Toxicological evaluation and preliminary exposure assessment on glycerol monocaprylate.

As a commonly used food preservative, glycerol monocaprylate (GMC) has limited information and lacked a comprehensive risk assessment. In this study, we conducted in vitro genotoxicity tests, a 90-day subchronic toxicity study, and dietary exposure assessment in China. Rats (n = 10/sex/group) were orally administered GMC at doses of 1.02, 2.04, and 4.08 g/kg BW/day along with a water and corn oil for 90 days, including satellite groups (n = 5/sex/group) in the control groups and 4.08 g/kg BW dose group for observation after 90 days. Body weight, food consumption, hematology, serum biochemistry, urinalysis, endocrine hormone level and other metrics were examined. GMC did not exhibit genotoxicity based on the genotoxicity tests results, and an acceptable daily intake (ADI) of 40.8 mg/kg BW/day was established based on the 90-day subchronic toxicity study. Estimated daily intake of GMC for general population and consumer population in China were 0.99 mg/kg BW/day and 3.19 mg/kg BW/day respectively, which were significantly lower than the ADI. Our findings suggest that GMC does not pose a known health risk to Chinese consumers at the current usage level.

Genotoxicity assessment of titanium dioxide nanoparticles using a standard battery of in vivo assays.

As one representative of nanometal oxides, titanium dioxide nanoparticles (TiO2-NPs) have been widely used, particularly in the food industry. The genotoxicity of TiO2-NPs has attracted great attention over the years. This study was undertaken to investigate the chromosome and DNA damage effects of TiO2-NPs (0, 50, 150, and 500 mg/kg BW) using rodent models. After a comprehensive characterization, we conducted a standard battery of in vivo genotoxicity tests, including the chromosomal aberration test (CA), micronucleus (MN) test, and the comet test. The results of all these tests were negative. There were no structural or numerical chromosomal abnormalities in mice bone marrow cells, no increase in the frequency of micronucleated polychromatic erythrocytes in mice bone marrow cells, and no elevation in % tail DNA in rat hepatocytes. This indicated that TiO2-NPs did not cause chromosomal damage or have a direct impact on DNA. These findings suggested that TiO2-NPs did not exhibit genotoxicity and provided valuable data for risk assessment purposes.

Development of metaverse for intelligent healthcare.

The metaverse integrates physical and virtual realities, enabling humans and their avatars to interact in an environment supported by technologies such as high-speed internet, virtual reality, augmented reality, mixed and extended reality, blockchain, digital twins and artificial intelligence (AI), all enriched by effectively unlimited data. The metaverse recently emerged as social media and entertainment platforms, but extension to healthcare could have a profound impact on clinical practice and human health. As a group of academic, industrial, clinical and regulatory researchers, we identify unique opportunities for metaverse approaches in the healthcare domain. A metaverse of 'medical technology and AI' (MeTAI) can facilitate the development, prototyping, evaluation, regulation, translation and refinement of AI-based medical practice, especially medical imaging-guided diagnosis and therapy. Here, we present metaverse use cases, including virtual comparative scanning, raw data sharing, augmented regulatory science and metaversed medical intervention. We discuss relevant issues on the ecosystem of the MeTAI metaverse including privacy, security and disparity. We also identify specific action items for coordinated efforts to build the MeTAI metaverse for improved healthcare quality, accessibility, cost-effectiveness and patient satisfaction.

Safety assessment of phytase transgenic maize 11TPY050 in Sprague-Dawley rats by 90-day feeding study.

The present study aimed to evaluate the subchronic toxicity of feeding with phytase-transgenic maize line 11TPY050 in Sprague-Dawley (SD) rats. Rats (n = 10/sex/group) were fed with 12.5%, 25% or 50% (w/w) transgenic maize diet, 12.5%, 25% or 50% (w/w) non-transgenic isoline OSL940 maize diet, or 50% (w/w) commercially available Zhengdan958 maize diet for 90 days. Daily clinical observations and weekly measurements of body weights and food consumption were conducted. Blood samples were collected on day 46 and day 91 for hematology and clinical chemistry evaluations. At the end of the study, macroscopic and microscopic examinations were performed. No effects on body weight and food consumption were observed. The results of hematology, clinical chemistry, and absolute and relative organ weights in the transgenic maize group were comparable to those in the parental maize group. Several statistical differences were not dose-related and were not considered to be biologically significant. Furthermore, the terminal necropsy and histopathological examination showed no treatment-related changes among the groups. The results from the present 90-day feeding study of phytase-transgenic maize 11TPY050 indicated no unexpected adverse effects in SD rats. The phytase transgenic maize 11TPY050 has substantial equivalence with non-transgenic maize.

Safety assessment of phytase transgenic maize 11TPY001 by 90-day feeding study in rats.

11TPY001 is a transgenic maize that expresses the Aspergillus niger phyA2 gene which could significantly improve phosphorus bioavailability in monogastric animals. The present study was conducted to investigate the potential health effects of phytase transgenic maize 11TPY001 through a 90-day subchronic rodent feeding study. Maize grains from 11TPY001 or its parental counterpart maize OSL963 were incorporated into rodent diets at 12.5%, 25% and 50% concentrations by mass and administered to Sprague-Dawley rats (n = 10/sex/group) for 90 days. An additional control group of rats (n = 10/sex/group) were fed with common maize Zhengdan958 diets at 50% by mass. All formulated diets were nutritionally balanced. Body weights, food intake, hematology, serum chemistry, absolute and relative organ weights were measured, and gross as well as microscopic pathology were examined. Compared with rats fed OSL963 maize and the common maize diet groups, no adverse diet-related differences were observed in rats fed 11TPY001 maize diets with respect to clinical signs of toxicity, body weight/gain, food consumption/efficiency, hematology, clinical chemistry, organ weights, and gross and microscopic pathology. Under the conditions of this study, the results indicated that 11TPY001 did not cause any treatment related adverse effects in rats compared with its non-transgenic parental maize OSL963.

Associations among dental insurance, dental visits, and unmet needs of US children.

BACKGROUND: In this study, the authors explored the associations between dental visits and unmet dental needs of children on the basis of their insurance type in the United States. METHODS: The authors used the National Health Interview Surveys from 1997 through 2014 to collect data on dental visits, unmet dental needs, and type of insurance for children aged 2 to 17 years in the United States. Unmet dental need was based on not receiving needed dental care during the past year because of financial constraints. Insurance types reported were private, Medicaid or public, other, and uninsured. The authors performed Pearson correlation coefficient analyses and used descriptive summary statistics. RESULTS: The number of uninsured children decreased by 58% from 1997 through 2014 with a substantial shift from private to public insurance coverage. Regardless of type, dental insurance status was associated positively with the use of dental services and negatively associated with levels of unmet dental needs. Unmet needs in the public insurance group decreased consistently since 2009. There was a significant negative correlation (P < .05) between dental visits and unmet dental needs with respect to public insurance, whereas there was no significant correlation for private insurance. CONCLUSIONS: Dental insurance played a significant role in children's use of dental services and their level of unmet dental needs. PRACTICAL IMPLICATIONS: The shift toward the use of public insurance along with a significant association between unmet needs and dental visits support the effectiveness of publicly funded programs in facilitating the use of dental services in the United States.

Tumor invasion depth is a useful pathologic assessment for predicting outcomes in cervical squamous cell carcinoma after neoadjuvant radiotherapy.

BACKGROUND: To evaluate whether tumor invasion depth can be a reliable and easily applicable pathologic assessment strategy to predict outcomes using surgically resected cervical squamous cell carcinoma specimens from patients who have received neoadjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). METHODS: We included 173 patients with cervical squamous cell carcinoma who received neoadjuvant CCRT (n = 125) or RT (n = 48) and underwent subsequent radical hysterectomy. Data for the pre-operative clinical International Federation of Gynecology and Obstetrics (FIGO) stage, post-operative pathologic FIGO stage, World Health Organization (WHO) double diameter measurement evaluation, response evaluation criteria in solid tumors (RECIST 1.1) criteria, tumor necrosis rate (TNR), and tumor regression grade (TRG) were investigated to identify correlations with outcomes related to distant metastasis and survival. The tumor invasion depth (TID) and the tumor invasion depth with cytokeratin immunostaining correction (TIDC) at the cervical internal surface were measured to assess their relations to patients' outcomes. RESULTS: Based on measurements taken via transvaginal ultrasound, the pre-operative clinical and post-operative pathologic FIGO staging as well as the WHO double diameter measurement evaluation and RECIST 1.1 criteria were predictive of distant metastasis and survival-related outcomes. Also, lymph node involvement was found to be an independent prognostic factor for recurrence and distant metastasis. Finally, univariate analysis showed both the TID and TIDC were highly related to distant metastasis, overall survival, and progression-free survival, irrespective of the clinical stage of carcinomas. CONCLUSION: The TID or TIDC measured at the cervical internal surface is a useful and easily applied pathologic prognostic factor for distant metastasis and survival outcomes in patients with cervical squamous cell carcinoma treated with neoadjuvant RT or CCRT.

F Wave Study in Amyotrophic Lateral Sclerosis: Assessment of Segmental Motoneuronal Dysfunction.

BACKGROUND: Dysfunctional spinal circuit may play a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). The purpose of this study was to use F waves for assessment of segmental motoneuronal excitability following upper motor neuron (UMN) dysfunctions in ALS. METHODS: We studied the F waves of 152 ulnar nerves recorded from abductor digiti minimi in 82 patients with ALS. Two groups of hands were defined based on the presence or absence of pyramidal signs in the same upper limb. The group with pyramidal signs in the upper limbs was designated as the P group, and the group without pyramidal signs in the upper limbs was designated as the NP group. RESULTS: The mean (P < 0.001), median (P < 0.001) and maximum (P = 0.035) F wave amplitudes, mean (P < 0.001), median (P < 0.001) and maximum (P = 0.003) F/M amplitude ratio, index repeating neuron (P < 0.001) and index repeater F waves (P < 0.001) of the P group were significantly increased compared with the NP group. No significant differences were identified for F wave chronodispersion (P = 0.628), mean F wave latency (P = 0.151), minimum F wave latency (P = 0.211), maximum F wave latency (P = 0.199), F wave persistence (P = 0.738), F wave duration (P = 0.152), F wave conduction velocity (P = 0.813) and number of giant F waves (P = 0.072) between the two groups. CONCLUSIONS: In this study, increased F wave amplitude, F/M amplitude ratio and number of repeater F waves reflected enhanced segmental motoneuronal excitability following UMN dysfunctions in ALS.

Neurobehavioral Assessment of Rats Exposed to Yttrium Nitrate during Development.

OBJECTIVE: The aim of this study was to assess the effects of yttrium nitrate on neurobehavioral development in Sprague-Dawley rats. METHODS: Dams were orally exposed to 0, 5, 15, or 45 mg/kg daily of yttrium nitrate from gestation day (GD) 6 to postnatal day (PND) 21. Body weight and food consumption were monitored weekly. Neurobehavior was assessed by developmental landmarks and reflexes, motor activity, hot plate, Rota-rod and cognitive tests. Additionally, brain weights were measured on PND 21 and 70. RESULTS: No significant difference was noted among all groups for maternal body weight and food consumption. All yttrium-exposed offspring showed an increase in body weight on PND 21; however, no significant difference in body weight for exposed pups versus controls was observed 2 weeks or more after the yttrium solution was discontinued. The groups given 5 mg/kg daily decreased significantly in the duration of female forelime grip strength and ambulation on PND 13. There was no significant difference between yttrium-exposed offspring and controls with respect to other behavioral ontogeny parameters and postnatal behavioral test results. CONCLUSION: Exposure of rats to yttrium nitrate in concentrations up to 45 mg/kg daily had no adverse effects on their neurobehavioral development.

[Assessment of the value of acute physiology and chronic health evaluation II/IV prognostic models in elderly patients with sepsis].

OBJECTIVE: To assess and compare the performance of acute physiology and chronic health evaluation II/IV (APACHEII/IV) prognostic models in elderly patients with sepsis. METHODS: A totally of 82 elderly patients with sepsis were retrospectively assessed in geriatric intensive care unit of General Hospital of Guangzhou Military Command between July 2011 and December 2011. APACHEII/IV scores were recorded within 24 hours after admission. The prognosis accuracy of both scores was assessed by area under the receiver operating characteristic curve (AUC). Based on the best cutoff value corresponding with the highest accuracy, patients were divided into the low and high risk of hospital mortality group. The predictive power of APACHEII/IV in total population and subgroups was compared. RESULTS: Patients with severe sepsis constituted 57.3% (47/82) of all patients with sepsis, and hospital mortality was 61.0% (50/82). APACHEII/IV scores of the patients were 17.5±6.3 and 55.8±22.3, and mortality rate was 22.5% (18.4/82) and 17.9% (14.6/82) respectively, with significant differences compared with actual mortality (both P<0.01). Both APACHEII/IV scores showed underestimation of hospital mortality in total population [standardized mortality ratio (SMR) with APACHEII=2.71, 95% confidence interval (95%CI) 1.92-3.48 and SMR with APACHEIV=3.33, 95%CI 2.79-4.37]. APACHEII (AUC 0.664±0.066), and APACHEIV presented poor estimation(AUC 0.716±0.056). There was no difference in accuracy in prognosticating hospital death prognosis between the two APACHE models (Z=0.991, P=0.322). Cutoff values of APACHEII/IV were >11 and >59. According to the value, patients were divided into the low and high risk hospital mortality group. There was no significant difference between actual mortality and prognostic mortality in APACHEII low risk group [0-11, 20.0% (3/15) vs. 1.6% (0.2/15), Z=-1.023, P=0.306]. The actual mortality in high risk group with APACHEII (>11) was significantly higher than prognostic mortality [70.1% (47/67) vs. 27.2% (18.2/67), t=6.989, P=0.000]. In the high risk group, APACHEII underestimated mortality (SMR=2.58, 95%CI 2.22-3.51). The actual mortality of the low (0-59) and high (>59) risk group of APACHEIV were higher than prognostic mortality [lower risk group: 44.0% (22/50) vs. 7.5% (3.8/50), Z=-2.235, P=0.025; higher risk group: 87.5% (28/32) vs. 34.1% (10.9/32), Z=-4.712, P=0.000]. Two groups of patients with APACHEIV score, the mortality was underestimated (low risk group: SMR=5.90, 95%CI 5.19-7.07; high risk group: SMR=2.56, 95%CI 2.07-3.24). Mortality rate of the low risk group with APACHEIV score was prone to be underestimated. CONCLUSIONS: The accuracy of APACHEII/IV are not ideal in foretelling mortality rate. Hospital mortality was underestimated with APACHEII in high risk patients, and it was underestimated with APACHEIV both in low and high risk patients, and it is even more prone to be underestimated in low risk group of APACHEIV. More accurate prognostic modality is in need in elderly patients with sepsis.

Fast model-based X-ray CT reconstruction using spatially nonhomogeneous ICD optimization.

Recent applications of model-based iterative reconstruction (MBIR) algorithms to multislice helical CT reconstructions have shown that MBIR can greatly improve image quality by increasing resolution as well as reducing noise and some artifacts. However, high computational cost and long reconstruction times remain as a barrier to the use of MBIR in practical applications. Among the various iterative methods that have been studied for MBIR, iterative coordinate descent (ICD) has been found to have relatively low overall computational requirements due to its fast convergence. This paper presents a fast model-based iterative reconstruction algorithm using spatially nonhomogeneous ICD (NH-ICD) optimization. The NH-ICD algorithm speeds up convergence by focusing computation where it is most needed. The NH-ICD algorithm has a mechanism that adaptively selects voxels for update. First, a voxel selection criterion VSC determines the voxels in greatest need of update. Then a voxel selection algorithm VSA selects the order of successive voxel updates based upon the need for repeated updates of some locations, while retaining characteristics for global convergence. In order to speed up each voxel update, we also propose a fast 1-D optimization algorithm that uses a quadratic substitute function to upper bound the local 1-D objective function, so that a closed form solution can be obtained rather than using a computationally expensive line search algorithm. We examine the performance of the proposed algorithm using several clinical data sets of various anatomy. The experimental results show that the proposed method accelerates the reconstructions by roughly a factor of three on average for typical 3-D multislice geometries.