, PI and GI ( P  >   0.05 ) . However, subjects with low susceptibility to depression had significantly more FT than subjects highly susceptible to depression. Conclusions : High susceptibility to depression does not play a significant role in the aetiology and severity of periodontitis in the population studied.     

Phosphorylation of tyrosine 1248-ERBB2 measured by chemiluminescence-linked immunoassay is an independent predictor of poor prognosis in primary breast cancer patients

ERBB2 (HER2/Neu) gene amplification and overexpression is associated with increased risk of metastases and shorter survival in breast cancer. Tyrosine 1248 is a major phosphorylation site of ERBB2 and reflects the activation status of the receptor. The aim of this study was to investigate the relationships between quantitative levels of pY1248-ERBB2 (p-ERBB2) and the expression of epidermal growth factor receptor (EGFR)-family members, and whether p-ERBB2 could provide additional prognostic value compared with established prognostic markers. For this purpose we developed a highly sensitive chemiluminescence-linked immunoassay (CLISA) and detected p-ERBB2 levels in 70 primary breast cancer biopsies. Phosphorylated ERBB2 correlated with EGFR and ERBB2, and inversely with oestrogen receptor (ER), progesterone receptor (PgR) and ERBB4 expression levels. Additionally, p-ERBB2 was associated with poor clinical outcome in univariate and multivariate Cox regression analysis. Further studies are needed to evaluate the predictive value of p-ERBB2.     

出血热误诊为上呼吸道感染1例

1病例报告患者,男,22岁,因间歇性全身乏力、肌肉酸痛2 wk,发冷1 wk,发热4 d入院.曾在我院查WBC 4.5×109/L,N 0.60,L 0.4,体温波动在38～40℃.初步诊断"上呼吸道感染",用阿莫西林、VC银翘片、清热解毒冲剂等治疗无效.查体:T 38.9℃,BP面性12/8 kPa.全身皮肤无出血点,双眼球结膜轻度充血,咽部充血,软腭未见充血点,心肺腹部未见阳性体征.实验室检查:WBC 7.85 × 109/L,N 0.79,L 0.21,HGB 150g/L,PCL30×109/L,尿蛋白3.2g/L,流行性出血热抗体( ).诊断:流行性出血热.入院后立即按照流行性出血热的治疗原则给予抗病毒、抗渗出、抗出血治疗.具体包括卧床休息,给予高热量,多维生素,易消化饮食;维持水、电解质、酸碱及血浆渗透压平衡;给予大剂量(5 g)Vit.C和Vit.E.同时给予氢化可地松100 mg/d,稀释后缓慢静脉滴注.入院后3 d患者的尿量由450 mL/d增至750 mL/d,肌酐204.6μmol/L,BUN 13.3 mmol/L.5 d尿量增加至4000 mL/d.经综合治疗10 d,肌酐和BUN检查等正常,痊愈出院,随访1 mo未见异常.     

Peripheral pulmonary lesions: ultrasonography and ultrasonically guided aspiration biopsy

Twenty-five patients, each of whom had peripheral intrathoracic lesions that were smaller than 5.0 X 5.0 cm in size and not diagnosed by conventional methods, underwent real-time sonography and ultrasonically guided aspiration biopsy. The lesions included 18 nodules, two infiltrates, and five cavitary lesions. Sonography showed homogeneous hypoechoic or isoechoic density with well-defined margins in 16 of the nodules, and heterogeneous echogenicity with irregular margins in infiltrates. The cavitary lesions showed a hyperechoic ring with a central sonolucent area. Biopsy specimens were successfully obtained by percutaneous aspiration under ultrasound guidance in 24 (96%) of the patients, and a positive diagnosis was established in 21 (84%) by cytology and/or histology. All 17 malignant lesions were diagnosed by aspiration biopsy, while only four of seven benign lesions were diagnosed by this method. Two patients (8%) experienced minimal pneumothorax after aspiration biopsy. We conclude that real-time sonography, including ultrasonically guided aspiration biopsy, is a useful and safe method for examination of peripheral intrathoracic lesions and has a high diagnostic yield.     

Cryptorchidism: A general surgical perspective

Background The treatment of cryptorchidism has changed, with surgery now advocated before the age of two years. Delayed treatment affects fertility, malignant potential and psychological stress. Aims To assess the pattern of referral of cryptorchid patients to a surgical clinic, management and follow-up. Methods A four-year review of 114 cryptorchid patients examined age at presentation, waiting time, timing of surgery and length of follow-up. Results The mean age at presentation to the surgical clinic was 6.7 years (neonatal to 71). The mean age at orchidopexy was 5.6 years. Seventy per cent had a surgical procedure within eight weeks of presentation to a surgeon. Seven per cent were kept under surveillance until a maximum age of three years before orchidopexy was considered. Only 29% proceeded to surgery before the age of two. Seventeen were referred to a paediatric urology unit for further management. Conclusions Orchidopexy seems prudent between one and two years of age. Only one-quarter of patients underwent early orchidopexy. It is vital that it is detected early, by paediatricians at birth or the general practitioners (GPs) at the six-week check up. Prompt referral to a surgeon with a paediatric interest is essential in order to permit surveillance or surgery.