Constraints on Dark Matter Properties from Observations of Milky Way Satellite Galaxies.

We perform a comprehensive study of Milky Way (MW) satellite galaxies to constrain the fundamental properties of dark matter (DM). This analysis fully incorporates inhomogeneities in the spatial distribution and detectability of MW satellites and marginalizes over uncertainties in the mapping between galaxies and DM halos, the properties of the MW system, and the disruption of subhalos by the MW disk. Our results are consistent with the cold, collisionless DM paradigm and yield the strongest cosmological constraints to date on particle models of warm, interacting, and fuzzy dark matter. At 95% confidence, we report limits on (i) the mass of thermal relic warm DM, m_{WDM}>6.5 keV (free-streaming length, λ_{fs}≲10h^{-1} kpc), (ii) the velocity-independent DM-proton scattering cross section, σ_{0}<8.8×10^{-29} cm^{2} for a 100 MeV DM particle mass [DM-proton coupling, c_{p}≲(0.3 GeV)^{-2}], and (iii) the mass of fuzzy DM, m_{ϕ}>2.9×10^{-21} eV (de Broglie wavelength, λ_{dB}≲0.5 kpc). These constraints are complementary to other observational and laboratory constraints on DM properties.

Medication related osteonecrosis of the jaws (MRONJ): Factors related to recurrence after treatment with surgery and platelet rich plasma (PRP) placement.

BACKGROUND: Medication-related osteonecrosis of the jaws (MRONJ) is a well-known complication associated with antiresorptive and antiangiogenic therapies. The purpose of this study was to analyse if there is any predictive factor of recurrence after local debridement plus platelet rich plasma (PRP) placement in MRONJ patients. MATERIAL AND METHODS: Seventy MRONJ patients treated at the department of Oral and Maxillofacial Surgery in La Paz Hospital (Madrid, Spain) were included in this retrospective study. All of them were treated surgically by local debridement and PRP placement. The observation period was between January 2012 and January 2019. Information regarding use, type, administration, and duration of therapy with BP/denosumab was recorded. The follow-up period ranged from 2-52 months. A descriptive analysis, a bivariate and a multivariate study were performed. RESULTS: Most of the patients were women (82.9%) between 50-70 years old (64.3%), with a stage II disease (74.3%). The therapy lasted more than 12 months in 54.8% of them. Zoledronic acid was the main antiresorptive used (44.3%), followed by oral administered BPs (29 patients, 41.4%) and denosumab (10 patients, 14.3%). Osteoporosis (48.6%), breast cancer (30%) and multiple myeloma (11.4%) were the main diseases because the patients were taking antirresorptives. 13 patients (18.6%) experienced recurrence. We found that breast cancer patients (p>0.0001), smokers (p>0.016), and administration of zoledronic acid (p>0.0001) were related to recurrence. After performing the multivariate model, we found that the only factor related to recurrence was smoking habit (Wald 3.837, p=0.05, OR 6.12). CONCLUSIONS: recurrence after local debridement plus PRP placement in our MRONJ series affected to 18.6% of patients. It seems to be more frequent in breast cancer patients, smokers, and after zoledronic acid administration. Smoking habit was the only independent factor related to recurrence in our series.

Expression of clec9a in the oral cancer microenvironment. A preliminary immunohistochemical pilot study.

BACKGROUND: The search for treatments to improve cancer survival has led to the emergence of immunotherapy and the study of the tumour microenvironment existing in neoplasms. This preliminary study aims to understand the clinical and pathological relationship of clec9a expression in oral cancer and to explore survival models for future studies. MATERIAL AND METHODS: Immunohistochemical study that included 26 patients with a diagnosis of oral squamous cell carcinoma (OSCC) in mobile tongue and floor of the mouth. Clinical and histopathological variables were recorded, and the biomarkers clec9a for dendritic cells and CD8 and CD4 for lymphocytes were used. RESULTS: Clec9a was expressed in 58% of the sample. It was more common in cases with low lymphoplasmacytic infiltration and in type 2 invasion patterns. It was significantly related to CD8 expression (p=0.055 and p=0.007). No prognostic risks were evident in the survival models studied (overall survival, disease-specific survival, disease-free survival). CONCLUSIONS: CLEC9A expression is present in the OSCC microenvironment and is mainly related to the presence of CD8 lymphocytes. The relationship of its expression with survival prognosis in OSCC could not be confirmed; however, this needs to be confirmed through future studies with larger sample size.

Preliminary study of the Craniofacial Pain and Disability Inventory-11: validation for patients with head and neck cancer.

BACKGROUND: Cancer involves numerous physical, psychological and emotional changes and has a negative impact on patients. Although there are a wide variety of questionnaires for general use in patients with cancer, very few are available that assess the pain, disability and craniomandibular functionality of patients with head and neck cancer (HNC) in a more specific manner. The purpose of this study is to present the preliminary behavior of the CF-PDI in its reduced version adapted for patients with HNC. MATERIAL AND METHODS: A total of 61 patients with HNC were included in a study to preliminarily analyze the internal consistency of the instrument, the convergent validity and the floor and ceiling effects. All the patients completed the informed consent document and a battery of 5 questionnaires: The Numerical Rating Scale (NRS), the Tampa Scale for Kinesiophobia for Temporomandibular Disorders (TSK-TMD), the Pain Catastrophizing Scale (PCS), the Quality of Life Questionnaire in patients with HNC (QLQ-HN) and the reduced version of the Craniofacial Pain and Disability Inventory (CF-PDI-11). Patients also performed 2 physical tests: measurements of the pain threshold on the masseter muscle and on the distal phalanx of the first finger; and the maximum mouth opening in neutral head position. RESULTS: Cronbach's α coefficient showed a very high internal consistency of 0.92. In terms of convergent validity, a statistically significant correlation was found between the CF-PDI-11 and the following variables: NRS, TSK-TMD, PCS, QLQ-HN, the threshold of pain in the distal phalanx of the first finger and the maximum interincisal opening. However, 21.3% of patients obtained the lowest possible score. The strongest correlation was found between the CF-PDI-11 and the QLQ-HN (r = 0.85, p <0.01). CONCLUSIONS: The preliminary version of the CF-PDI-11 shows that it could be a valid and reliable instrument to measure pain, disability and quality of life in patients with HNC.

Oral mucositis. Is it present in the immunotherapy of the immune checkpoint pd1/pd-l1 against oral cancer? A systematic review.

BACKGROUND: Oral mucositis (OM) is a painful lesion that takes place in the mucosa of the oral cavity, usually its etiology is associated with drug therapies in cancer patients. It is presented as well-defined ulcers whose painful symptomatology sometimes implies the suspension of oncological treatment or parenteral feeding, being therefore an important adverse effect, marking the evolution of these types of therapies against cancer. The present work aim is to know the prevalence of oral mucositis in oral cancer immunotherapy compared to its prevalence in standard therapy. MATERIAL AND METHODS: A protocol was developed for a systematic review following PRISMA® guidelines and a focused question (PICO) was constructed. A comprehensive literature search was conducted on electronic databases including PubMed, the SCOPUS database, the Cochrane library and the Web of Science (WOS). RESULTS: Six clinical trials were included that met the different inclusion criteria. In these articles, a discrepancy between the prevalence of OM in patients treated with chemotherapy and patients treated with immunotherapy related to the immune checkpoint PD-1/PD-L1 (Nivolumab and Pembrolizumab) was observed. CONCLUSIONS: The prevalence of oral mucositis is lower in new immunotherapy with monoclonal antibodies against oral cancer than drugs used so far (chemotherapy drugs [methotrexate, cisplatin] as well as cetuximab). However, more studies should be carried out to confirm these data.

Genome-wide profiling of non-smoking-related lung cancer cells reveals common RB1 rearrangements associated with histopathologic transformation in EGFR-mutant tumors.

BACKGROUND: The etiology and the molecular basis of lung adenocarcinomas (LuADs) in nonsmokers are currently unknown. Furthermore, the scarcity of available primary cultures continues to hamper our biological understanding of non-smoking-related lung adenocarcinomas (NSK-LuADs). PATIENTS AND METHODS: We established patient-derived cancer cell (PDC) cultures from metastatic NSK-LuADs, including two pairs of matched EGFR-mutant PDCs before and after resistance to tyrosine kinase inhibitors (TKIs), and then performed whole-exome and RNA sequencing to delineate their genomic architecture. For validation, we analyzed independent cohorts of primary LuADs. RESULTS: In addition to known non-smoker-associated alterations (e.g. RET, ALK, EGFR, and ERBB2), we discovered novel fusions and recurrently mutated genes, including ATF7IP, a regulator of gene expression, that was inactivated in 5% of primary LuAD cases. We also found germline mutations at dominant familiar-cancer genes, highlighting the importance of genetic predisposition in the origin of a subset of NSK-LuADs. Furthermore, there was an over-representation of inactivating alterations at RB1, mostly through complex intragenic rearrangements, in treatment-naive EGFR-mutant LuADs. Three EGFR-mutant and one EGFR-wild-type tumors acquired resistance to EGFR-TKIs and chemotherapy, respectively, and histology on re-biopsies revealed the development of small-cell lung cancer/squamous cell carcinoma (SCLC/LuSCC) transformation. These features were consistent with RB1 inactivation and acquired EGFR-T790M mutation or FGFR3-TACC3 fusion in EGFR-mutant tumors. CONCLUSIONS: We found recurrent alterations in LuADs that deserve further exploration. Our work also demonstrates that a subset of NSK-LuADs arises within cancer-predisposition syndromes. The preferential occurrence of RB1 inactivation, via complex rearrangements, found in EGFR-mutant tumors appears to favor SCLC/LuSCC transformation under growth-inhibition pressures. Thus RB1 inactivation may predict the risk of LuAD transformation to a more aggressive type of lung cancer, and may need to be considered as a part of the clinical management of NSK-LuADs patients.

Detection of Cross-Correlation between Gravitational Lensing and γ Rays.

In recent years, many γ-ray sources have been identified, yet the unresolved component hosts valuable information on the faintest emission. In order to extract it, a cross-correlation with gravitational tracers of matter in the Universe has been shown to be a promising tool. We report here the first identification of a cross-correlation signal between γ rays and the distribution of mass in the Universe probed by weak gravitational lensing. We use data from the Dark Energy Survey Y1 weak lensing data and the Fermi Large Area Telescope 9-yr γ-ray data, obtaining a signal-to-noise ratio of 5.3. The signal is mostly localized at small angular scales and high γ-ray energies, with a hint of correlation at extended separation. Blazar emission is likely the origin of the small-scale effect. We investigate implications of the large-scale component in terms of astrophysical sources and particle dark matter emission.

A novel mobile application to determine mandibular and tongue laterality discrimination in women with chronic temporomandibular disorder.

BACKGROUND: Chronic pain from temporomandibular disorders (TMDs) is caused by a somatosensory disturbance due to sustained activation of central nervous system nociceptive pathways, which can induce changes in neuroplasticity in the thalamus, basal ganglia and limbic system, as well as disturbances in the somatosensory, prefrontal and orbitofrontal cortex and cognitive impairment. The main objective of this study was to determine the discrimination capacity of mandibular and tongue laterality between women with chronic TMDs and asymptomatic women. MATERIAL AND METHODS: This descriptive-comparative study examined 2 groups with a total of 30 women. All participants were between the ages of 23 and 66 years and were assigned to the chronic TMD group or the asymptomatic group according to the inclusion criteria. We employed a mobile application developed specifically for this study to measure the accuracy and reaction time (RT) of mandibular and tongue laterality discrimination. RESULTS: The chronic TMD group had a lower success rate in laterality discrimination (mean mandibular accuracy of 40% and mean tongue accuracy of 67%) than the asymptomatic group (mean mandibular accuracy of 61% and mean tongue accuracy of 90%). These results showed statistically significant differences between the groups for mandibular laterality discrimination (d, 1.14; p<0.01) and tongue laterality discrimination (d, 0.79; p=0.03). The asymptomatic group had faster RTs than the chronic TMD group. The data revealed statistically significant differences for the right mandibular RT (d, 0.89; p=0.02) and right tongue RT (d, 0.83; p=0.03). However, there were no significant differences for left mandibular and left tongue RT. CONCLUSIONS: We found that the women with chronic TMDs had a lower success rate and slower RTs in the discrimination of mandibular laterality when compared with the asymptomatic women.

Detection of CMB-Cluster Lensing using Polarization Data from SPTpol.

We report the first detection of gravitational lensing due to galaxy clusters using only the polarization of the cosmic microwave background (CMB). The lensing signal is obtained using a new estimator that extracts the lensing dipole signature from stacked images formed by rotating the cluster-centered Stokes QU map cutouts along the direction of the locally measured background CMB polarization gradient. Using data from the SPTpol 500 deg^{2} survey at the locations of roughly 18 000 clusters with richness λ≥10 from the Dark Energy Survey (DES) Year-3 full galaxy cluster catalog, we detect lensing at 4.8σ. The mean stacked mass of the selected sample is found to be (1.43±0.40)×10^{14}M_{⊙} which is in good agreement with optical weak lensing based estimates using DES data and CMB-lensing based estimates using SPTpol temperature data. This measurement is a key first step for cluster cosmology with future low-noise CMB surveys, like CMB-S4, for which CMB polarization will be the primary channel for cluster lensing measurements.

Cosmological Constraints from Multiple Probes in the Dark Energy Survey.

The combination of multiple observational probes has long been advocated as a powerful technique to constrain cosmological parameters, in particular dark energy. The Dark Energy Survey has measured 207 spectroscopically confirmed type Ia supernova light curves, the baryon acoustic oscillation feature, weak gravitational lensing, and galaxy clustering. Here we present combined results from these probes, deriving constraints on the equation of state, w, of dark energy and its energy density in the Universe. Independently of other experiments, such as those that measure the cosmic microwave background, the probes from this single photometric survey rule out a Universe with no dark energy, finding w=-0.80_{-0.11}^{+0.09}. The geometry is shown to be consistent with a spatially flat Universe, and we obtain a constraint on the baryon density of Ω_{b}=0.069_{-0.012}^{+0.009} that is independent of early Universe measurements. These results demonstrate the potential power of large multiprobe photometric surveys and pave the way for order of magnitude advances in our constraints on properties of dark energy and cosmology over the next decade.

Prevalence of oral side effects of chemotherapy and its relationship with periodontal risk: a cross sectional study.

PURPOSE: To determine the prevalence of professionally reported oral side effects of chemotherapy and the self-reported oral side effects and whether both prevalences could be related to the periodontal risk of the patients. METHODS: A cross-sectional study with patients undergoing chemotherapy treatment was carried out. Demographic, oral hygiene habits, and cancer-related data were collected while the patient was receiving the chemotherapy infusion. Patient's oral status, measured according to the oral-assessment guide for patients in hospital environments, patient-related outcomes (PROMs), measured by a visual analogue scale, and patient's periodontal risk were analyzed using validated questionnaires. Data was reported in means and standard deviations (SD) in quantitative variables and in counts, prevalence, and 95% confidence intervals (CI) in qualitative variables. ANOVA test and chi-squared tests were used to compare oral side effects among different periodontal risk groups. RESULTS: Three hundred sixty-nine patients were included in the study. The prevalence of professionally reported oral side effects was 86.99% (95% confidence interval CI 83.54%; 90.44%). The prevalence of self-reported oral side effects was 89.70% (95% CI 86.59; 92.82). The most common oral side effects were xerostomia (73.4%), dysgeusia (61.8%), and dry lips (54.2%). More oral alterations were found in patients with worse periodontal risk (p < 0.001). CONCLUSIONS: The prevalence of oral side effects (professional or self-reported) is higher than 85% in patients undergoing chemotherapy. This prevalence increases as the risk of developing periodontal disease does.

Oral squamous cell carcinoma of tongue: Histological risk assessment. A pilot study.

BACKGROUND: More than 90% of malignant tumors diagnosed in the oral cavity are Oral Squamous Cell Carcinomas (OSCC) whose preferred location is the tongue. Classically, this disease has affected men preferentially, although recent studies suggest that trends are changing and the proportion of women with OSCC is increasing. In addition, the prevalence of oral cancer is also determined by some risk factors as alcohol consumption and tobacco. Currently, the Tumor, Node, Metastasis (TNM) classification is employed to defined tumor stage and based on this guide specific treatments are established. However, 5-year-survival does not exceed 50% of cases. The objective of this study is to determine whether a histological risk pattern indicative of higher recurrence might be present in T1-T2 tumors located in the anterior two thirds of the tongue. MATERIAL AND METHODS: Samples from 26 patients with OSCC were analyzed and histological risk pattern of recurrent and non-recurrent tumors were compared. We have analyzed histological variables described in Anneroth and Brandwein-Gensler classifications. Additionally, we have also examined both clinical variables such as age, sex or comorbidities, as well as habits such as tobacco or alcohol consumption. RESULTS: We found that sex (male) and keratinization degree (high or moderate) are directly related with OSCC recurrence. In fact, free illness time is lower in men and higher in those cases with minimal or no keratinization. CONCLUSIONS: Based on the variables analyzed, it has not been possible to establish a histological risk pattern that, complementary to the TNM classification, could have a predictive role in these early-stage tongue carcinomas.

Oral and dental health status in patients with eating disorders in Madrid, Spain.

BACKGROUND: The aim of the present study was to describe and compare the oral and dental health status of two groups, one diagnosed with eating disorders (EDs), and another group without this pathology, assessing the following oral manifestations: dental alterations, periodontal disorders, soft tissue disorders, non-stimulated salivary flow, and oral pH. MATERIAL AND METHODS: This comparative transversal epidemiological study included 179 participants, of whom 59 were diagnosed with EDs (Eating Disorder Group: EDG) and 120 had no antecedents of EDs (No Eating Disorder Group: NEDG). All patients fulfilled the following inclusion criteria: women aged over 18 years, diagnosed with an ED by a specialist, patients who had undergone at least 1 year monitoring by the Clinical Nutrition Unit, and had not received any periodontal treatment during the previous 6 months. Both groups were homogeneous in terms of sex, age, education, and socioeconomic level. Oral exploration was performed, registering clinical variables, as well as sociodemographic and socioeconomic data, oral hygiene habits, and smoking. Statistical significance was established as p<0.05 (confidence level > 95%). RESULTS: The dental erosion (DE) was the most significative feature of dental alterations. The degree of DE was significantly greater in the EDG (p<0.001). A significant association between soft tissue lesions and EDs was found (p<0.001) A notable difference in non-stimulated salivary flow was found between the groups (p<0.001). No significant differences between the groups were found for periodontal status, dental caries, or oral hygiene practices. CONCLUSIONS: On the basis of the results obtained, it is necessary to carry out oral/dental examination as soon as an ED is diagnosed with regular check-ups thereafter.

Bisphosphonate-related osteonecrosis. Application of adipose-derived stem cells in an experimental murine model.

BACKGROUND: Bisphosphonate-related osteonecrosis of the jaw is a pathological condition without effective established treatment and preventive strategies. The aim of this study was to analyse the effect of adipose-derived stem cells (ASC) in an experimental murine model of osteonecrosis. MATERIAL AND METHODS: 38 Wistar rats were injected intraperitoneally with zoledronic acid. After treatment, upper jaw molars were extracted. The animals were randomly assigned to one of two groups. In the control group, saline solution was applied over the alveolar sockets after the tooth extractions. In the treatment group, ASCs were applied instead of saline solution. The control and treatment groups were subdivided based on the time of euthanasia. A clinical and histological analysis was performed. RESULTS: The presence of osteonecrosis in alveolar bone was observed in a similar distribution in both groups. In the ASC-treated group, new bone formation was greater than in controls. CONCLUSION: In this study, application of ASCs showed greater new bone formation in an osteonecrosis-like murine model. Previous inhibited post-extraction bone remodelling could be reactivated, and these findings appeared to be secondary to implantation of ASCs.

Biventricular impact of mild to moderate fetal pulmonary valve stenosis.

OBJECTIVES: To define the pattern of fetal echocardiographic changes associated with isolated pulmonary valve stenosis (PS) and to correlate the echocardiographic findings with neonatal outcome and the need for postnatal pulmonary valvuloplasty within the first 12 months postpartum. METHODS: This was a prospective cohort study between January 2009 and October 2015 of 16 fetuses with isolated PS and 48 controls matched by gestational age at ultrasound examination (± 2 weeks) evaluated at the Fetal Cardiology Unit at BCNatal (Barcelona). Standard fetal ultrasound and comprehensive echocardiography, which included cardiovascular morphometric parameters, and systolic and diastolic functional and timing measurements, were performed in all cases. Baseline characteristics and perinatal outcome were retrieved from clinical records. Cases were followed up until 12 months of age, and admission to intensive care unit, days of hospitalization, need for prostaglandins and requirement for postnatal surgery were reviewed. Fetal PS cases were analyzed according to the need for postnatal pulmonary valvuloplasty. RESULTS: The study groups were similar in terms of baseline, fetal ultrasound and perinatal characteristics. Median gestational age at diagnosis of PS was 33.4 (range, 20.0-36.5) weeks. Most cases corresponded to mild or moderate PS; only three fetuses had reversed flow in the ductus arteriosus before delivery. Six (37.5%) newborns, including all three with reversed flow in the ductus arteriosus prenatally, required postnatal pulmonary valvuloplasty. Fetuses with PS presented with larger and more globular hearts, with increased myocardial wall thickness in the third trimester. Despite preserved right ventricular (RV) ejection fraction and systolic longitudinal motion, PS cases showed increased right cardiac output and signs of diastolic dysfunction, with higher ductus venosus pulsatility index (0.72 ± 0.32 vs 0.53 ± 0.16, P = 0.004) and tricuspid E/E' ratio (7.52 ± 3.07 vs 5.76 ± 1.79, P = 0.022). In addition, fetuses with PS displayed a compensatory increase in left ventricular (LV) radial and longitudinal motion, as shown by a higher ejection fraction (79.3 ± 8.23% vs 67.6 ± 11.3%, P = 0.003) and mitral annular-plane systolic excursion (5.94 ± 1.38 vs 5.0 ± 1.22 mm, P = 0.035). Finally, fetuses requiring postnatal pulmonary valvuloplasty showed a different pattern of echocardiographic findings from those not requiring valvuloplasty, with a significantly smaller RV and pulmonary valve diameter, reduced tricuspid annular-plane systolic excursion (5.08 ± 1.59 vs 8.07 ± 1.93 mm, P = 0.028), increased LV cardiac output (340 ± 16 vs 176 ± 44 mL/min/kg, P = 0.003) and more pronounced signs of LV diastolic dysfunction (mitral E' velocity, 5.78 ± 0.90 vs 8.16 ± 1.58 cm/s, P = 0.008). CONCLUSIONS: Fetuses with PS present with more hypertrophic, larger and more globular hearts in the third trimester of pregnancy, associated with a higher right cardiac output and impaired biventricular relaxation. In addition, signs of increased LV contraction were observed. Our data suggest that RV and LV functional parameters could be useful for predicting the need for postnatal pulmonary valvuloplasty. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Beneficial changes on plasma apolipoproteins A and B, high density lipoproteins and oxidized low density lipoproteins in obese women after bariatric surgery: comparison between gastric bypass and sleeve gastrectomy.

BACKGROUND: The beneficial effects in lipid profiles after obesity surgery might be associated with the decrease in cardiovascular risk. However, direct comparison between different surgical techniques has not been extensively performed. METHODS: In the present study we compare 20 obese women submitted to laparoscopic Roux en Y gastric bypass (RYGB) with 20 women submitted to sleeve gastrectomy (SG). Twenty control women matched for age and baseline cardiovascular risk were also included. Both patients and controls were followed up for 1 year after surgery or conventional treatment with diet and exercise, respectively. Lipid profiles were measured at baseline, 6 and 12 months later. Carotid intima-media thickness was measured by ultrasonography at baseline and at the end of the study. RESULTS: Women submitted to bariatric surgery showed a decrease in total cholesterol, triglycerides, oxidized-LDL and ApoB, and an increase in HDL and ApoA concentrations that occurred regardless of the surgical procedure. LDL concentrations, however, decreased only after RYGB whereas Lp(a) showed no changes. We did not observe any correlation between the changes in serum lipid concentrations and those in carotid intima-media thickness. CONCLUSIONS: Sleeve gastrectomy and gastric bypass induce a similar beneficial effect on serum lipids in women with high cardiovascular risk 1 year after surgery.