Apolipoprotein E-ε2 and Resistance to Atherosclerosis in Midlife: The PESA Observational Study.

BACKGROUND: APOE is a known genetic contributor to cardiovascular disease, but the differential role APOE alleles play in subclinical atherosclerosis remains unclear. METHODS: The PESA (Progression of Early Subclinical Atherosclerosis) is an observational cohort study that recruited 4184 middle-aged asymptomatic individuals to be screened for cardiovascular risk and multiterritorial subclinical atherosclerosis. Participants were APOE-genotyped, and omics data were additionally evaluated. RESULTS: In the PESA study, the frequencies for APOE -ε2, -ε3, and -ε4 alleles were 0.060, 0.844, and 0.096, respectively. This study included a subcohort of 3887 participants (45.8±4.3 years of age; 62% males). As expected, APOE-ε4 carriers were at the highest risk for cardiovascular disease and had significantly greater odds of having subclinical atherosclerosis compared with ε3/ε3 carriers, which was mainly explained by their higher levels of low-density lipoprotein (LDL)-cholesterol. In turn, APOE-ε2 carriers were at the lowest risk for cardiovascular disease and had significantly lower odds of having subclinical atherosclerosis in several vascular territories (carotids: 0.62 [95% CI, 0.47-0.81]; P=0.00043; femorals: 0.60 [0.47-0.78]; P=9.96×10-5; coronaries: 0.53 [0.39-0.74]; P=0.00013; and increased PESA score: 0.58 [0.48-0.71]; P=3.16×10-8). This APOE-ε2 atheroprotective effect was mostly independent of the associated lower LDL-cholesterol levels and other cardiovascular risk factors. The protection conferred by the ε2 allele was greater with age (50-54 years: 0.49 [95% CI, 0.32-0.73]; P=0.00045), and normal (<150 mg/dL) levels of triglycerides (0.54 [0.44-0.66]; P=4.70×10-9 versus 0.90 [0.57-1.43]; P=0.67 if ≥150 mg/dL). Omics analysis revealed an enrichment of several canonical pathways associated with anti-inflammatory mechanisms together with the modulation of erythrocyte homeostasis, coagulation, and complement activation in ε2 carriers that might play a relevant role in the ε2's atheroprotective effect. CONCLUSIONS: This work sheds light on the role of APOE in cardiovascular disease development with important therapeutic and prevention implications on cardiovascular health, especially in early midlife. REGISTRATION: URL: https://www.clinicaltrials.gov: NCT01410318.

Structural insights into the Smirnoff-Wheeler pathway for vitamin C production in the Amazon fruit camu-camu.

l-Ascorbic acid (AsA, vitamin C) is a pivotal dietary nutrient with multifaceted importance in living organisms. In plants, the Smirnoff-Wheeler pathway is the primary route for AsA biosynthesis, and understanding the mechanistic details behind its component enzymes has implications for plant biology, nutritional science, and biotechnology. As part of an initiative to determine the structures of all six core enzymes of the pathway, the present study focuses on three of them in the model species Myrciaria dubia (camu-camu): GDP-d-mannose 3',5'-epimerase (GME), l-galactose dehydrogenase (l-GalDH), and l-galactono-1,4-lactone dehydrogenase (l-GalLDH). We provide insights into substrate and cofactor binding and the conformational changes they induce. The MdGME structure reveals a distorted substrate in the active site, pertinent to the catalytic mechanism. Mdl-GalDH shows that the way in which NAD+ association affects loop structure over the active site is not conserved when compared with its homologue in spinach. Finally, the structure of Mdl-GalLDH is described for the first time. This allows for the rationalization of previously identified residues which play important roles in the active site or in the formation of the covalent bond with FAD. In conclusion, this study enhances our understanding of AsA biosynthesis in plants, and the information provided should prove useful for biotechnological applications.

LT and SOX9 expression are associated with gene sets that distinguish Merkel cell polyomavirus (MCPyV)-positive and MCPyV-negative Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive malignant neuroendocrine tumour. There are two subsets of MCC, one related to Merkel cell polyomavirus (MCPyV) and the other to ultraviolet radiation (UVR). MCPyV-positive and MCPyV-negative MCCs have been considered to be different tumours, as the former harbour few DNA mutations and are not related to UVR, and the latter usually arise in sun-exposed areas and may be found in conjunction with other keratinocytic tumours, mostly squamous cell carcinomas. Two viral oncoproteins, large T antigen (LT; coded by MCPyV_gp3) and small T antigen (sT; coded by MCPyV_gp4), promote different carcinogenic pathways. OBJECTIVES: To determine which genes are differentially expressed in MCPyV-positive and MCPyV-negative MCC; to describe the mutational burden and the most frequently mutated genes in both MCC subtypes; and to identify the clinical and molecular factors that may be related to patient survival. METHODS: Ninety-two patients with a diagnosis of MCC were identified from the medical databases of participating centres. To study gene expression, a customized panel of 172 genes was developed. Gene expression profiling was performed with nCounter technology. For mutational studies, a customized panel of 26 genes was designed. Somatic single nucleotide variants (SNVs) were identified following the GATK Best Practices workflow for somatic mutations. RESULTS: The expression of LT enabled the series to be divided into two groups (LT positive, n = 55; LT negative, n = 37). Genes differentially expressed in LT-negative patients were related to epithelial differentiation, especially SOX9, or proliferation and the cell cycle (MYC, CDK6), among others. Congruently, LT displayed lower expression in SOX9-positive patients, and differentially expressed genes in SOX9-positive patients were related to epithelial/squamous differentiation. In LT-positive patients, the mean SNV frequency was 4.3; in LT-negative patients it was 10 (P = 0.03). On multivariate survival analysis, the expression of SNAI1 [hazard ratio (HR) 1.046, 95% confidence interval (CI) 1.007-1.086; P = 0.02] and CDK6 (HR 1.049, 95% CI 1.020-1.080; P = 0.001) were identified as risk factors. CONCLUSIONS: Tumours with weak LT expression tend to co-express genes related to squamous differentiation and the cell cycle, and to have a higher mutational burden. These findings are congruent with those of earlier studies.

Merkel cell carcinoma (MCC) is an aggressive form of skin tumour. There are two subtypes of MCC: one of them is related to a virus called Merkel cell polyomavirus (MCPyV); the other one is related to persistent exposure to sunlight. The aim of this research was to find differences between these subtypes in their molecular behaviour (the genes that are expressed and the mutations that may be found). To do this, we carried out two studies, one to investigate gene expression (the process cells use to convert the instructions in our DNA into a functional product such as a protein) and one to look at gene mutations (changes in the DNA sequence). We found that the tumours that were not related to MCPyV expressed genes related to epithelial differentiation (the process by which unspecialized cells gain features characteristics of epithelial cells, which, among other things, make up the outer surface of the body), which means that the origin of both MCC subtypes may be different. We also found that MCPyV-related tumours had fewer mutations. Our findings are important because they help us to understand the biology of the MCC subtypes and could help with the development of new treatments for people diagnosed with skin tumours.

Urticarial mycosis fungoides: A distinctive presentation with blood involvement and a peculiar immunophenotype.

Mycosis fungoides (MF) has been widely reported to mimick a considerable number of different dermatoses, including scarring alopecia, bullous dermatoses or cysts, and comedones. In atypical presentations, histopathology is essential for the diagnosis. We present two cases of MF with clinical urticarial lesions and a striking blood involvement that responded to mogamulizumab treatment. Histopathologically, both cases had classic MF features and shared a peculiar immunophenotype, with positivity for CD25 and FOXP3. Differential diagnoses included urticarial lymphomatoid drug reactions and other lymphomas, like T-cell prolymphocytic leukemia, atypical Sézary syndrome, or adult T-cell lymphocytic leukemia. A low suspicion threshold is necessary for the diagnosis of atypical presentations of MF.

Influence of vaginal birth on lumbopelvic muscle mechanical properties on urinary incontinence.

OBJECTIVE: To identify differences in the muscle mechanical properties of the pelvic floor (PF) and lumbar paravertebral (LP) muscles between young nulliparous and uni/multiparous women. Secondarily, specific behaviors, depending on the presence or absence or urinary incontinence (UI), were also researched. DESIGN: Case-control study. SETTING: Higher education institution. PARTICIPANTS: One hundred young women participated, divided into two groups depending on whether they had vaginal birth (nulliparous or uni/multiparous). Each group included women with and without UI. MAIN MEASURES: A muscle mechanical properties (tone, stiffness, decrement-inverse of elasticity-, and viscoelastic properties: relaxation and creep) assessment of the PF and LP muscles were performed with a hand-held tonometer. RESULTS: Tone and stiffness of both sides of the PF presented group by UI interaction (p < 0.05), with uni/multiparous women with UI showing higher tone and stiffness compared to multiparous women without UI. In LP muscles, uni/multiparous women showed greater tone and stiffness on the right and left sides [-2.57 Hz (95% confidence interval -4.42,-0.72) and -79.74 N/m (-143.52,-15.97); -2.20 Hz (-3.82,-0.58) and -81.30 N/m (-140.66-,21.95), respectively], as well as a decrease in viscoelastic properties compared to nulliparous women [relaxation: 2.88 ms (0.31,5.44); creep: 0.15 (0.01,0.30); relaxation: 2.69 ms (0.13,5.25); creep: 0.14 (0,0.28), respectively]. CONCLUSIONS: Vaginal birth and UI have a differential influence on the muscle mechanical properties of the PF and LP muscles. The determination of muscle mechanical properties by externally applied hand-held tonometry improves the knowledge of the lumbopelvic status, with applicability in clinical and research fields.

Perineural Infiltration: A Comprehensive Review of Diagnostic, Prognostic, and Therapeutic Implications.

ABSTRACT: Perineural infiltration refers to a neoplastic cell involvement in, around, and through the nerves. It is considered as one of the neoplastic dissemination pathways. Thus, its identification is crucial to establish the prognosis of some malignant skin neoplasms, such as squamous cell carcinoma, and explains the locally aggressive behavior of cutaneous neoplasms, such as microcystic adnexal carcinoma. We have conducted a review of malignant and benign skin tumors in which perineural infiltration has been described, and we also discuss some histopathological findings that may simulate perineural infiltration.

Subclinical atherosclerosis and accelerated epigenetic age mediated by inflammation: a multi-omics study.

AIMS: Epigenetic age is emerging as a personalized and accurate predictor of biological age. The aim of this article is to assess the association of subclinical atherosclerosis with accelerated epigenetic age and to investigate the underlying mechanisms mediating this association. METHODS AND RESULTS: Whole blood methylomics, transcriptomics, and plasma proteomics were obtained for 391 participants of the Progression of Early Subclinical Atherosclerosis study. Epigenetic age was calculated from methylomics data for each participant. Its divergence from chronological age is termed epigenetic age acceleration. Subclinical atherosclerosis burden was estimated by multi-territory 2D/3D vascular ultrasound and by coronary artery calcification. In healthy individuals, the presence, extension, and progression of subclinical atherosclerosis were associated with a significant acceleration of the Grim epigenetic age, a predictor of health and lifespan, regardless of traditional cardiovascular risk factors. Individuals with an accelerated Grim epigenetic age were characterized by an increased systemic inflammation and associated with a score of low-grade, chronic inflammation. Mediation analysis using transcriptomics and proteomics data revealed key pro-inflammatory pathways (IL6, Inflammasome, and IL10) and genes (IL1B, OSM, TLR5, and CD14) mediating the association between subclinical atherosclerosis and epigenetic age acceleration. CONCLUSION: The presence, extension, and progression of subclinical atherosclerosis in middle-aged asymptomatic individuals are associated with an acceleration in the Grim epigenetic age. Mediation analysis using transcriptomics and proteomics data suggests a key role of systemic inflammation in this association, reinforcing the relevance of interventions on inflammation to prevent cardiovascular disease.

"Delaying Rot Emergence in Persian Lime (Citrus×latifolia) Through Antifungal Hybrid Films Containing Litsea glaucescens Essential Oil".

Herein we describe the in situ inhibitory activity of three hybrid films (FL1, FL2, and FL3) against two wild strains of Colletotrichum gloeosporioides and Penicillium digitatum as causal agents of rot in Persian limes. The films FL2 and FL3 contained 1.0 and 1.3 % weight/volume Litsea glaucescens essential oil (LgEO) and significantly (p<0.05) delayed rot emergence in Persian limes caused by both pathogens up to 10 days. The physicochemical properties of LgEO and hybrid films were obtained, whereas detailed HPLC profiling revealed that fruit covered with these films significantly (p<0.01) preserved reducing sugars (sucrose, fructose, and glucose), organic acids (citric acid, ascorbic acid, malic acid, and oxalic acid), and flavonoids with nutraceutical activity (hesperidin, eriocitrin, naruritin, neohesperidin, diosmin, vitexin, rutin, and quercetin). This evidence sustains that the composites generated in this investigation improve the shelf life of Persian limes and conserve their nutraceutical content.

Influence of parallel pins on the angle deviation for placement of dental implants: an in vitro study.

The aim of the present study was to analyze and compare the angle deviation of two, four and six adjacent dental implants placed with and without straight parallel pins. MATERIALS AND METHODS: Two hundred and forty (240) dental implants were selected and randomly allocated into the following study groups: Two dental implants placed with straight parallel pins (Ref.: 144-100, BioHorizons, Birmingham, AL, USA) (n = 10) (2PP); Two dental implants placed without parallel pins (n = 10) (2withoutPP); Four dental implants placed with straight parallel pins hT(n = 10) (4PP); Four dental implants placed without parallel pins (n = 10) (4withoutPP); Six dental implants placed with straight parallel pins (n = 10) (6PP) and Six dental implants placed without parallel pins (n = 10) (6withoutPP). The dental implants randomly assigned to groups 2PP and 2withoutPP were placed into standardized polyurethane models of partially edentulous upper jaws in tooth positions 2.4 and 2.6, the dental implants randomly assigned to groups 4PP and 4withoutPP were placed into standardized polyurethane models of fully edentulous upper jaws in tooth positions 1.6, 1.4, 2.4 and 2.6, and the dental implants randomly assigned to groups 6PP and 6withoutPP were placed into standardized polyurethane models of fully edentulous upper jaws in tooth positions 1.6, 1.4, 1.2, 2.2, 2.4 and 2.6. Afterwards, postoperative CBCT scans and digital impressions were aligned in a 3D implant-planning software to compare the angle deviation (°) of two, four and six adjacent dental implants placed with and without straight parallel pins using the General Linear Model statistical analysis. RESULTS: Statistically significant differences were found between the angle deviation of 2 dental implants placed with straight parallel pins (p < 0.0001) and between the angle deviation of 4 dental implants placed with straight parallel pins (p = 0.0024); however, no statistically significant differences were found in the angle deviation of 6 dental implants placed with straight parallel pins (p = 0.9967). CONCLUSION: The use of a straight parallelization pin results in lower angle deviation between two and four adjacent dental implants; however, it is not effective for a larger number of dental implants.

Is EEG Entropy a Useful Measure for Alzheimer's Disease?

BACKGROUND: The number of individuals diagnosed with Alzheimer's disease (AD) has increased, and it is estimated to continue rising in the coming years. The diagnosis of this disease is challenging due to variations in onset and course, its diverse clinical manifestations, and the indications for measuring deposit biomarkers. Hence, there is a need to develop more precise and less invasive diagnostic tools. Multiple studies have considered using electroencephalography (EEG) entropy measures as an indicator of the onset and course of AD. Entropy is deemed suitable as a potential indicator based on the discovery that variations in its complexity can be associated with specific pathologies such as AD. METHODOLOGY: Following PRISMA guidelines, a literature search was conducted in 4 scientific databases, and 40 articles were analyzed after discarding and filtering. RESULTS: There is a diversity in entropy measures; however, Sample Entropy (SampEn) and Multiscale Entropy (MSE) are the most widely used (21/40). In general, it is found that when comparing patients with controls, patients exhibit lower entropy (20/40) in various areas. Findings of correlation with the level of cognitive decline are less consistent, and with neuropsychiatric symptoms (2/40) or treatment response less explored (2/40), although most studies show lower entropy with greater severity. Machine learning-based studies show good discrimination capacity. CONCLUSIONS: There is significant difficulty in comparing multiple studies due to their heterogeneity; however, changes in Multiscale Entropy (MSE) scales or a decrease in entropy levels are considered useful for determining the presence of AD and measuring its severity.

Papillary dermal elastolysis histopathology mimicking folliculotropic mycosis fungoides.

Papillary dermal elastolysis is a rare acquired disease of the elastic tissue that mainly affects elderly women with a clinical presentation of small firm papules in the neck, the supraclavicular areas and the upper back. Histopathologically, it is characteristic to find a complete or almost complete absence of elastic fibers in the papillary dermis with stains such as orcein or Verhoeff-Van Gieson. We present the case of an adult female patient presenting a clinical picture of years of evolution of elastic skin-colored papules on her neck, occasionally pruritic. Two biopsies were performed. In one of them an inflammatory infiltrate affecting the hair follicles was observed, and she was diagnosed with mycosis fungoides. The other biopsy showed a total absence of elastic fibers in the papillary dermis and was diagnosed as elastolysis of the papillary dermis. In early stages of papillary dermal elastolysis, a perivascular and periadnexal lymphocytic inflammatory infiltrate has been described, as is the case described above. It is important for dermatopathologist to know this atypical but possible presentation, as it may require a differential diagnosis with other entities such as follicular mycosis fungoides.

Median raphe cysts: A clinico-pathologic and immunohistochemical study of 52 cases.

BACKGROUND: Median raphe cysts (MRC) are epithelial-lined cystic lesions of the genital area that do not communicate with the urethra or the overlying epidermis. Immunohistochemically, MRC show positivity for cytokeratin (CK) 5-6, CK 7, carcinoembryonic antigen, p63 and uroplakin III (URO III). GATA3 and human milk fat globulin 1 (HMFG1) are immunohistochemical markers that have been not previously studied in MRC. METHODS: We conducted a study of 52 patients diagnosed with MRC in the Pathology Departments of eight hospitals between 1990 and 2016. The monoclonal antibodies used were CK5-6, CK7, CK20, URO III, p63, GATA3, and HMFG1. HMFG1 was studied in five cases of apocrine hidrocystomas and compared with five cases of MRC from our series. RESULTS: CK 5-6, CK7, and p63 expression showed strong positivity in the urothelial epithelium of 48 cases. CK20 was focally positive in areas of mucinous differentiation in three cases. GATA3 showed intense nuclear staining in 30 cases. HMFG1 was positive in three cases of MRC and in three cases of apocrine hidrocystoma. CONCLUSION: Positivity of GATA3 and CK7 in MRC supports the urothelial origin of these cysts. We found no differences in HMFG1 expression between MRC and apocrine hidrocystomas.

Reliability and Validity of the Colombian Version of the Revised Sociosexual Orientation Inventory.

Sociosexuality refers to an individual's disposition to have casual sex without establishing affective bonds and has been widely studied worldwide using the Revised Sociosexual Orientation Inventory (SOI-R; Penke & Asendorpf, 2008). Despite its many validations in different cultural contexts, no psychometric analyses of this instrument have been conducted in Spanish-speaking Latin American countries. To address this gap in the literature, we examined the psychometric properties of the SOI-R in Colombia. In a cross-sectional study with a large sample of participants (N = 812; 64% women), we conducted exploratory and confirmatory factor analyses to identify different factor structures and determine which had the best fit for our sample and examined the reliability of the scale. Results showed that a three-factor structure, with sociosexual behaviors, attitudes, and desire as first-order factors, and global sociosexuality as a second-order factor, had the best fit indexes. Each factor presented good reliability indexes. Replicating already established gender differences, we also found that men scored higher on each factor when compared to women. These findings show that the SOI-R is a reliable and valid instrument to assess sociosexuality in countries where sociosexuality research is underrepresented.

Biopsy type does not affect the number of stages during Mohs micrographic surgery: a retrospective study.

Mohs micrographic surgery (MMS) is the treatment of choice for high-risk basal cell carcinoma (BCC). However, there are no evidence-based recommendations regarding which biopsy type is more appropriate to obtain tumour samples prior to MMS. Shave or punch biopsies are performed depending on the clinical characteristics of the tumour, surgeon experience and local protocols. However, biopsy type might result in difficult histopathological interpretation and influence the practical implementation of MMS. We performed a retrospective study on 208 consecutive BCCs treated with MMS. Of the 208 BCC biopsies, 42 (20.2%) were obtained by the shave method and 166 (79.8%) via punch. Those obtained with the shave technique had a mean of 1.64 stages vs. 1.69 stages with the punch technique (P = 0.130). These findings suggest biopsy type does not affect Mohs surgery performance. The biopsy type of choice is the one deemed adequate for each specific case to obtain a diagnosis and tumour subtyping.

Cutaneous Metastasis of Alveolar Rhabdomyosarcoma in a Child.

ABSTRACT: Rhabdomyosarcoma (RMS) is one of the most common soft tissue sarcomas in children. This lesion is classically included in the generic group of "small round blue cell tumors" along with other entities that share similar microscopic features. Although the head and neck region is a frequent site for primary tumors, cutaneous metastases of RMS involving this anatomical location are rare in the pediatric population. We report a case of a 12-year old girl previously diagnosed with a primary alveolar RMS involving the left maxillary sinus, presenting with a metastatic lesion on the skin of the left temple area. Along with a brief review of the previous case reports on the topic, we highlight the initial immunohistochemistry panel useful for diagnosing this tumor.

Binding Specificity of a Novel Cyclo/Maltodextrin-Binding Protein and Its Role in the Cyclodextrin ABC Importer System from Thermoanaerobacterales.

Extracellular synthesis of functional cyclodextrins (CDs) as intermediates of starch assimilation is a convenient microbial adaptation to sequester substrates, increase the half-life of the carbon source, carry bioactive compounds, and alleviate chemical toxicity through the formation of CD-guest complexes. Bacteria encoding the four steps of the carbohydrate metabolism pathway via cyclodextrins (CM-CD) actively internalize CDs across the microbial membrane via a putative type I ATP-dependent ABC sugar importer system, MdxEFG-(X/MsmX). While the first step of the CM-CD pathway encompasses extracellular starch-active cyclomaltodextrin glucanotransferases (CGTases) to synthesize linear dextrins and CDs, it is the ABC importer system in the second step that is the critical factor in determining which molecules from the CGTase activity will be internalized by the cell. Here, structure-function relationship studies of the cyclo/maltodextrin-binding protein MdxE of the MdxEFG-MsmX importer system from Thermoanaerobacter mathranii subsp. mathranii A3 are presented. Calorimetric and fluorescence studies of recombinant MdxE using linear dextrins and CDs showed that although MdxE binds linear dextrins and CDs with high affinity, the open-to-closed conformational change is solely observed after α- and ß-CD binding, suggesting that the CM-CD pathway from Thermoanaerobacterales is exclusive for cellular internalization of these molecules. Structural analysis of MdxE coupled with docking simulations showed an overall architecture typically found in sugar-binding proteins (SBPs) that comprised two N- and C-domains linked by three small hinge regions, including the conserved aromatic triad Tyr193/Trp269/Trp378 in the C-domain and Phe87 in the N-domain involved in CD recognition and stabilization. Structural bioinformatic analysis of the entire MdxFG-MsmX importer system provided further insights into the binding, internalization, and delivery mechanisms of CDs. Hence, while the MdxE-CD complex couples to the permease subunits MdxFG to deliver the CD into the transmembrane channel, the dimerization of the cytoplasmatic promiscuous ATPase MsmX triggers active transport into the cytoplasm. This research provides the first results on a novel thermofunctional SBP and its role in the internalization of CDs in extremely thermophilic bacteria.

Multiple-Perpetrator and Solo-Offender Sexual Assaults Between Strangers: Differences and Predictive Variables.

Multiple-perpetrator rape is an under-studied topic, but there has been a recent increase in studies on the differences between multiple-perpetrator sexual offenses and the ones perpetrated by solo offenders. This study aims to have a deeper understanding of the differences between multiple-perpetrator and solo-offender sexual assaults committed by strangers, from a sample of 400 sexual aggressions reported to the Spanish police in 2010. Differences were explored on variables related to characteristics of perpetrators, the assault (approach, control, maintenance, termination, and sexual behavior), and the victims. Data were obtained from police files on sexual assaults committed around the country. Significant differences found were similar to other studies conducted in other countries and proved that multiple perpetrator assaults committed by strangers are a different subtype. Additionally, four predictive variables of multiple-perpetrator rape were identified: older age (OR = 0.943, 95% CI = [0.92, 0.97]), alcohol or drug use (OR = 2.499, 95% CI = [1.50, 4.32]), non-Spanish nationals (OR = 1.980, 95% CI = [1.14, 3.45]), and use of violence to control the victim (OR = 2.465, 95% CI = [1.03, 5.90]). The cultural and leisure characteristics of Spanish society provide facilitating opportunities for multiple-perpetrator rapes and prevention strategies should be urgently addressed.

Effect of the computer-aided static navigation technique on the accuracy of bicortical mini-implants placement site for maxillary skeletal expansion appliances: an in vitro study.

The objective of the present study was to evaluate and compare the effect of the computer-aided static navigation technique on the accuracy of the maxillary skeletal expansion (MSE) appliances. MATERIAL AND METHODS: Forty orthodontic self-drilling mini-implants were placed in ten anatomically based standardized polyurethane models of a completely edentulous upper maxilla, manufactured using a 3D impression procedure. The four orthodontic self-drilling mini-implants for anchoring the MSE appliance were digitally planned on 3D planning software, based on preoperative cone-beam computed tomography (CBCT) scan and a 3D extraoral surface scan. Afterwards, the surgical templates were virtually planned and manufactured using stereolithography. Subsequently, the orthodontic self-drilling mini-implants were placed an postoperative CBCT scans were performed. Finally, coronal entry-point, apical end-point and angular deviations were calculated using a t-test for independent samples or a non-parametric Signed Rank test. RESULTS: Statistically significant differences were not shown at coronal entry-point (p = 0.13), apical end-point (p = 0.41) and angular deviations (p = 0.27) between the planned and performed orthodontic self-drilling mini-implants. CONCLUSIONS: Computer-aided static navigation technique enables accurate orthodontic mini-implant placement for the MSE appliances.

Comparative analysis of two navigation techniques based on augmented reality technology for the orthodontic mini-implants placement.

To analyze and compare the accuracy and root contact prevalence, comparing a conventional freehand technique and two navigation techniques based on augmented reality technology for the orthodontic self-drilling mini-implants placement. Methods Two hundred and seven orthodontic self-drilling mini-implants were placed using either a conventional freehand technique (FHT) and two navigation techniques based on augmented reality technology (AR TOOTH and AR SCREWS). Accuracy across different dental sectors was also analyzed. CBCT and intraoral scans were taken both prior to and following orthodontic self-drilling mini-implants placement. The deviation angle and horizontal were then analyzed; these measurements were taken at the coronal entry point and apical endpoint between the planned and performed orthodontic self-drilling mini-implants. In addition, any complications resulting from mini-implant placement, such as spot perforations, were also analyzed across all dental sectors.Results The statistical analysis showed significant differences between study groups with regard to the coronal entry-point (p < 0.001), apical end-point(p < 0.001) and angular deviations (p < 0.001). Furthermore, statistically significant differences were shown between the orthodontic self-drilling mini-implants placement site at the coronal entry-point (p < 0.0001) and apical end-point (p < 0.001). Additionally, eight root perforations were observed in the FHT group, while there were no root perforations in the two navigation techniques based on augmented reality technology.Conclusions The navigation techniques based on augmented reality technology has an effect on the accuracy of orthodontic self-drilling mini-implants placement and results in fewer intraoperative complications, comparing to the conventional free-hand technique. The AR TOOTH augmented reality technique showed more accurate results between planned and placed orthodontic self-drilling mini-implants, comparing to the AR SCREWS and conventional free-hand techniques. The navigation techniques based on augmented reality technology showed fewer intraoperative complications, comparing to the conventional free-hand technique.

Structural Characterization of L-Galactose Dehydrogenase: An Essential Enzyme for Vitamin C Biosynthesis.

In plants, it is well-known that ascorbic acid (vitamin C) can be synthesized via multiple metabolic pathways but there is still much to be learned concerning their integration and control mechanisms. Furthermore, the structural biology of the component enzymes has been poorly exploited. Here we describe the first crystal structure for an L-galactose dehydrogenase [Spinacia oleracea GDH (SoGDH) from spinach], from the D-mannose/L-galactose (Smirnoff-Wheeler) pathway which converts L-galactose into L-galactono-1,4-lactone. The kinetic parameters for the enzyme are similar to those from its homolog from camu camu, a super-accumulator of vitamin C found in the Peruvian Amazon. Both enzymes are monomers in solution and have a pH optimum of 7, and their activity is largely unaffected by high concentrations of ascorbic acid, suggesting the absence of a feedback mechanism acting via GDH. Previous reports may have been influenced by changes of the pH of the reaction medium as a function of ascorbic acid concentration. The structure of SoGDH is dominated by a (ß/α)8 barrel closely related to aldehyde-keto reductases (AKRs). The structure bound to NAD+ shows that the lack of Arg279 justifies its preference for NAD+ over NADP+, as employed by many AKRs. This favors the oxidation reaction that ultimately leads to ascorbic acid accumulation. When compared with other AKRs, residue substitutions at the C-terminal end of the barrel (Tyr185, Tyr61, Ser59 and Asp128) can be identified to be likely determinants of substrate specificity. The present work contributes toward a more comprehensive understanding of structure-function relationships in the enzymes involved in vitamin C synthesis.