Effect of power arm length combined with additional anterior torque on the axial orientation of the maxillary incisors during en-masse retraction: A finite element analysis.

INTRODUCTION: This study aimed to clarify the effect of power arm length combined with additional torque incorporated into the archwire on the controlled movement of the anterior teeth using the finite element method. METHODS: An adult patient requiring medium anchorage after extraction of the maxillary first premolars was selected for this study. The power arms were placed between the lateral incisor and the canine at 3 levels: 3 mm, 6 mm, and 9 mm. A 150 g of retraction force was applied from each height of the anterior hook to the first molar tube, with 0°, 5°, and 10° of applied lingual root torque on the incisors. RESULTS: A 3-mm hook with 10° of applied torque, a 6-mm hook with 5° of applied torque, or a 9-mm hook with no extra torque constituted the best combinations targeted at controlling the inclination of incisors during retraction. Extrusion and distal tipping of the canine were observed. Moreover, mesial tipping and mesiopalatal rotation of the molar were unavoidable. Finally, intercanine and intermolar widths were decreased. CONCLUSIONS: Adding extra torque on the incisors or using high torque brackets is recommended for patients with maxillary first premolar extraction.

Three-dimensional comparison of continuous and segmented arch techniques in the traction of palatally impacted canines using a non-linear finite element analysis.

OBJECTIVE: To compare the three-dimensional (3D) effects of canine traction on the maxillary teeth when using two different traction methods, the continuous and the segmented arch wire techniques; then to test whether adding a transpalatal arch (TPA) would affect their response to traction. DESIGN: Finite element analysis. METHODS: A cone-beam computed tomography (CBCT) scan of a patient with bilateral palatally impacted canines was chosen, from which a 3D model was derived and imported into ABAQUS. Two arch wires were modelled, a continuous round one and a segmented rectangular one. Four models were obtained by adding a TPA to both techniques. A 100° imposed rotation was then applied at the intersection between the vertical loop and the horizontal segment of each wire. Initial displacement of the maxillary tooth in the labio-lingual and in the vertical directions was measured. The absolute maximum principal stress of the periodontal ligament (PDL) was also assessed. RESULTS: Traction using a continuous arch wire led to different movement patterns of all teeth, some of them were tipped in a labial direction while others were lingually tipped. Traction using a segmented arch wire resulted in a retroclination of the posterior teeth and a proclination of the anterior teeth with a high level of stress on the premolars' PDL. Adding the TPA only affected the displacement of the first molars. The right side showed a maximum displacement of the first premolar, while the left side showed it on the lateral. The total displacement on the right side was higher than the left side. CONCLUSION: The segmented technique caused a uniform displacement of all teeth while the continuous one showed a non-uniform displacement. The angulation and position of the vertical loop affected the displacement of the maxillary teeth. The addition of a TPA acted only on the first molars.

Factors influencing the perception of profile beauty in Class III dental compensation: A comparative cross-sectional study according to three categories of assessors.

INTRODUCTION: The main objective of this study was to evaluate the different factors influencing the perception of female profile facial beauty in Class III patients with protruded mandible that can be treated with orthodontic dental compensation: (1)severity of the protrusion, (2) the upper incisors inclination and (3) the presence of jawlines. The secondary objective was to determine if the rater's gender and profession played a role in the assessment of the preferred profile. METHODS: A normal and smiling photographs of a female subject with normal facial and skeletal profile criteria were digitally manipulated to obtain 3 different mandibular sagittal positions: 0mm, +4mm and +8mm. Each position of the chin was evaluated with the presence or not of jawlines. In the smiling profiles, the same chin modifications were scored, and the maxillary incisor inclination was changed from 0 to +10 degrees with 5 degrees increments. A total of 320 raters (107 dentists, 103 orthodontists and 110 laypeople) scored the attractiveness of the different images using a Visual Analogue Scale. The limit of statistical significance was P<0.05. Generalized estimating equation (GEE) models were conducted to assess the predictors of variations in ratings within each set of photos, as well as the interactions of predictors where adjusted odds ratios (aOR) and their 95% confidence intervals were calculated and reported. RESULTS: In the profiles without a smile, image +4mm chin (Class III treated by compensation) and image +8-mm mandible (Class III not treated) were selected as the most and least attractive images, respectively, by almost all groups with no difference. The presence of jawlines has a positive role in facial attractiveness. In the smiling profiles, all the examiners showed a preference for image +4-mm chin and a slight protrusion of maxillary incisors (+5 degrees). No significant difference was found between genders in this study. CONCLUSIONS: Class III treated by compensation (+4mm) are more attractive than non-treated Class III (+8mm) by almost all groups with no difference. The presence of jawlines has a positive role in facial attractiveness. In the smiling profiles, all the examiners showed a preference for image +4-mm chin and a slight protrusion of maxillary incisors (+5 degrees). Orthodontists older than 50 years old are aware of the difficulty to treat a skeletal Class III and tend to accept it due to their long career experience. No significant difference was found between genders in this study.

Emotional and behavioral changes in French children during the COVID-19 pandemic: a retrospective study.

COVID-19 outbreak caused severe disruptions in daily life, partly due to limitations implemented to prevent the spreading. In France, it included school closures during a national lockdown, then a reopening of schools, with access depending on viral status of students and teachers. Those changes had an impact on children's mental health. We conducted an online cross-sectional study using a parental self-administered survey in December 2021 to explore the emotional and behavioral changes (EBC) during this 5th wave (W5) and retrospectively since the first one (W1) in their children and their multidimensionality with principal factor analysis (PCA) and stability analysis. Out of 4552 parent responders, 62.4% (n = 2839) noticed negative EBC during W1 and 54.1% (n = 2462) during W5 of the pandemic. Only 10.0% of the responders noticed negative EBC at W1 but not during the W5. In younger children (3-6 years old) with significant EBC, PCA revealed three main dimensions at W1 and W5: restlessness, depression and anxiety. In older children (7-13 years old), PCA showed partially similar dimensions: depression-suicidality, anxiety and withdrawal. Almost all correlations between dimensions at W1 and W5 were significantly positive. Every EBC was stable across waves, except for one. Recall bias concerning the EBC during W1 and lack of data concerning parental mental health should be taken into account. Our stability analysis found a strong correlation between dimensions at W1 and W5. Our results highlighted the impact of the COVID-19 outbreak on children's mental health and the predictive aspect of its early deterioration.

Effect of Different Surface Treatments on the Shear Bond Strength of Metal Orthodontic Brackets Bonded to CAD/CAM Provisional Crowns.

BACKGROUND: The aim of this study was to find the best surface treatment for CAD/CAM provisional crowns allowing the optimal bond strength of metal brackets. METHODS: The sample consists of 30 lower bicuspids and 180 provisional crowns. The provisional crowns were randomly divided into six different groups. Orthophosphoric acid etching (37%) was applied to 30 lower bicuspids. The provisional crowns had undergone different surface treatments. Group 1: No treatment (Control Group). Group 2: Diamond bur. Group 3: Sandblasting. Group 4: Plastic Conditioner. Group 5: Diamond bur and Plastic Conditioner. Group 6: Sandblasting and Plastic Conditioner. The brackets in all groups were identically placed using Transbond XT® Primer and Transbond XT® Paste. Then, the entire sample underwent an artificial aging procedure, and a measurement of the bond strength was conducted. After debonding, the surface of the crowns was examined to determine the quantity of the adhesive remnant. RESULTS: Bonding to natural crowns recorded the highest average, followed by the averages of groups 5 and 6. However, group 1 recorded the lowest average. Groups 2 and 4 had very close averages, as well as groups 5 and 6. A statistically significant difference between the averages of all groups was recorded (p < 0.001) except for groups 2 and 4 (p = 0.965) on the one hand, and groups 5 and 6 (p = 0.941) on the other hand. DISCUSSION: The bonding of brackets on provisional crowns is considered a delicate clinical procedure. In fact, unlike natural crowns, the orthophosphoric acid usually used does not have any effect on the surface of provisional crowns. CONCLUSIONS: Using a diamond bur combined with the plastic conditioner and sandblasting combined with that same product resulted in a bond strength close to natural crown.

Meta-analysis of personal and familial co-occurrence of Attention Deficit/Hyperactivity Disorder and Bipolar Disorder.

BACKGROUND: Attention Deficit Disorder / Hyperactivity (ADHD) and Bipolar Disorder (BD) are highly comorbid disorders. Studies have raised the hypothesis of shared genetic, neurobiological, and clinical factors. This would entail an excess risk of co-occurrence of both disorders. OBJECTIVE: We present the first meta-analysis of individual and familial associations between ADHD and BD. METHODS: From 2688 references, 59 were included, with a total of 550,379 ADHD patients, 57,799 BD patients and 12,608,137 controls. RESULTS: Personal history of ADHD increased the risk of BD (OR = 6.06), and conversely individuals with BD had an increased risk of ADHD (OR = 8.94). First-degree relatives of ADHD patients had an increased risk of BD (OR = 1.94). Offspring of individuals with BD had a higher risk for ADHD (OR = 2.33). Finally, first-degree relatives of BD patients had an increased risk of ADHD (OR = 2.71). CONCLUSION: We show a clear epidemiological overlap between ADHD and BD, as well as a strong familial association which advocates in favor of a more systematic screening.

In-vivo durability of Pro Seal in patients with fixed orthodontic appliances: A controlled clinical trial.

BACKGROUND: This clinical trial aimed at studying the durability of an orthodontic sealant (Pro Seal) used on tooth surfaces for protection against white spot lesions. METHODS: A total of 35 patients (18 females, 17 males; 17.57 ± 1.36 years) were recruited. Eligibility criteria included healthy patients of both sexes (age > 14 years), absence of labial caries, absence of defective enamel, absence of extensive restorations, and optimum oral hygiene. The participants received a single application of Pro Seal on the bonded teeth. The sealant covered the labial enamel surrounding the brackets. Participants were recalled monthly after sealant application, during which sealant layers were evaluated using an ultraviolet lamp. The assessment was realized using an index similar to the adhesive remnant index (ARI). RESULTS: A total of 30 participants completed the trial. ARI values dropped significantly (P < 0.001) and reached <1.5 at T1 on the index used. An ARI value of 2 was chosen as the threshold below which a tooth presented an insufficient sealant layer. The right and left sides of both jaws did not show any statistically significant difference (P > 0.05). ARI values of homolateral teeth revealed few statistically significant differences between upper and lower teeth. No statistically significant difference between the two sexes (P > 0.05) existed. No harm or disturbance was reported by any of the participants. CONCLUSIONS: This study demonstrated that a single application of Pro Seal is effective for 4 weeks and should be renewed monthly. No interjaw, intrajaw, or intersex significant differences were found.

Cytotoxicity of V-Prep Versus Phosphoric Acid Etchant on Oral Gingival Fibroblasts.

The most used etchant in dental daily practice is the phosphoric acid (P.A.; 37%). However, acid etchants can induce necrosis on the oral mucosa and cause the ulceration of periodontal tissue when a rubber dam is not used. V-prep is a new practical alternative, and it has satisfactory results. It is used as a preparation before the application of a resin-modified glass ionomer composite (RMGIC) to bond the orthodontic brackets. The aim of this study was to investigate the effect of the V-prep on oral gingival fibroblasts cells by comparing the cell damage and cell viability after the use of V-prep and a conventional phosphoric acid etchant with different application times and concentrations. Therefore, Gingival fibroblasts passage 6 (GFP6) was grown and treated with an acid etchant and V-prep at three different concentrations (1:1, 1:2 and 1:10) for two different application durations (30 s and 1 min). The morphological changes, cell death and cell viability were assessed. Pyknosis, karyolysis, nucleus reversible and irreversible damages and membrane destruction were observed for both of the etchants at the higher concentrations and longer application durations. Mann-Whitney U-tests were used for the statistical analyses. The application of the V-prep for 30 s showed better values than the acid etchant did in the cell damage analysis and cell viability analysis (p = 0.03). V-prep at a 1:10 concentration applied for a 30 s duration can preserve the viability of gingival fibroblasts cells up to 100%. The toxicity of V-prep is equal or lower than the toxicity of the acid etchant that is commonly used in dentistry. Thus, the V-prep can be used with precautions intra-orally, and it should be applied on the enamel as a gel for 30 s only before it is rinsed and removed.

The impact of vaccination on the burden of invasive pneumococcal disease from a nationwide surveillance program in Lebanon: an unexpected increase in mortality driven by non-vaccine serotypes.

BACKGROUND: The impact of pneumococcal conjugate vaccines (PCVs) on the burden of invasive pneumococcal disease (IPD) and serotype distribution was examined across age groups from data collected by the Lebanese Inter-Hospital Pneumococcal Surveillance Program. METHODS: Between 2005 and 2020, 593 invasive Streptococcus pneumoniae isolates were collected from 79 hospitals throughout Lebanon. Serotypes and antimicrobial resistance (AMR) profiles were identified, and trends compared over 3 eras: PCV7, post-PCV7/ pre-PCV13, and PCV13 eras. RESULTS: The prevalence of PCV7 serotypes decreased significantly from 43.6% in the PCV7 era to 17.8% during the PCV13 era (p<0.001). PCV13-only serotypes remained stable in the PCV13 compared to the post-PCV7 eras, especially serotypes 1 and 3, whereas non-vaccine types (NVT) increased throughout the study period, especially 24 and 16F. The mortality rate increased substantially from 12.5% (PCV7 era) to 24.8% (PCV13 era). A significant decrease in AMR was observed across the three study eras. CONCLUSION: PCVs substantially impacted IPD and AMR in vaccinated and unvaccinated populations despite an increase in mortality driven by NVT. Broadening the recommendation of vaccination to include older age-groups, using higher valency vaccines, and implementing stringent antimicrobial stewardship are likely to further impact the burden of IPD.

Three-dimensional comparison of the effects of sliding mechanics in labial and lingual orthodontics using the finite element method.

INTRODUCTION: The extraction of maxillary first premolars is usually the treatment of choice to resolve crowding, alveolar protrusion, or Class II malocclusion. The demand for a lingual orthodontic treatment is increasing because of its esthetic value; therefore, understanding lingual biomechanics is essential to every clinician. This study compared the 3-dimensional (3D) effects of sliding mechanics in labial and lingual orthodontics using the finite element method. METHODS: Twelve 3D finite element models were created with different power arm heights and miniscrew positions. A 150 g of retraction force was applied from the head of the miniscrew to the power arm. The 3D displacement of the original nodes was measured, and the stress distribution on defined element zones of the periodontal ligament. RESULTS: Different force directions led to different movement patterns and stress distribution. The lingual models showed a more important lingual crown tipping, extrusion, and higher stress values than the labial models. Results were not affected by the vertical position of the miniscrew. CONCLUSIONS: Bodily en-masse retraction was not achieved in all models. Adding extra torque to the archwires is essential to prevent excessive lingual crown tipping. The lingual appliance induced more lingual tipping and extrusion of the anterior teeth. Expanding the archwire is important to minimize the risk of intercanine width reduction. The vertical position of the miniscrew does not affect the results of en-masse retraction.

[Impacts of the covid-19 pandemic on children and adolescents]. / Impacts de la pandémie de Covid-19 sur les enfants et adolescents.

IMPACTS OF THE COVID-19 PANDEMIC ON CHILDREN AND ADOLESCENTS. The Covid-19 pandemic and the lockdown measures taken to limit the spread of the virus have caused significant changes in the daily lives of the whole population including children and adolescents. School closure and physical distancing significantly interfere with their learning and social life deeply impacting their health and education. The most vulnerable children (personal history of mental health or neurodevelopmental disorders, chronic physical illness) were also those the most significantly affected by the Sars-CoV-2 pandemic. However, data remains scarce today, and it remains a major challenge to conduct longitudinal studies that will enable the development of primary prevention programs in the general population and secondary prevention programs in already affected children.

RÉSUMÉ IMPACTS DE LA PANDÉMIE DE COVID-19 SUR LES ENFANTS ET ADOLESCENTS. L'épidémie de Covid-19 et les mesures prises pour limiter la propagation du virus ont provoqué des modifications importantes dans la vie quotidienne des enfants et adolescents ainsi que de leur famille. Ces changements, avec notamment les fermetures itératives des écoles et la distanciation physique, ont eu un impact sur la santé mentale des enfants et des adolescents ainsi que sur leur scolarité et leurs apprentissages. Des conséquences plus importantes ont été mises en évidence chez les enfants les plus vulnérables, notamment ceux porteurs d'un trouble du neurodéveloppement ou d'un trouble psychiatrique. Les données restent cependant aujourd'hui peu nombreuses, et il est donc important de conduire des études longitudinales permettant d'établir des programmes de prévention primaire en population générale et secondaire au sein des populations les plus vulnérables.

Silencing PEX26 as an unconventional mode to kill drug-resistant cancer cells and forestall drug resistance.

Promoting the macroautophagy/autophagy-mediated degradation of specific proteins and organelles can potentially be utilized to induce apoptosis in cancer cells or sensitize tumor cells to therapy. To examine this concept, we enriched for autophagosomes from histone deacetylase inhibitor (HDACi)-sensitive U937 lymphoma cells and isogenic HDACi-resistant cells. Mass spectrometry on autophagosome-enriched fractions revealed that HDACi-resistant cells undergo elevated pexophagy, or autophagy of the peroxisome, an organelle that supports tumor growth. To disturb peroxisome homeostasis, we enhanced pexophagy in HDACi-resistant cells via genetic silencing of peroxisome exportomer complex components (PEX1, PEX6, or PEX26). This consequently sensitized resistant cells to HDACi-mediated apoptosis, which was rescued by inhibiting ATM/ataxia-telangiectasia mutated (ATM serine/threonine kinase), a mediator of pexophagy. We subsequently engineered melanoma cells to stably repress PEX26 using CRISPR interference (CRISPRi). Melanoma cells with repressed PEX26 expression showed evidence of both increased pexophagy and peroxisomal matrix protein import defects versus single guide scrambled (sgSCR) controls. In vivo studies showed that sgPEX26 melanoma xenografts recurred less compared to sgSCR xenografts, following the development of resistance to mitogen-activated protein kinase (MAPK)-targeted therapy. Finally, prognostic analysis of publicly available datasets showed that low expression levels of PEX26, PEX6 and MTOR, were significantly associated with prolonged patient survival in lymphoma, lung cancer and melanoma cohorts. Our work highlighted that drugs designed to disrupt peroxisome homeostasis may serve as unconventional therapies to combat therapy resistance in cancer.Abbreviations: ABCD3/PMP70: ATP binding cassette subfamily D member 3; ACOX1: acyl-CoA oxidase 1; AP: autophagosome; COX: cytochrome c oxidase; CQ: chloroquine; CRISPRi: clustered regularly interspaced short palindromic repeats interference; DLBCL: diffuse large B-cell lymphoma; GO: gene ontology; dCas9: Cas9 endonuclease dead, or dead Cas9; HDACi: histone deacetylase inhibitors; IHC: Immunohistochemistry; LAMP2: lysosomal associated membrane protein 2; LCFAs: long-chain fatty acids; LFQ-MS: label-free quantitation mass spectrometry; LPC: lysophoshatidylcholine; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; PBD: peroxisome biogenesis disorders; PTS1: peroxisomal targeting signal 1; ROS: reactive oxygen species; sgRNA: single guide RNA; VLCFAs: very-long chain fatty acids; Vor: vorinostat; WO: wash-off.

Poor visuo-spatial orientation and path memorization in children with dyslexia.

PURPOSE: Given the importance of spatial representation and navigation in the natural environment and the presence of sensory motor integration impairment in dyslexic children the aim of this study was to explore the capability in spatial orientation task in dyslexic children. MATERIALS AND METHODS: We included forty children: 26 dyslexic children (mean age: 10.1 ± 0.3 years old) and 14 typically developing (TD) children (mean age: 10.1 ± 0.4 years old). Children have to walk on an unguided isosceles rectangle triangle of 3 meters that was marked on the ground of a room, during two visual conditions: eyes open and eyes closed. Their paths were recorded using the HTC Vive system (Base + Trackers) with a refresh rate of 90 Hz with accuracy < 0.05 mm. RESULTS: Results underlined that both groups of children reported poor performance during eyes closed condition. Moreover, dyslexic children, reported poor spatial orientation capabilities in the most difficult conditions, that is during reproduction of hypotenuse and angle of 45 deg. CONCLUSIONS: We suggested that visual information is important during walking; the poor body orientation observed in dyslexic children could be due to a deficient integration of the sensorial inputs (visual, vestibular and proprioceptive). Further studies testing vestibular/cerebellar rehabilitation could be useful for these kinds of children.HighlightsChildren with dyslexia showed poor spatial orientation capabilities compared to typically developing children, particularly when visual inputs are not available and in the most difficult conditions (like rotation of the body).Poor motor abilities reported by children with dyslexia could be due to cerebrocerebellar pathways impairments.

The curve of Spee and its levelling in different vertical skeletal patterns: A 3D set-up study.

OBJECTIVES: Primary: to compare intra-arch measurements [Curve Of Spee (COS) depth, space required to level the COS (δ), uprighting angles of 1st and 2nd lower molars (αM1 & αM2), respectively] between different vertical skeletal patterns. Secondary: to explore the relationship between those measurements in each vertical skeletal pattern. METHODS: 90 Plaster models were scanned and transformed into digital models using 3Shape Ortho System™ intra oral scanner. COS depth, (δ), αM1 & αM2 were measured on digital models using 3Shape Ortho Analyser™ software. The latter was used to achieve the virtual set-up. The sample was dividied into 3 groups according to the vertical skeletal pattern which was identified by measuring the FMA˚ angle (Frankfort mandibular plane) on a lateral cephalogram using Dolphin imaging software. RESULTS: The deepest COS was present in the hypodivergent group (P-value=0.001). No difference for the additional arch space required to level the COS (δ) between different vertical skeletal patterns (P-value=0.063). αM2 is the same in all 3 groups, whereas αM1 is greater in normodivergents compared to hyperdivergents (P-value=0.012). A positive correlation exists between the deepest point of the COS and the uprighting angles, αM1 and αM2. No correlation between (δ) and the different parameters evaluated (deepest point of the COS, αM1 and αM2). CONCLUSIONS: Additional arch space required to level the COS presented no correlation with the vertical skeletal pattern. Levelling the lower arch was carried out by extrusion of the premolars and uprighting of the posterior teeth; confirming that well-planned orthodontic mechanics can minimize side effects (flaring of the lower incisors) encountered during treatment.

Effects of enamel deproteinization with different application times on the shear bond strength of a self-etching primer: An in vitro study.

OBJECTIVE: The aim of this in vitro study was to evaluate the effects of enamel deproteinization on the shear bond strength of a self-etching primer Transbond Plus™(TBP), with different application times of sodium hypochlorite (NaOCl 5.25%), primarily and secondarily on the adhesive remnant index score. MATERIALS AND METHODS: One hundred twenty-five freshly extracted human premolars were randomly and blindly divided into five groups according to the enamel surface preparation, as follows (n=25): group 1(control): Etching with 37% phosphoric acid for 15seconds+Bonding; group 2 (control): TBP™ without NaOCl, group 3: 60seconds NaOCl+TBP™, group 4: 30seconds NaOCl+TBP™, group 5: 15seconds NaOCl+TBP™. The same composite resin was used (Transbond XT™) to bond the orthodontic metal brackets. After the immersion of the teeth in distilled water at 37°C for 24hours the shear bond strength was measured using the universal testing machine and the adhesive remnant index score (ARI) was evaluated under an optical microscope (25×). RESULTS: The mean SBS values (inMPa) of the groups were respectively: group 1: 13.03±5.36; group 2: 12.28±3.06; group 3: 12.38±4.55; group 4: 12.98±5.76; and group 5: 11.73±5.67. Enamel deproteinization increased the SBS for groups 3 and 4, but no statistically significant difference was found between the five groups (P=0.883). Group 1 showed the highest ARI scores, with 52% of the teeth retaining all the adhesive (score 3). However, for all the other groups, scores 0 and 1 were predominant, with less than half of the adhesive or no adhesive at all remaining on the teeth. CONCLUSIONS: Enamel deproteinization with sodium hypochlorite (5.25%) and the variation of its application time has no effect on the SBS of the self-etching primer Transbond Plus ™.

The MNK1/2-eIF4E Axis Supports Immune Suppression and Metastasis in Postpartum Breast Cancer.

Breast cancer diagnosed within 10 years following childbirth is defined as postpartum breast cancer (PPBC) and is highly metastatic. Interactions between immune cells and other stromal cells within the involuting mammary gland are fundamental in facilitating an aggressive tumor phenotype. The MNK1/2-eIF4E axis promotes translation of prometastatic mRNAs in tumor cells, but its role in modulating the function of nontumor cells in the PPBC microenvironment has not been explored. Here, we used a combination of in vivo PPBC models and in vitro assays to study the effects of inactivation of the MNK1/2-eIF4E axis on the protumor function of select cells of the tumor microenvironment. PPBC mice deficient for phospho-eIF4E (eIF4ES209A) were protected against lung metastasis and exhibited differences in the tumor and lung immune microenvironment compared with wild-type mice. Moreover, the expression of fibroblast-derived IL33, an alarmin known to induce invasion, was repressed upon MNK1/2-eIF4E axis inhibition. Imaging mass cytometry on PPBC and non-PPBC patient samples indicated that human PPBC contains phospho-eIF4E high-expressing tumor cells and CD8+ T cells displaying markers of an activated dysfunctional phenotype. Finally, inhibition of MNK1/2 combined with anti-PD-1 therapy blocked lung metastasis of PPBC. These findings implicate the involvement of the MNK1/2-eIF4E axis during PPBC metastasis and suggest a promising immunomodulatory route to enhance the efficacy of immunotherapy by blocking phospho-eIF4E. SIGNIFICANCE: This study investigates the MNK1/2-eIF4E signaling axis in tumor and stromal cells in metastatic breast cancer and reveals that MNK1/2 inhibition suppresses metastasis and sensitizes tumors to anti-PD-1 immunotherapy.

The Microbiome of the Lebanese Wild Apple, Malus trilobata, is a Rich Source of Potential Biocontrol Agents for Fungal Post-harvest Pathogens of Apples.

The widespread use of harmful fungicides in the agricultural sector has led to a demand for safer alternatives to protect against crop pathogens. The domestic apple is the second most highly consumed fruit in the world and encounters several pre- and post-harvest fungal and bacterial phytopathogens. The goal of this study was to explore the uncharacterized microbiome of a wild apple, Malus trilobata, as a potential source of novel biocontrol agents for two post-harvest fungi that affect commercial apples: Botrytis cinerea and Penicillium expansum. We sampled microflora associated with the leaves, bulk soil, and roots of Malus trilobata in two regions of Lebanon: Ehden reserve in the north and Dhour EL Choueir near Beirut. The two regions have different soil types Dhour EL Choueir and samples from the two regions showed very different microbial compositions, with greater microbial diversity among those from Ehden reserve. Molecular characterization revealed a wide variety of genera displaying activity against the two fungal pathogens, including several with previously unknown antifungal activity: Bosea, Microlunatus, Microbacterium, Mycetecola, Rhizobium and Paraphoma. In total, 92 strains inhibited Penicillium expansum (39%) and 87 strains inhibited Botrytis cinerea (38%) out of 237 screened. Further chemical and genetic characterization of one or more selected strains could pave the way for future development of new biocontrol agents for post-harvest applications.

Inhibiting the MNK1/2-eIF4E axis impairs melanoma phenotype switching and potentiates antitumor immune responses.

Melanomas commonly undergo a phenotype switch, from a proliferative to an invasive state. Such tumor cell plasticity contributes to immunotherapy resistance; however, the mechanisms are not completely understood and thus are therapeutically unexploited. Using melanoma mouse models, we demonstrated that blocking the MNK1/2-eIF4E axis inhibited melanoma phenotype switching and sensitized melanoma to anti-PD-1 immunotherapy. We showed that phospho-eIF4E-deficient murine melanomas expressed high levels of melanocytic antigens, with similar results verified in patient melanomas. Mechanistically, we identified phospho-eIF4E-mediated translational control of NGFR, a critical effector of phenotype switching. Genetic ablation of phospho-eIF4E reprogrammed the immunosuppressive microenvironment, exemplified by lowered production of inflammatory factors, decreased PD-L1 expression on dendritic cells and myeloid-derived suppressor cells, and increased CD8+ T cell infiltrates. Finally, dual blockade of the MNK1/2-eIF4E axis and the PD-1/PD-L1 immune checkpoint demonstrated efficacy in multiple melanoma models regardless of their genomic classification. An increase in the presence of intratumoral stem-like TCF1+PD-1+CD8+ T cells, a characteristic essential for durable antitumor immunity, was detected in mice given a MNK1/2 inhibitor and anti-PD-1 therapy. Using MNK1/2 inhibitors to repress phospho-eIF4E thus offers a strategy to inhibit melanoma plasticity and improve response to anti-PD-1 immunotherapy.

Evaluation of the distance between the root apices of the upper first molars and the hard palate in an Eastern Mediterranean population: A retrospective study.

OBJECTIVE: The aims of this retrospective study were, first to evaluate the distance between the root apices of the upper first molars and the palatal plane (PP), and second to determine the validity (accuracy) of the use of cephalometric radiographs or panoramic X-rays compared to cone beam computed tomography (CBCT) in determining this distance. MATERIAL AND METHODS: The distance was calculated from the root apices of the first molars to PP, on the cephalometric radiographs of 204 subjects and then 57 measurements were compared to those obtained on panoramic X-rays and CBCT images, in order to find a statistically significant difference according to age, sex, side, vertical and sagittal skeletal patterns, and to determine if 2D radiographs are suitable for this task. RESULTS: The distance increased significantly in subjects after 20 years of age and in hyperdivergent patients, but was not influenced by sex, side or anteroposterior position of the mandible. No statistical significance was found between the calculated measurements on cephalometric and CBCT radiographs, but both were different from those taken on panoramic X-rays. CONCLUSIONS: Cephalometric radiographs are reliable in the assessment of the distance between the roots of the upper molars and the PP. In hyperdivergent and adult patients, posterior teeth have enough space between their roots and the upper limit of the hard palate to undergo intrusion mechanics using miniscrews, but care must be taken while planning and managing these movements in order to minimize the unwanted side effects.