Hypoxia can contribute to the induction of the Epstein-Barr virus (EBV) lytic cycle.

BACKGROUND: Like other herpes viruses, latent Epstein-Barr virus (EBV) infection can be reactivated to lytic replication. Reactivation can be achieved by treatment with various reagents, including tetradecanoyl phorbol acetate (TPA) and Ca2+ ionophores. Relatively little is known about the physiological factors related to reactivation of EBV. Previous studies have demonstrated that G0/G1 cell cycle arrest is associated with EBV activation, and that hypoxic conditions can induce cell cycle arrest. In the present study we investigated the effect of hypoxia on reactivation of EBV. OBJECTIVE AND METHODS: Hypoxic culture conditions were established and the expression of Zta protein and the number of EBV DNA copies were measured in B95-8 cells maintained under these conditions. RESULTS: Hypoxia treatment not only increased the expression of the EBV immediate-early protein Zta (which mediates the switch between the latent and lytic form of infection), but also increased the number of EBV DNA copies in B95-8 cells. CONCLUSIONS: EBV in latent infection can be activated to lytic infection by hypoxia treatment.     

Use of multiple displacement amplification to amplify genomic DNA before sequencing of the alpha and beta haemoglobin genes

AIMS: To evaluate the technique of multiple displacement amplification (MDA) for whole genome amplification from small volume blood samples before sequencing in a clinical test to identify haemoglobin gene mutations. METHODS: Phage phi29 DNA polymerase was used to perform MDA, starting with either 1 micro l of blood or 1 ng of previously isolated blood DNA from 23 patients. The amplified products were then evaluated using a clinical test that involves sequencing the haemoglobin genes to detect mutations. The results were compared with the current clinical test method that uses genomic DNA isolated using column based technology. RESULTS: The MDA technique produced large quantities (theoretically approximately 2 mg) of DNA. The amplification procedure was extremely easy and took about four hours (less than one hour of hands on technician time and three hours for amplification). When MDA products were used in the same clinical test protocol as genomic DNA isolated using column technology, there was 100% concordance for detection of a variety of point mutations in the alpha1, alpha2, and beta globin genes. CONCLUSIONS: The MDA technique is useful for overcoming the problem of insufficient genomic DNA in clinical specimens requiring haemoglobin gene sequencing and could be useful for other clinical applications.     

3-(1H-pyrrol-2-yl)-2-oxazolidinones as novel monoamine oxidase type A inhibitors

A novel series of 5-substituted-3-(1H-pyrrol-2-yl)-2-oxazolidinones 2a-s has been described as pyrrole analogues of toloxatone and befloxatone, two phenyl-oxazolidinones active as anti-MAO agents and used in antidepressant therapy. Tested against MAO-A and MAO-B enzymes, the majority of 2a-s show highly potent inhibitory effect against the A isoform of the enzyme, with Ki values in the range 0.52-0.004 microM, whilst their anti-MAO-B activity is considerably lower (Ki = >100-0.5 microM). Structurally, 2a-s differs for the substituent inserted at the C5 position of the 2-oxazolidinone ring (hydroxymethyl (2a-d), methoxymethyl (2e-h), azidomethyl (2i-l), methylaminomethyl (2m-p), and aminomethyl (2q-s)), and the size of the alkyl chain at the pyrrole N1 position (methyl, ethyl, allyl, or benzyl). As a rule, apart from the C5 substitution, the bulkier is the alkyl group at the pyrrole-N1, the lower is the anti-MAO-A activity of the compounds, being the N1-methyl derivatives 2a, 2e, 2i, and 2q among the most potent (K(iMAO-A) = 0.087-0.004 microM) and A-selective (A-selectivity ratio: >11,111-41) compounds in this series. Exceptions are represented by the N1-benzyl derivative 2d (K(iMAO-A) = 0.009 microM) and the N1-allylpyrrole 2o (K(iMAO-A) = 0.04 microM). In comparison with the reference drugs, these highly active derivatives are more potent than toloxatone, slightly less potent than befloxatone, and several times more A-selective than both the references. Such results indicate that 2a-s may represent a new promising series of antidepressant agents.     

血清、尿液β2-m对Graves'病患者检测的临床意义

目的：探讨血清、尿液β2-微球蛋白（β2-mieroglobulin，β2-m）对毒性弥漫性甲状腺肿（graves diseases，Graves）患者β2-m含量与甲状腺激素的关系，了解其变化情况及临床意义。方法：采用放射免疫分析和化学发光免疫分析测定了82例Graves病初发未治疗组与同一组经治疗的69例缓解组及13例未缓解组。并和40例健康对照组进行血清、尿液β2-m含量与FT3、FL4、TGA、TMA血清检测。结果：初发组与未缓解组β2-m含量与FT3、FT4含量显著高于健康对照组（P〈0．01）。经治疗组β2-m含量与FT3、FT4含量同步缓解而下降至正常，与未治疗组对比（P〈0．01）。对比健康正常组差异无显著性（P〉0．05）。82例Graves病初发组TGA阳性率为48．7％（40／82），TMA阳性率为53．66％（44／82）。未缓解组TGA阳性率为15．38％（2／13），TMA阳性率为23．07％（3／13）。缓解组TGA、TMA仍有13．04％、15．94％阳性。结论：甲状腺疾病患者β2-m含量与甲状腺激素有密切关系，提示β2-m可作为Graves病疗效观察、病情变化及预后判断的一项辅助诊断指标。     

Pathologic study and clinical significance of Hürthle cell papillary thyroid carcinoma.

Hürthle cell papillary thyroid carcinoma is a variant of papillary thyroid carcinoma (PTC). Its pathologic and clinical significance has not been well documented. The authors studied the relative incidence of Hürthle cell PTC and the relationship of Hürthle cell PTC to other variants of thyroid carcinoma. Three hundred eighty consecutive cases of thyroid carcinoma were reviewed to identify cases with focal or extensive areas of Hürthle cell PTC, classic PTC, Hürthle cell carcinoma (ie, non-Hürthle cell PTC), and follicular carcinoma. In addition, the status of lymphoid infiltrate in the tumor, stromal invasion with desmoplastic reaction, vascular invasion, and distant and lymph node metastasis were noted by microscopic examination, review of clinical charts, or both. A total of 24 (HCs) and 42 PTCs with Hürthle cells were identified. The latter category was divided into pure Hürthle cell PTC or extensive Hürthle cell (HPTC) (28 cases) and PTC or Hürthle cell carcinoma with focal areas of Hürthle cell PTC (14 cases). The Hürthle cell PTC/Hürthle cell carcinoma ratio was lower than that of PTC/follicular carcinoma (39:289) (P = 0.001). Follicular or solid structures were present in all HPTCs. HPTCs were associated with frequent stromal intrathyroid and extrathyroid invasion, but they tended to have a lower rate of lymph node metastasis (8/28) compared with classic PTC with stromal invasion (108:200) (P = 0.12) and a lower rate of distant metastasis (2:28) compared with Hürthle cell carcinoma (15:24) (P = 0.02) or follicular carcinoma (13:39) (P = 0.04). Warthin-like Hürthle cell PTC (10 cases) was associated with extrathyroid invasion in five cases. In Hürthle cell PTC associated with tall cell variant (10 cases), areas of gradual transition between Hürthle cell PTC and tall cell variant were identified. The latter variant showed the highest rate of extrathyroid stromal and vascular invasion with distant metastasis and patient death compared with all Hürthle cell PTCs and classic PTCs. In conclusion, Hürthle cell PTC is frequently associated with tall cell variant. It has a higher potential for extrathyroid invasion than classic PTC and has vascular invasion and distant metastasis characteristics intermediate between those of classic PTC and Hürthle cell carcinoma with or follicular carcinoma. Hürthle cell PTC tends to show a greater likelihood of extrathyroid invasion when associated with Warthin-like features and tall cell variant PTC, and higher vascular invasion and distant metastasis when associated with tall cell variant.     

Systematic review of accelerometer-based methods for 24-h physical behavior assessment in young children (0–5 years old)

Background

Accurate accelerometer-based methods are required for assessment of 24-h physical behavior in young children. We aimed to summarize evidence on measurement properties of accelerometer-based methods for assessing 24-h physical behavior in young children.

Methods

We searched PubMed (MEDLINE) up to June 2021 for studies evaluating reliability or validity of accelerometer-based methods for assessing physical activity (PA), sedentary behavior (SB), or sleep in 0–5-year-olds. Studies using a subjective comparison measure or an accelerometer-based device that did not directly output time series data were excluded. We developed a Checklist for Assessing the Methodological Quality of studies using Accelerometer-based Methods (CAMQAM) inspired by COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN).

Results

Sixty-two studies were included, examining conventional cut-point-based methods or multi-parameter methods. For infants (0—12 months), several multi-parameter methods proved valid for classifying SB and PA. From three months of age, methods were valid for identifying sleep. In toddlers (1—3 years), cut-points appeared valid for distinguishing SB and light PA (LPA) from moderate-to-vigorous PA (MVPA). One multi-parameter method distinguished toddler specific SB. For sleep, no studies were found in toddlers. In preschoolers (3—5 years), valid hip and wrist cut-points for assessing SB, LPA, MVPA, and wrist cut-points for sleep were identified. Several multi-parameter methods proved valid for identifying SB, LPA, and MVPA, and sleep.

Despite promising results of multi-parameter methods, few models were open-source. While most studies used a single device or axis to measure physical behavior, more promising results were found when combining data derived from different sensor placements or multiple axes.

Conclusions

Up to age three, valid cut-points to assess 24-h physical behavior were lacking, while multi-parameter methods proved valid for distinguishing some waking behaviors. For preschoolers, valid cut-points and algorithms were identified for all physical behaviors. Overall, we recommend more high-quality studies evaluating 24-h accelerometer data from multiple sensor placements and axes for physical behavior assessment. Standardized protocols focusing on including well-defined physical behaviors in different settings representative for children’s developmental stage are required. Using our CAMQAM checklist may further improve methodological study quality.

PROSPERO Registration number

CRD42020184751.

     

女性单纯声带肥厚和声带小结的嗓音参数分析比较

目的：通过比较和分析单纯声带肥厚和声带小结的嗓音参数的变化,评价这些参数在两种疾病中诊断及疗效。方法：应用Dr.Speech(DSS)软件对成人女性30例单纯声带肥厚和声带小结患者做噪音测试,对其主要声学参数进行比较分析。结果：声带小结的嗓音声学参数、基频微扰、声门噪声能量NEE值均较声厚的各指标高。其中声门噪声能量在声结中异常者占99．6％,声带肥厚占80％,两组之间有显著性差异（P＜0．05）。其频微扰和振幅微扰的异常占有率,两组之间无显著性差异（P＞0．05）。结论：嗓音参数对诊断和区别声带肥厚和声结有一定的价值,特别是声门噪声能量有更高的敏感性,对诊断和治疗声带疾病有一定的价值。     

先天性心脏病常温不停跳心内矫治术 ——经正中小切口途径

【目的】介绍先天性心脏病在常温不停跳下,经胸骨正中小切口行心内直视手术的效果。【方法】1999年10月至2000年9月,12例先天性心脏病患者经胸骨下段正中小切口,在常温体外循环下,不阻断主动脉进行心内矫治术。包括房间隔缺损(ASD)7例,室间隔缺损(VAD)3例,房间隔缺损并肺动脉狭窄(PS)1例,肺动脉狭窄1例。年龄4～44岁,中位数16.1岁。【结果】全组体外循环时间14～48min,中位数30min,7例术后即拔管,平均辅助呼吸时间1.8h,术中平均用血140mL,术后平均输血110mL,无低心排综合症,心律失常,栓塞、肺部和脑部并发症及伤口感染发生。病人恢复快,疤痕隐蔽。随访无残余漏。【结论】在常温不停跳下经胸骨下段正中小切口行先天性心脏病心内直视术,可提高心肺保护效果,减少手术创伤和手术并发症,有利于促进术后康复和取得良好美容效果。     

A digest of the Evidence-Based Clinical Practice Guideline for Nephrotic Syndrome 2020

Clinical and Experimental Nephrology -