Advocacy in gender affirming care.

Healthcare advocacy is the duty and privilege of all healthcare providers, but especially for those who care for children. Intersex and gender diverse youth face significant barriers across many aspects of life, with access to competent gender affirming healthcare chief among them. Understanding the importance of both institutional and individual efforts in healthcare advocacy is paramount to improving healthcare access and outcomes for this population.

In silico modelling of apoptosis induced by photodynamic therapy.

Photodynamic therapy (PDT) is an emergent technique used for the treatment of several diseases. After PDT, cells die by necrosis, apoptosis or autophagy. Necrosis is produced immediately during photodynamic therapy by high concentration of reactive oxygen species, apoptosis and autophagy are triggered by mild or low doses of light and photosensitizer. In this work we model the cell response to low doses of PDT assuming a bi-dimensional matrix of interacting cells. For each cell of the matrix we simulate in detail, with the help of the Gillespie's algorithm, the two main chemical pathways leading to apoptosis. We unveil the role of both pathways in the cell death rate of the tumor, as well as the relevance of several molecules in the process. Our model suggests values of concentrations for several species of molecules to enhance the effectiveness of PDT.

Association between dental hygiene, gingivitis and overweight or the risk of overweight in primary teeth of 4- and 5-year-old preschoolers in México.

OBJECTIVE: To determine the association between dental hygiene, gingivitis and overweight or the risk of overweight according to body mass index (BMI). METHODS: A cross-sectional study was performed with 1527 preschoolers. The children were divided into 4 groups: (i) absence of visible plaque and normal weight; (ii) absence of visible plaque and risk of overweight or overweight; (iii) presence of visible plaque and normal weight; and (iv) presence of visible plaque and risk of overweight or overweight. The clinical parameters evaluated were as follows: body mass index, degree of urban marginalization, dental caries, the simplified oral hygiene index and gingival status. Bivariate analysis and multivariate binary logistic regression models were used to identify associations between variables. RESULTS: The highest mean of gingivitis (0.28) was observed in the groups with visible plaque with normal weight and with overweight and risk of overweight. The presence of visible plaque and risk of overweight or overweight were positively associated (P = .0001) with the mean of gingivitis (OR = 8.28, 95% CI = 3.30-19.8). The absence of visible plaque and risk of overweight or overweight (P = .0001) were also positively associated with the presence of gingivitis (OR = 2.44, 95% CI = 0.68-8.06). This is after both models were adjusted by gender and degree of marginalization. CONCLUSIONS: The professionals should develop interdisciplinary approaches to (i) propose appropriate interventions to improve oral health in overweight preschoolers; and (ii) propose interventions to decrease the overweight with the possibility of also reducing its association with gingivitis.

Anti-myelin antibodies play an important role in the susceptibility to develop proteolipid protein-induced experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. It is an autoimmune disorder in which activated T cells cross the blood-brain barrier (BBB) to initiate an inflammatory response that leads to demyelination and axonal damage. The key mechanisms responsible for disease initiation are still unknown. We addressed this issue in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. It is widely known that EAE manifests only in certain strains when immunized with myelin proteins or peptides. We studied the differential immune responses induced in two mouse strains that are susceptible or resistant to EAE induction when they are immunized with the 139-151 peptide of proteolipid protein, an encephalitogenic peptide capable of inducing EAE in the susceptible strain. The adequate combination of major histocompatibility complex alleles and myelin peptides triggered in susceptible mice a T helper type 17 (Th17) response capable of inducing the production of high-affinity anti-myelin immunoglobulin (Ig)G antibodies. These were not detected in resistant mice, despite immunization with the encephalitogenic peptide in junction with complete Freund's adjuvant and pertussis toxin, which mediate BBB disruption. These data show the pivotal role of Th17 responses and of high-affinity anti-myelin antibodies in EAE induction and that mechanisms that prevent their appearance can contribute to resistance to EAE.

Characterization of periodontal biofilm in Down syndrome patients: a comparative study.

UNLABELLED: The aim of this study was to characterize the main periodontal bacterial species in Down syndrome (DS) patients with and without periodontitis. METHOD: This cross-sectional study involved 75 DS patients, 45 with and 30 without periodontitis. Informed consent, health and dental questionnaires and periodontitis diagnosis were performed PCR and LAMP assays were performed on subgingival dental plaque sample. RESULTS: Tannerella forsythia was the most frequent bacteria detected in the group with and without periodontitis (95.5 and 63.3%) followed by Treponema denticola (88.8 and 50%) and Porphyromonas gingivalis (53.3 and 25% respectively). There were statistical differences between groups (p < 0.05). Pg fimA type I was the most frequent Porphyromonas gingivalis genotype. Two different sets of primers (Aa-F/Aa-R and ltx3/ltx4) were used to detect Aggregatibacter actinomycetemcomitans and different frequencies were obtained, (68% and 14.6% respectively), they had a weak correlation (Cohen Kappa = 0.16). After sequencing of PCR products, ltx3/ltx4 showed more specificity. JP2 clone of A. actinomycetemcomitans was not detected in any sample. CONCLUSIONS: The composition of oral biofilm is fundamental for the development of periodontal disease independently of immunological alterations associated with DS. The frequency of detection of A. actinomycetemcomitans reported in the literature has a wide range, because the primers and probes applied

Long-term follow-up of cardiac arrest survivors: Protocol of the DESAC (Devenir des survivants d'Arrets Cardiaques) study, a French multicentric prospective cohort.

Background: While the short-term prognosis of cardiac arrest patients - nearly 250,000 new cases per year in Europe - has been extensively studied, less is known regarding the mid and long-term outcome of survivors. Objective: The aim of the DESAC study is to describe mid- and long-term survival rate and functional status of cardiac arrest survivors, and to assess the influence of pre and intra hospital therapeutic strategies on these two outcomes. Methods: Between Jul 2015 and Oct 2018, adult patients over 18 years who were discharged alive from any intensive care units (public and private hospitals) in the Ile-de-France area (Paris and suburbs, France) after a non-traumatic cardiac arrest were screened for participation in this multicentric study. Survivors were included after they signed (or the proxies) an informed consent before discharge during initial hospitalisation. We calculated that including 600 patients in total would allow an 80% power to demonstrate a 2 years survival rate difference of 10% between patients who did and those who did not receive therapeutic hypothermia after resuscitation. Pre- and in-hospital data related to the circumstances surrounding the event and to the therapeutic interventions (such as cardio-pulmonary resuscitation, defibrillation, emergent coronary revascularization, neuroprotective therapeutics) were collected. After discharge, patients were interviewed at 3 months, 6 months and every year thereafter for a minimum follow-up of 26 months and a maximum follow-up of 48 months. Information on vital status, occurrence of cardiovascular events, medications and a comprehensive assessment of the functional status (qualitive of life as assessed by the Short-Form General Health Survey (SF36) scale, activities of daily living (ADL) scale, neurological Cerebral Performance Categories (CPC) and Overall Performance Categories (OPC) scales, socio-professional activities) were collected at follow-up interviews. Discussion: The DESAC study should provide important information regarding several dimensions of the mid and long-term prognosis of cardiac arrest survivors and on the benefit (and potentially harm) of early therapeutic strategies.

Intestinal adenocarcinoma originating from an undiagnosed Meckel's diverticulum.

Meckel's diverticulum is a congenital anomaly leading to the formation of a true diverticulum in the distal small intestine. Though most are asymptomatic and discovered incidentally, Meckel's diverticuli can give rise to a wide range of symptoms. Rarely, this can be a malignancy, most commonly a carcinoid tumor. Other cancers have also been reported, with adenocarcinomas being particularly rare. Here, we report the case of a 62-year-old man presenting to the emergency room with vague gastrointestinal symptoms. Subsequent workup revealed a 3 cm mass in the distal jejunum/proximal ileum, which was located within a previously undiagnosed Meckel's diverticulum. The mass was sent to pathology, who confirmed an adenocarcinoma arising from a small bowel diverticulum. This case serves as an important reminder of the malignant potential of a Meckel's diverticulum and adds to the ongoing discussion regarding whether prophylactic diverticulectomy should be recommended to patients with a known Meckel's diverticulum.

Mesenchymal stem cells derived from dental tissues.

Regeneration of tissues occurs naturally due to the existence of stem cells with the capacity to self-regenerate and differentiate; however, regenerative capacity decreases with age, and in many cases, regeneration is not sufficient to repair the damage produced by degenerative, ischaemic, inflammatory, or tumour-based diseases. In the last decade, advances have been made in the understanding of stem cells, the genes that control the alternative fates of quiescence and differentiation, and the niches that provide specific signals that modulate cell fate decisions. Embryonic stem-cell research is shedding light on the secrets of development. Adult stem cells (AS cells) are available from several sources. Bone marrow and connective tissue have been used in preliminary clinical trials for regenerative therapy. Recently, several types of AS cells have been isolated from teeth, including dental pulp stem cells, stem cells from human exfoliated deciduous teeth, periodontal ligament stem cells, dental follicle progenitor stem cells and stem cells from apical papilla. Preliminary data suggest that these cells have the capacity to differentiate into osteoblasts, adipocytes, chondrocytes and neural cells. If confirmed, these data would support the use of these cells, which are easily obtained from extracted teeth, in dental therapies, including in regenerative endodontics, providing a new therapeutic modality.

Synthesis, Characterization, Quantum-Chemical Calculations and Cytotoxic Activity of 1,8-Naphthalimide Derivatives with Non-Protein Amino Acids.

BACKGROUND: The 1,8-Naphthalimides constitute an important class of biologically active, DNAbinding compounds. There are no available data on the synthesis of 1,8-naphthalimide derivatives with nonprotein amino acids and their biological activity. The aim of this paper was to determine the synthesis, structural characterization and cytotoxic activity of new 1-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)cycloalkane-1- carboxylic acids with 5-, 6-, 7-, 8- and 12-membered rings as well as 2-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)- yl)adamantane-2-carboxylic acid and 1-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-1,2,3,4-tetrahydronaphthalene- 1-carboxylic acid. METHODS: The target compounds were obtained by an interaction of 1,8-naphthalic anhydride with a series of non-protein amino acids. The optimized geometry and harmonic vibrational frequencies have been calculated by DFT employing B3LYP functional using 6-31G(d,p) basis set. An ab initio (MP2 and Hartee-Fock) and DFT (different functionals) using several basis sets have been applied for NMR calculations. The cytotoxic effects of the synthesized compounds are assessed against two human tumor cell lines, namely K-562 (chronic myeloid leukemia) and HUT-78 (cutaneous T-cell lymphoma) after 72 h exposure, using the MTT-dye reduction assay. The apoptogenic effects and the ability to modulate the NFκB-signaling pathways were determined using commercially available ELISA kits. RESULTS: All compounds inhibited the growth of malignant cells at micromolar concentrations whereby compound 4b (1-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)cyclohexane-1-carboxylic acid) demonstrated superior activity in both cell lines with IC50 values comparable to those of the reference anticancer drug melphalan. CONCLUSION: New 1,8-naphthalimide derivatives with non-protein amino acids were successfully synthesized. Quantum-chemical calculations were performed to elucidate the structure of the newly synthesized compounds. There is a proper alignment between theoretical and experimental results. The cytotoxicity of the synthesized products against two human tumor cell lines, namely K-562 and HUT-78 was evaluated. All compounds inhibited the growth of malignant cells at micromolar concentrations. The pharmacodynamics evaluation of compound 4b showed that its cytotoxicity is mediated by induction of apoptosis and inhibition of NFκB-signaling.

National survey on edentulism and its geographic distribution, among Mexicans 18 years of age and older (with emphasis in WHO age groups).

To determine the prevalence of edentulism in adults aged 18 years and older in Mexico and to describe its distribution in 20 of the 32 States in Mexico, highlighting the experience in the WHO age groups. A secondary analysis of the National Performance Evaluation Survey 2002-2003 (representative at the state level and part of the Word Health Survey) was undertaken. The sample design was probabilistic, stratified and through conglomerates. Data on dental conditions were available only for 20 of the 32 states of Mexico, leading to a total of 24 159 households (N = 54 638 654). The percentage of edentulism was determined as the proportion of subjects that self-reported complete loss of teeth. Data were analyzed using the SVY module for complex surveys in STATA 8.2. The mean age was 41.3 +/- 17.0 years (range 18-99). An estimated 6.3% (N = 3 437 816) of the population > or =18 years was edentulous. Lowest prevalences were observed in the states of Tlaxcala, Puebla and the Estado de Mexico with 3.4%, 3.8% and 4.5%, respectively. Highest prevalences were observed in San Luis Potosí, Colima, and Michoacán with 10.3%, 10.2% and 10.1%, respectively. Following the WHO age groups, the prevalence ranged from 2.4% in the 35-44 group through 25.5% in the 65-74 group. No obvious association between socio-economic and socio-demographic indicators at the state level and prevalence of edentulism was found. The prevalence of complete tooth loss observed in the present study varied greatly across states, although no straightforward association was found with socio-economic and socio-demographic indicators at the state level. This study could serve as a baseline to enable future evaluations of the oral status of Mexican adults and elders, following WHO age groups.

[Differences in the management of patients with atrial fibrillation according to whether primary care or the specialist initiates treatment with direct oral anticoagulants. The SILVER-AP and BRONCE-AP studies]. / Diferencias en el manejo de los pacientes con fibrilación auricular según inicie el tratamiento con anticoagulantes orales de acción directa el médico de atención primaria o el especialista. Estudios SILVER-AP y BRONCE-AP.

OBJECTIVES: To determine the clinical characteristics and management of patients with non-valvular atrial fibrillation (NVAF) treated with direct oral anticoagulants (DOAC) according to who initiates their prescription, the Primary Care (PC) physician or referring the patient to a specialist. MATERIAL AND METHODS: Two observational, cross-sectional and multicentre studies were compared for this purpose. The SILVER-AP study was performed in those autonomous communities in which the PC physician can prescribe DOAC directly, and the BRONCE-AP study in those autonomous communities in which the PC physician has to refer the patient to the specialist to start treatment with DOAC. Patients on chronic treatment with anticoagulants, in whom therapy was changed, and those that were on current treatment with DOAC for at least 3months, were included. RESULTS: A total of 1,036 patients (790 from SILVER-AP study and 246 from BRONCE-AP study) were included. Compared with the BRONCE-AP study, those patients included in SILVER-AP were older and had more comorbidities, as well as a higher thromboembolic and haemorrhagic risk (CHA2DS2-VASc 4.3±1.6 vs. 3.8±1.8; P<.001; HAS-BLED 2.1±0.8 vs. 1.8±1.0; P<.001). Therapeutic adherence and satisfaction with treatment were high. Low doses of DOAC were frequently prescribed, particularly with dabigatran. CONCLUSIONS: Those patients in whom the PC physician can prescribe DOAC directly have a worse clinical profile, as well as a higher thromboembolic and haemorrhagic risk than those patients in whom the PC physician has to refer to the specialist.

Clinical characteristics and management of patients with atrial fibrillation treated with direct oral anticoagulants according to blood pressure control.

OBJECTIVE: To determine the clinical characteristics and management of hypertensive patients with nonvalvular atrial fibrillation (AF) treated with direct oral anticoagulants (DOACs) according to blood pressure (BP) control. METHODS: For this purpose, data from two observational, cross-sectional and multicenter studies were combined. In both studies, patients on chronic treatment with anticoagulants and that were on current treatment with DOACs at least for 3 months were included. Adequate BP was defined as a systolic BP<140mmHg and a diastolic BP<90mmHg (<140/85mmHg if diabetes). RESULTS: Overall, 1036 patients were included. Of these, 881 (85%) had hypertension that were finally analyzed. The presence of other risk factors and cardiovascular disease was common. Mean BP was 132.6±14.3/75.2±9.2mmHg and 70.5% of patients achieved BP goals. Those patients with a poor BP control had more frequently diabetes, and a history of prior labile INR. Patients had a high thromboembolic risk, but without significant differences according to BP control. By contrast, more patients with a poor BP control had a higher bleeding risk (HAS-BLED ≥3: 24.0% vs 35.4%; P<0.001). HAS-BLED score was an independent predictor of poor BP control (odds ratio 1.435; 95% confidence interval 1.216-1.693; P<0.001). Satisfaction with anticoagulant treatment was independent of BP control. CONCLUSIONS: More than two thirds of our patients with hypertension and AF anticoagulated with DOACs achieve BP targets, what is clearly superior to that reported in the general hypertensive population.

Photodynamic therapy: Toward a systemic computational model.

We have designed a systemic model to understand the effect of Photodynamic Therapy (PDT) on long time scales. The model takes into account cell necrosis due to oxygen reactive species, cell apoptosis through the caspase pathway and the competition between healthy and tumor cells. We attempted to describe the system using state of the art computational techniques (necrosis and apoptosis) and simple models that allow a deeper understanding of the long time scale processes involved (healing and tumor growth). We analyzed the influence of the surface and tumor depth on the effectiveness of different treatment plans and we proposed, for the set of parameters used in this work, an optimum timing between sessions of PDT.

Childhood trauma and psychotic experiences in a general population sample: A prospective study on the mediating role of emotion regulation.

BACKGROUND: The causal role of childhood trauma for psychosis is well established, but the mechanisms that link trauma to psychosis are largely unknown. Since childhood trauma is known to cause difficulties in emotion regulation (ER) and patients with psychosis show impaired ER, we hypothesize that impaired ER explains why people with a background of trauma are prone to psychotic experiences. METHODS: The study used a longitudinal cohort design based on a community sample (N=562) from Germany, Indonesia, and the United States. Childhood trauma was assessed at baseline. ER and psychotic experiences (defined as positive symptom frequency and related distress) were measured repeatedly at a 4-, 8-, and 12-month follow-up. Cross-lagged panel and longitudinal mediation analyses with structural equation modeling were used to test the predictive value of ER on psychotic experiences and its mediating role in the association of childhood trauma and psychotic experiences. RESULTS: The cross-lagged paths from impaired ER to symptom distress (but not frequency) were significant. However, there was also evidence for the reverse causation from symptom frequency and distress to impaired ER. ER partially mediated the significant prospective paths from childhood trauma to symptom distress. CONCLUSION: The findings demonstrate that ER plays a role in translating childhood trauma into distressing psychotic experiences in later life. Moreover, the findings point to a maintenance mechanism in which difficulties in ER and symptom distress exacerbate each other. Thus, ER could be a promising target for interventions aimed at prevention of psychosis.

Implications of the anatomical classification of the neovascular form of age-related macular degeneration. / Implicaciones de la clasificación anatómica de la forma neovascular de la degeneración macular asociada a la edad.

OBJECTIVE: To present the clinical relevance of the anatomical classification of the neovascular form of Age-Related Macular Degeneration (AMD). METHODS: Critical analysis of the current situation in the management of patients with neovascular AMD, by reviewing the available scientific evidence with regards to the classification of the types of neovascular lesion by angiography and optical coherence tomography (OCT). RESULTS: The classification of the neovascular lesion type secondary to AMD by OCT in type 1 lesions (under the pigment epithelium), type 2 (subretinal), and type 3 (retinal angiomatous proliferation), provides an added value in allowing to establish a long-term visual prognosis, an estimate of the number of treatments that a certain case may require, and a stratification of the risk for secondary geographic atrophy. CONCLUSIONS: Incorporating OCT to the initial qualitative analysis of cases with neovascular AMD offers an added value superior to that provided by the angiography, with the relevant clinical implications.

Alcohol intake impairs glucose counterregulation during acute insulin-induced hypoglycemia in IDDM patients. Evidence for a critical role of free fatty acids.

In this study, we assessed the effects of alcohol intake on glucose counterregulation in response to acute insulin-induced hypoglycemia in IDDM patients and in normal control subjects. Nine euglycemic IDDM patients and 9 normal control subjects were studied. After a baseline period, insulin (0.15 U/kg) was administered subcutaneously to induce hypoglycemia. Each IDDM patient was studied 3 times. In the first study, alcohol was orally administered as wine. In the second (control) study, water was administered instead of wine. In the third study, wine was given; however, a continuous infusion of heparin plus intralipid was administered to prevent the fall in plasma free fatty acid. Normal control subjects underwent only the alcohol and the control studies. In IDDM patients alcohol intake impairs, whereas in normal subjects it supports glucose counterregulation. Alcohol intake is associated with normal catecholamine responses in both IDDM diabetic patients and normal subjects. In both IDDM patients and normal subjects, hepatic glucose production in the recovery phase of the alcohol study was normal. Plasma glucose rate of disappearance was significantly increased by alcohol intake in IDDM (13.72 +/- 0.82 vs. 11.84 +/- 0.53 mumol.kg-1 x min-1; P < 0.05). Alcohol intake in both normal subjects and IDDM patients decreased plasma free fatty acid (267 +/- 22 vs. 156 +/- 20 microM; P < 0.01 and 356 +/- 29 vs. 96 +/- 12 microM; P < 0.01). We hypothesized that in IDDM patients, deficient glucose recovery during alcohol intake is the result of the ability of alcohol to depress lipolysis.

Rigiscan evaluation of specific nervous impairment in patients with diabetes and erectile disorders.

OBJECTIVE: A proposed new, minimally invasive, and painless method for studying impairment of the autonomic system of the penile region in type 2 diabetes patients. RESEARCH DESIGN AND METHODS: Thirteen subjects were selected from 150 patients with type 2 diabetes and erectile dysfunction who were studied in accordance with the National Institutes of Health consensus. The 13 subjects (group A), aged 55 +/- 8 years, had acceptable metabolic control (HbA1c, < 8%); no arterial or venous diseases or initial Peyronie's disease, as evaluated by penile Doppler ultrasonography and intracavernous prostaglandin E1 injection; and penile tumescence at the base (PTB) < 30 mm. Group B consisted of 13 control subjects with the same characteristics, including mean age (53.1 +/- 9 years), metabolic control (HbA1c, 7.3 +/- 0.7%), and duration of disease (8.3 +/- 0.7 years), but PTB was > 30 mm. Student's t test was used to evaluate differences in the results of autonomic cardiovascular tests, somatic tests (vibration perception threshold [VPT]), and diabetic neuropathy score (DNS) in both groups. The coefficient of variation of PTB was evaluated using the Rigiscan device (Dacomed, Minneapolis, MN), and Bayes' test was used to test sensitivity, specificity, and positive predictive values of the cardiovascular tests. RESULTS: Patients with PTB < 30 mm had significant (P < 0.05) impairment of parasympathetic tests (lying to standing, P < 0.02; standing to lying, P < 0.04; squat test, P < 0.03) compared with subjects with higher PTB values. No difference in DNS and VPT at the base and tip of the penis was found between the two groups. The variability of the test is 10% in normal subjects and 15% in both groups of patients. PTB sensitivity was 54%, specificity 89%, and positive predictive value 79%. CONCLUSIONS: In patients with diabetes and without vascular diseases, the PTB evaluated by Rigiscan is related to impairment of the autonomic nervous system. A PTB value < 30 mm may be considered a useful, noninvasive marker in studying parasympathetic damage of the penile region.

Foraging Allocation in the Honey Bee, Apis mellifera L. (Hymenoptera, Apidae), Tuned by the Presence of the Spinosad-Based Pesticide GF-120.

Agroecosystem management commonly involves the use of pesticides. As a result, a heterogeneous landscape is created, in which suitable and unsuitable spaces are defined by the absence/presence of pesticides. In this study, we explored how foragers of the honey bee, Apis mellifera L., adapt to such context. We specifically evaluated the effect of GF-120, a spinosad-based fruit fly toxic bait, on the allocation of foragers between food sources under the hypothesis that foragers will move from food sources with GF-120 to food sources without it. We thus carried out three experiments: in experiment 1, a group of foragers was trained to collect honey solution from a feeder; next, this feeder offered a GF-120/honey solution. A minority of foragers continued collecting the GF-120/honey solution. In experiment 2, we trained two groups of foragers from a colony to two food sources equally rewarding. Next, GF-120 was added to one of the food sources. We found that the majority of foragers moved from the GF-120-treated feeder to the feeder without GF-120 and that the minority that continued visiting the GF-120-treated feeder did not collect the GF-120/honey solution. In a third experiment, we wanted to know if foragers in an experimental setup as in experiment 1 would perform waggle dances: none of the foragers that collected GF-120/honey were observed dancing. Our results emphasize the importance of "food refuges" for non-target species, since they minimize the impact of agrochemicals upon them.