Association between maternal gestational diabetes mellitus and high‐sensitivity C‐reactive protein levels in 8‐year‐old children: The Yamanashi Adjunct Study of the Japan Environment and Children’s Study (JECS)

Gestational diabetes mellitus (GDM) is one of the most common pregnancy‐related complications; it is associated with adverse pregnancy outcomes and metabolic disorders in offspring, consistent with the concept of the developmental origins of health and disease. This cohort study of women without diabetes (n = 761), who were part of the Yamanashi Adjunct Study of the Japan Environment and Children’s Study, aimed to explore the associations between maternal GDM and their offspring’s level of high‐sensitivity C‐reactive protein (hsCRP), a biomarker of inflammatory and cardiovascular diseases. We analyzed the associations between GDM and the offspring’s hsCRP levels using a multiple logistic regression model. A mother with GDM significantly increased the risk for high hsCRP level by 4.07‐fold (≥2.0 mg/L) in the child. As such, maternal GDM was significantly associated with increased serum hsCRP levels in 8‐year‐old children.     

血管内皮细胞和成纤维细胞混合移植对人工真皮血管化的影响

目的观察同种血管内皮细胞和成纤维细胞移植对人工真皮血管化的促进作用。方法在27只Wistar大鼠背部造成2．5 cm×2．5 cm全层皮肤缺损创面(2处／只),将其分为血管内皮细胞组:将血管内皮细胞混入0．5 ml纤维蛋白胶中,按1．0×105／cm2的密度均匀喷洒于移植床;混合组:将血管内皮细胞和成纤维细胞混入等量纤维蛋白胶后,同前密度喷洒于移植床;对照组:按同样方法喷洒等量纤维蛋白胶。随后各组移植人工真皮,每组9只大鼠18处创面。于移植后5、10 d切取移植的真皮及周围组织行HE、血管内皮生长因子(VEGF)、Masson和墨汁灌注染色,观察新生血管生长情况。于移植后5 d行伊文思蓝灌注,以分光光度计定量检测法测定微血管形成情况。结果移植后5 d,HE、VEGF、Masson和墨汁灌注染色均可见各组移植床有新生血管长入。HE染色见血管内皮细胞组、混合组新生血管数量分别为(14．2±3．6)、(12．1±2．5)条,较对照组[(3．9±1．6)条]明显增多(P<0．05)。移植后10 d,人工真皮内及移植床均有微血管形成,且胶原组织的合成增加。移植后5 d,经伊文思蓝灌注,收集并检测血管内皮细胞组、混合组真皮组织溶出的上清液,吸光度值分别为0．167±0．058、0．155±0．046,均高于对照组的0．066±0．024(P<0．05)。结论同种血管内皮细胞和成纤维细胞移植可促进创面愈合过程中的血管新生,加速人工真皮移植后血管化过程,促进类真皮组织的成熟。     

Orthogonal antibody testing for COVID-19 among healthcare workers in a non-epidemic place and time: Japan’s Iwate Prefecture,May 18-31, 2020

Of the 47 prefectures in Japan, Iwate had the fewest cases of coronavirus disease 2019 (COVID-19), with the first diagnosis officially confirmed on July 28, 2020. A baseline serological survey of COVID-19 antibodies is essential to accurately evaluate an epidemic outbreak. The primary purpose of this study was to determine pre-epidemic prevalence of COVID-19 antibodies among healthcare workers, using two laboratory-based quantitative tests. In addition, a point-of-care (POC) qualitative test, rapid, simple, and convenient for primary care clinics, was compared with the laboratory-based tests. All antibody tests were performed on serum from 1,000 healthcare workers (mean age, 40 ± 11 years) in Iwate Prefectural Central Hospital, May 29-31, 2020. A COVID-19 case was defined as showing positive results in both laboratory-based quantitative tests. None of 1,000 samples had positive results in both of the laboratory immunoassays. The POC test showed positive results in 33 of 1,000 samples (3.3%) (95% confidence interval: 2.19-4.41), but no samples were simultaneously positive in both laboratory-based tests. In conclusion, COVID-19 cases were not serologically confirmed by a baseline control study of healthcare workers at our hospital in late May, 2020. Moreover, the POC qualitative test may offer no advantage in areas with very low prevalence of COVID-19, due to higher false-positive reactions compared with laboratory-based quantitative immunoassays.     

Activation of proprotein convertase in the mouse habenula causes depressive-like behaviors through remodeling of extracellular matrix

The lateral habenula (LHb) attracts a growing interest as a regulator of monoaminergic activity which were frequently reported to be defective in depression. Here we found that chronic social defeat stress (CSDS) increased production of pro-inflammatory cytokines in LHb associated with mobilization of monocytes and remodeling of extracellular matrix by increased matrix metalloproteinase (MMP) activity. RNA-seq analysis identified proprotein convertase Pcsk5 as an upstream regulator of MMP activation, with upregulation in LHb neurons of mice with susceptibility to CSDS. PCSK5 facilitated motility of microglia in vitro by converting inactive pro-MMP14 and pro-MMP2 to their active forms, highlighting its role in mobilization of microglia and monocytes in neuroinflammation. Suppression of Pcsk5 expression via small interfering RNA (siRNA) ameliorated depressive-like behaviors and pathological mobilization of monocytes in mice with susceptibility to CSDS. PCSK5-MMPs signaling pathway could be a target for development of the antidepressants targeting the inflammatory response in specific brain regions implicated in depression.Subject terms: Cellular neuroscience, Gene expression analysis     

Blockade of menstrual cycle by thyroidectomy in Japanese monkeys (Macaca fuscata fuscata)

To examine the role of thyroid hormones in the seasonal breeding cycle in Japanese monkeys (Macaca fuscata fuscata), sexually mature females were thyroidectomized (n=6) in early December, during the midbreeding season, or they received sham operations (n=4). They were housed indoors individually, and blood samples were collected two to three times a week to monitor gonadotropin and gonadal steroid hormone secretions. Control monkeys exhibited ovulatory cycles during the breeding season. The mean dates of onset and end of the ovulatory cycles were October 22±13 d and February 25±14 d, respectively. These dates coincided well with those of our colonies under captivity. By contrast, three of the six thyroidectomized monkeys terminated ovulatory cycles immediately after operations; the remaining three monkeys ovulated only once or twice after thyroid removal. The mean dates of onset and end of the ovulatory cycles of thyroidectomized monkeys were October 18±4 d and December 31±4 d, respectively. This was a significantly earlier termination of the ovulatory cycles than in controls. Mean concentrations of plasma thyroxine of control monkeys were maintained throughout the experimental period, whereas plasma thyroxine concentrations of thyroidectomized monkeys decreased abruptly to undetectable levels. Thyroidectomized monkeys exhibited significantly higher levels of plasma prolactin (PRL) than controls. Moreover, even in control monkeys, plasma PRL increased during the transition out of the breeding season. These results suggest that thyroid hormones play an important role in the regulation of ovulatory cycles in Japanese monkeys, directory or indirectly, possibly by mediating the changes of PRL secretion.     

Diagnostic value of 123I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) single photon emission computed tomography (SPECT) in patients with chest pain. Comparison with rest-stress 99mTc-tetrofosmin SPECT and coronary angiography.

BACKGROUND: Basic and clinical studies have indicated that 15-(p-[(123)I] iodophenyl)-3-(R, S) methylpentadecanoic acid (BMIPP) single photon emission computed tomography (SPECT) can identify ischemic myocardium without evidence of myocardial infarction by the regional decline of tracer uptake. The present study compared BMIPP SPECT with rest-stress myocardial perfusion imaging (MPI) findings and coronary angiography (CAG) in 150 patients with acute chest pain. METHODS AND RESULTS: Patients with acute chest pain who underwent all of the following tests were selected: MPI at rest-stress, BMIPP SPECT at rest and CAG. Organic coronary artery stenosis (>or=75%) was observed in 46 patients, 27 patients had total or subtotal coronary occlusion by spasm in the spasm provocation test on CAG and the remaining 77 patients had no significant coronary artery stenosis or spasm. The sensitivity of BMIPP at rest to detect organic stenosis was significantly higher (54%) than that of rest-MPI (33%, p<0.005), but lower than that of stress-MPI (76%, p=0.05). The sensitivity of BMIPP at rest to detect spasm was significantly higher (63%) than that of both rest-MPI (15%; p<0.001) and stress-MPI (19%; p<0.001). Overall, the sensitivity of BMIPP at rest to detect both organic stenosis and spasm was significantly higher (58%) than that of rest-MPI (26%; p<0.001), despite having no significance with that of stress-MPI (55%). The specificity was not significantly different among the three imaging techniques. CONCLUSION: Resting BMIPP SPECT is an alternative method to stress MPI for identifying patients with not only organic stenosis but also spasm without the need for a stress examination.