Positive selection in gamete interaction proteins in Carnivora.

The absence of robust interspecific isolation barriers among pantherines, including the iconic South American jaguar (Panthera onca), led us to study molecular evolution of typically rapidly evolving reproductive proteins within this subfamily and related groups. In this study, we delved into the evolutionary forces acting on the zona pellucida (ZP) gamete interaction protein family and the sperm-oocyte fusion protein pair IZUMO1-JUNO across the Carnivora order, distinguishing between Caniformia and Feliformia suborders and anticipating few significant diversifying changes in the Pantherinae subfamily. A chromosome-resolved jaguar genome assembly facilitated coding sequences, enabling the reconstruction of protein evolutionary histories. Examining sequence variability across more than 30 Carnivora species revealed that Feliformia exhibited significantly lower diversity compared to its sister taxa, Caniformia. Molecular evolution analyses of ZP2 and ZP3, subunits directly involved in sperm-recognition, unveiled diversifying positive selection in Feliformia, Caniformia and Pantherinae, although no significant changes were linked to sperm binding. Structural cross-linking ZP subunits, ZP4 and ZP1 exhibited lower levels or complete absence of positive selection. Notably, the fusion protein IZUMO1 displayed prominent positive selection signatures and sites in basal lineages of both Caniformia and Feliformia, extending along the Caniformia subtree but absent in Pantherinae. Conversely, JUNO did not exhibit any positive selection signatures across tested lineages and clades. Eight Caniformia-specific positive selected sites in IZUMO1 were detected within two JUNO-interaction clusters. Our findings provide for the first time insights into the evolutionary trajectories of ZP proteins and the IZUMO1-JUNO gamete interaction pair within the Carnivora order.

Development and validation of an HPLC-DAD method for the quantification of cannabigerol, cannabidiol, cannabinol and cannabichromene in human plasma and mouse matrices.

Cannabigerol, cannabidiol, cannabinol and cannabichromene are non-psychoactive phytocannabinoids, highly present in Cannabis sativa, for which numerous therapeutical applications have been described. However, additional pre-clinical and clinical data, including toxicopharmacokinetic and pharmacodynamic studies, remain required to support their use in clinical practice and new therapeutic applications. To support these studies, a new high performance liquid chromatography technique (HPLC) with diode-array detection (DAD) was developed and validated to quantify these cannabinoids in human plasma and mouse matrices. Sample extraction was accomplished by protein precipitation and double liquid-liquid extraction. Simvastatin and perampanel were used as internal standards in human and mouse matrices, respectively. Chromatographic separation was achieved in 16 min on an InfinityLab Poroshell® 120 C18 column (4.6 mm × 100 mm, 2.7 µm) at 40 °C. A mobile phase composed of water/acetonitrile was pumped with a gradient elution program at 1.0 mL min-1. The technique revealed linearity in the defined concentration ranges with a determination coefficient of over 0.99. Intra and inter-day accuracy and precision values ranged from -14.83 to 13.97% and 1.08 to 13.74%, respectively. Sample stability was assessed to ensure that handling and storage conditions did not compromise analyte concentrations in different matrices. Carry-over was absent and recoveries were over 77.31%. This technique was successfully applied for the therapeutic monitoring of cannabidiol and preliminary pre-clinical studies with cannabigerol and cannabidiol. All samples were within calibration ranges, with the exception of cannabigerol after intraperitoneal administration. This is the first HPLC-DAD technique that simultaneously quantifies cannabinoids in these biological matrices, supporting future pre-clinical and clinical investigations.

Conventional and digital maxillary occlusal record for the manufacture of complete-arch implant-supported fixed prostheses: randomized controlled clinical trial.

OBJECTIVES: To evaluate the trueness of the digital maxillary occlusal records in comparison with the conventional records for the fabrication of complete-arch implant-supported fixed prostheses. MATERIALS AND METHODS: This randomized controlled clinical trial followed the recommendations of the CONSORT statement. Twenty participants who used a mandibular interim complete-arch fixed prosthesis and conventional complete maxillary dentures were included in the study. The participants were randomized into two types of maxillary occlusal records: conventional (COR) and digital (DOR) (TRIOS; Shape A/S). After fabricating the prostheses, the distribution and number of occlusal contact points, and the time taken to obtain the maxillary occlusal record and work model were evaluated. Descriptive analysis was used to evaluate the distribution of occlusal contact points. The Wilcoxon test was employed for assessing the number of occlusal contact points, while the Mann-Whitney U test was used for the time taken to obtain the working casts and the maxillary occlusal record and occlusal adjustment times (p < 0.05). RESULTS: There was a similarity in the jaw relation recording methods regarding the distribution of occlusal contact points. There was no difference in the number of occlusal contact points between the anterior (p = 0.439) and posterior (p = 0.227) teeth. No relationship was observed between the distribution and number of occlusal contact points (COR, p = 0.288; DOR, p = 0.183). DOR required less occlusal and clinical adjustment time, on the other hand more laboratory and total workflow time than COR (p < 0.001). CONCLUSION: The DOR may be an option for obtaining the functional space necessary for the assembly of teeth in complete-arch implant-supported fixed prostheses; however, it requires more working time. CLINICAL RELEVANCE: The digital occlusal recording method can be used to assess the interocclusal space for the virtual tooth setup of a complete-arch implant-supported fixed prosthesis.

Factors associated with return of home oral fluid kits by suspected cases of measles, cohort study, London and South East of England, 2016-2018.

A testing rate for measles above 80% is required by the WHO European Region Measles Elimination strategy to verify elimination. To comply with this rate, we explored factors associated with the return of oral fluid kits (OFK) by suspected measles cases. We described the cases and conducted a mixed-effects analysis to assess the relationship between socio-demographic and public health management characteristics and the likelihood of returning an OFK to the reference laboratory. Of 3,929 cases who were sent a postal OFK, 2,513 (67%) returned the kit. Adjusting for confounding, registration with a general practitioner (GP) (aOR:1.48, 95%CI:1.23-1.76) and living in a less deprived area (aOR:1.35, 95%CI:1.04-1.74) were associated with an increased likelihood of returning the OFK. The odds of returning the OFK also increased if the HPT contacted the parents/guardians of all cases prior to sending the kit and confirmed their address (aOR:2.01, 95%CI:1.17-3.42). Cases notified by a hospital (aOR:1.94, 95%CI:1.31-2.87) or GP (aOR:1.52; 95%CI:1.06-2.16) also had higher odds of returning the OFK. HPTs may want to consider these factors when managing suspected cases of measles since this may help in increasing the testing rates to the WHO-recommended level.

Collaborative effort to catalyze the implementation of the Global Initiative for Childhood Cancer in the Central American subregion.

In Central America, childhood cancer is one of the leading causes of death. It is also a significant disease burden to health systems, with social and economic implications for families. The World Health Organization (WHO), the Executive Secretary of the Council of Ministers of Health of Central America and the Dominican Republic (SE-COMISCA), the Pan American Health Organization (PAHO), and St Jude Children's Research Hospital are working collaboratively to strengthen the health system's response to childhood cancer in Central America and the Dominican Republic. This collaboration's primary objective is to support the development of national pediatric cancer plans for each country in the subregion and improve overall survival rates and quality of care for children with cancer through a more comprehensive universal health coverage package. This collaborative effort has led to: (i) the development of childhood cancer national action plans; (ii) the launch of awareness and promotion campaigns; (iii) the design of childhood cancer educational material for children and their families; and (iv) a platform for professionals working in childhood cancer to share good practices and successful experiences. The countries of the subregion together with PAHO and St Jude Children's Research Hospital are working to develop standardized evidence-based clinical practice guidelines on childhood cancer for the region. This brief communication reports on this collaborative work.

En Centroamérica, el cáncer infantil es una de las principales causas de muerte. La enfermedad también supone una carga considerable para los sistemas de salud y tiene implicaciones sociales y económicas para las familias. La Organización Mundial de la Salud (OMS), la Secretaría Ejecutiva del Consejo de Ministros de Salud de Centroamérica y República Dominicana (SE-COMISCA), la Organización Panamericana de la Salud (OPS) y el St Jude Children's Research Hospital están trabajando conjuntamente para fortalecer la respuesta de los sistemas de salud frente al cáncer infantil en Centroamérica y República Dominicana. El objetivo principal de esta colaboración es respaldar la elaboración de un plan nacional sobre el cáncer pediátrico para cada país de la subregión y mejorar las tasas de supervivencia global y la calidad de la atención que se presta a la población infantil con cáncer mediante un programa más completo de cobertura universal de salud. Este esfuerzo de colaboración ha dado lugar a: a) la elaboración de planes de acción nacionales sobre el cáncer infantil; b) la puesta en marcha de campañas de concientización y promoción; c) el diseño de materiales educativos sobre el cáncer en la infancia para la población infantil y sus familias; y d) una plataforma para que los profesionales que trabajan en cáncer infantil intercambien buenas prácticas y experiencias exitosas. Los países de la subregión, junto con la OPS y el St Jude Children's Research Hospital, están trabajando en la elaboración para Centroamérica de unas directrices de práctica clínica sobre cáncer infantil que estén estandarizadas y basadas en la evidencia.

Na América Central, o câncer infantil é uma das principais causas de morte. O câncer também representa uma carga importante de doença para os sistemas de saúde, com implicações sociais e econômicas para as famílias. A Organização Mundial da Saúde (OMS), a Secretaria Executiva do Conselho de Ministros da Saúde da América Central e da República Dominicana (SE-COMISCA), a Organização Pan-Americana da Saúde (OPAS) e o St Jude Children's Research Hospital estão trabalhando em colaboração para fortalecer a resposta do sistema de saúde ao câncer infantil na América Central e na República Dominicana. O principal objetivo dessa colaboração é apoiar o desenvolvimento de planos nacionais para o câncer pediátrico em cada país da sub-região e melhorar as taxas gerais de sobrevida e a qualidade do atendimento a crianças com câncer por meio de um pacote mais abrangente de cobertura universal de saúde. Os resultados desse esforço colaborativo foram: a) desenvolvimento de planos de ação nacionais para o câncer infantil; b) lançamento de campanhas de conscientização e promoção; c) criação de material educativo sobre o câncer infantil para as crianças e suas famílias; e d) uma plataforma para que os profissionais que trabalham com câncer infantil compartilhem boas práticas e experiências bem-sucedidas. Os países da sub-região, juntamente com a OPAS e o St Jude Children's Research Hospital, estão trabalhando para desenvolver diretrizes regionais de prática clínica para o câncer infantil padronizadas e baseadas em evidências.

Current Drug Development Overview: Targeting Voltage-Gated Calcium Channels for the Treatment of Pain.

Voltage-gated calcium channels (VGCCs) are targeted to treat pain conditions. Since the discovery of their relation to pain processing control, they are investigated to find new strategies for better pain control. This review provides an overview of naturally based and synthetic VGCC blockers, highlighting new evidence on the development of drugs focusing on the VGCC subtypes as well as mixed targets with pre-clinical and clinical analgesic effects.

Mycobacterium tuberculosis Cell Wall Antigens Induce the Formation of Immune Complexes and the Development of Vasculitis in an Experimental Murine Model.

Tuberculosis (TB) of the central nervous system (CNS) presents high mortality due to brain damage and inflammation events. The formation and deposition of immune complexes (ICs) in the brain microvasculature during Mycobacterium tuberculosis (Mtb) infection are crucial for its pathobiology. The relevance of ICs to Mtb antigens in the pathogenesis of CNS-TB has been poorly explored. Here, we aimed to establish a murine experimental model of ICs-mediated brain vasculitis induced by cell wall antigens of Mtb. We administered a cell wall extract of the prototype pathogenic Mtb strain H37Rv to male BALB/c mice by subcutaneous and intravenous routes. Serum concentration and deposition of ICs onto blood vessels were determined by polyethylene glycol precipitation, ELISA, and immunofluorescence. Histopathological changes in the brain, lung, spleen, liver, and kidney were evaluated by hematoxylin and eosin staining. Our results evidenced that vasculitis developed in the studied tissues. High serum levels of ICs and vascular deposition were evident in the brain, lung, and kidneys early after the last cell wall antigen administration. Cell wall Mtb antigens induce strong type III hypersensitivity reactions and the development of systemic vasculitis with brain vascular changes and meningitis, supporting a role for ICs in the pathogenesis of TB.

Partially digital workflow for making complete-arch implant-supported fixed prostheses: A dental technique.

This article describes a technique for making complete-arch implant-supported fixed prostheses by using intraoral scanning and computer-aided design and computer-aided manufacturing (CAD-CAM) technology for the fabrication of a metal substructure and conventional processing for the prosthesis base. For this, a device was designed to accurately capture the position of multiple implants and the associated digitalized surgical guide, and the metal substructure was planned and milled directly in cobalt-chromium. The color of the gingiva and artificial teeth was selected by using the intraoral scanner software program, and the prosthesis base was processed conventionally. The straightforward methods used to fabricate the prostheses eliminated possible errors associated with conventional substructure casting and occlusal registration.

Device trueness in passivity and misfit of CAD-CAM frameworks: Conventional versus printed casts.

STATEMENT OF PROBLEM: Obtaining a passive and well-adapted framework is challenging when intraoral scanning edentulous arches with multiple implants. The trueness of the printed casts is unclear. PURPOSE: The purpose of this clinical study was to evaluate the trueness of frameworks made from conventional and printed casts regarding clinical passivity and misfit. MATERIAL AND METHODS: Ten participants with complete mandibular fixed implant-supported interim prostheses retained by 4 implants were included. Each participant had a conventional impression and a digital scan made. The digital scan was made using an innovative device. Both conventional and digital casts were made, and the virtual images were used for milling the digital framework in cobalt chromium alloy. All frameworks were evaluated for passivity and marginal vertical misfit with the single screw test, with 4 attempts consisting of the tightened screw position, a test with all screws tightened, and an interspersed tightening test. The Kruskal-Wallis test was used to evaluate the trueness of the tested device for framework construction through the single screw test on vertical marginal misfit in the conventional and printed groups (α=.008). The Friedman test was used to assess the effect of test type (α=.05), and the Wilcoxon test was used to identify group-to-group differences (α=.017). RESULTS: The absence of space between the framework and the abutments and interferences during its placement, as well as good stability, were observed clinically. In laboratory analysis, greater framework misfits were observed in the printed group compared with the conventional group when the single screw test was applied. Comparing the 3 tests used, the greatest misfits were observed when the framework was screwed onto the printed cast. CONCLUSIONS: The innovative device tested for the intraoral scanning of multiple implants had clinically acceptable accuracy for the construction of passive and adapted frameworks. The conventional cast was more accurate than the printed cast, with lower misfit values, in all tests.

Incidence of opioid-induced esophageal dysfunction.

BACKGROUND: Retrospective studies have suggested that long-term use of opioids can cause esophageal motility dysfunction. A recent clinical entity known as opioid-induced esophageal dysfunction (OIED) has been postulated. There is no data from prospective studies assessing the incidence of opioid-induced effects on the esophagus. AIM: Evaluate the incidence of OIED during chronic opioid therapy. METHODS: From February 2017 to August 2018, all patients seen in the Pain Unit of the hospital, who started opioid treatment for chronic non-neoplastic pain and who did not present esophageal symptoms previously, were included. The presence of esophageal symptoms was assessed using the Eckardt score after 3 months and 1 year since the start of the study. In February 2021, the clinical records of all included patients were reviewed to assess whether esophageal symptoms were present and whether opioid therapy was continued. In patients presenting with esophageal symptoms, an endoscopy was performed and, if normal, a high-resolution esophageal manometry was performed. For a confidence level of 95%, a 4% margin of error and an estimated prevalence of 4%, a sample size of 92 patients was calculated. RESULTS: 100 patients were included and followed while taking opioids, for a median of 31 months with a range between 4 and 48 months. Three women presented with dysphagia during the first 3 months of treatment, being diagnosed with esophagogastric junction outflow obstruction; type II and type III achalasia. The cumulative incidence of OIED was 3%; 95%-CI: 0-6%. CONCLUSIONS: Chronic opioid therapy in patients with chronic non-neoplastic pain is associated with symptomatic esophageal dysfunction.

Accuracy and reproducibility of real and virtual occlusal contact points in implant-supported fixed prostheses.

AIM: To evaluate the accuracy and reproducibility of real and virtual occlusal contact points in implant-supported, fixed complete dentures. MATERIALS AND METHODS: The study included 19 participants using mandibular interim complete-arch fixed prosthesis supported by 3 or 4 implants as opposed to conventional removable complete dentures. At installation, an examiner installed the prostheses and verified the occlusal contact points through 2 methods: recording the real contact points with carbon paper (RC) followed by occlusal photography and intraoral scanning (VC) to record the virtual contact points to obtain a screen print of the software. Then, the two images were randomized to determine the order to be inserted into Microsoft PowerPoint for blind and paired evaluation. The independent variables consisted of the distribution of occlusal contacts points (qualification through pre-defined scores based on the position of the contact points on the surfaces of the teeth) and the reproducibility of the methods by verifying the number of occlusal points. For this, a descriptive analysis was used to evaluate the distribution of occlusal contacts points and the Wilcoxon test for the reproducibility of the occlusal contact points between the methods (p<0.05). RESULTS: The methods had 100% and 73.6% real and virtual occlusal contact points, respectively, which is considered clinically excellent. There was no significant difference regarding the reproducibility of the methods by the number of occlusal contact points (RC: x̅13.32; VC: x̅13.68; p=0.715). CONCLUSION: The use of the tested intraoral scanner can be an easy and fast tool for studying and mapping the occlusion, and storing data for future treatment, with the conventional method being the preferred method for performing the occlusal adjustment.

Rs1h-/y exon 3-del rat model of X-linked retinoschisis with early onset and rapid phenotype is rescued by RS1 supplementation.

Animal models of X-linked juvenile retinoschisis (XLRS) are valuable tools for understanding basic biochemical function of retinoschisin (RS1) protein and to investigate outcomes of preclinical efficacy and toxicity studies. In order to work with an eye larger than mouse, we generated and characterized an Rs1h-/y knockout rat model created by removing exon 3. This rat model expresses no normal RS1 protein. The model shares features of an early onset and more severe phenotype of human XLRS. The morphologic pathology includes schisis cavities at postnatal day 15 (p15), photoreceptors that are misplaced into the subretinal space and OPL, and a reduction of photoreceptor cell numbers by p21. By 6 mo age only 1-3 rows of photoreceptors nuclei remain, and the inner/outer segment layers and the OPL shows major changes. Electroretinogram recordings show functional loss with considerable reduction of both the a-wave and b-wave by p28, indicating early age loss and dysfunction of photoreceptors. The ratio of b-/a-wave amplitudes indicates impaired synaptic transmission to bipolar cells in addition. Supplementing the Rs1h-/y exon3-del retina with normal human RS1 protein using AAV8-RS1 delivery improved the retinal structure. This Rs1h-/y rat model provides a further tool to explore underlying mechanisms of XLRS pathology and to evaluate therapeutic intervention for the XLRS condition.

Workplace exposures associated with COVID-19: evidence from a case-control study with multiple sampling periods in England, August-October 2020.

We investigated risk factors associated with COVID-19 by conducting a retrospective, frequency-matched case-control study, with three sampling periods (August-October 2020). We compared cases completing routine contact tracing to asymptomatic population controls. Multivariable analyses estimated adjusted odds ratios (aORs) for non-household community settings. Meta-analyses using random effects provided pooled odds ratios (pORs). Working in healthcare (pOR 2.87; aORs 2.72, 2.81, 3.08, for study periods 1-3 respectively), social care (pOR 4.15; aORs 2.46, 5.06, 5.41, for study periods 1-3 respectively) or hospitality (pOR 2.36; aORs 2.01, 2.54, 2.63, for study periods 1-3 respectively) were associated with increased odds of being a COVID-19 case. Additionally, working in bars, pubs and restaurants, warehouse settings, construction, educational settings were significantly associated. While definitively determining where transmission occurs is impossible, we provide evidence that in certain sectors, the impact of mitigation measures may only be partial and reinforcement of measures should be considered in these settings.

Evaluation design of the patient-centred pathways of early palliative care, supportive ecosystems and appraisal standard (InAdvance): a randomised controlled trial.

BACKGROUND: Palliative care aims to contribute to pain relief, improvement with regard to symptoms and enhancement of health-related quality of life (HRQoL) of patients with chronic conditions. Most of the palliative care protocols, programmes and units are predominantly focused on patients with cancer and their specific needs. Patients with non-cancer chronic conditions may also have significantly impaired HRQoL and poor survival, but do not yet receive appropriate and holistic care. The traditional focus of palliative care has been at the end-of-life stages instead of the relatively early phases of serious chronic conditions. The 'Patient-centred pathways of early palliative care, supportive ecosystems and appraisal standard' (InAdvance) project implements and evaluates early palliative care in the daily clinical routine addressing patients with complex chronic conditions in the evolution towards advanced stages. The objective of the current study is to evaluate the acceptability, feasibility, effectiveness and cost-effectiveness of this novel model of palliative care in the relatively early phases in patients with chronic conditions. METHODS: In this study, a single blind randomised controlled trial design will be employed. A total of 320 participants (80 in each study site and 4 sites in total) will be randomised on a 1:1 basis to the Palliative Care Needs Assessment (PCNA) arm or the Care-as-Usual arm. This study includes a formative evaluation approach as well as a cost-effectiveness analysis with a within-trial horizon. Study outcomes will be assessed at baseline, 6 weeks, 6 months, 12 months and 18 months after the implementation of the interventions. Study outcomes include HRQoL, intensity of symptoms, functional status, emotional distress, caregiving burden, perceived quality of care, adherence to treatment, feasibility, acceptability, and appropriateness of the intervention, intervention costs, other healthcare costs and informal care costs. DISCUSSION: The InAdvance project will evaluate the effect of the implementation of the PCNA intervention on the target population in terms of effectiveness and cost-effectiveness in four European settings. The evidence of the project will provide step-wise guidance to contribute an increased evidence base for policy recommendations and clinical guidelines, in an effort to augment the supportive ecosystem for palliative care. TRIAL REGISTRATION: ISRCTN, ISRCTN24825698 . Registered 17/12/2020.

Enhancing epidemiological surveillance of the emergence of the SARS-CoV-2 Omicron variant using spike gene target failure data, England, 15 November to 31 December 2021.

When SARS-CoV-2 Omicron emerged in 2021, S gene target failure enabled differentiation between Omicron and the dominant Delta variant. In England, where S gene target surveillance (SGTS) was already established, this led to rapid identification (within ca 3 days of sample collection) of possible Omicron cases, alongside real-time surveillance and modelling of Omicron growth. SGTS was key to public health action (including case identification and incident management), and we share applied insights on how and when to use SGTS.

Mycobacterium tuberculosis Infection Induces BCSFB Disruption but No BBB Disruption In Vivo: Implications in the Pathophysiology of Tuberculous Meningitis.

Central nervous system (CNS) tuberculosis is the most lethal and devastating form among the diseases caused by Mycobacterium tuberculosis. The mechanisms by which M. tuberculosis bacilli enter the CNS are still unclear. However, the BBB and the BCSFB have been proposed as possible routes of access into the brain. We previously reported that certain strains of M. tuberculosis possess an enhanced ability to cause secondary CNS infection in a mouse model of progressive pulmonary tuberculosis. Here, we evaluated the morphostructural and molecular integrity of CNS barriers. For this purpose, we analyzed through transmission electron microscopy the ultrastructure of brain parenchymal microvessels and choroid plexus epithelium from animals infected with two mycobacterial strains. Additionally, we determined the expression of junctional proteins and cytokines by immunological techniques. The results showed that the presence of M. tuberculosis induced disruption of the BCSFB but no disruption of the BBB, and that the severity of such damage was related to the strain used, suggesting that variations in the ability to cause CNS disease among distinct strains of bacteria may also be linked to their capacity to cause direct or indirect disruption of these barriers. Understanding the pathophysiological mechanisms involved in CNS tuberculosis may facilitate the establishment of new biomarkers and therapeutic targets.

Trueness of a device for intraoral scanning to capture the angle and distance between implants in edentulous mandibular arches.

STATEMENT OF PROBLEM: The digitalization of completely edentulous arches presents limitations because of the lack of anatomic structures for best-fit alignment during the image generation process of the scanner's software program. PURPOSE: The purpose of this clinical study was to evaluate a new device for intraoral scanning and to analyze its usefulness in capturing the 3-dimensional (3D) position of implants in edentulous mandibular arches. MATERIAL AND METHODS: The 3D positions of 40 implants in 10 participants with fixed interim mandibular prostheses were evaluated by comparing 3 scanning techniques. Images were generated in 2 experimental groups, with digital scan bodies (group SC) and with the scanning device (group SD) and in a control group (group CT) in which images were obtained by laboratory scanning of casts produced from splinted impression copings. The standard tessellation language (STL) files were superimposed by using a reverse engineering software program to measure the 3D coordinate system. Variations in implant linear displacements (Δx, Δy, and Δz), total 3D displacement (Δx2+Δy2+Δz2), and angle projections (ΔθXY, ΔθXZ, and ΔθYZ) were statistically analyzed (α=.05). The distances between the implants were also measured. The Spearman correlation coefficient (α=.05) was used to find the correlation between the 3D coordinates and the distances between the implants. RESULTS: Group SD had lower values for linear displacement than group SC; however, this difference was not statistically significant except for implant #2. The overall evaluation showed a significant difference with better accuracy for group SD. Concerning angular displacements, group SD showed lesser angular variation for the 3 projection planes. For the distances between the implants, significant differences were only observed for the "all" assessment in which group SD behaved similarly to group CT, while group SC showed the highest values (P<.05). No correlation was detected between the axes (x, y, and z) and the distances between the implants. CONCLUSIONS: The evaluated scanning device led to improved trueness for linear, angular displacements, and distances between implants in mandibular edentulous arches.

A systematic review and meta-analysis of the effectiveness and adverse events of gabapentin and pregabalin for sciatica pain.

AIM: This SR aims to assess the effectiveness of pregabalin and gabapentin on pain and disability caused by acute sciatica and the adverse events associated with their clinical use. DESIGN: Systematic review. DATABASES: Electronic databases of Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Clinical Trials.gov were searched from their inception until March 1st of 2021. SELECTION CRITERIA: Randomized trials (RCT) with adults>18 years old with acute sciatica for a minimum of 1 week and a maximum of 1 year (at least moderate pain). DATA TREATMENT: The outcomes were pain, disability and adverse events. Data was summarized using odds ratio and mean difference. GRADE was used to calculate the level of evidence. RESULTS: Eight RCT involving 747 participants were included. The effect of pregabalin was assessed in 3 RCT and in one three-arm trial (pregabalin vs limaprost vs a combination of limaprost and pregabalin). Two trials assessed the effect of gabapentin compared with placebo and one compared with tramadol. One study assessed the effect of gabapentin vs pregabalin in a crossover head-to-head trial. A statistically significant improvement on leg pain at 2 weeks and leg pain with movement at 3 and 4 months was found in a RCT comparing gabapentin with placebo. There were no statistically differences on the remaining time periods assessed for leg pain, low back pain and functional disability. CONCLUSIONS: This SR provides clear evidence for lack of effectiveness of pregabalin and gabapentin for sciatica pain management. In view of this, its routine clinical use cannot be supported.

Association between polymorphisms in the vitamin D receptor and susceptibility to multiple sclerosis.

OBJECTIVES: Multiple sclerosis (MS) is a neurodegenerative chronic inflammatory. Mutations in the vitamin D receptor (VDR) gene can substantially affect serum vitamin D levels or alter its functionality, and can consequently increase susceptibility to developing MS. The objective of this study was to evaluate the association between polymorphisms in the VDR gene and risk of MS in a (Spanish) Caucasian population. PATIENTS AND METHODS: We conducted a retrospective case-control study comprising 209 patients with relapsing-remitting multiple sclerosis (RRMS) and 836 controls of Caucasian origin from southern Spain. The ApaI (rs7975232), BsmI (rs1544410), Cdx2 (rs11568820), FokI (rs2228570), and TaqI (rs731236) gene polymorphisms were determined by allelic discrimination real-time PCR using TaqMan probes. RESULTS: The recessive logical regression model, adjusted for age and sex, revealed that the TT genotype for VDR FokI (rs2228570) polymorphism was associated with higher risk of MS (P = 0.0150; OR = 1.82; 95% CI = 1.12-2.94; TT vs. CT + CC). No association between the other polymorphisms and development of MS was found in any of the models analyzed. The haplotype analysis, adjusted for age, smoking, and sex, did not find any statistically significant association between the haplotypes analyzed and risk of MS. CONCLUSIONS: The VDR FokI (rs2228570) polymorphism was significantly associated with developing MS. We found no influence of the ApaI (rs7975232), BsmI (rs1544410), Cdx2 (rs11568820), FokI (rs2228570), and TaqI (rs731236) gene polymorphisms on the risk of developing MS in our patients.

Oral submucous fibrosis presenting with histopathological lichenoid changes as predominant feature: Report of five cases and review of the literature.

Oral submucous fibrosis (OSF) is a precancerous condition of the oral cavity associated with habitual chewing of quid, with a high incidence among populations of the Indian subcontinent and Southeast Asia. Clinically, its initial manifestation may mimic oral lichen planus or lichen sclerosus. If the habit is not halted, the mucosa gets leathery and thickened, and fibrous bands form causing significant morbidity. Microscopically, it is characterized by atrophic epithelium, loss of rete ridges, and hyalinization of lamina propria. Of note, these hallmark histopathological features may be overlooked in the unusual presence of lichenoid interface changes, which may lead to the wrong diagnosis. We present herein five cases in which the rare joint appearance of OSF and lichenoid reaction features posed a diagnostic challenge. Due to its progressive nature and malignant potential, the presence of oral lichenoid changes overlying submucous hyalinization, in the right clinical and demographic setting, should raise suspicion of OSF and prompt actions directed at quid-chewing discontinuation.