AZGP1 deficiency promotes angiogenesis in prostate cancer.

BACKGROUND: Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive. METHOD: AZGP1 knockout and overexpressing prostate cancer cells were generated using a lentiviral system. The effects of AZGP1 under- or over-expression in prostate cancer cells were evaluated by in vitro cell proliferation, migration, and invasion assays. Heterozygous AZGP1± mice were obtained from European Mouse Mutant Archive (EMMA), and prostate tissues from homozygous knockout male mice were collected at 2, 6 and 10 months for histological analysis. In vivo xenografts generated from AZGP1 under- or over-expressing prostate cancer cells were used to determine the role of AZGP1 in prostate cancer tumor growth, and subsequent proteomics analysis was conducted to elucidate the mechanisms of AZGP1 action in prostate cancer progression. AZGP1 expression and microvessel density were measured in human prostate cancer samples on a tissue microarray of 215 independent patient samples. RESULT: Neither the knockout nor overexpression of AZGP1 exhibited significant effects on prostate cancer cell proliferation, clonal growth, migration, or invasion in vitro. The prostates of AZGP1-/- mice initially appeared to have grossly normal morphology; however, we observed fibrosis in the periglandular stroma and higher blood vessel density in the mouse prostate by 6 months. In PC3 and DU145 mouse xenografts, over-expression of AZGP1 did not affect tumor growth. Instead, these tumors displayed decreased microvessel density compared to xenografts derived from PC3 and DU145 control cells, suggesting that AZGP1 functions to inhibit angiogenesis in prostate cancer. Proteomics profiling further indicated that, compared to control xenografts, AZGP1 overexpressing PC3 xenografts are enriched with angiogenesis pathway proteins, including YWHAZ, EPHA2, SERPINE1, and PDCD6, MMP9, GPX1, HSPB1, COL18A1, RNH1, and ANXA1. In vitro functional studies show that AZGP1 inhibits human umbilical vein endothelial cell proliferation, migration, tubular formation and branching. Additionally, tumor microarray analysis shows that AZGP1 expression is negatively correlated with blood vessel density in human prostate cancer tissues. CONCLUSION: AZGP1 is a negative regulator of angiogenesis, such that loss of AZGP1 promotes angiogenesis in prostate cancer. AZGP1 likely exerts heterotypical effects on cells in the tumor microenvironment, such as stromal and endothelial cells. This study sheds light on the anti-angiogenic characteristics of AZGP1 in the prostate and provides a rationale to target AZGP1 to inhibit prostate cancer progression.

p53 stabilisation potentiates [177Lu]Lu-DOTATATE treatment in neuroblastoma xenografts.

PURPOSE: Molecular radiotherapy is a treatment modality that is highly suitable for targeting micrometastases and [177Lu]Lu-DOTATATE is currently being explored as a potential novel treatment option for high-risk neuroblastoma. p53 is a key player in the proapoptotic signalling in response to radiation-induced DNA damage and is therefore a potential target for radiosensitisation. METHODS: This study investigated the use of the p53 stabilising peptide VIP116 and [177Lu]Lu-DOTATATE, either alone or in combination, for treatment of neuroblastoma tumour xenografts in mice. Initially, the uptake of [177Lu]Lu-DOTATATE in the tumours was confirmed, and the efficacy of VIP116 as a monotherapy was evaluated. Subsequently, mice with neuroblastoma tumour xenografts were treated with placebo, VIP116, [177Lu]Lu-DOTATATE or a combination of both agents. RESULTS: The results demonstrated that monotherapy with either VIP116 or [177Lu]Lu-DOTATATE significantly prolonged median survival compared to the placebo group (90 and 96.5 days vs. 50.5 days, respectively). Notably, the combination treatment further improved median survival to over 120 days. Furthermore, the combination group exhibited the highest percentage of complete remission, corresponding to a twofold increase compared to the placebo group. Importantly, none of the treatments induced significant nephrotoxicity. Additionally, the therapies affected various molecular targets involved in critical processes such as apoptosis, hypoxia and angiogenesis. CONCLUSION: In conclusion, the combination of VIP116 and [177Lu]Lu-DOTATATE presents a promising novel treatment approach for neuroblastoma. These findings hold potential to advance research efforts towards a potential cure for this vulnerable patient population.

The association between malocclusion and health-related quality of life in adolescents: A mediation analysis.

This study investigated the role of oral health-related functional limitations and social well-being, self-perceived health, psychosocial factors, and social support in mediating the impact of malocclusion on health-related quality of life (HRQoL). A school-based 6-month cohort study was conducted with 376 12-year-old deprived adolescents. Measures at baseline included malocclusion (DAI score), dental caries, sociodemographic characteristics, psychosocial traits (self-esteem, sense of coherence, oral health beliefs), and social support. The oral health-related functional limitations and symptoms (social well-being) domains of the CPQ11-14 , self-perceived health, and HRQoL (Kiddo-KINDL) were evaluated at the 6-month follow-up. Associations between observed and latent variables (social support, psychosocial factors, and HRQoL) were evaluated using structural equation modelling, according to the Wilson and Cleary theoretical model. Malocclusion was indirectly associated with worse HRQoL, mediated by functional limitations, social well-being, and self-perceived health. Better psychosocial status was directly associated with better HRQoL, and higher social support was indirectly associated with better HRQoL via psychosocial factors. Dental caries experience, female sex, and lower family income were indirectly associated with worse HRQoL. The impact of malocclusion on HRQoL was mediated by oral health-related functional limitations, social well-being, and self-perceived health. Sociodemographic and psychosocial factors, and social support also impacted HRQoL.

Rheumatoid meningitis: a case series report and review of modern therapeutic schemes and outcome.

INTRODUCTION: Rheumatoid meningitis (RM) is an extremely rare extra-articular complication of rheumatoid arthritis (RA), with approximately 165 cases reported world-wide. RM exhibits a broad range of symptoms, with stroke-like episodes and seizures being the most common manifestations. The primary differential diagnoses include vascular and infectious diseases. The influence of immunomodulatory medications on the pathophysiology of RM remains unclear. There are no consensus guidelines on therapeutic regimen. METHODS: We present four patients with prior history of RA that developed different neurological syndromes in correlation to radiological leptomeningitis. Clinical presentations, comorbid conditions, supplementary diagnostic assessments, treatments, and prognosis are provided. A literature review of recent immunosuppressive management in RM patients was performed. RESULTS: Three patients presented to hospital with recurrent focal seizures. Only two suffered meningism, reporting headache and fever. Magnetic resonance imaging (MRI) showed different grades of leptomeningitis across all cases. Notably, three cases demonstrated bilateral involvement extending to the pachymeninges. Two patients exhibited pronounced CSF mononuclear inflammation while extended microbiological evaluations yielded negative results. Two patients required biopsy for confirmation. The initiation of immunosuppressive therapy marked a turning point for three patients who previously exhibited progressive deterioration. Mortality was absent in all cases. CONCLUSIONS: Our experience remarks the elusive nature of RM. Rigorous exclusionary diagnostics are imperative to differentiate RM from mimicking conditions. Clinical manifestations oscillate between transient episodes and progressive neurological impairments, punctuated by frequent epileptic seizures. In scenarios where clinical worsening persists or where clinical and radiological evaluations are inconclusive, aggressive immunosuppressive therapy is recommended.

Contextual and individual factors associated with traumatic dental injuries in deprived 12-year-old schoolchildren: A cohort study.

AIM: Traumatic dental injuries (TDIs) among children and adolescents have been acknowledged as of public health concern worldwide. The aim of the study was to assess the relationship between contextual and individual characteristics and TDIs in 12-year-old schoolchildren. MATERIALS AND METHODS: A cohort study was conducted with 355 schoolchildren living in deprived communities in the city of Manaus, Brazil. Contextual factors (place of residence and socio-economic indicators) and individual characteristics, including sex, family income, parents/guardians years of schooling, overjet and open bite (Dental Aesthetic Index), self-esteem (Rosenberg Self-Esteem Scale), sense of coherence (Sense of Coherence Scale), oral health beliefs, social support (Social Support Appraisals) were assessed at baseline. TDIs were measured at baseline and at 2-year follow-up using the O'Brien Index. Data were analysed through confirmatory factor analysis and structural equation modeling. RESULTS: The baseline prevalence of TDIs was 17.6% and the incidence of TDIs at 2-year follow-up was 26.8%. Better psychosocial status had a direct protective effect on the incidence of TDIs (ß = -.184). Better contextual characteristics (ß = -.135) and greater overjet (ß = -.203) were directly associated with poor psychosocial status. Higher schooling of parents/guardians directly predicted better psychosocial status (ß = .154). Psychosocial status mediated the relationship of greater overjet (ß = .036), contextual factors (ß = .024) and parental/guardian schooling (ß = -.027) with TDIs. CONCLUSIONS: Contextual factors and individual characteristics predicted TDIs. Psychosocial status was a relevant individual attribute in the causal network of TDIs, due to the direct effect on the incidence of TDIs as well as a mediator on the influence of contextual factors, overjet and parents/guardians schooling on the incidence of TDIs.

From Anxiety to Hardiness: The Role of Self-Efficacy in Spanish CCU Nurses in the COVID-19 Pandemic.

Background and Objectives: Evidence shows that throughout the COVID-19 pandemic, nurses suffered from emotional symptoms, yet in spite of this, few studies within "positive psychology" have analyzed the emergence/promotion of positive traits, such as hardiness. In this context, the present study aimed to test a model regarding the mediating role of self-efficacy between anxiety experienced at the beginning of the COVID-19 pandemic and hardiness assessed six months later among nurses in critical care units (CCU) in Spain. Materials and Methods: An observational, descriptive, prospective longitudinal study with two data collection periods: (1) from the 1 to the 21 June 2020 (final phase of the state of alarm declared in Spain on 14 March) in which socio-demographic and occupational variables, anxiety (Depression, Anxiety and Stress Scale, DASS-21), self-efficacy (General Self-Efficacy Scale, GSES) and basal resilience (Resilience Scale-14, RS-14) were assessed, and (2) a follow-up 6 months later (January-March 2021) in which hardiness (Occupational Hardiness Questionnaire, OHQ) was evaluated. To analyze the data, multivariate regressions were performed using the PROCESS macro (simple mediation, model 4). Results: A total of 131 Spanish nurses from CCUs, with a mean age of 40.54 years (88.5% women) participated in the study. Moderate and severe levels of anxiety were observed in 19.1% of the sample. Significant and positive correlations were observed between self-efficacy, hardiness and resilience (all p < 0.001). Significant negative correlations were observed between anxiety and self-efficacy (p < 0.001), hardiness (p = 0.027) and resilience (p = 0.005). The indirect effect of anxiety on hardiness through self-efficacy was significant (Effect (SE) = -0.275 (0.100); LLCI = -0.487, ULCI = -0.097), contributing to 28% of the variance, including resilience (p = 0.015), age (p = 0.784), gender (p = 0.294) and years of experience (p = 0.652) as covariates. A total mediation was observed (non-significant anxiety-hardiness direct effect; Effect (SE) = -0.053 (0.215), t = 0.248, p = 0.804, LLCI = -0.372, ULCI = 0.479). Conclusions: The results suggest that in Spanish CCU nurses, anxiety experienced at the beginning of the COVID-19 pandemic may contribute to the development of hardiness through positive resources such as self-efficacy.

Identification and experimental validation of druggable epigenetic targets in hepatoblastoma.

BACKGROUND & AIMS: Hepatoblastoma (HB) is the most frequent childhood liver cancer. Patients with aggressive tumors have limited therapeutic options; therefore, a better understanding of HB pathogenesis is needed to improve treatment. HBs have a very low mutational burden; however, epigenetic alterations are increasingly recognized. We aimed to identify epigenetic regulators consistently dysregulated in HB and to evaluate the therapeutic efficacy of their targeting in clinically relevant models. METHODS: We performed a comprehensive transcriptomic analysis of 180 epigenetic genes. Data from fetal, pediatric, adult, peritumoral (n = 72) and tumoral (n = 91) tissues were integrated. Selected epigenetic drugs were tested in HB cells. The most relevant epigenetic target identified was validated in primary HB cells, HB organoids, a patient-derived xenograft model, and a genetic mouse model. Transcriptomic, proteomic and metabolomic mechanistic analyses were performed. RESULTS: Altered expression of genes regulating DNA methylation and histone modifications was consistently observed in association with molecular and clinical features of poor prognosis. The histone methyltransferase G9a was markedly upregulated in tumors with epigenetic and transcriptomic traits of increased malignancy. Pharmacological targeting of G9a significantly inhibited growth of HB cells, organoids and patient-derived xenografts. Development of HB induced by oncogenic forms of ß-catenin and YAP1 was ablated in mice with hepatocyte-specific deletion of G9a. We observed that HBs undergo significant transcriptional rewiring in genes involved in amino acid metabolism and ribosomal biogenesis. G9a inhibition counteracted these pro-tumorigenic adaptations. Mechanistically, G9a targeting potently repressed the expression of c-MYC and ATF4, master regulators of HB metabolic reprogramming. CONCLUSIONS: HBs display a profound dysregulation of the epigenetic machinery. Pharmacological targeting of key epigenetic effectors exposes metabolic vulnerabilities that can be leveraged to improve the treatment of these patients. IMPACT AND IMPLICATIONS: In spite of recent advances in the management of hepatoblastoma (HB), treatment resistance and drug toxicity are still major concerns. This systematic study reveals the remarkable dysregulation in the expression of epigenetic genes in HB tissues. Through pharmacological and genetic experimental approaches, we demonstrate that the histone-lysine-methyltransferase G9a is an excellent drug target in HB, which can also be harnessed to enhance the efficacy of chemotherapy. Furthermore, our study highlights the profound pro-tumorigenic metabolic rewiring of HB cells orchestrated by G9a in coordination with the c-MYC oncogene. From a broader perspective, our findings suggest that anti-G9a therapies may also be effective in other c-MYC-dependent tumors.

Perinatal Protein Restriction Impacts Nuclear O-GalNAc Glycosylation in Cells of Liver and Brain Structures of the Rat.

BACKGROUND: Post-translational modifications are key factors in the modulation of nuclear protein functions controlling cell physiology and an individual's health. OBJECTIVES: This study examined the influence of protein restriction during the perinatal period on the nuclear O-N-acetylgalactosamine (O-GalNAc) glycosylation of cells from the liver and parts of the brain in the rat. METHODS: Pregnant Wistar rats were divided into 2 groups on day 14 of pregnancy and fed ad libitum 1 of 2 isocaloric diets containing 24% (well-fed) or 8% (protein-restricted diet) casein until the end of the experiment. Male pups were studied after weaning at 30 d of life. Animals and their organ/tissues (liver, cerebral cortex, cerebellum and hippocampus) were weighed. Cell nuclei were purified, and the presence in nucleus and cytoplasm of all factors required for the initiation of O-GalNAc glycan biosynthesis, i.e., the sugar donor (UDP-GalNAc), enzyme activity (ppGalNAc-transferase) and the glycosylation product (O-GalNAc glycans), were evaluated by western blotting, fluorescent microscopy, enzyme activity, enzyme-lectin sorbent assay and mass spectrometry. RESULTS: The perinatal protein deficit reduced progeny weight, as well as the cerebral cortex and cerebellum weight. UDP-GalNAc levels in the cytoplasm and nuclei of the liver, the cerebral cortex, cerebellum, or hippocampus were not affected by the perinatal dietary protein deficits. However, this deficiency affected the ppGalNAc-transferase activity localized in the cerebral cortex and hippocampus cytoplasm as well as in the liver nucleus, thus reducing the "writing" ppGalNAc-transferase activity of O-GalNAc glycans. In addition, liver nucleoplasm from protein-restricted offspring revealed a significant reduction in the expression of O-GalNAc glycans on important nuclear proteins. CONCLUSIONS: Our results report an association between the consumption of a protein-restricted diet by the dam and her progeny with the modulation in the offspring' liver nuclei O-GalNAc glycosylation, which may ultimately regulate nuclear protein functions.

Is obstructive sleep apnea associated with increased arterial stiffness in patients with COPD?

PURPOSE: To evaluate arterial stiffness, a predictor of vascular damage was assessed by means of pulse wave velocity (PWV) in patients with chronic obstructive pulmonary disease (COPD) and comorbid obstructive sleep apnea (OSA), namely overlap syndrome (OS). METHODS: Consecutive stable patients with COPD were evaluated for OSA by means of overnight polysomnography in the laboratory. A clinical assessment was performed according to a strict protocol, including two COPD questionnaires: the COPD assessment test and the modified Medical Research Council scale. COPD severity was graded according to the guidelines of the Global Initiative for Chronic Obstructive Lung Disease. Arterial stiffness was assessed by means of PWV, using a standard technique. RESULTS: Of 102 patients with COPD, 51 had associated OSA. The OS group had more men than the COPD group (73% vs. 47%, respectively; p < 0.01). Both groups had similar ages (66.2 ± 9.2 years vs. 69.6 ± 10.7, p = 0.09) and airflow limitation (p = 0.37). Hypertension was found in 22% of COPD patients, as opposed to 17% patients in the OS group (p = 0.29). High PWV values were present in 42% of the patients. Patients with COPD and OS had the same PWV values (9.8 vs. 10.5 m/s, p = 0.34). There were no differences in central blood pressure, peripheral blood pressure, and augmentation index between the two groups (p > 0.05). CONCLUSION: High PWV values were frequently observed in patients with COPD. However, there was no difference in PWV between patients with OS and those with COPD alone.

Trop2 is a driver of metastatic prostate cancer with neuroendocrine phenotype via PARP1.

Resistance to androgen deprivation therapy, or castration-resistant prostate cancer (CRPC), is often accompanied by metastasis and is currently the ultimate cause of prostate cancer-associated deaths in men. Recently, secondary hormonal therapies have led to an increase of neuroendocrine prostate cancer (NEPC), a highly aggressive variant of CRPC. Here, we identify that high levels of cell surface receptor Trop2 are predictive of recurrence of localized prostate cancer. Moreover, Trop2 is significantly elevated in CRPC and NEPC, drives prostate cancer growth, and induces neuroendocrine phenotype. Overexpression of Trop2 induces tumor growth and metastasis while loss of Trop2 suppresses these abilities in vivo. Trop2-driven NEPC displays a significant up-regulation of PARP1, and PARP inhibitors significantly delay tumor growth and metastatic colonization and reverse neuroendocrine features in Trop2-driven NEPC. Our findings establish Trop2 as a driver and therapeutic target for metastatic prostate cancer with neuroendocrine phenotype and suggest that high Trop2 levels could identify cancers that are sensitive to Trop2-targeting therapies and PARP1 inhibition.

Periradicular surgery: a longitudinal registry study of ten-year outcomes and factors predictive of post-surgical extraction.

AIM: This historical prospective cohort study of the adult population of Sweden is based on data from a national registry: the primary aim was to evaluate the long-term survival of teeth after periradicular surgery. A secondary aim was to identify factors predictive of extraction within 10 years of registration of periradicular surgery. METHODOLOGY: The cohort consisted of all individuals who had undergone periradicular surgery to treat apical periodontitis, as reported to the Swedish Social Insurance Agency (SSIA) during 2009. The cohort was followed until December 31, 2020. Subsequent registrations of extractions were collected for Kaplan-Meier survival analyses and survival tables. The patients' sex, age, dental service provider and tooth group were also retrieved from SSIA. Only one tooth per individual was included in the analyses. Multivariable regression analysis was used and P < 0.05 was considered statistically significant. The reporting guidelines STROBE and PROBE were followed. RESULTS: After data cleaning, and exclusion of 157 teeth, 5 622 teeth/individuals remained for analysis. The mean age of the individuals at the time of the periradicular surgery was 60.5 years (range 20-97, standard deviation 13.31); 55% were women. At the end of the follow-up, that is, up to 12 years, a total of 34.1% of the teeth had been reported as extracted. The multivariate logistic regression analysis, based on follow-up data at 10 years after registration of the periradicular surgery, included 5 548 teeth, of which 1 461 (26.3%) had been extracted. Significant associations between the independent variables tooth group and dental care setting (both P < 0.001) and the dependent variable extraction were found. The highest odds ratio (OR) for extraction applied to tooth group: compared to maxillary incisors and canines, mandibular molars were at greatest risk of extraction (OR 2.429, confidence interval 1.975-2.987, P < 0.001). CONCLUSIONS: After periradicular surgery in predominantly elderly people in Sweden, approximately three quarters of the teeth are retained over a 10-year period. The type of tooth is associated with extraction: mandibular molars are at greater risk of extraction than maxillary incisors and canines.

Effects of Low-Level Laser Therapy and Purified Natural Latex (Hevea brasiliensis) Protein on Injured Sciatic Nerve in Rodents: Morpho-Functional Analysis.

The present study analyzed the effects of low-level laser therapy (LLLT) and the purified natural latex protein (Hevea brasiliensis, F1 protein) on the morpho-function of sciatic nerve crush injuries in rats. One-hundred and eight male Wistar rats were randomly allocated to six groups (n = 18): 1. Control; 2. Exposed (nerve exposed); 3. Injury (injured nerve without treatment); 4. LLLT (injured nerve irradiated with LLLT (15 J/cm2, 780 nm)); 5. F1 (injured nerve treated with F1 protein (0.1%)); and 6. LLLT + F1 (injured nerve treated with LLLT and F1). On the 1st, 7th, 14th, and 56th days after injury, a functional sensory analysis of mechanical allodynia and mechanical hyperalgesia and a motor analysis of grip strength and gait were performed. After 3, 15, and 57 days, the animals were euthanized for morphometric/ultrastructural analyses. The treatments applied revealed improvements in morphometric/ultrastructural parameters compared to the injured group. Sensory analyses suggested that the improvements observed were associated with time progression and not influenced by the treatments. Motor analyses revealed significant improvements in grip strength from the 7th day in the LLLT group and in gait from the 56th day in all treated groups. We concluded that even though the morphological analyses showed improvements with the treatments, they did not influence sensory recovery, and LLLT improved motor recovery.

Brainstem Modulates Parkinsonism-Induced Orofacial Sensorimotor Dysfunctions.

Parkinson's Disease (PD), treated with the dopamine precursor l-3,4-dihydroxyphenylalanine (L-DOPA), displays motor and non-motor orofacial manifestations. We investigated the pathophysiologic mechanisms of the lateral pterygoid muscles (LPMs) and the trigeminal system related to PD-induced orofacial manifestations. A PD rat model was produced by unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. Abnormal involuntary movements (dyskinesia) and nociceptive responses were determined. We analyzed the immunodetection of Fos-B and microglia/astrocytes in trigeminal and facial nuclei and morphological markers in the LPMs. Hyperalgesia response was increased in hemiparkinsonian and dyskinetic rats. Hemiparkinsonism increased slow skeletal myosin fibers in the LPMs, while in the dyskinetic ones, these fibers decreased in the contralateral side of the lesion. Bilateral increased glycolytic metabolism and an inflammatory muscle profile were detected in dyskinetic rats. There was increased Fos-B expression in the spinal nucleus of lesioned rats and in the motor and facial nucleus in L-DOPA-induced dyskinetic rats in the contralateral side of the lesion. Glial cells were increased in the facial nucleus on the contralateral side of the lesion. Overall, spinal trigeminal nucleus activation may be associated with orofacial sensorial impairment in Parkinsonian rats, while a fatigue profile on LPMs is suggested in L-DOPA-induced dyskinesia when the motor and facial nucleus are activated.

Is Down syndrome a risk factor or contraindication for dental implants? A systematic review.

STATEMENT OF PROBLEM: Whether oral rehabilitation with dental implants in patients with Down syndrome leads to an increased complication rate is unclear. PURPOSE: The purpose of this systematic review was to determine the effectiveness of dental implants placed in patients with Down syndrome and whether the condition is a risk factor or contraindication for dental implant placement. MATERIAL AND METHODS: Searches were conducted in 6 databases, including the non-peer-reviewed literature, up to February 2021 by 2 independent reviewers according to established inclusion and exclusion criteria to answer this question: Is Down syndrome a risk factor or contraindication for oral rehabilitation with dental implants? RESULTS: A total of 655 studies were initially found in the databases. Five were included in this systematic review, all of which were observational studies. A total of 50 patients with 186 implants were evaluated, with a reported effectiveness of 79.1%. The risk of bias assessment determined that 3 of the 5 studies had a high risk of bias. CONCLUSIONS: Treatment with dental implants in patients with Down syndrome is a suitable option, but more complications are to be expected than with patients without this condition. Controlled studies with better methodological design and less risk of bias should be developed to improve the scientific evidence for the treatment of these patients.

What is the Effectiveness of Premaxilla Surgical Repositioning and its Stabilization Methods in Mixed Dentition Patients With Bilateral Cleft Lip and Palate?

OBJECTIVE: Verify the effectiveness of surgical repositioning of the premaxilla and its stabilization methods in patients with bilateral cleft lip and palate during mixed dentition. DESIGN: Systematic review. MATERIAL AND METHODS: The search was conducted in 7 databases (eg, Medline via PubMed; Scopus; Central Cochrane; LILACS; Embase, Web of Science; and Sigle via OpenGrey until August 2021), using the descriptors "premaxilla", "cleft Palate", and "bone transplantation". INCLUSION CRITERIA: Clinical trials and observational studies that have patients with bilateral cleft who had a need for superior/posterior repositioning of the premaxilla on mixed dentition; Studies in any language was evaluted whitout time restriction of publication. RESULTS: From 5572 records, 6 studies were included in the review with a total sample of 212 patients. Regarding the type of stabilization used in the premaxilla, the hybrid method (rigid and complementary semi-rigid stabilization) predominated, being observed in 184 patients (86.8%). A total of 17 failures were identified related to the surgical repositioning of the premaxilla, corresponding to 8% of the total number of surgeries. A meta-analysis of prevalence was performed, only with the retrospective studies. It was observed that the effectiveness rate of premaxilla repositioning was 92%, with a CI between 0.04 and 0.13, with all included studies showing a similar failure rate (0.08-0.09). The included studies also showed great homogeneity in this analysis (I2 = 0%; P = .75). CONCLUSION: Although there are several alternatives and techniques for repositioning and stabilizing the premaxilla, the statistical result did not differ between the different techniques.

Genomic Analysis of Vascular Invasion in HCC Reveals Molecular Drivers and Predictive Biomarkers.

BACKGROUND AND AIMS: Vascular invasion (VI) is a critical risk factor for HCC recurrence and poor survival. The molecular drivers of vascular invasion in HCC are open for investigation. Deciphering the molecular landscape of invasive HCC will help identify therapeutic targets and noninvasive biomarkers. APPROACH AND RESULTS: To this end, we undertook this study to evaluate the genomic, transcriptomic, and proteomic profile of tumors with VI using the multiplatform cancer genome atlas (The Cancer Genome Atlas; TCGA) data (n = 373). In the TCGA Liver Hepatocellular Carcinoma cohort, macrovascular invasion was present in 5% (n = 17) of tumors and microvascular invasion in 25% (n = 94) of tumors. Functional pathway analysis revealed that the MYC oncogene was a common upstream regulator of the mRNA, miRNA, and proteomic changes in VI. We performed comparative proteomic analyses of invasive human HCC and MYC-driven murine HCC and identified fibronectin to be a proteomic biomarker of invasive HCC (mouse fibronectin 1 [Fn1], P = 1.7 × 10-11 ; human FN1, P = 1.5 × 10-4 ) conserved across the two species. Mechanistically, we show that FN1 promotes the migratory and invasive phenotype of HCC cancer cells. We demonstrate tissue overexpression of fibronectin in human HCC using a large independent cohort of human HCC tissue microarray (n = 153; P < 0.001). Lastly, we showed that plasma fibronectin levels were significantly elevated in patients with HCC (n = 35; mean = 307.7 µg/mL; SEM = 35.9) when compared to cirrhosis (n = 10; mean = 41.8 µg/mL; SEM = 13.3; P < 0.0001). CONCLUSIONS: Our study evaluates the molecular landscape of tumors with VI, identifying distinct transcriptional, epigenetic, and proteomic changes driven by the MYC oncogene. We show that MYC up-regulates fibronectin expression, which promotes HCC invasiveness. In addition, we identify fibronectin to be a promising noninvasive proteomic biomarker of VI in HCC.

Is the at-home bleaching treatment applied only on the lingual surface as effective as that on the buccal surface? A randomized clinical trial.

OBJECTIVES: This double-blind randomized clinical trial compared the effectiveness and bleaching sensitivity (BS) of at-home dental bleaching performed on the buccal surface and on the lingual surface. METHODS: Using a split-mouth design, 25 patients were assigned to two bleaching groups: 10% hydrogen peroxide (White Class 10%, FGM) applied once daily for 60 min to the buccal surface (BSB) and 10% hydrogen peroxide (White Class 10%, FGM) applied once daily for 60 min to the lingual surface (LSB), both for 14 days. The color was evaluated before bleaching, after the first and second weeks, and 1 month after the bleaching using Vita Classical and Vita Bleachedguide scales and a Vita Easyshade spectrophotometer. BS was recorded daily using a 0-4 numerical rating scale and a 0-10 visual analogue scale. The following statistical tests were used: color changes (Mann-Whitney), absolute risk of BS (McNemar's exact), and the intensity of BS (Mann-Whitney). In all statistical tests, the significance level was 5%. RESULTS: Significant bleaching was observed after the end of bleaching in both groups, with higher bleaching effectiveness for BSB when compared to LSB (p < 0.05). Regarding BS, no significant difference was observed between groups (p = 1.00). CONCLUSIONS: The 10% hydrogen peroxide (White Class 10%, FGM) applied in at-home bleaching performed on the lingual surface did not promote a similar result of color change compared to on the buccal surface. Regarding BS, there was no significant difference between the groups. CLINICAL RELEVANCE: The at-home bleaching performed on the lingual surface promotes a lower result in the color change. BS is similar between the groups. CLINICAL TRIAL REGISTRATION NUMBER: RBR-283byt.

Effectiveness of soil conditioners to enhance salt extraction ability of Salicornia ramosissima in saline-sodic soil for different soil moisture contents.

Soil salinity is considered one of the main types of soil degradation in semiarid environments around the globe. This work aims to evaluate the effectiveness of soil conditioners to enhance the growth and salt extraction ability of Salicornia ramosíssima for different soil moisture contents. Salicornia plants were cultivated in pots in which the soils were treated with the following conditioners: control; gypsum + organic matter; elemental sulfur + organic matter; and gypsum + elemental sulfur + organic matter. Salicornia plants were subjected to two soil moisture rates - at 35 and 85% field capacity. Soil conditioners associated with higher contents of soil moisture promoted significant increases, compared to control, in fresh (6.20 - 11.13 g) and dry matter (1.20 - 2.07 g), relative biomass (100 - 179%) as well as significantly increased the concentrations of Na+ (56.09 - 65.64 mg kg-1) and Cl- (110.83 - 150.0 mg kg-1) in plant tissues. Soil conditioners significantly increased salt extraction ability under the two moisture levels, mainly by promoting higher values for both transfer factor and phytoremediation potential. The best performance of Salicornia in terms of plant yield and salt extraction, regardless of the moisture level, was the gypsum + organic matter.Novelty statementThere are no studies in the literature relating the use of conditioners as a strategy to enhance Salicornia's ability to extract salts.This work contributes to the management of salinized areas around the globe in two main aspects. The first is that many of these salt-degraded areas are desertified and through this study, it is possible to revegetate and recover them. The second one is that, since Salicornia is a plant with economic value, this can serve as an incentive for farmers to grow Salicornia in saline areas.

Augmented Humanity: A Systematic Mapping Review.

Augmented humanity (AH) is a term that has been mentioned in several research papers. However, these papers differ in their definitions of AH. The number of publications dealing with the topic of AH is represented by a growing number of publications that increase over time, being high impact factor scientific contributions. However, this terminology is used without being formally defined. The aim of this paper is to carry out a systematic mapping review of the different existing definitions of AH and its possible application areas. Publications from 2009 to 2020 were searched in Scopus, IEEE and ACM databases, using search terms "augmented human", "human augmentation" and "human 2.0". Of the 16,914 initially obtained publications, a final number of 133 was finally selected. The mapping results show a growing focus on works based on AH, with computer vision being the index term with the highest number of published articles. Other index terms are wearable computing, augmented reality, human-robot interaction, smart devices and mixed reality. In the different domains where AH is present, there are works in computer science, engineering, robotics, automation and control systems and telecommunications. This review demonstrates that it is necessary to formalize the definition of AH and also the areas of work with greater openness to the use of such concept. This is why the following definition is proposed: "Augmented humanity is a human-computer integration technology that proposes to improve capacity and productivity by changing or increasing the normal ranges of human function through the restoration or extension of human physical, intellectual and social capabilities".

Magnitude and Shape of the Forces Applied on the Foot Rest and Paddle by Elite Kayakers.

The study aimed to investigate the magnitude and shape of the forces applied on the foot rest, foot strap, and paddle. Thirteen elite male kayakers participated in this study and performed a 2-min test simulating 500 m race pace in a kayak ergometer. Forces applied by the kayakers on the paddle, foot rest, and foot strap were measured with load cells and recorded by an electronic measuring system. The magnitude of the peak forces applied on the foot rest (left: 543.27 ± 85.93; right: 524.39 ± 88.36) approximately doubled the ones applied on the paddle (left: 236.37 ± 19.32; right: 243.92 ± 28.89). The forces on the foot strap were similar in magnitude to the paddle forces (left: 240.09 ± 74.92; right: 231.05 ± 52.01). A positive correlation was found between the peak forces applied on the foot rest and paddle on the same side (p < 0.001). When comparing the best and worst kayakers' performance, the best showed greater forces magnitudes and synchronization of the peak forces. Analyses of the force-time curves, including not only the forces applied by the kayaker on the paddle but also the ones applied on the foot rest and strap, should be considered relevant in terms of technique analyses.