SARS-CoV-2 Spike Protein Enhances Carboxypeptidase Activity of Angiotensin-Converting Enzyme 2.

In this study, we investigated whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein may modify angiotensin-converting enzyme 2 (ACE2) activity in the plasma, heart, kidney, liver, lung, and six brain regions (amygdala, brain stem, cortex, hippocampus, hypothalamus, and striatum) of diabetic and hypertensive rats. We determine ACE2 activity in the plasma and lysates of heart, kidney, liver, lung, and six brain regions. MLN-4760 inhibits ACE2 activity in the plasma and all organs. On the other hand, soluble ACE2 (sACE2) activity increased in the plasma of diabetic rats, and there was no change in the plasma of hypertensive rats. ACE2 activity was augmented in the liver, brain stem, and striatum, while it decreased in the kidney, amygdala, cortex, and hippocampus of diabetic rats. ACE2 activity increased in the kidney, liver, and lung, while it decreased in the heart, amygdala, cortex, and hypothalamus of hypertensive rats. We measured the ACE2 content via enzyme-linked immunosorbent assay and found that ACE2 protein levels increased in the heart, while it decreased in the plasma, kidney, brain stem, cortex, hippocampus, hypothalamus, and striatum of diabetic rats. ACE2 protein levels decreased in the brain stem, cortex, hippocampus, and hypothalamus of hypertensive rats. Our data showed that the spike protein enhanced ACE2 activity in the liver and lungs of diabetic rats, as well as in the heart and three of the brain regions (cortex, hypothalamus, and striatum) of hypertensive rats.

A reinterpretation of human breast anatomy includes all the layers of the anterior body wall.

Mammary glands define mammals as a group, yet a comprehensive anatomical description of the mammary gland does not exist for almost any mammalian species. In humans, the anatomical and surgical literature provide conflicting and incomplete descriptions of the gross anatomy of the breast. We dissected 9 male and 15 female human body donors to clarify this gross anatomy. We found that, like other epidermally derived glands of the body, the mammary glandular tissue is constrained to a membrane-bound, central structure referred to as the corpus mammae in the surgical literature, and not dispersed throughout the breast as typically described in the anatomical literature. The major fasciae of the human anterior body wall, including the superficial fatty Camper's fascia and the deeper membranous Scarpa's fascia, both contribute to the structure of the breast. This anatomical arrangement suggests that, as the mammary gland invaginates posteriorly from the integument during embryological development, the mammary fat pad most likely derives from Camper's fascia, and growth of Scarpa's fascia around this fat pad forms the anterior and posterior lamellae of the breast pocket. Anteriorly, Scarpa's fascia becomes a double layer that creates the surface structure of the breast. Posteriorly, Scarpa's fascia forms a circummammary ligament that (1) stabilizes the breast against the thoracic wall and (2) is continuous with Scarpa's fascia on the rest of the anterior body wall. The suspensory ligaments of the breast represent the typical retinaculae cuti found consistently throughout the human body wall, and do not directly attach to the skin. Instead, these retinaculae attach to the anterior or posterior lamella of Scarpa's fascia.

Pericervical Dentin Metrics in Mandibular First Molars Determined with Digital Periapical Radiography and Cone-beam Computed Tomography.

INTRODUCTION: Pericervical root dentin is decisive for the long-term mechanical integrity of root-filled teeth. Current treatment protocol does not include a customized step to determine the pretreatment residual pericervical root dentin. OBJECTIVE: To determine and compare the residual root dentin and canal width using digital periapical radiography (DPR) and cone-beam computed tomography (CBCT) at the apical limit of the pericervical area (PCA) in mandibular first molars. METHODS: DPR and CBCT images of 60 patients with age between 22 and 76 years were used to determine (a) the mesiodistal widths of the root canal (pericervical dimensions [PCL]-C) and the root (PCL-R) of mandibular first molars at the apical limit of the PCA and (b) the intracanal distance from the apical limit of the PCA to the radiographic apex (intracanal distance [ICD]). The correlation between the PCL and ICD measurements obtained from DPR and CBCT were evaluated. RESULTS: Values between 0.10-0.80 mm and 0.00-1.10 mm were obtained for PCL-C using DPR and CBCT respectively (95% CI). The PCL values between 0.90-2.30 mm and 0.00-2.30 mm were obtained from DPR and CBCT respectively (95% CI). The ICD ranged between 4.6-12.3 mm in DPR and 4.40-12.0 mm in CBCT (95% CI). The comparative analysis showed differences from -0.9 to 0.5 mms for PCL and -2.00 to 1.5 mms for ICD between DPR and CBCT techniques respectively. CONCLUSION: The PCL and ICD determined from DPR and CBCT provided the pericervical dentin metrics that could be utilized clinically as a guideline for decision-making in endodontic treatment.

Allogeneic Bone Marrow Mesenchymal Stromal Cell Transplantation Induces Dentin Pulp Complex-like Formation in Immature Teeth with Pulp Necrosis and Apical Periodontitis.

INTRODUCTION: Dental pulp regeneration is challenging in endodontics. Cellular therapy is an alternative approach to induce dental pulp regeneration. Mesenchymal stromal cells (MSCs) have the capacity to induce dental pulp-like tissue formation. In this study, we evaluated the capacity of allogeneic bone marrow MSCs (BM-MSCs) to regenerate pulp following necrosis and apical periodontitis in children's permanent immature apex teeth. METHODS: Patients aged 8 to 12 years with pulp necrosis and apical periodontitis were evaluated. The study included 15 teeth (13 incisors and 2 molars) from 14 patients (8 boys and 6 girls). Radiographic evaluation showed periapical radiolucency and immature apex teeth. There was no response to cold or electric pulp testing. The root canal of each tooth was cleaned, shaped, and Ca(OH)2 used as an interappointment medication. Cryopreserved allogeneic BM-MSCs were thawed, expanded, incorporated into preclotted platelet-rich plasma, and implanted into the tooth's pulp cavity. They were sealed with bioceramic cement and composite. Sensibility, apical foramen, calcium deposits within the root canal, and resolution of periapical lesions were evaluated in each tooth over the following 12 months. RESULTS: Based on 9 variables established for dental pulp-like tissue regeneration, all MSC-treated teeth showed evidence of successful regeneration. Clinical and radiographic evaluation of the treated teeth showed periapical lesion healing, sensitivity to cold and electricity, decreased width of the apical foramen, and mineralization within the canal space. CONCLUSIONS: Transplantation of allogeneic MSCs induces the formation of dental pulp-like tissue in permanent immature apex teeth with pulp necrosis and apical periodontitis. Implant of MSCs constitutes a potential therapy in regenerative endodontics in pediatric dentistry. Future studies incorporating a larger sample size may confirm these results.

Substance P/calcitonin gene-related peptide and their receptors expression in human periodontal ligament after root canal preparation with five different systems.

AIM: The purpose of this study was to quantify the effect of five different root canal preparation instruments on Substance P (SP), Calcitonin gene-related peptide (CGRP) and their receptors expression in healthy human periodontal ligament. METHODOLOGY: STROBE guidelines were used to design a study using 60 periodontal ligament samples obtained from healthy lower premolars where extraction was indicated for orthodontic reasons. Prior to extraction 40 of these premolars were equally divided into four groups and root canals were prepared using different systems: Mtwo, Reciproc Blue, HyFlex EDM and Plex-V. Ten premolars were prepared with hand files and served as a positive control group. The remaining 10 premolars where extracted without treatment and served as a negative control group. All periodontal ligament samples were processed to measure the expression of SP, CGRP and their receptors by radioimmunoassay. Kruskal-Wallis and Duncan tests were performed to determine statistically significant differences between the groups for each variable. RESULTS: Greater expression of all the peptides measured were found in the hand-file preparation group, followed by the Reciproc Blue, Mtwo, HyFlex EDM and Plex-V groups. The lower SP, CGRP and their receptors values were for the intact teeth control group. Kruskal-Wallis test showed statistically significant differences amongst groups (p < .001). Dunn post-hoc tests showed statistically significant differences in SP, CGRP and their receptors expression between the intact teeth and the hand-file and Reciproc Blue groups. Hand-file group showed significant differences with the other groups, except with Reciproc Blue, where no differences were observed in any of the peptides measured. Finally, no differences were observed between Plex-V and HyFlex in any of the peptides measured. CONCLUSIONS: Root canal preparation with hand files and Reciproc Blue generates the highest expression of SP, CGRP, NK1 and CGRP1R in human periodontal ligament, whilst Plex-V and HyFlex maintain the basal expression of neuropeptides and their receptors. Mtwo showed intermediate results between Reciproc Blue and HyFlex.

Immunolocalization of Sphingolipid Catabolism Enzymes along the Nephron: Novel Early Urinary Biomarkers of Renal Damage.

The objective of this study was to investigate whether the activity of enzymes involved in sphingolipid catabolism could be biomarkers to predict early renal damage in streptozotocin (STZ)-induced diabetic rats and Angiotensin II (Ang II)-induced hypertension rats. Diabetic and hypertensive rats had no changes in plasma creatinine concentration. However, transmission electron microscopy (TEM) analysis showed slight ultrastructural changes in the glomeruli and tubular epithelial cells from diabetic and hypertensive rats. Our results show that the acid sphingomyelinase (aSMase) and neutral sphingomyelinase (nSMase) activity increased in the urine of diabetic rats and decreased in hypertensive rats. Only neutral ceramidase (nCDase) activity increased in the urine of diabetic rats. Furthermore, the immunofluorescence demonstrated positive staining for the nSMase, nCDase, and sphingosine kinase (SphK1) in glomerular mesangial cells, proximal tubule, ascending thin limb of the loop of Henle, thick ascending limb of Henle's loop, and principal cells of the collecting duct in the kidney. In conclusion, our results suggest that aSMase and nCDase activity in urine could be a novel predictor of early slight ultrastructural changes in the nephron, aSMase and nCDase as glomerular injury biomarkers, and nSMase as a tubular injury biomarker in diabetic and hypertensive rats.

Oral lactoferrin administration does not impact the diversity or composition of the infant gut microbiota in a Peruvian cohort.

IMPORTANCE: Previous studies have suggested that oral lactoferrin enhances diversity in the gut microbiota in infants while inhibiting the growth of opportunistic pathogens. However, the effect of lactoferrin on infant gut microbiota over time has yet to be thoroughly studied. Our study suggests that lactoferrin oral treatment in infants aged 12-18 months does not affect gut microbiome diversity and composition over time. To our knowledge, this is the first study to report the effect of lactoferrin on infant gut microbiome composition over time and helps elucidate its impact on infant health and its therapeutic potential.

Effectiveness, efficiency, and apical extrusion of 2 rotaries and 2 reciprocating systems in removing filling material during endodontic retreatment. A systematic review.

Background: This systematic review investigated the effectiveness, efficiency and apical extrusion of the debris of two rotary and two reciprocating single-file systems used for the removal of filling material from straight root canals. Material and Methods: A literature search was performed in the Medline, ISI Web of Science, and Scopus databases for relevant articles matching the keyword search strategy. Effectiveness was determined with studies dealing with the ability of the instruments to remove filling material from root canals. Efficiency was assessed with studies dealing with the time needed to completely remove the root canal filling, and apical extrusion was determined with studies that measured the amount of filling material extruded through the apex. Results: From the 424 articles initially found, 406 were excluded for being non-relevant or not fulfilling the selection criteria. Another 9 articles were excluded after methodology evaluation. Finally, 9 studies were included in the systematic review. Conclusions: None of the reviewed systems is effective to completely remove the filling materials from straight root canals, and all systems appear to be equally time-efficient, although this variable shows different results. In terms of apical extrusion, the analyzed reciprocating systems extrude more material toward the periapical tissues than the continuous rotation systems. Key words:Systematic review, rotary files, reciprocating files, apical extrusion, endodontic retreatment.

Criterios sobre la dimensión Contenidos del programa Filosofía, Ciencia y Salud, según residentes / Criteria for the Contents dimension of the Philosophy, Science and Health program, according to residents

Fundamento: el perfeccionamiento constante de la superación de los egresados de la universidad médica exige el constante análisis de los programas de formación en el posgrado y la especialización. Objetivo: valorar la dimensión Contenidos del programa Filosofía, Ciencia y Salud según criterios de residentes de especialidades de las ciencias médicas. Métodos: se realizó una investigación en la Universidad de Ciencias Médicas de Villa Clara entre diciembre 2018-2020. Se utilizaron métodos teóricos: análisis-síntesis, histórico-lógico e inducción-deducción; empíricos: cuestionario para obtener criterios de los residentes acerca de los aspectos relacionados con la dimensión Contenidos del programa, para sus recomendaciones y modificaciones. Resultados: en las valoraciones emitidas por los residentes destacaron la preferencia de la mayoría por mantener la asignatura como está conformada según sus temas y tiempo de impartición, respecto a los contenidos recibidos, el indicador Interés obtuvo las más altas cifras, entre ellos, la Bioética sobresalió como la mejor valorada en los tres indicadores propuestos, entre los cuales la Asequibilidad fue la de menor puntuación. Los datos revelaron consenso sobre mantener la distribución del fondo de tiempo por temas y las formas organizativas de la enseñanza como se ofrecen en el programa, y la mayoría reconoció que es novedoso. Conclusiones: se valoró la dimensión Contenidos del programa Filosofía, Ciencia y Salud para residentes de especialidades de las ciencias médicas, de donde emergieron modificaciones para perfeccionar su metodología y alcance educativo-cultural.

Background: the steady improvement of the upgrading of the graduates of the medical university requires the constant analysis of the training programs in the postgraduate and specialization. Objectives: to assess the Contents dimension of the Philosophy, Science and Health program according to the criteria of residents of medical sciences specialties. Methods: an investigation was carried out at the Villa Clara University of Medical Sciences from December 2018 to 2020. Theoretical methods were used: analysis-synthesis, historical-logical and induction-deduction; Empirical: questionnaire to obtain criteria from residents about aspects related to the content dimension of the program, for their recommendations and modifications. Results: in the evaluations issued by the residents, the preference of the majority to maintain the subject as it is made up according to its topics and teaching time, regarding the contents received, the Interest indicator obtained the highest figures, among them, Bioethics. Stood out as the best valued in the three proposed indicators, among which Affordability was the one with the lowest score. The data revealed a consensus on maintaining the distribution of the time fund by subject and the organizational forms of teaching as offered in the program, and most recognized that it is novel. Conclusions: the Contents dimension of the Philosophy, Science and Health program for residents of medical sciences specialties was evaluated, from which modifications emerged to improve its methodology and educational-cultural scope.

The effect of orthodontic forces on calcitonin gene-related peptide (CGRP) expression in the human periodontal ligament and its relationship with the human dental pulp.

Background: The purpose of this study was to quantify the effect of moderate and severe orthodontic forces on Calcitonin gene-related peptide (CGRP) expression in the healthy human periodontal ligament (PDL) and its possible relationship with the human dental pulp. Material and Methods: Ninety human periodontal ligament samples were obtained from healthy premolars where extraction was indicated for orthodontic reasons. Prior to extraction, teeth were divided in 3 groups of 30 samples each: I) Untreated teeth control group; II) Moderate force group: A 56 g force was applied to the premolars for 24 hours; and III) Severe force group: A 224 g force was applied to the premolars for 7 days. All periodontal ligament samples were processed and CGRP was measured by radioimmunoassay. Results: Greater CGRP expression was found in the severe force group, followed by the moderate force group. The lower CGRP values were for the untreated teeth. Kruskal-Wallis test showed statistically significant differences between groups (p<0.001). LSD post hoc tests showed statistically significant differences in CGRP expression between the untreated teeth and the severe forces group (p<0.001). Differences between the moderate and severe force groups were statistically significant (p<0.001). There was no statistically significant differences between the untreated teeth and the moderate forces group (p<0.261). Conclusions: CGRP expression in human periodontal ligament increases when teeth are submitted to severe orthodontic forces. This elevated expression of CGRP, which is proportional to the applied force, may affect the way the dental pulp responds to different stimuli from the orthodontic forces. Key words:Calcitonin gene-related peptide, orthodontic force, human periodontal ligament, neurogenic inflammation.

Temporal trends in anticoagulation management for US active duty personnel with atrial fibrillation.

ObjectivesThis study aims to investigate US active duty (AD) military members diagnosed with atrial fibrillation (AF) and the temporal trends of systemic anticoagulation (AC). Our secondary objective is to study the AC prescriptions in AD military members diagnosed with AF and associated military dispositions and deployment rates. DESIGN AND SETTING: A retrospective investigation of Tricare pharmacy AC prescriptions within the San Antonio Military Health System from January 2004 to July 2019 for AD individuals diagnosed with AF was performed. PARTICIPANTS: 386 AD personnel with non-valvular AF were analysed (mean age 35.0±9.4 years; mean body mass index, 28.3±4.3 kg/m2; 93% male; 57% Caucasian, 94% paroxysmal AF). OUTCOMES: The temporal trends of systemic AC prescriptions were the primary outcome measures. The association between AC prescriptions and military dispositions and deployments were secondary outcomes of interest. STATISTICAL ANALYSIS: The association between AC management, future deployments and military disposition was analysed using χ2 and Fisher's exact test for categorical variables. The t-test was used for comparison of continuous variables. RESULTS: CHA2DS2-VASc and HAS-BLED scores were low (0.39±0.65 and 0.86±0.63, respectively). 127 (33%) members received warfarin and 58 (15%) received direct oral anticoagulants (DOACs). Rates of military retention were not different between AC histories (no AC (64%) vs warfarin (75%) vs DOAC (65%); p=0.425). There was a significant trend of more recent utilisation of DOACs compared with warfarin (p<0.0001). When adjusted for temporal changes in deployment rates, there was no significant difference in deployment between AC groups (no AC (39%) vs warfarin (49%) vs DOAC (27%); p=0.9472). CONCLUSIONS: This is the first report describing AC utilisation in US AD military members with AF. Young AD personnel with low stroke and bleeding risks do not commonly receive AC prescriptions. DOAC prescription rates are increasing and predominate over warfarin for AC indications.

In Vitro Comparison of MTA and BC RRM-Fast Set Putty as Retrograde Filling Materials.

OBJECTIVE: To compare, in vitro, the bioceramic materials (MTA and BC RRM-fast set putty) capacity to prevent microleakage of Enterococcus faecalis over time. METHODS: An experimental design was made with forty extracted human teeth, coronally cut, and prepared to be placed in a leakage system under sterile conditions. They were randomly divided into two experimental groups: thirty teeth (fifteen for each of retrograde filling material MTA and BC RRM-fast set putty) and a control group: ten teeth (five positive control, five negative control). The 3 mm root-ends were submerged in a brain-heart infusion broth with a red phenol indicator. The coronal access of each sample was inoculated with E. faecalis every seven days to maintain bacterial viability. The lower chamber was evaluated daily for 30 days to observe the turbidity of the culture medium and establish the presence and day of the filtration. Calculation of the colony-forming units (CFU) was performed for each leaked sample. Fisher's Exact Test was used to verify the association between the presence or absence of leakage of the samples by type of bioceramic material used and the Mann-Whitney U test to verify the existence of a difference between the average of CFU by type of bioceramic material used. The significance level used was α=0.05 and a 95% confidence level, as a decision rule for rejecting the null hypothesis. RESULTS: Of the total samples prepared for each group, leakage was found in 60.0% (9/15) of the MTA group and 40.0% (6/15) of the BC RRM-fast set putty group. All positive controls filtered on the first day of evaluation, while 20% (1/5) of the negative control leaked in the second week. There was no significant difference in leakege between the two groups, nor concerning the bacterial count (P=0.101) and the type of cement used (P=1.000). CONCLUSION: BC RRM-fast set putty was comparable to MTA in resisting bacterial microleakage during the observation time.

The hypoxia-dependent angiogenic process in dental pulp.

BACKGROUND: In this review, we analyzed the existing literature to elucidate how the hypoxia-dependent angiogenic processes work in dental pulp. Angiogenesis is an essential biological process in the maturation and homeostasis of teeth. It involves multiple sequential steps such as endothelial cell proliferation and migration, cell-to-cell contact, and tube formation. HIGHLIGHT: Clinical implications of understanding the process of angiogenesis include how the mineralization processes of dental pulp occur and how dental pulp maintains its homeostasis, preventing irreversible inflammation or necrosis. CONCLUSION: The angiogenesis process in dental pulp regulates adequate concentrations of oxygen required for mineralization in root development and defense mechanisms against chronic stimuli.

Use of scaffolds and regenerative materials for the treatment of immature necrotic permanent teeth with periapical lesion: Umbrella review.

BACKGROUND: Current treatment of immature necrotic permanent teeth with a periapical lesion is regenerative endodontics, which is based on tissue engineering under the triade of stem cells, scaffolds and bioactive molecules. OBJECTIVES: This Umbrella Review was aimed to evaluate the success of scaffold and regenerative materials used for the treatment of these teeth, in terms of apical closure, tooth length increase, widening of root canal walls, tissue vitality and periapical lesion repair. METHODS: An extensive literature research was carried out in the Medline, ISI Web of Science, and Scopus databases for relevant systematic reviews matching the keyword search strategy. Based on inclusion and exclusion criteria, reviewers independently rated the quality of each study to determine their level of evidence. Methodological quality assessment of each article was obtained using A Measurement Tool to Assess Systematic Reviews (AMSTAR)-2 tool, and risk of bias was assessed with the Risk of Bias in Systematic Reviews (ROBIS) tool. RESULTS: After removing duplicates, 155 articles were found; from which 133 were excluded for being non-relevant and 15 other due to exclusion criteria. One more was discarded after methodological quality evaluation, for a total of six articles remaining. The most common scaffold used was the blood clot, others used were poly lactic-co-glycolic acid and platelet-rich fibrin matrix. The most common regeneration material used was Mineral Trioxide Aggregate (MTA), followed by Biodentine. An increase in tooth length and widening of root canal walls were reported in all selected studies with different proportions, as well as periapical lesion repair. ROBIS analysis showed that only one article had low bias, two were classified as unclear bias, while the remaining three had high risk of bias. DISCUSSION: An exhaustive literature search was carried out applying language filters, high-quality indexed journals, year of publication, which ensures the best quality articles were included. Blood clot was the most used scaffold as is the most easy to place inside the canal and does not require to extract blood from the patient. The use of MTA and Biodentine as sealing materials has been associated with thickening of canal walls, apical closure and reduced signs and symptoms of apical periodontitis. However, most of the included reviews assessed were case reports and only in a few of them were clinical trials included. There is also a lack of risk of bias analysis in most reviews. CONCLUSION: The blood clot is the most common scaffold used for inducing regeneration during the treatment of immature necrotic teeth. Tooth length increase and widening of root canal walls are the most common criteria used in the studies as success indicators. MTA and Biodentine did not show differences in the results analysed. Quality assessment and bias risk evaluation showed that it is necessary to design better studies with rigorous methodology to recommend a trustable and predictable protocol for the treatment of immature necrotic permanent teeth with periapical lesions. REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42021248404.

Dental Pulp Regeneration Induced by Allogenic Mesenchymal Stromal Cell Transplantation in a Mature Tooth: A Case Report.

INTRODUCTION: Cellular therapy constitutes a new therapeutic alternative in regenerative endodontics. In this case report, we evaluated the capacity of allogeneic mesenchymal stromal cells (MSCs) to induce dental pulp and apical bone regeneration in a tooth previously endodontically treated. METHODS: A healthy 55-year-old female patient consulting for swelling and a sinus tract associated with tooth #8 was referred for an endodontic evaluation. Previously, tooth #8 had undergone root canal treatment and apical resection and had no response to thermal or electric pulp testing. Radiographically, tooth #8 showed root canal treatment, a cut apex angle, and periapical radiolucency. The root canal was recleaned and shaped, and calcium hydroxide was used as an interappointment medication. Cryopreserved allogeneic bone marrow MSCs were thawed, expanded, incorporated into preclotted platelet-rich plasma, and implanted into the pulp cavity of tooth #8. The cervical part of the canal was sealed with bioceramic cement and a composite. RESULTS: After 14 months of MSC transplantation, tooth #8 showed sensitivity to cold and electric pulp tests. Radiographic and cone-beam computed tomographic imaging showed signs of increased periapical bone density, healing of the periapical lesion, and almost complete apical remodeling. CONCLUSIONS: This case report shows periodontal bone formation, apex remodeling, and dental pulp regeneration induced by allogeneic MSC transplantation in a mature nonvital tooth. Allogeneic MSCs may constitute a first-line therapy in regenerative endodontics.

Characteristics of United States military pilots with atrial fibrillation and deployment and retention rates.

INTRODUCTION: Atrial fibrillation (AF) is an arrhythmia that impacts deployment and retention rates for United States military pilots. This study aims to characterize United States active duty (AD) pilots with AF and review deployment and retention rates associated with medical and ablative therapies. METHODS: An observational analysis was performed to assess AD pilots diagnosed with AF in the largest military regional healthcare system from 2004 to 2019. Baseline characteristics and AF management were reviewed. RESULTS: 27 AD pilots (mean age, 37.3 ± 7.9 years; mean BMI, 27.3 ± 3.1 kg/m2; 100% male sex) were diagnosed with AF during the study dates. 17 (63%) were Air Force branch pilots with hypertension as the most common risk factor (26%). There were overall low CHA2DS2-VASc scores (mean 0.29 ± 0.47). 22 (82%) pilots were equally treated with medical rate and rhythm strategies (41% and 41%, respectively). 16 (59%) underwent pulmonary vein isolation (PVI) with zero complications. 11 (41%) pilots received warfarin and 5 (19%) received a direct oral anticoagulant for stroke prevention. After diagnosis, 12 (44%) pilots deployed and 25 (93%) were retained in military. PVI was not associated with a change in subsequent deployments rates (PVI, 38% vs no PVI, 55%; p = 0.3809) or retention rates (PVI, 94% vs no PVI, 91%; p = 0.7835). CONCLUSIONS: United States military pilots diagnosed with AF are younger patients with few traditional AF risk factors and  they receive medical rate and rhythm strategies equally. Many pilots maintain deployment eligibility and most remain on AD status after diagnosis. PVI is not associated with differences in retention or deployment rates. Further prospective study is needed to further evaluate these findings.

Neurovascular dysfunction and vascular amyloid accumulation as early events in Alzheimer's disease.

Alzheimer's disease (AD) is clinically characterized by a progressive loss of cognitive functions and short-term memory. AD patients present two distinctive neuropathological lesions: neuritic plaques and neurofibrillary tangles (NFTs), constituted of beta-amyloid peptide (Aß) and phosphorylated and truncated tau proteins. Aß deposits around cerebral blood vessels (cerebral amyloid angiopathy, CAA) is a major contributor to vascular dysfunction in AD. Vascular amyloid deposits could be early events in AD due to dysfunction in the neurovascular unit (NVU) and the blood-brain barrier (BBB), deterioration of the gliovascular unit, and/or decrease of cerebral blood flow (CBF). These pathological events can lead to decreased Aß clearance, facilitate a neuroinflammatory environment as well as synaptic dysfunction and, finally, lead to neurodegeneration. Here, we review the histopathological AD hallmarks and discuss the two-hit vascular hypothesis of AD, emphasizing the role of neurovascular dysfunction as an early factor that favors vascular Aß aggregation and neurodegeneration. Addtionally, we emphasize that pericyte degeneration is a key and early element in AD that can trigger amyloid vascular accumulation and NVU/BBB dysfunction. Further research is required to better understand the early pathophysiological mechanisms associated with NVU alteration and CAA to generate early biomarkers and timely treatments for AD.

Gene Expression of Vascular Endothelial Growth Factor A and its Receptors in Dental Pulp of Immature and Mature Teeth.

OBJECTIVE: Vascular endothelial growth factor A (VEGFA) and its receptors are essential proteins for the angiogenic activity of dental pulp. Angiogenesis fundamentally provides oxygen and nutrients to cells for root formation and defence mechanisms. The angiogenic potential of dental pulp should be understood and considered for the conservative and regenerative endodontics. The purpose of this research was to measure the VEGFA expression and its receptors such as vascular endothelial growth factor receptors 1, -2 (VEGFR1, VEGFR2) and Neuropilin 1 (NRP1) in human dental pulp from molars with immature and mature apexes. METHODS: VEGFA system mRNAs expressions were assessed in dental pulp obtained from freshly extracted human third molars divided into immature (n=8) and mature (n=8) apexes. RNAs were extracted from the samples. Each sample's cDNA was synthetized and the target genes VEGFA, VEGFR1, VEGFR2, NRP1 expression profiles obtained by RT2-PCR. Analysis was based on the Student's t-test comparing the replicate 2-ΔCt values for each gene. P values of <0.05 were considered significant. RESULTS: In teeth with mature apexes, VEGFA (P=0.0002), NRP1 (P=0.0001), VEGFR1 (P=0.0057) and VEGFR2 (P=0.018259) significantly increased statistically with respect to the immature apexes group. CONCLUSION: Within the limitation of the present investigation, it can be concluded that the angiogenic process seems to be a physiological process in the dental pulp due to the studied angiogenic growth factor are expressed in both immature and mature dental pulps. VEGFA and its receptors are expressed significantly higher in mature apex teeth than immature apex teeth.