ABSTRACT
Germline gain of function variations in the AKT3 gene cause brain overgrowth syndrome with megalencephaly and diffuse bilateral cortical malformations. Here we report a child with megalencephaly, who is a carrier of a novel heterozygous missense variant in the AKT3 gene NM_005465.7:c.964G>T,p.Asp322Tyr. The phenotype of this patient is associated with pituitary deficiencies diagnosed at 2 years of age: growth hormone (GH) deficiency responsible for growth delay and central hypothyroidism. After 6 months of GH treatment, intracranial hypertension was noted, confirmed by the observation of papilledema and increased intracranial pressure, requiring the initiation of acetazolamide treatment and the discontinuation of GH treatment. This is the second reported patient described with megalencephaly and AKT3 gene variant associated with GH deficiency . Other endocrine disorders have also been reported in few cases with hypothyroidism and hypoglycemia. Pituitary deficiency may be a part of the of megalencephaly phenotype secondary to germline variant in the AKT3 gene. Special attention should be paid to growth in these patients and search for endocrine deficiency is necessary in case of growth retardation or hypoglycemia.
Subject(s)
Germ-Line Mutation , Megalencephaly , Mutation, Missense , Proto-Oncogene Proteins c-akt , Humans , Megalencephaly/genetics , Megalencephaly/pathology , Mutation, Missense/genetics , Proto-Oncogene Proteins c-akt/genetics , Germ-Line Mutation/genetics , Male , Child, Preschool , Phenotype , Hypothyroidism/genetics , Hypothyroidism/pathology , Hypothyroidism/complications , Female , Human Growth Hormone/deficiency , Human Growth Hormone/geneticsABSTRACT
AIMS: To evaluate the incidence of the skin reactions secondary to continuous subcutaneous insulin infusion (CSII) or continuous glucose monitoring (CGM), sensors and the characteristics of affected children with type 1 diabetes. METHODS: An observational, retrospective, single-centre study included 198 children with type 1 diabetes, (46% girls, mean age 11.75 years). A standardised questionnaire was completed with the patient during current care to evaluate the skin reactions (mean and percentage), the type of reaction, their impact and the treatment) and the characteristics of affected children with univariate and multivariate analysis. RESULTS: Sixty-seven children (33.8%) reported active skin reactions: 45 children with CSII (30.4%) and 46 with CGM (23.5%). Children with skin reactions were younger (mean age 10.6 yo versus 12.34 yo, p < 0.05), with a younger age at the diagnosis of diabetes (5.59 yo versus 7.08 yo, p < 0.05). Atopy was more frequent in the group with skin reactions (76.1% versus 54.1% p < 0.05). On multivariate analysis, only the personal history of atopy was associated with skin reactions: OR 2.56 [1.16-5.97] (p < 0.05). CONCLUSION: This study confirms the high incidence of skin reactions to adhesive devices used in the treatment of type 1 diabetes in children.
Subject(s)
Diabetes Mellitus, Type 1 , Insulin , Female , Humans , Child , Male , Insulin/adverse effects , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/epidemiology , Hypoglycemic Agents/adverse effects , Blood Glucose Self-Monitoring , Incidence , Retrospective Studies , Blood Glucose , Insulin, Regular, Human/therapeutic use , Insulin Infusion Systems/adverse effectsABSTRACT
BACKGROUND: Congenital adrenal hyperplasia (CAH) is a disease that is part of neonatal screening. There are many causes of false-positive results on neonatal screening, and maternal opioid consumption during pregnancy is suspected to increase 17-hydroxyprogesterone (17-OHP) levels at birth. The aim of this study was to determine the effect of maternal drug consumption on 17-OHP values on neonatal screening. MATERIAL AND METHODS: We studied 17-OHP levels of term newborns with reported maternal drug consumption born at the Maternity Hospital of Nancy between 2002 and 2018. These infants were matched with newborns of mothers without drug addiction. The 17-OHP levels, withdrawal syndromes, birth parameters, and maternal characteristics were compared between the two groups. RESULTS: The study included 241 patients (121 in the drug-exposed group, 120 in the control group). The mean 17-OHP levels in newborns of mothers with substance addiction were 9.83 nmol/L compared to 4.90 nmol/L (p=0.0001) in the control group. Newborns exposed to drugs were smaller (p=0.0001), lighter (p=0.0001), had smaller head circumference (p=0.0001), and had lower Apgar scores (p=0.004 at 1 min and p=0.0001 at 5 min). The 17-OHP level did not differ in cases of withdrawal syndrome in drug-exposed newborn (p=0.911). CONCLUSION: A significant increase in 17-OHP levels was observed in newborns exposed to drugs, with no influence of withdrawal syndrome on 17-OHP levels. Maternal substance addiction may be associated with moderately increased 17-OHP levels during neonatal screening.
Subject(s)
Adrenal Hyperplasia, Congenital , Opioid-Related Disorders , Substance Withdrawal Syndrome , Humans , Infant, Newborn , Female , Pregnancy , Progesterone , Neonatal Screening/methods , Adrenal Hyperplasia, Congenital/diagnosis , 17-alpha-Hydroxyprogesterone , Mothers , Opioid-Related Disorders/diagnosisABSTRACT
PURPOSE: Anorexia nervosa (AN) is a serious mental illness. It is frequently accompanied by a history of childhood maltreatment (CM) that may constitute a specific ecophenotype in patients with eating disorders necessitating special assessment and management. This retrospective study tested whether in patients with AN, CM-related chronic stress may manifest through low-grade inflammation reflected by an increase in white blood cell ratios (neutrophil-to-lymphocyte ratio, NLR, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio). METHODS: Participants (N = 206) were enrolled at an eating disorder daycare unit in Montpellier, France, from March 2013 and January 2020. CM was assessed using the childhood trauma questionnaire (CTQ). The Eating Disorder Examination Questionnaire (EDE-Q) and the MINI were used to assess AN severity and the other clinical characteristics, respectively. RESULTS: NLR was higher in patients with AN and history of CM (p = 0.029) and in patients with AN and history of emotional abuse (p = 0.021), compared with patients with AN without history of CM. In multivariate analysis, emotional abuse (ß = 0.17; p = 0.027) contributed significantly to NLR variability. CONCLUSION: In patients with AN, NLR is a low-grade inflammation marker that is influenced by various sociodemographic, clinical and biological factors. It is more directly affected by some CM types, especially emotional abuse, than by the presence/absence of CM history. Future studies should focus on mediators between CM and increased inflammation, such as interoceptive awareness, emotional dysregulation, food addiction, and stress sensitization. LEVEL OF EVIDENCE: III. Evidence obtained from well-designed cohort or case-control analytic studies.
Subject(s)
Anorexia Nervosa , Child Abuse , Anorexia Nervosa/psychology , Child , Child Abuse/psychology , Cohort Studies , Humans , Inflammation , Lymphocytes , Neutrophils , Retrospective StudiesABSTRACT
The development of biofouling is a major problem for marine industries. The conception of antifouling and fouling release coatings, with controlled physical-chemical properties is a promising strategy. Among them, amphiphilic systems, such as those composed of a hydrophobic polydimethylsiloxane matrix and a hydrophilic polyethyleneglycol additive are the most efficient and up to date. Despite their effectiveness, these systems are questioned due to the petrochemical origin of PDMS. The aim of this project was to substitute the PDMS matrix with a biopolymer, poly(3-hydroxybuyrate-co-3-hydroxyvalerate) and to improve its anti-adhesion properties through the elaboration of an amphiphilic system, via the addition of PEG or PHBHHx-b-PEG copolymer. The results, including the physico-chemical properties of PHBHV based coatings and static adhesion tests on a marine bacterium, Bacillus 4J6 and a diatom, Phaeodactylum tricornutum are compared with those of PDMS and PEG-modified PDMS coatings. Real antiadhesion activity was obtained for the PHBHV/PHBHHx-b-PEG system for a promising eco-friendly strategy.
Subject(s)
Biofouling , Diatoms , Biofouling/prevention & control , Polyethylene Glycols , Polymers , Surface PropertiesABSTRACT
Automated closed-loop (CL) insulin therapy has come of age. This major technological advance is expected to significantly improve the quality of care for adults, adolescents and children with type 1 diabetes. To improve access to this innovation for both patients and healthcare professionals (HCPs), and to promote adherence to its requirements in terms of safety, regulations, ethics and practice, the French Diabetes Society (SFD) brought together a French Working Group of experts to discuss the current practical consensus. The result is the present statement describing the indications for CL therapy with emphasis on the idea that treatment expectations must be clearly defined in advance. Specifications for expert care centres in charge of initiating the treatment were also proposed. Great importance was also attached to the crucial place of high-quality training for patients and healthcare professionals. Long-term follow-up should collect not only metabolic and clinical results, but also indicators related to psychosocial and human factors. Overall, this national consensus statement aims to promote the introduction of marketed CL devices into standard clinical practice.
Subject(s)
Diabetes Mellitus, Type 1 , Insulin Infusion Systems , Insulin , Adolescent , Adult , Child , Diabetes Mellitus, Type 1/drug therapy , France , Humans , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosageABSTRACT
Current pulpotomy is limited in its ability to induce regeneration of the dental-pulp (DP) complex. Hydrogels are reported to be well-suited for tissue engineering and are unlikely to induce an inflammatory response that might damage the remaining tissue. The present study investigated the molecular and cellular actors in the early inflammatory/immune response and deciphered M1/M2 macrophage polarisation to a chitosan-enriched fibrin hydrogel in pulpotomised rat incisors. Both fibrin and fibrin-chitosan hydrogels induced a strong increase in interleukin-6 (IL-6) transcript in the DP when compared to the DP of untreated teeth. Gene expression of other inflammatory mediators was not significantly modified after 3 h. In the viable DP cell population, the percentage of leukocytes assessed by flow cytometry was similar to fibrin and fibrin-chitosan hydrogels after 1 d. In this leukocyte population, the proportion of granulocytes increased beneath both hydrogels whereas the antigen-presenting cell, myeloid dendritic cells, T cells and B cells decreased. The natural killer (NK) cell population was significantly decreased only in DPs from teeth treated with fibrin-chitosan hydrogel. Immunolabeling analysis of the DP/hydrogel interface showed accumulation of neutrophil granulocytes in contact with both hydrogels 1 d after treatment. The DP close to this granulocyte area contained M2 but no M1 macrophages. These data collectively demonstrated that fibrin-chitosan hydrogels induced an inflammatory/immune response similar to that of the fibrin hydrogel. The results confirmed the potential clinical use of fibrin-chitosan hydrogel as a new scaffold for vital-pulp therapies.
Subject(s)
Chitosan/chemistry , Dental Pulp/immunology , Dental Pulp/pathology , Fibrin/chemistry , Hydrogels/chemistry , Immunity , Incisor/immunology , Pulpotomy , Animals , Female , Gene Expression Regulation , Humans , Inflammation Mediators/metabolism , Macrophage Activation , Macrophages/metabolism , Neutrophils/metabolism , Prosthesis Implantation , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Comorbidity of bipolar disorder (BD) and eating disorders (ED) is common and increases the course and severity of BD. However, the impact of comorbid BD on the clinical profile of ED patients remains unclear. Most studies have focused on patients primarily assessed for BD and data on patients with a primary diagnosis of ED are sparse. We investigated the association between a dual diagnosis and severity in terms of clinical, neuropsychological dimensions and daily functioning. METHOD: Two hundred and sixty-one patients with ED were consecutively recruited. BD was screened with the MINI and further confirmed in the French expert centre network. The severity of ED symptoms was assessed with the EDE-Q and EDI-2, daily functioning with the FAST. The neurocognitive assessment targeted attention, set-shifting and decision-making. RESULTS: Forty-nine patients screened positive for BD, but diagnosis was confirmed in only thirty patients (11.5% of the cohort). After multiple adjustments, comorbidity was associated with greater severity on the total score and three subscales of the EDE-Q and on four of the ten dimensions of the EDI-2. Comorbid BD was associated with lower daily functioning but not with lower neuropsychological performance. LIMITATIONS: Sample referred to specialist clinics not large enough to authorize an analysis by subtype and cross-sectional evaluation. CONCLUSION: The association between ED and BD increases ED severity for most of these core features. It negatively impacts daily functioning. The results also highlight issues about the validity of screening tools to detect BD in patients with ED.
Subject(s)
Bipolar Disorder/complications , Feeding and Eating Disorders/complications , Severity of Illness Index , Adolescent , Adult , Aged , Bipolar Disorder/diagnosis , Bipolar Disorder/psychology , Cross-Sectional Studies , Disability Evaluation , Feeding and Eating Disorders/diagnosis , Feeding and Eating Disorders/psychology , Female , Humans , Logistic Models , Male , Middle Aged , Neuropsychological Tests , Psychiatric Status Rating Scales , Young AdultABSTRACT
The use by diabetes patients of real-time continuous interstitial glucose monitoring (CGM) or the FreeStyle Libre® (FSL) flash glucose monitoring (FGM) system is becoming widespread and has changed diabetic practice. The working group bringing together a number of French experts has proposed the present practical consensus. Training of professionals and patient education are crucial for the success of CGM. Also, institutional recommendations must pay particular attention to the indications for and reimbursement of CGM devices in populations at risk of hypoglycaemia. The rules of good practice for CGM are the precursors of those that need to be enacted, given the oncoming emergence of artificial pancreas devices. It is necessary to have software combining user-friendliness, multiplatform usage and average glucose profile (AGP) presentation, while integrating glucose and insulin data as well as events. Expression of CGM data must strive for standardization that facilitates patient phenotyping and their follow-up, while integrating indicators of variability. The introduction of CGM involves a transformation of treatment support, rendering it longer and more complex as it also includes specific educational and technical dimensions. This complexity must be taken into account in discussions of organization of diabetes care.
Subject(s)
Blood Glucose Self-Monitoring , Patient Education as Topic , Practice Guidelines as Topic , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/therapy , France , Humans , Retrospective StudiesABSTRACT
AIM: To assess the impact on fear of hypoglycaemia and treatment satisfaction with an artificial pancreas system used for 2 consecutive months, as well as participant acceptance of the artificial pancreas system. METHODS: In a randomized crossover trial patient-related outcomes associated with an evening-and-night artificial pancreas and sensor-augmented pump therapy were compared. Both intervention periods lasted 8 weeks. The artificial pancreas acceptance questionnaire (range 0-90, higher scores better), Hypoglycaemia Fear Survey II (range 0-72, higher scores worse) and Diabetes Treatment Satisfaction Questionnaire (range 0-36, higher scores better) were completed by 32 participants. Semi-structured interviews were conducted after study completion in a subset of six participants. Outcomes were compared using a repeated-measures anova model or paired t-test when appropriate. RESULTS: The total artificial pancreas acceptance questionnaire score at the end of the artificial pancreas period was 69.1 (sd 14.7; 95% CI 63.5, 74.7), indicating a positive attitude towards the artificial pancreas. No significant differences were found among the scores at baseline, end of sensor-augmented pump therapy period or end of the artificial pancreas period with regard to fear of hypoglycaemia [28.2 (sd 17.5), 23.5 (sd 16.6) and 23.5 (sd 16.7), respectively; P = 0.099] or diabetes treatment satisfaction [29.0 (sd 3.9), 28.2 (sd 5.2) and 28.0 (sd 7.1), respectively; P = 0.43]. Themes frequently mentioned in the interviews were 'positive effects at work', 'improved blood glucose', 'fewer worries about blood glucose', but also 'frequent alarms', 'technological issues' and 'demand for an all-in-one device'. CONCLUSIONS: The psychological outcomes of artificial pancreas and sensor-augmented pump therapy were similar. Current artificial pancreas technology is promising but user concerns should be taken into account to ensure utility of these systems.
Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Fear/psychology , Hypoglycemia/psychology , Hypoglycemic Agents/administration & dosage , Insulin Infusion Systems , Insulin/administration & dosage , Pancreas, Artificial , Patient Satisfaction , Adult , Blood Glucose/metabolism , Cross-Over Studies , Diabetes Mellitus, Type 1/metabolism , Female , Humans , Hypoglycemia/chemically induced , Hypoglycemic Agents/adverse effects , Insulin/adverse effects , Male , Middle Aged , Surveys and QuestionnairesABSTRACT
Patients with eating disorders (EDs) frequently report a history of childhood trauma (CT). We investigated whether certain subtypes of CT are associated with more severe features of EDs, independently of psychiatric comorbidity, and whether they act additively. One hundred and ninety-two patients with DSM-V-defined EDs were consecutively recruited. Five clinical characteristics were assessed: restraint, eating, shape and weight concerns on the EDE-Q, and daily functioning. CT was assessed by the childhood traumatism questionnaire. The clinical features were associated with at least one CT subtype (emotional, sexual or physical abuse, emotional neglect). Multivariate analyses adjusted for lifetime comorbid psychiatric disorders revealed that emotional abuse independently predicted higher eating, shape and weight concerns and lower daily functioning, whereas sexual and physical abuse independently predicted higher eating concern. A dose-effect relationship characterised the number of CT subtypes and the severity of the clinical features, suggesting a consistent and partly independent association between CT and more severe clinical and functional characteristics in EDs. Emotional abuse seems to have the most specific impact on ED symptoms. Last, not all CT subtypes have the same impact but they do act additively.
Subject(s)
Feeding and Eating Disorders/diagnosis , Adolescent , Adult , Aged , Child , Child Abuse, Sexual , Demography , Emotions , Feeding and Eating Disorders/etiology , Female , Humans , Male , Middle Aged , Multivariate Analysis , Physical Abuse , Stress, Psychological , Surveys and Questionnaires , Young AdultABSTRACT
Proinflammatory cytokines exert cytotoxic effects on ß-cells, and are involved in the pathogenesis of type I and type II diabetes and in the drastic loss of ß-cells following islet transplantation. Cytokines induce apoptosis and alter the function of differentiated ß-cells. Although the MAP3 kinase tumor progression locus 2 (Tpl2) is known to integrate signals from inflammatory stimuli in macrophages, fibroblasts and adipocytes, its role in ß-cells is unknown. We demonstrate that Tpl2 is expressed in INS-1E ß-cells, mouse and human islets, is activated and upregulated by cytokines and mediates ERK1/2, JNK and p38 activation. Tpl2 inhibition protects ß-cells, mouse and human islets from cytokine-induced apoptosis and preserves glucose-induced insulin secretion in mouse and human islets exposed to cytokines. Moreover, Tpl2 inhibition does not affect survival or positive effects of glucose (i.e., ERK1/2 phosphorylation and basal insulin secretion). The protection against cytokine-induced ß-cell apoptosis is strengthened when Tpl2 inhibition is combined with the glucagon-like peptide-1 (GLP-1) analog exendin-4 in INS-1E cells. Furthermore, when combined with exendin-4, Tpl2 inhibition prevents cytokine-induced death and dysfunction of human islets. This study proposes that Tpl2 inhibitors, used either alone or combined with a GLP-1 analog, represent potential novel and effective therapeutic strategies to protect diabetic ß-cells.
Subject(s)
Diabetes Mellitus, Type 2/etiology , MAP Kinase Kinase Kinases/metabolism , Peptides/metabolism , Venoms/metabolism , Apoptosis , Chronic Disease , Cytokines , Diabetes Mellitus, Type 2/pathology , Exenatide , Humans , InflammationABSTRACT
UNLABELLED: Low bone mass is a consequence of anorexia nervosa (AN). This study assessed the effects of energy deficiency on various bone and hormonal parameters. The interrelationships between energy deficiency and bone remodelling, glucose homeostasis and adipokines underscore the importance of preventing energy deficiency to limit demineralisation and hormonal alterations in AN patients. INTRODUCTION: Low areal bone mineral density (aBMD) is a well-known consequence of AN. However, the impact of reduced energy expenditure on bone metabolism is unknown. This study assessed the effects of energy deficiency on bone remodelling and its potential interactions with glucose homeostasis and adipose tissue-derived hormones in AN, a clinical model for reduced energy expenditure. METHODS: Fifty women with AN and 50 age-matched controls (mean age 18.1 ± 2.7 and 18.0 ± 2.1 years, respectively) were enrolled. aBMD was determined with DXA. Resting energy expenditure (REEm), a marker of energy status, was indirectly assessed by calorimetry. Bone turnover markers, undercarboxylated osteocalcin (ucOC), parameters of glucose homeostasis, adipokines and growth factors were concomitantly evaluated. RESULTS: AN patients presented low aBMD at all bone sites. REEm, bone formation markers, ucOC, glucose, insulin, HOMA-IR, leptin and IGF-1 were significantly reduced, whereas the bone resorption marker, leptin receptor (sOB-R) and adiponectin were elevated in AN compared with CON. In AN patients, REEm was positively correlated with weight, BMI, whole body (WB) fat mass, WB fat-free soft tissue, markers of bone formation, glucose, insulin, HOMA-IR, leptin and IGF-1 and negatively correlated with the bone resorption marker and sOB-R. Biological parameters, aBMD excepted, appeared more affected by the weight variation in the last 6 months than by the disease duration. CONCLUSIONS: The strong interrelationships between REEm and bone remodelling, glucose homeostasis and adipokines underscore the importance of preventing energy deficiency to limit short- and long-term bone demineralisation and hormonal alterations in AN patients.
Subject(s)
Adipokines/blood , Anorexia Nervosa/physiopathology , Blood Glucose/metabolism , Bone Remodeling/physiology , Energy Metabolism/physiology , Adolescent , Anorexia Nervosa/blood , Anorexia Nervosa/complications , Anthropometry/methods , Biomarkers/blood , Body Weight/physiology , Bone Density/physiology , Bone Diseases, Metabolic/blood , Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/physiopathology , Case-Control Studies , Female , Homeostasis/physiology , Humans , Intercellular Signaling Peptides and Proteins/blood , Menstruation/physiology , Time Factors , Young AdultABSTRACT
Recent experimental data suggest that circulating serotonin interacts with bone metabolism, although this is less clear in humans. This study investigated whether serum serotonin interferes with bone metabolism in young women with anorexia nervosa (AN), a clinical model of energy deprivation. Serum serotonin, markers of bone turnover [osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), type I-C telopeptide breakdown products (CTX)], leptin, soluble leptin receptor (sOB-R), and insulin-like growth factor-1 (IGF-1) and its binding protein (IGFBP-3) were assessed. Whole body, spine, hip, and radius areal bone mineral density BMD (aBMD) were assessed by dual-energy X-ray absorptiometry in 21 patients with AN and 19 age-matched controls. Serum serotonin, leptin, IGF-1, IGFBP-3, OC, PINP, and aBMD at all sites, radius excepted, were significantly reduced in AN whereas CTX and sOB-R were increased compared with controls. Serum serotonin levels were positively correlated with weight, body mass index, whole body fat mass, leptin, and IGF-1, and negatively with CTX for the entire population. Low serum serotonin levels are observed in patients with AN. Although no direct link between low serum serotonin levels and bone mass was identified in these patients, the negative relationship between serotonin and markers of bone resorption found in all population nevertheless suggests the implication of serotonin in bone metabolism. Impact of low serum serotonin on bone in AN warrants further studies.
Subject(s)
Anorexia Nervosa/blood , Bone Resorption/blood , Serotonin/blood , Adolescent , Anorexia Nervosa/complications , Anorexia Nervosa/physiopathology , Anthropometry , Bone Density , Bone Resorption/complications , Bone Resorption/physiopathology , Case-Control Studies , Female , Hormones , HumansABSTRACT
Dental pulp is a dynamic tissue able to resist external irritation during tooth decay by using immunocompetent cells involved in innate and adaptive responses. To better understand the immune response of pulp toward gram-negative bacteria, we analyzed biological mediators and immunocompetent cells in rat incisor pulp experimentally inflamed by either lipopolysaccharide (LPS) or saline solution (phosphate-buffered saline [PBS]). Untreated teeth were used as control. Expression of pro- and anti-inflammatory cytokines, chemokine ligands, growth factors, and enzymes were evaluated at the transcript level, and the recruitment of the different leukocytes in pulp was measured by fluorescence-activated cell-sorting analysis after 3 h, 9 h, and 3 d post-PBS or post-LPS treatment. After 3 d, injured rat incisors showed pulp wound healing and production of reparative dentin in both LPS and PBS conditions, testifying to the reversible pulpitis status of this model. IL6, IL1-ß, TNF-α, CCL2, CXCL1, CXCL2, MMP9, and iNOS gene expression were significantly upregulated after 3 h of LPS stimulation as compared with PBS. The immunoregulatory cytokine IL10 was also upregulated after 3 h, suggesting that LPS stimulates not only inflammation but also immunoregulation. Fluorescence-activated cell-sorting analysis revealed a significant, rapid, and transient increase in leukocyte levels 9 h after PBS and LPS stimulation. The quantity of dendritic cells was significantly upregulated with LPS versus PBS. Interestingly, we identified a myeloid-derived suppressor cell-enriched cell population in noninjured rodent incisor dental pulp. The percentage of this population, known to regulate immune response, was higher 9 h after inflammation triggered with PBS and LPS as compared with the control. Taken together, these data offer a better understanding of the mechanisms involved in the regulation of dental pulp immunity that may be elicited by gram-negative bacteria.
Subject(s)
Dental Pulp/immunology , Pulpitis/immunology , T-Lymphocytes/immunology , Animals , Chemokine CCL2/analysis , Chemokine CXCL1/analysis , Chemokines/analysis , Cytokines/analysis , Dendritic Cells/pathology , Dental Pulp/enzymology , Dentin, Secondary/immunology , Disease Models, Animal , Female , Gram-Negative Bacteria/immunology , Inflammation Mediators/analysis , Interleukin-10/analysis , Interleukin-1beta/analysis , Interleukin-6/analysis , Leukocytes/classification , Lipopolysaccharides/immunology , Matrix Metalloproteinase 9/analysis , Nitric Oxide Synthase Type II/analysis , Pulpitis/enzymology , Rats , Rats, Sprague-Dawley , T-Lymphocytes, Regulatory/pathology , Time Factors , Tumor Necrosis Factor-alpha/analysisABSTRACT
AIM: The benefits of retrospective continuous glucose monitoring (retroCGM) recording have been widely explored in clinical studies, and many diabetes physicians routinely use this examination. However, the method of interpretation of CGM recordings has never been precisely described. METHOD: An expert French panel of physicians met for two days to discuss several aspects of retroCGM use and to produce a position statement. RESULTS: The guidelines cover the indications for retroCGM, the general organization and practical implementation of CGM recordings, a description of the different devices available and guidelines for the interpretation of retroCGM recordings. CONCLUSION: This consensus document should help clinicians in the proper use of retroCGM.
Subject(s)
Blood Glucose Self-Monitoring , Blood Glucose/analysis , Diabetes Mellitus , HumansABSTRACT
Drug-induced adverse effects are one of the main avoidable causes of hospitalization in older people. Numerous lists of potentially inappropriate medications for older people have been published, as national and international guidelines for appropriate prescribing in numerous diseases and for different age categories. The present review describes the general rules for an appropriate prescribing in older people and summarizes, for the main conditions encountered in older people, medications that are too often under-prescribed, the precautions of use of the main drugs that induce adverse effects, and drugs for which the benefit to risk ratio is unfavourable in older people. All these data are assembled in educational tables designed to be printed in a practical pocket format and used in daily practice by prescribers, whether physicians, surgeons or pharmacists.
Subject(s)
Aged , Drug Prescriptions , Practice Patterns, Physicians' , Age Factors , Aged, 80 and over , Drug Prescriptions/standards , Drug Prescriptions/statistics & numerical data , Drug-Related Side Effects and Adverse Reactions/epidemiology , Humans , Inappropriate Prescribing/prevention & control , Inappropriate Prescribing/statistics & numerical data , Medication Errors/prevention & control , Medication Errors/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical dataABSTRACT
AIMS: To test in an outpatient setting the safety and efficacy of continuous subcutaneous insulin infusion (CSII) driven by a modular model predictive control (MMPC) algorithm informed by continuous glucose monitoring (CGM) measurement. METHODS: 13 patients affected by type 1 diabetes participated to a non-randomized outpatient 42-h experiment that included two evening meals and overnight periods (in short, dinner & night periods). CSII was patient-driven during dinner & night period 1 and MMPC-driven during dinner&night period 2. The study was conducted in hotels, where patients could move around freely. A CGM system (G4 Platinum; Dexcom Inc., San Diego, CA, USA) and insulin pump (AccuChek Combo; Roche Diagnostics, Mannheim, Germany) were connected wirelessly to a smartphone-based platform (DiAs, Diabetes Assistant; University of Virginia, Charlottesville, VA, USA) during both periods. RESULTS: A significantly lower percentage of time spent with glucose levels <3.9 mmol/l was achieved in period 2 compared with period 1: 1.96 ± 4.56% vs 12.76 ± 15.84% (mean ± standard deviation, p < 0.01), together with a greater percentage of time spent in the 3.9-10 mmol/l target range: 83.56 ± 14.02% vs 62.43 ± 29.03% (p = 0.04). In addition, restricting the analysis to the overnight phases, a lower percentage of time spent with glucose levels <3.9 mmol/l (1.92 ± 4.89% vs 12.7 ± 19.75%; p = 0.03) was combined with a greater percentage of time spent in 3.9-10 mmol/l target range in period 2 compared with period 1 (92.16 ± 8.03% vs 63.97 ± 2.73%; p = 0.01). Average glucose levels were similar during both periods. CONCLUSIONS: The results suggest that MMPC managed by a wearable system is safe and effective during evening meal and overnight. Its sustained use during this period is currently being tested in an ongoing randomized 2-month study.
Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 1/drug therapy , Hypoglycemia/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin Infusion Systems , Insulin/administration & dosage , Pancreas, Artificial , Adult , Aged , Algorithms , Ambulatory Care , Blood Glucose Self-Monitoring/methods , Diabetes Mellitus, Type 1/blood , Drug Chronotherapy , Female , Humans , Hypoglycemia/blood , Male , Meals , Middle Aged , Time Factors , Treatment OutcomeABSTRACT
Ever since 2006, Nantes University dental educators have started organising lectures led by the mother of a young patient suffering from ectodermic dysplasia (patient-educator) to help second-year students to better understand how important it is for their future dental work to better understand basic sciences. In this study, we have analysed this training experience on students' motivation. For this purpose, students were asked to complete questionnaires 10 days after the patient-educator's lecture (early assessment; n = 193) and 4 years later, during the last year of their dental studies (delayed assessment; n = 47). Moreover, 3 years after the first lecture, we analysed the ability of students to diagnose a mother carrying the ectodermic dysplasia genetic disorder, using a case-based learning exercise with a patient showing dental features similar to those exposed by the patient-educator (measure of knowledge; n = 42). Ten days after the lecture, the early assessment shows that all the students were interested in the lecture and 59% of the students declared being motivated to find out more about genetics whilst 54% declared the same thing about embryology courses. Moreover, 4 years later, 67% of the students remembered the patient-educator's lecture a little or very well. Three years after the course, 83% of the students diagnosed ectodermal dysplasia whilst studying the case-based example that listed typical dental phenotypes. In conclusion, this study shows that this original educational approach enhances dental students' motivation in learning basic sciences and that patient-educators could offer many benefits for students and patients.
Subject(s)
Dental Care for Chronically Ill/standards , Ectodermal Dysplasia/diagnosis , Ectodermal Dysplasia/therapy , Education, Dental/methods , Educational Measurement , Female , France , Humans , Male , Surveys and QuestionnairesABSTRACT
AIMS: To assess the accuracy and reliability of the two most widely used continuous glucose monitoring (CGM) systems. METHODS: We studied the Dexcom®G4 Platinum (DG4P; Dexcom, San Diego, CA, USA) and Medtronic Paradigm Veo Enlite system (ENL; Medtronic, Northridge, CA, USA) CGM systems, in 24 patients with type 1 diabetes. The CGM systems were tested during 6-day home use and a nested 6-h clinical research centre (CRC) visit. During the CRC visit, frequent venous blood glucose samples were used as reference while patients received a meal with an increased insulin bolus to induce an aggravated postprandial glucose nadir. At home, patients performed at least six reference capillary blood measurements per day. A Wilcoxon signed-rank test was performed using all data points ≥15 min apart. RESULTS: The overall mean absolute relative difference (MARD) value [standard deviation (s.d.)] measured at the CRC was 13.6 (11.0)% for the DG4P and 16.6 (13.5)% for the ENL [p < 0.0002, confidence interval of difference (CI Δ) 1.7-4.3%, n = 530]. The overall MARD assessed at home was 12.2 (12.0)% for the DG4P and 19.9 (20.5)% for the ENL (p < 0.0001, CI Δ = 5.8-8.7%, n = 839). During the CRC visit, the MARD in the hypoglycaemic range [≤3.9 mmol/l (70 mg/dl)], was 17.6 (12.2)% for the DG4P and 24.6 (18.8)% for the ENL (p = 0.005, CI Δ 3.1-10.7%, n = 117). Both sensors showed higher MARD values during hypoglycaemia than during euglycaemia [3.9-10 mmol/l (70-180 mg/dl)]: for the DG4P 17.6 versus 13.0% and for the ENL 24.6 versus 14.2%. CONCLUSIONS: During circumstances of intended use, including both a CRC and home phase, the ENL was noticeably less accurate than the DG4P sensor. Both sensors showed lower accuracy in the hypoglycaemic range. The DG4P was less affected by this negative effect of hypoglycaemia on sensor accuracy than was the ENL.