Category: Nevin Manimala

BMC Cancer. 2022 Jan 18;22(1):79. doi: 10.1186/s12885-022-09170-7.

ABSTRACT

BACKGROUND: Long non-coding RNA (LncRNA) HOTAIR was amplified and overexpressed in many human carcinomas, which could serve as a useful target for cancer early detection and treatment. The ^99mTc radiolabeled antisense oligonucleotides (ASON) could visualize the expression of HOTAIR and provide a diagnostic value for malignant tumors. The aim of this study was to evaluate whether liposome-coated antisense oligonucleotide probe ^99mTc-HYNIC-ASON targeting HOTAIR can be used in in vivo imaging of HOTAIR in malignant glioma xenografts.

METHODS: The ASON targeting LncRNA HOTAIR as well as mismatched ASON (ASONM) were designed and modified. The radiolabeling of ^99mTc with two probes were via the conjugation of bifunctional chelator HYNIC. Then probes were purified by Sephadex G25 and tested for their radiolabeling efficiency and purity, as well as stability by ITLC (Instant thin-layer chromatography) and gel electrophoresis. Then the radiolabeled probes were transfected with lipofectamine 2000 for cellular uptake test and the next experimental use. Furthermore, biodistribution study and SPECT imaging were performed at different times after liposome-coated ^99mTc-HYNIC-ASON/ASONM were intravenously injected in glioma tumor-bearing mice models. All data were analyzed by statistical software.

RESULTS: The labeling efficiencies of ^99mTc-HYNIC-ASON and ^99mTc-HYNIC-ASONM measured by ITLC were (91 ± 1.5) % and (90 ± 0.6) %, respectively, and both radiochemical purities were more than 89%. Two probes showed good stability within 12 h. Gel electrophoresis confirmed that the oligomers were successfully radiolabeled no significant degradation were found. Biodistribution study demonstrated that liposome-coated antisense probes were excreted mainly through the kidney and bladder and has higher uptake in the tumor. Meanwhile, the tumor was clearly shown after injection of liposome coated ^99mTc-HYNIC-ASON, and its T/M ratio was higher than that in the non-transfection group and mismatched group. No tumor was seen in mismatched and blocking group.

CONCLUSION: The liposome encapsulated ^99mTc-HYNIC-ASON probe can be used in the in vivo, real-time imaging of LncRNA HOTAIR expression in malignant glioma.

PMID:35042456 | DOI:10.1186/s12885-022-09170-7

Zhonghua Yi Xue Za Zhi. 2022 Jan 18;102(3):228-234. doi: 10.3760/cma.j.cn112137-20210720-01614.

ABSTRACT

Objective: To assess the relationship between health-related quality of life (HRQOL) and spinal sagittal parameters in patients with degenerative and isthmic spondylolisthesis before and after surgery, and to provide a biomechanical basis for improving the clinical prognosis of such patients. Methods: A retrospective analysis of 63 patients with lumbar spondylolisthesis who received lumbar fusion surgery in the Department of Spine Surgery, Tianjin Union Medical Center from December 2017 to June 2020 was carried out. There were 16 males and 47 females with a mean age of (59±8) years. Subgroup analyses were conducted based on disease type (degenerative lumbar spondylolisthesis (DS) and the isthmic spondylolisthesis (IS)) and HRQOL scores. Patients were evaluated post-operatively to observe the improvement of symptoms and quality of life. The relationship between operative related factors, HRQOL scores before and after surgery, and spino-pelvic sagittal parameters (including sagittal axis of the spine, lumbar lordosis angle, pelvic incidence angle, pelvic tilt angle (PT), sacral tilt angle, matching degree of pelvic incidence angle (PI) and lumbar lordosis angle (LL), lumbar 1 vertebra plumb line, upper lumbar curve, lower lumbar curve) in the two groups were analyzed. The correlation between the improvement of HRQOL scores and spino-pelvic sagittal parameters in the DS group and the IS group was analyzed and compared. Results: There were significant differences between postoperative HRQOL scores compared with those before the operation in both the DS and IS groups at three times of follow-up after the operation (all P<0.05). There was no difference in the last HRQOL score, the number of surgical segments, operation time and intraoperative blood loss between the two groups (all P>0.05). The parameters of PT and PI-LL in DS patients with VAS back pain score>3 and ≤3 were statistically different (13.7°±6.4° vs 26.6°±7.4°, 5.1°±8.2° vs 18.2°±13.1°, respectively, both P<0.05), similar results were obtained in IS patients (14.1°±6.9° vs 16.4°±8.7°, 2.9°±9.7° vs 6.8°±9.8°, respectively, both P<0.05). In addition, the parameters of PT and PI-LL between patients with ODI>20 and ≤20 were all statistically different in the two groups at the last follow-up after surgery (all P<0.05). The improvement of VAS back pain score in DS and IS groups was significantly related to the improvement of PT value, respectively (r=0.76, 0.78, both P<0.05). The PT, LL and PI-LL were significantly correlated with the ODI in the DS group (r=0.60, 0.62, 0.50, all P<0.05). There was also a correlation between the improvement of ODI and PT, LL and PI-LL in the IS group, respectively (r=0.22, 0.41, 0.76, all P<0.05). Conclusions: Certain correlation exists between the HRQOL and spinal sagittal parameters in patients with degenerative and isthmic spondylolisthesis before and after surgery. For the treatment of lumbar spondylolisthesis and improvement of quality of life, the primary goal is to reconstruct the matching degree of the lumbar lordosis angle and PI, and to reduce the PT value to the normal range by tilting the pelvis forward.

PMID:35042293 | DOI:10.3760/cma.j.cn112137-20210720-01614

Zhonghua Yi Xue Za Zhi. 2022 Jan 18;102(3):216-221. doi: 10.3760/cma.j.cn112137-20211018-02299.

ABSTRACT

Objective: To clarify the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant on the performance of existing molecular diagnostic assays, and investigate the detection ability of clinical laboratories across China. Methods: The first nationwide external quality assessment (EQA) for molecular detection of Delta variant was carried out based on the non-infectious phage virus-like particles samples, which were prepared by genetic engineering methods and distributed to 8 488 laboratories nationwide. The EQA panel was composed of three Delta variant samples (7.5×10², 1.5×10³ and 6.0×10³ copies/ml), one non-variant weak positive sample and one negative sample. The percentage of agreement (PA) of Delta variant samples with different concentration, the PA of Delta variant and non-variant samples with 7.5×10² copies/ml, the PA of assays used by more than 100 laboratories for Delta variant samples with different concentration and the PA of Delta variant and non-variant samples with 7.5×10² copies/ml were calculated and analyzed. Results: The data from 8 127 laboratories were available for evaluation. The testing capability of 98.77% (8 027/8 127) of the participating laboratories was found to be competent in reporting correct results for all samples. The overall percentage of agreement (OPA), negative percentage of agreement (NPA) and positive percentage of agreement (PPA) of the samples were 99.64% (40 490/40 635), 99.73% (8 105/8 127), 99.62% (32 385/32 508), respectively. With the decrease of the concentration of the samples, the PPA of Delta variant samples decreased. The PPAs were 99.41% and 99.51% for Delta variant and non-variant samples with 7.5×10² copies/ml, respectively, with no statistical difference (P=0.392). The OPA, NPA and PPA of the assays used by more than 100 laboratories were all greater than 98%, and no statistical difference of the PPAs was identified between Delta variant and non-variant samples with 7.5×10² copies/ml (P>0.05). Conclusions: Delta variant fails to impair the performance of current molecular diagnostic assays in China. The clinical laboratories have the same detection capabilities for Delta variant and non-variant samples. However, in certain laboratories, further improvement is required to ensure the accurate detection of weak positive samples.

PMID:35042291 | DOI:10.3760/cma.j.cn112137-20211018-02299

Zhonghua Yi Xue Za Zhi. 2022 Jan 18;102(3):222-227. doi: 10.3760/cma.j.cn112137-20210728-01681.

ABSTRACT

Objective: To find out the relationship of the progression rate of amyotrophic lateral sclerosis (ALS) patients with relevant clinical indicators at initial visit so as to enrich the knowledge of ALS at its early stage. Methods: The clinical data of 282 patients diagnosed with ALS at Neurology Department of the First Medical Center, Chinese PLA General Hospital from June 2016 to March 2021 were collected in order to make a retrospective analysis of the dynamic change of the progression rate (ΔFS) and influencing factors, and thus a classification of the progression rate will be summarized. Results: Among 282 patients, 164 were males and 118 were females. The age of onset was (53±11) years old. The ΔFS had a negative exponential relationship with delay time of diagnosis no matter what kinds of onset the patients experienced (upper limb onset, lower limb onset or bulbar onset). The ΔFS for the limb function sub-group had a similar functional relationship with diagnostic delay in patients with either upper limb onset or lower limb onset. The statistical model indicated that the disease progression rate of ALS at initial visit can be classified into three types (high speed type: ΔFS≥1.0 score/month; moderate speed type: 0.5≤ΔFS<1.0 score/month; low speed type: ΔFS<0.5 score/month). The critical values of the three types in patients with upper limb onset were 8 and 20 months, while 9 and 24 months for lower limb onset patients, and 9 and 36 months for bulbar onset patients. At initial visit, there were significant statistical differences among these three types in age at onset (P=0.008), diagnostic delay (P<0.001), ALS functional rating scale-revised (ALSFRS-R) score (P<0.001) and onset site (P=0.006). The age at onset in moderate speed type was significantly greater than that of the slow speed type [(54.9±10.4) years vs (50.2±9.6) years, P=0.002]. The diagnostic delay in high speed type [6 (4, 10) months] was significantly shorter than that in moderate speed type [12 (8, 19) months, P<0.001] and low speed type [22 (14, 36) months, P<0.001], and the moderate speed type was shorter in comparison with low speed type (P<0.001). As for the ALSFRS-R score, the high speed type [36(32, 39)] was significantly lower than the moderate speed type [39 (36, 42), P<0.001] and low speed type [42 (39, 44), P<0.001], and the moderate speed type was lower in comparison with low speed type (P=0.002). The proportion of cases with upper limb onset in high speed type (20.3%) was significantly lower than that in low speed type (42.2%, P<0.001) and moderate speed type (37.5%, P=0.014). By contrast, the proportion of cases with lower limb onset in high speed type (39.2%) was significantly higher than that in low speed type (28.9%, P=0.023), however no difference was shown between the fast speed type and moderate speed type (32.0%, P=0.061). There was no difference among these three progression types in patients with bulbar onset. Conclusions: The disease progression rate of ALS at initial visit can be classified into three types including high speed, moderate speed and low speed. At early stage of ALS, ΔFS is affected by onset age, onset site, diagnostic delay and ALSFRS-R score.

PMID:35042292 | DOI:10.3760/cma.j.cn112137-20210728-01681

Int J Urol. 2022 Jan 18. doi: 10.1111/iju.14781. Online ahead of print.

ABSTRACT

OBJECTIVE: We evaluated the impact of Gleason pattern 5 presence on prognosis among de novo metastatic hormone-sensitive prostate cancer patients with a Gleason score ≥8.

METHODS: The data of 559 patients diagnosed as metastatic hormone-sensitive prostate cancer with a Gleason score ≥8, who were initially treated with androgen deprivation therapy from 2008 to 2016, were retrospectively collected. Patients were divided into two groups as high and low volume based on the CHAARTED trial criteria.

RESULTS: The median overall survival of the 559 metastatic hormone-sensitive prostate cancer patients with Gleason score ≥8 was 70 months, with a median follow-up period of 36 months. Gleason pattern 5 was confirmed in 341 patients (61.0%), in which primary Gleason pattern 5 was confirmed in 164 patients (29.3%). The number of patients with high metastatic volume group was 363 (64.9%). In total and high metastatic volume groups, hemoglobin and lactate dehydrogenase were significant factors for predicting overall survival, but both Gleason pattern 5 and primary Gleason pattern 5 did not show a statistically significant difference. In the low-volume metastatic group, the median overall survival in patients with or without primary Gleason pattern 5 was 40 and 78 months, respectively. In multivariate analysis, only primary Gleason pattern 5 was an independent predictive factor for overall survival in the low-volume metastatic group (hazard ratio 2.76, 95% confidence interval 1.88-8.67; P = 0.0026).

CONCLUSION: The presence of Gleason pattern 5 was not associated with overall survival in metastatic hormone-sensitive prostate cancer with a Gleason score ≥8. In low-metastatic volume metastatic hormone-sensitive prostate cancer, primary Gleason pattern 5 was a poor prognostic factor, which might show a separate treatment option for this group.

PMID:35042278 | DOI:10.1111/iju.14781

Radiat Res. 2022 Jan 18. doi: 10.1667/RADE-21-00122.1. Online ahead of print.

ABSTRACT

High-dose radiation in childhood such as is used in radiation therapy causes cognitive decline, but there is insufficient research on the cognitive effects of low- to medium-dose radiation. We aimed to reveal the association between atomic bomb radiation exposure in childhood and late-life neurocognitive function. In 2011 and 2013, we mailed the Neurocognitive Questionnaire (NCQ) to subjects who were 12 years old or younger at the time of the atomic bombing. We converted the four NCQ subscales (metacognition, emotional regulation, motivation/organization, and processing speed) to T scores and defined the highest 10% of the controls (exposure dose < 5 mGy) as impaired. We used a generalized linear mixed model to evaluate the effect of radiation exposure on T scores and percentage impaired. We enrolled 859 participants. At the time of the bombing, the mean (SD) age was 6.7 (3.8) years for the control (N = 390) and 6.1 (3.8) years for the exposed (N = 469). At the time of replying to the questionnaire, the mean age of all the participants was 73.7 (3.8) years of age. After adjusting for cofactors, older age was related to the decline of all neurocognitive subscales. Sex and education level had relevance to some of the subscales. For neurocognitive function, exposure dose was not related except to percentage impaired, motivation/organization. Late-life neurocognitive function in atomic bomb survivors exposed as children was associated with age, but not clearly with radiation dose. More studies are needed to evaluate the effect of low-dose radiation during childhood on long-term neurocognitive function.

PMID:35042238 | DOI:10.1667/RADE-21-00122.1

Thorac Cardiovasc Surg. 2022 Jan 18. doi: 10.1055/s-0041-1741004. Online ahead of print.

ABSTRACT

BACKGROUND: Intraoperative and postoperative bleeding associated with allogeneic blood transfusion and reoperation is still a common and feared complication in patients undergoing surgery due to acute Type A Aortic Dissection (aTAAD). The aim of our study was to identify risk factors for higher transfusion rates.

METHODS: In this retrospective single center study we evaluated pre -, intra-, and postoperative data of 121 patients with aTAAD. Depending on the median of received packed red blood cells (PRBCs), patients were divided into Group A (<8 PRBC, n = 53) and Group B (≥8 PRBC n = 68). Statistical analyses (descriptive statistics, univariable and multivariable logistic regression) were performed using SPSS software 25.0. Statistical significance was assumed at p-value <0.05.

RESULTS: A total of 120 patients received a blood product during their perioperative course. Among others we identified age, hemorrhagic pericardial effusion, and dual antiplatelet therapy as preoperative risk factors, low rectal temperature as intraoperative risk factor and low body temperature, positive fluid balance, high lactate level and beginning development of acute renal failure as postoperative risk factors.

CONCLUSION: Our study identifies several factors which predict a higher likelihood of bleeding and consecutive blood transfusion. Knowledge of these factors could influence the therapy to reduce transfusion requirements and lead to a targeted and more efficient use of coagulation products.

PMID:35042245 | DOI:10.1055/s-0041-1741004

Blood Adv. 2022 Jan 18:bloodadvances.2021006144. doi: 10.1182/bloodadvances.2021006144. Online ahead of print.

ABSTRACT

Antitumor therapy with CD19-targeted chimeric antigen-receptor-modified T (CAR T) cells is highly efficient. However, treatment is often complicated by a unique profile of unpredictable neurotoxic side effects of varying degrees known as immune effector cell-associated neurotoxicity syndrome (ICANS). Here, in 96 patients receiving CAR T-cells for refractory B-cell malignancies at two major CAR T-cell centers, we examined whether serum levels of neurofilament light chain (NfL), a marker of neuroaxonal injury, correlate with the severity of ICANS. Serum NfL levels were measured before and after infusion of CAR T cells using a single-molecule enzyme-linked immunosorbent assay and correlated with the severity of ICANS. Elevated NfL serum levels prior to treatment were associated with more severe ICANS, in both unadjusted and adjusted analyses (p<0.01). Multivariate statistical models revealed a significant increase in NfL levels after CAR T-cell infusion (p<0.05), which correlated with the severity of ICANS (p<0.001). Pre-existing neuroaxonal injury, characterized by higher NfL levels before CAR T-cell treatment, correlated with the severity of subsequent ICANS. Thus, serum NfL level might serve as a predictive biomarker for assessing the severity of ICANS and for improving patient monitoring following CAR T-cell transfusion. However, these preliminary results should be validated in a larger prospective cohort of patients.

PMID:35042236 | DOI:10.1182/bloodadvances.2021006144

J Appl Biomech. 2022 Jan 17:1-10. doi: 10.1123/jab.2021-0143. Online ahead of print.

ABSTRACT

Ratio scaling is the most common magnitude normalization approach for net joint moment (NJM) data. Generally, researchers compute a ratio between NJM and (some combination of) physical body characteristics (eg, mass, height, limb length, etc). However, 3 assumptions must be verified when normalizing NJM data this way. First, the regression line between NJM and the characteristic(s) used passes through the origin. Second, normalizing NJM eliminates its correlation with the characteristic(s). Third, the statistical interpretations following normalization are consistent with adjusted linear models. The study purpose was to assess these assumptions using data collected from 16 males and 16 females who performed a single-leg squat. Standard inverse dynamics analyses were conducted, and ratios were computed between the mediolateral and anteroposterior components of the knee NJM and participant mass, height, leg length, mass × height, and mass × leg length. Normalizing NJM-mediolateral by mass × height and mass × leg length satisfied all 3 assumptions. Normalizing NJM-anteroposterior by height and leg length satisfied all 3 assumptions. Therefore, if normalization of the knee NJM is deemed necessary to address a given research question, it can neither be assumed that using (any combination of) participant mass, height, or leg length as the denominator is appropriate nor consistent across joint axes.

PMID:35042188 | DOI:10.1123/jab.2021-0143

Phys Biol. 2022 Jan 18. doi: 10.1088/1478-3975/ac4c9b. Online ahead of print.

ABSTRACT

Bacterial growth in microfluidic droplets is relevant in biotechnology, in microbial ecology, and in understanding stochastic population dynamics in small populations. However, it has proved challenging to automate measurement of absolute bacterial numbers within droplets, forcing the use of proxy measures for population size. Here we present a microfluidic device and imaging protocol that allows high-resolution imaging of thousands of droplets, such that individual bacteria stay in the focal plane and can be counted automatically. Using this approach, we track the stochastic growth of hundreds of replicate Escherichia coli populations within droplets. {We find that, for early times, the statistics of the growth trajectories obey the predictions of the Bellman-Harris model, in which there is no inheritance of division time. Our approach should allow further testing of models for stochastic growth dynamics, as well as contributing to broader applications of droplet-based bacterial culture.

PMID:35042205 | DOI:10.1088/1478-3975/ac4c9b