Comparison between a new multiplex electrochemiluminescence assay and the WHO reference enzyme-linked immunosorbent assay to measure serum antibodies against pneumococcal serotype-specific polysaccharides

Background

Two electrochemiluminescence (ECL) assays were developed which, together, can simultaneously measure serum antibodies against pneumococcal capsular polysaccharides (PnPS) for 17 serotypes. The assays were validated for the 13 PnPS included in the 13-valent pneumococcal conjugate vaccine (PCV13). As recommended by the World Health Organization (WHO), we compared the ECL assays with the WHO reference enzyme-linked immunosorbent assay (ELISA) and derived a threshold corresponding to the 0.35?µg/mL threshold established for the WHO reference ELISA for the non-inferiority comparison and licensure of new PCVs against invasive pneumococcal disease.

Frequency-specific effects of low-intensity rTMS can persist for up to 2 weeks post-stimulation: A longitudinal rs-fMRI/MRS study in rats

BackgroundEvidence suggests that repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, alters resting brain activity. Despite anecdotal evidence that rTMS effects wear off, there are no reports of longitudinal studies, even in humans, mapping the therapeutic duration of rTMS effects.ObjectiveHere, we investigated the longitudinal effects of repeated low-intensity rTMS (LI-rTMS) on healthy rodent resting-state networks (RSNs) using resting-state functional MRI (rs-fMRI) and on sensorimotor cortical neurometabolite levels using proton magnetic resonance spectroscopy (MRS).MethodsSprague-Dawley rats received 10 min LI-rTMS daily for 15 days (10 Hz or 1 Hz stimulation, n = 9 per group). MRI data were acquired at baseline, after seven days and after 14 days of daily stimulation and at two more timepoints up to three weeks post-cessation of daily stimulation.Results10 Hz stimulation increased RSN connectivity and GABA, glutamine, and glutamate levels. 1 Hz stimulation had opposite but subtler effects, resulting in decreased RSN connectivity and glutamine levels. The induced changes decreased to baseline levels within seven days following stimulation cessation in the 10 Hz group but were sustained for at least 14 days in the 1 Hz group.ConclusionOverall, our study provides evidence of long-term frequency-specific effects of LI-rTMS. Additionally, the transient connectivity changes following 10 Hz stimulation suggest that current treatment protocols involving this frequency may require ongoing “top-up” stimulation sessions to maintain therapeutic effects.     

In silico repurposing the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing clear cell renal carcinoma

The pituitary tumor-transforming gene 1 (PTTG1), also known as Securin, is considered an oncogene. This study aimed to investigate the role of PTTG1 in clear cell renal cell carcinoma (ccRCC) using in silico bioinformatics approaches. A pan-cancer analysis using The Cancer Genome Atlas (TCGA) data indicated that among all cancer types copy number amplification of PTTG1 gene was most frequently found in ccRCC. However, amplification of PTTG1 gene copy number did not correlate with the increase of mRNA level in ccRCC, and did not predict the patients' overall survival. Instead, ccRCC was correlated with overexpression of PTTG1 mRNA, and its expression level was stage-dependent increased in cancer patients. An outlier analysis using the Oncomine database suggested that PTTG1 mRNA expression served as a good biomarker for ccRCC. Pathway analysis for upregulated genes enriched in PTTG1-high expressing ccRCC patients found that PTTG1 overexpression was associated with mitotic defects. Mining drug sensitivity data using the Cancer Therapeutics Response Portal (CTRP) discovered that PTTG1-high expressing ccRCC cell lines were susceptible to a Rac1 (Ras-related C3 botulinum toxin substrate 1) inhibitor NSC23766. Therefore, this study provides an in silico insight into the role of PTTG1 in ccRCC, and repurposes the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing ccRCC.     

Is weight-based IV dosing of trastuzumab preferable to SC fixed-dose in some patients? A systematic scoping review

Trastuzumab, a key treatment for HER2-positive breast cancer, is available in weight-based IV and fixed-dose (600 mg) SC formulations. While the Phase 3 HannaH trial indicated non-inferiority of the SC formulation, there is some concern that the target plasma concentration may not be reached in overweight/obese patients whereas low-body-weight patients may be at risk of toxicity.This scoping review evaluated whether overweight/obese patients are at risk of below-target exposure with fixed-dose SC trastuzumab, whether low-body-weight patients are at risk of increased toxicity, especially cardiotoxicity, and whether IV and SC trastuzumab are equivalent in terms of treatment-emergent adverse events (TEAEs) (e.g. infections). Thirty-seven publications that met the eligibility criteria were included.Body weight is not an important determinant of exposure to trastuzumab at steady state (i.e. pre-dose cycle 8); however, real-world evidence suggests that the target concentration (20 μg/mL) may not be reached with the first SC dose in overweight/obese patients. There is no evidence that low-body-weight patients are at increased risk of cardiotoxicity with SC trastuzumab, although this may be confounded by the higher rate of cardiovascular comorbidities in overweight patients. In Phase 3 trials, SC trastuzumab was associated with higher rates of ISRs, ADAs and SAEs, the latter often requiring hospitalization and occurring during adjuvant treatment when patients are not burdened by chemotherapy.The route of administration of trastuzumab (IV vs SC) in different treatment settings should be discussed with the patient, taking into account the risks and benefits associated with each route.     

Benign EEG variants in the sleep–wake cycle: A prospective observational study using the 10–20 system and additional electrodes

ObjectivesTo study the prevalence of benign EEG variants (BEVs) in the sleep–wake cycle among 1163 consecutive patients.MethodsProspective, observational EEG study using the 10–20 system with systematically two additional anterior-temporal electrodes. Depending on clinical indications, other electrodes were added. REM sleep identification was based on its characteristic EEG grapho-elements and rapid eye movements, clearly detectable with the additional anterior-temporal and fronto-polar electrodes due to eye proximity. The video-EEG monitoring duration was between 24 hours and eight days.ResultsWe identified 710 patients (61%) with BEVs. Positive occipital sharp transients of sleep (POSTs) were observed in 36.4% of participants, mu rhythm in 22.4%, lambda waves in 16.7%, wicket spikes (WS) in 15%, 14- and 6-Hz positive bursts in 8.3%, benign sporadic sleep spikes (BSSS) in 3.3%, rhythmic mid-temporal theta burst of drowsiness (RMTD) in 2.15%, midline theta rhythm in 2.1% and six-Hz spike and wave (SW) bursts in 0.1%. WS and RMTD were present during wakefulness, NREM (14.1%, 1.3%, respectively) and REM sleep (3.3%, 1.1%, respectively). Mu rhythm was also observed during NREM (1.5%) and REM sleep (7.7%). Fourteen- and 6-Hz positive bursts were present during NREM (4.5%) and REM sleep (6.5%). BSSS and six-Hz SW bursts were only observed during NREM sleep.ConclusionsThe prevalence of BEVs is much higher than current estimates. POSTs and WS can no longer be considered as unusual patterns but physiological patterns of NREM sleep. RMTD and mu rhythm may be observed during NREM and REM sleep.     

Effectiveness of chondrofascial ‘cigar’ graft in contouring the nasal dorsum

Irregularities of the nasal dorsum after rhinoplasty are frustrating for the patient and the surgeon. Different grafts and implants have been adopted to camouflage this nasal imperfection. This study was performed to assess the outcome of a composite chondrofascial ‘cigar’ graft for contouring an irregular nasal dorsum. Thirty-six patients who underwent rhinoplasty between May 2014 and October 2016 were studied prospectively. The cartilaginous core of the graft was obtained from the septal or conchal cartilage, while the graft outer sleeve was harvested from the right lateral thigh fascia lata. The graft was secured over the nasal dorsum through an external rhinoplasty approach. The patients were followed up for at least 18 months postoperative. All participants were evaluated objectively by two independent rhinoplasty surgeons and subjectively by Rhinoplasty Outcome Evaluation (ROE) score. Donor site morbidity was also assessed. All patients had satisfactory aesthetic results with no apparent irregularities detected over the nasal dorsum. The ROE score improved, from a mean of 20.94 ± 8.67 (range 8–58) preoperatively to a mean of 79.56 ± 10.65 (range 50–96) postoperatively. Insignificant donor site morbidity was encountered, with inconsequential effects. The chondrofascial cigar graft is a reliable method for contouring dorsal irregularities, particularly in patients with thin nasal skin.     

乙型肝炎病毒感染者血清干扰素诱导基因20 kDa蛋白表达水平及其临床意义

目的观察乙型肝炎病毒感染者血清干扰素诱导基因20 kDa蛋白（ISG20）蛋白表达变化及其临床意义。 方法选取2017年3月至2018年6月汉中市中心医院收治的HBV感染所致慢性乙型肝炎患者（CHB组）67例、肝硬化患者（LC组）58例、肝癌患者（HCC组）54例和同期体检47例健康者（对照组）。采用酶联免疫吸附法检测各组研究对象血清ISG20蛋白水平。比较不同组患者血清ISG20水平差异。采用Spearman相关分析探讨血清ISG20水平与各组患者年龄、性别、红细胞计数、白细胞计数、血小板计数、天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、总胆红素（TBil）、直接胆红素（DBil）、白蛋白、凝血酶原、甲胎蛋白（AFP）、HBV DNA的相关性。 结果对照组患者血清ISG20水平为9.4（0.82～25.72）ng/ml，显著低于CHB组[18.6（1.87～56.32）ng/ml，Z =－1.567、P = 0.034]和HCC组[28.2（3.09～81.42）ng/ml，Z = －1.854、P = 0.021]。HCC组患者血清ISG20水平显著高于CHB组（Z =－1.431、P = 0.041）和LC组[12.9（2.81～77.54）ng/ml，Z =－1.987、P = 0.029）。HCC组不同Child-Pugh分级患者血清ISG20水平差异有统计学意义（H = 6.976、P = 0.031）。HCC组患者血清ISG20水平与AST（r = 0.323、P < 0.001）、ALT（r = 0.248、P = 0.036）、TBil（r = 0.221、P = 0.031）、DBil（r = 0.215、P = 0.043）、AFP（r = 0.176、P = 0.044）呈正相关，与白蛋白呈负相关（r =－0.239、P = 0.019）。 结论HBV感染者，尤其是HBV感染所致HCC患者，血清ISG20水平升高。血清ISG20水平与HBV感染疾病进展和临床参数有一定的相关性。     

Low-dose naltrexone inhibits the epithelial-mesenchymal transition of cervical cancer cells in vitro and effects indirectly on tumor-associated macrophages in vivo

The metastasis of cervical cancer has always been a clinical challenge. We investigated the effects of low-dose naltrexone (LDN) on the epithelial mesenchymal transition of cervical cancer cells in vitro as well as its influence on macrophage polarization and associated cytokines in vivo. The results suggested that LDN supressed the proliferation, migration and invasion abilities and promote their apoptosis in Hela cells, whereas the opioid growth factor receptor (OGFr) silenced significantly reversed these effects in vitro. Knockdown the expression of OGFr, the inhibitory of LDN on EMT was weakened. LDN could inhibit cervical cancer progression in nude mice. In additon, LDN indirectly reduced the number of tumor-associated macrophages (TAMs), mainly M2 macrophages, and decreased expression of anti-inflammatory factor IL-10 in the serum of nude mice. These findings demonstrate that LDN could be a potential treatment for cervical cancer.