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61, 95% CI 0.51-0.71). In addition, the pooled result revealed that elevated miR-196a expression in tumor tissues (HR = 2.54, 95% CI 1.79-3.61, PHeterogeneity=0.000, I2 = 75.8%) or serum/plasma (HR = 4.06, 95% CI 2.67-6.18, PHeterogeneity=0.668, I2 = 0%) of patients was an unfavorable survival biomarker, which was consistent with the data from databases (adrenocortical carcinoma HR = 5.70; esophageal carcinoma HR = 1.93; brain lower grade glioma HR = 2.91; GSE40267 HR = 2.47, 95% CI 1.2-5.07; TCGA HR = 1.82, 95% CI 1.21-2.74; GSE19783 HR = 4.24, 95% CI 1-18.06). In short, our results demonstrated that miR-196a in tumor tissue or serum/plasma could be used as a prognostic and diagnostic values for cancers.The poor success rate of treating patients with aggressive sepsis in SARS-CoV-2 infections has highlighted again the challenges of managing systemic inflammatory conditions. In this issue of JEM, Rodrigues et al. (https//doi.org/10.1084/jem.20201707) discuss the role of inflammasome activation in COVID-19 disease severity, opening new possibilities for therapeutic management of sepsis syndromes.

What are the long-term developmental, reproductive and genetic consequences of mitochondrial replacement therapy (MRT) in primates?

Longitudinal investigation of MRT rhesus macaques (Macaca mulatta) generated with donor mtDNA that is exceedingly distant from the original maternal counterpart suggest that their growth, general health and fertility is unremarkable and similar to controls.

Mitochondrial gene mutations contribute to a diverse range of incurable human disorders. MRT via spindle transfer in oocytes was developed and proposed to prevent transmission of pathogenic mtDNA mutations from mothers to children.

The study provides longitudinal studies on general health, fertility as well as transmission and segregation of parental mtDNA haplotypes to various tissues and organs in five adult MRT rhesus macaques and their offspring.

MRT was achieved by spindle transfer between metaphase II oocytes from genetically divergent rhesus macaque populations. After fertilization of oocytes with sperm, heter recurrence.

This work has been funded by the grants from the Burroughs Wellcome Fund, the National Institutes of Health (RO1AG062459 and P51 OD011092), National Research Foundation of Korea (2018R1D1A1B07043216) and Oregon Health & Science University institutional funds. The authors declare no competing interests.

This work has been funded by the grants from the Burroughs Wellcome Fund, the National Institutes of Health (RO1AG062459 and P51 OD011092), National Research Foundation of Korea (2018R1D1A1B07043216) and Oregon Health & Science University institutional funds. The authors declare no competing interests.Acceptance and commitment therapy (ACT) has shown benefit for improving diet, physical activity, and weight among adults who are overweight and obese. However, research to-date in this area has primarily evaluated ACT delivered through in-person interventions, which has more limited access relative to online formats. Isoproterenol sulfate The present study evaluated an online guided self-help program that integrated ACT with nutrition education to improve healthy eating and physical activity. A sample of 79 adults who were overweight/obese was randomized to receive the 8-week ACT on Health program plus weekly phone coaching or to a waitlist. Participants completed 5.5 ACT sessions on average (out of 8) and reported moderately high program satisfaction. Participants in the ACT condition improved significantly more than the waitlist at posttreatment on the primary outcome of healthy eating index (HEI; based on 24-hr recall assessments) and almost all secondary outcomes assessing self-reported eating behaviors, weight, mental health, weight self-stigma, and psychological inflexibility. However, no intervention effects were found for self-reported physical activity. At 8-week follow-up, improvements were maintained for most outcomes in the ACT condition, but not for the HEI. Improvements in psychological inflexibility mediated treatment effects on some outcomes, but not HEI or weight. Overall, delivering ACT through online guided self-help combined with nutrition education appears promising for improving healthy eating, weight, and self-stigma, but results for physical activity and long-term behavior change are unclear, possibly due to limitations in the ACT on Health program.

To evaluate nasal soft and hard tissue changes immediately post-rapid maxillary expansion (RME) and to assess the stability of these changes using cone beam computed tomography (CBCT).

A total of 35 treatment group (TG) patients (18 girls, 17 boys; 9.39 ± 1.4) had a pre-RME CBCT and a post-RME CBCT approximately 66 days after expansion, and 25 patients had a follow-up CBCT 2.84 years later. A total of 28 control group (CG; no RME) patients (16 girls, 12 boys; 8.81 ± 1.6) had an initial CBCT and a CBCT an average of 2.25 years later. Soft and hard tissue nasal landmarks were measured in transverse, sagittal, and coronal planes of space on CBCT scans. Differences within the same group were evaluated by paired t-tests or Wilcoxon signed-rank tests. Long-term comparisons between TG and CG were evaluated by independent-sample t-tests or Wilcoxon rank-sum tests.

Immediately post-RME, there were statistically significant mean increases of 1.6 mm of alar base width, 1.77 mm of pyriform height, and 3.57 mm of pyriform width (P < .05). CG showed the significant increases over 2.25 years (P < .001). Compared with CG, the long-term evaluation of TG demonstrated only pyriform height and pyriform width showed a statistically significant difference (P < .01).

Although RME produced some significant increase on the nasal soft tissue immediately after expansion, it regressed to the mean of normal growth and development over time. However, long-term evaluation of TG compared with CG showed only pyriform height and pyriform width to be affected by RME.

Although RME produced some significant increase on the nasal soft tissue immediately after expansion, it regressed to the mean of normal growth and development over time. However, long-term evaluation of TG compared with CG showed only pyriform height and pyriform width to be affected by RME.

To evaluate the influence of a midline diastema on dentofacial esthetic perceptions of orthodontists, restorative dental specialists or prosthodontists, and laypersons in a frontal facial evaluation performed by means of video.

Two individuals aged between 20 and 25 years, one of each gender, with presence of a midline diastema were selected. An acrylic resin mockup was made of the maxillary anterior region, simulating ideal conditions of smile esthetics. Four standardized frontal view videos of the complete face were filmed of each individual in the following situations with the ideal smile (unchanged mockup) and with the presence of midline diastemas of 0.5, 1.0, and 1.5 mm created by the mockup. In all videos, the patient said a certain sentence and, at the end, simulated a posed smile. Dentofacial esthetic perceptions of all four videos of each individual were evaluated by 51 orthodontists, 51 restorative dental specialists or prosthodontists, and 51 laypersons by means of visual analog scales. Data were evaluated using analysis of variance and Tukey post hoc test, with the level of significance set at 5%.

The most attractive videos for all groups of examiners were those without diastema and with a diastema of 0.5 mm, for both the woman and the man. For a diastema of 1 mm or 1.5 mm, the dentofacial characteristics were considered unesthetic.

Diastemas equal to or greater than 1 mm negatively influence dentofacial esthetics in a frontal facial evaluation performed by means of video.

Diastemas equal to or greater than 1 mm negatively influence dentofacial esthetics in a frontal facial evaluation performed by means of video.

To evaluate the tongue and oral cavity proper volume in pre- and post-bilateral sagittal split osteotomy (BSSO) patients, and to establish whether there was a correlation between them.

A retrospective study that evaluated 12 patients' pre- and post-surgical computed tomography records satisfying the inclusion criteria. Borders were defined for measurement of tongue and oral cavity proper volume. The volume assessment was carried out using 3D slice software.

The mean difference of tongue volume was 5.7 ± 1.7 cm3, which showed high statistical significance. The mean difference of oral cavity proper volume (OCVP) was 6.9 ± 3.4 cm3 and indicated high statistical significance. A very strong positive correlation existed between pre- and post-surgical tongue volume. Positive correlation was also evident between pre and post - surgical OCVP. Medium positive correlation was noted when the difference between pre- and post-surgical tongue and OCVP were assessed.

There was a significant change in volume of tongue and oral cavity proper after BSSO advancement surgery. The space around the tongue, position of tongue, and maxillary and mandibular relationship influence the volume of tongue and oral cavity proper.

There was a significant change in volume of tongue and oral cavity proper after BSSO advancement surgery. The space around the tongue, position of tongue, and maxillary and mandibular relationship influence the volume of tongue and oral cavity proper.

To compare the dental and skeletal treatment effects after total arch distalization using modified C-palatal plates (MCPPs) on adolescent patients with hypo- and hyperdivergent Class II malocclusion.

The study group included 40 patients with Class II malocclusion (18 boys and 22 girls, mean age = 12.2 ± 1.4 years) treated with MCPPs. Fixed orthodontic treatment started with the distalizing process in both groups. Participants were divided into hypo- or hyperdivergent groups based on their pretreatment Frankfort mandibular plane angle (FMA) ≤22° or ≥28°, respectively. Pre- and posttreatment lateral cephalograms were digitized, and 23 variables were measured and compared for both groups using paired and independent t-tests.

The hyper- and hypodivergent groups showed 2.7 mm and 4.3 mm of first molar crown distalizing movement, respectively (P < .001). The hypodivergent group had a slight 2.2° crown distal tipping of first molars compared with 0.3° in the hyperdivergent group. After distalization, the FMA increased 3.1° and 0.3°, in the hypodivergent and hyperdivergent groups, respectively (P < .001). SNA decreased in the hypodivergent group, while other skeletal variables presented no statistically significant differences in the changes between the groups.

The hypodivergent group showed more distal and tipping movement of the maxillary first molar and increased FMA than the hyperdivergent group. Therefore, clinicians must consider vertical facial types when distalizing molars using MCPPs in Class II nonextraction treatment.

The hypodivergent group showed more distal and tipping movement of the maxillary first molar and increased FMA than the hyperdivergent group. Therefore, clinicians must consider vertical facial types when distalizing molars using MCPPs in Class II nonextraction treatment.