Vulnerability to Sympathetic Stress Does Not Persist in Takotsubo Stress Cardiomyopathy

ObjectiveOur objective was to investigate whether dobutamine stress echocardiography (DSE) could induce abnormal cardiac function in takotsubo stress cardiomyopathy (TSC) patients in a stable condition after the acute attack.Methods and ResultsThis was a case-control study and a substudy of the Stockholm Myocardial Infarction With Normal Coronaries (SMINC) study. Twenty-two patients with a previous episode of TSC and 22 sex- and age-matched control subjects were recruited from the SMINC study and investigated with the use of DSE. All TSC patients had a previous normal cardiovascular magnetic resonance investigation. Tissue Doppler imaging–derived time phases of the cardiac cycle were recorded to calculate myocardial performance index (MPI) to assess ventricular function. Compared with control subjects at rest, TSC patients had a slightly but significantly higher left ventricular MPI (LV-MPI; 0.53 vs 0.59; P = .01) and as a trend higher right ventricular MPI (0.38 vs 0.47; P = .08), although during DSE these variables did not differ significantly.ConclusionWe found no difference in standard diastolic parameters between TSC and control subjects, but a significant higher value in LV-MPI in the TSC group at rest. However, no such difference could be demonstrated during DSE between the groups, indicating that vulnerability to sympathetic stimulation does not persist in TSC patients.     

Cytokine expression profile in the bone‐anchored hearing system: 12‐week results from a prospective randomized,controlled study

Objective

To study the effect of implanting the percutaneous bone‐anchored hearing system (BAHS) itself and inflammation of the peri‐abutment skin warrant clarification. In this study, we aimed to acquire further insight into the immune responses related to BAHS surgery and peri‐implant skin inflammation.

Materials and Methods

During surgery and 12 weeks post‐implantation, skin biopsies were obtained. If applicable, additional biopsies were taken during cases of inflammation. The mRNA expression of IL‐1β, IL‐6, IL‐8, TNFα, IL‐17, IL‐10, TGF‐ß, MIP‐1α, MMP‐9, TIMP‐1, COL1α1, VEGF‐A, FGF‐2 TLR‐2, and TLR‐4 was quantified using qRT‐PCR.

Results

Thirty‐five patients agreed to the surgery and 12‐week biopsy. Twenty‐two patients had mRNA of sufficient quality for analysis. Ten were fitted with a BAHS using the minimally invasive Ponto surgery technique. Twelve were fitted with a BAHS using the linear incision technique with soft‐tissue preservation. Five biopsies were obtained during episodes of inflammation. The post‐implantation mRNA expression of IL‐1β (P = .002), IL‐8 (P = .003), MMP9 (P = .005), TIMP‐1 (P = .002), and COL1α1 (P < .001) was significantly up‐regulated. IL‐6 (P = .009) and FGF‐2 (P = .004) mRNA expression was significantly down‐regulated after implantation. Within patients, no difference between post‐implantation mRNA expression (at 12 weeks) and when inflammation was observed. Between patients, the expression of IL‐1β (P = .015) and IL‐17 (P = .02) was higher during cases of inflammation compared with patients who had no inflammation at 12‐week follow‐up.

Conclusions

As part of a randomized, prospective, clinical trial, the present study reports the molecular profile of selected cytokines in the soft tissue around BAHS. Within the limit of this study, the results showed that 12 weeks after BAHS implantation the gene expression of some inflammatory cytokines (IL‐8 and IL‐1β) is still relatively high compared with the baseline, steady‐state, expression. The up‐regulation of anabolic (COL1α1) and tissue‐remodeling (MMP‐9 and TIMP1) genes indicates an ongoing remodeling process after 12 weeks of implantation. The results suggest that IL‐1β, IL‐17, and TNF‐α may be interesting markers associated with inflammation.     

Perception or reality: Can thermal perceptions inform management of firefighters in the heat?

Accurately assessing the physiological status of firefighters during work in the heat is critical to ensuring their safety. Evaluating core temperatures (T_c) in the field is problematic due to cost and limitations in technology and accuracy. As such, fire services rely on individual perceptions of wellbeing. The present study aimed to establish whether perceptual responses measured using the perceptual strain index (PeSI), calculated from rate of perceived exertion (RPE) and thermal sensation (TS), could reliably predict the physiological strain (PSI) encountered by experienced firefighters working in a hot environment. We conducted two firefighting simulations (set-pace and self-paced) in a purposefully built heat chamber (100 ± 5°C) comprised of two 20-min periods separated by a 10-min recovery outside the chamber. Physiological strain was measured via heart rate (HR) and gastrointestinal temperature (T_gi) and compared with PeSI at 5-min intervals. To evaluate the predictive ability of the PeSI for PSI, mean differences and the 95% limits of agreement (LOA) were established, along with correlation coefficients at each 5-min interval. Moderately significant correlations occurred in the second work bout of the self-paced trial only (10 min: r = 0.335, 15 min: r = 0.498, 20 min r = 0.439) with no other correlations observed at any other time during either trial or during the rest periods. Bland-Altman analysis revealed mean differences of ?0.74 ± 2.70 (self-paced) and +0.04 ± 2.04 (set-paced) between PeSI and PSI with the 95% LOA being ?4.77 to 3.28 (self-paced) and ?4.01 to 2.01 (set-paced). The wide LOA and lack of correlations observed between perceptual and physiological strain in both self-paced and set-paced work trials indicate that PeSI is not sufficiently reliable as a sole measure of wellbeing for firefighters working in the heat. Hence, we recommend that fire services prioritise the development of reliable and effective monitoring tools for use in the field.     

Protein Content and Methyl Donors in Maternal Diet Interact to Influence the Proliferation Rate and Cell Fate of Neural Stem Cells in Rat Hippocampus

Maternal diet during pregnancy and early postnatal life influences the setting up of normal physiological functions in the offspring. Epigenetic mechanisms regulate cell differentiation during embryonic development and may mediate gene/environment interactions. We showed here that high methyl donors associated with normal protein content in maternal diet increased the in vitro proliferation rate of neural stem/progenitor cells isolated from rat E19 fetuses. Gene expression on whole hippocampi at weaning confirmed this effect as evidenced by the higher expression of the Nestin and Igf2 genes, suggesting a higher amount of undifferentiated precursor cells. Additionally, protein restriction reduced the expression of the insulin receptor gene, which is essential to the action of IGFII. Inhibition of DNA methylation in neural stem/progenitor cells in vitro increased the expression of the astrocyte-specific Gfap gene and decreased the expression of the neuron-specific Dcx gene, suggesting an impact on cell differentiation. Our data suggest a complex interaction between methyl donors and protein content in maternal diet that influence the expression of major growth factors and their receptors and therefore impact the proliferation and differentiation capacities of neural stem cells, either through external hormone signals or internal genomic regulation.     

Choroidal structural changes determined by the binarization method after intravitreal aflibercept treatment in neovascular age-related macular degeneration

AIM: To assess the choroidal structural alterations after intravitreal injection of aflibercept in neovascular age-related macular degeneration (nAMD). METHODS: Fifty eyes with treatment-naïve nAMD were evaluated at baseline, 3rd, and 12th month. Fifty eyes of 50 healthy subjects were also included as controls. Choroidal thickness (CT) was measured in the subfoveal region. Total circumscribed choroidal area (CA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI) was calculated using Image J. RESULTS: At baseline, subfoveal CT was increased in nAMD patients compared to controls (P=0.321). Eyes with nAMD had a significantly increased total circumscribed CA and SA (P=0.041, 0.005, respectively). The CVI was decreased (P=0.038). In the 3rd month, the subfoveal CT, LA, and CVI revealed a decrease (P=0.005, P=0.039, 0.043, respectively). In the 12th month, subfoveal CT, LA, and CVI were decreased in comparison to baseline measures (P<0.001, 0.006, 0.010, respectively). CONCLUSION: Significant structural alterations are found after intravitreal aflibercept treatment during the 12-month follow-up, in particular at the third month, in eyes with nAMD.     

外周血CD4+CXCR5+Tfh水平对肺炎克雷伯菌感染者预后的影响

目的　检测肺炎克雷伯菌感染者外周血CD4+CXCR5+滤泡辅助性T细胞（T follicular helper cell, Tfh）水平，探讨其对患者预后的影响。方法　选取2017年7月—2019年5月于本院ICU住院治疗的147例患者为研究对象，根据患者入院后是否出现肺炎克雷伯菌感染，将其分为感染组（69例）和未感染组（78例）。采用流式细胞术检测147例患者外周血CD4+CXCR5+Tfh水平。采用单因素分析肺炎克雷伯菌感染的影响因素；采用单因素分析和多因素Logistic回归分析肺炎克雷伯菌感染者预后的影响因素。结果　感染组的住院时间、入住ICU时间、入住ICU时APACHE II评分、机械通气时间及心血管疾病、多器官功能障碍综合征、接受手术、恶性肿瘤患者比例均高于未感染组，差异均有统计学意义（P均＜0.05）。感染组外周血CD4+CXCR5+Tfh水平、死亡患者比例均高于未感染组（P均＜0.05）。感染组中死亡患者外周血CD4+CXCR5+Tfh水平高于生存患者（P＜0.05）。CD4+CXCR5+Tfh、碳青霉烯类耐药、入住ICU时APACHE II评分是影响肺炎克雷伯菌感染者死亡的独立危险因素（P均＜0.05）。结论　外周血CD4+CXCR5+Tfh水平在肺炎克雷伯菌感染者中显著升高，CD4+CXCR5+Tfh可能通过参与机体免疫应答影响感染者的预后。检测CD4+CXCR5+Tfh水平不仅对判断感染者的免疫状态有重要意义，也可为肺炎克雷伯菌感染者治疗提供依据。     

Microdensitometry of osteopontin as an immunohistochemical prognostic biomarker in colorectal carcinoma tissue microarrays: potential and limitations of the method in ‘biomarker pathology’

Prall F, Maletzki C & Linnebacher M
(2012) Histopathology  61, 823–832 Microdensitometry of osteopontin as an immunohistochemical prognostic biomarker in colorectal carcinoma tissue microarrays: potential and limitations of the method in ‘biomarker pathology’ Aims: To explore the potential and limitations of ‘biomarker pathology’ with quantitative immunohistochemistry on tissue microarrays, taking osteopontin and colorectal carcinoma as a model system. Methods and results: Microdensitometry for quantitative evaluation of osteopontin immunohistochemistry (clone OP3N) on digital microphotographs using the public domain software ImageJ was observed to be straightforward to perform and reliable. However, using colorectal carcinoma cell lines (n = 11) the correlation between densitometric evaluations of Western blots and microdensitometry of immunocytochemistry of slide cultures was only moderate. A virtual resampling method to simulate tissue microarrays showed that, due to heterogeneity of immunostaining, tumours were misclassified in nearly 20% of the arrays, even if four punches were used. With regard to prognosis, microdensitometric evaluation of a tissue microarray made of a clinicopathologically well‐characterized series of colorectal carcinomas with long‐term follow‐up (222 cases evaluable in the tissue microarray, UICC Stages I–III/R0) showed a moderate survival advantage of patients with high osteopontin expression by microdensitometry. Conclusions: These results challenge the basic assumption that microdensitometry is a precise technique for the quantification of proteins detected by immunohistochemistry and delineate drawbacks encountered when working with tissue microarrays in clinicopathological studies.     

Surgery for oligometastatic disease in non-small-cell lung cancer

In general, patients with additional metastatic nodules or distant metastases of a non-small-cell lung cancer (NSCLC) have a poor prognosis. However, published results suggest that in carefully selected patients with synchronous or metachronous metastatic lesions, long-term survival can be obtained when a complete resection of the primary site and metastasis – mostly single brain or adrenal – is achieved. Different subgroups of patients with metastatic NSCLC exist and a distinction should be made between additional malignant nodules in the ipsilateral and contralateral lung, malignant pleural effusion and extrathoracic, single or multiple metastases. Patients with additional malignant nodules in the same lobe or ipsilateral nonprimary lobe have a better prognosis than suggested by the current tumor–node–metastasis (TNM) classification. The other subgroups have a poor prognosis. In view of recent data from a large, international database, proposals have been made for the new TNM classification that will be introduced in 2009.