Global transcriptomic analysis in avocado nursery trees reveals differential gene expression during asymptomatic infection by avocado sunblotch viroid (ASBVd).

Avocado sunblotch viroid (ASBVd) is the type species of the family Avsunviroidae and the causal agent of avocado sunblotch disease. The disease is characterised by the presence of chlorotic lesions on avocado fruit, leaves and/or stems. Infected trees may remain without chlorosis for extended periods of time, though distorted growth and reduced yield has been observed in these cases. The molecular effects of ASBVd on avocado, and members of the Avsunviroidae on their respective hosts in general, remain poorly understood. Host global transcriptomic studies within the family Pospiviroidae have identified several host pathways that are affected during these plant-pathogen interactions. In this study, we used RNA sequencing to investigate host gene expression in asymptomatic avocado nursery trees infected with ASBVd. Transcriptome data showed that 631 genes were differentially expressed, 63 % of which were upregulated during infection. Plant defence responses, phytohormone networks, gene expression pathways, secondary metabolism, cellular transport as well as protein modification and degradation were all significantly affected by ASBVd infection. This work represents the first global gene expression study of ASBVd-infected avocado, and the transcriptional reprogramming observed during this asymptomatic infection improves our understanding of the molecular interactions underlying broader avsunviroid-host interactions.

The mortality rate of patients with open abdomen and contributing factors - a three-year audit in a major academic trauma unit.

BACKGROUND: Damage control surgery (DCS) is a widely used approach in trauma. An open abdomen carries complications, increased morbidity and mortality. This study aims to quantify the mortality rate, determine contributory factors and factors influencing the decision to perform DCS and assess morbidity in patients undergoing open abdomen. METHODS: A retrospective review was conducted on 205 patients in Charlotte Maxeke Johannesburg Academic Hospital Trauma Unit. The mortality rate was evaluated over a 24-hour, 7-day and 28-day period. Data were collected by a data collection sheet from 1 January 2016 to 31 December 2018. RESULTS: Of the 205 patients, 193 were male and the median age was 34.34 years. Penetrating trauma was the most predominant mechanism of injury in 162 (79%), with gunshot injuries seen in the majority (130/162). The mortality rate was 55/205 (26.8%) for open abdomen patients, 19/55 (34.5%) within the first 24 hours, 22/55 (40%) in the 24-hours to 7-days period, and 14/55 (25.4%) in the 8-day to 28-day period. Statistically significant factors contributing to mortality were haemodynamic instability, hypothermia, coagulopathy, massive transfusion, vasopressors, and significant associated injuries. Morbidities were entero-atmospheric fistula (EAF) in 7.3% (Clavien-Dindo grade IIIa), surgical site infection in 45.3% (Clavien-Dindo grade I) and ventral hernia in 10.24% (Clavien-Dindo grade IIIb). CONCLUSION: Most open abdomens were performed in males, with gunshot injuries being the most common mechanism. The majority of mortalities were within the 24-hours to 7-days period. The most common morbidity associated with an open abdomen was surgical site infection.

Behçet's disease uveitis.

Uveitis in Behçet's disease (BD) is frequent (40% of cases) and is a major cause of morbidity. The age of onset of uveitis is between 20 and 30 years. Ocular involvement includes anterior, posterior or panuveitis. It is non-granulomatous. Uveitis may be the first sign of the disease in 20% of cases or it may appear 2 or 3 years after the first symptoms. Panuveitis is the most common presentation and is more commonly found in men. Bilateralisation usually occurs on average 2 years after the first symptoms. The estimated risk of blindness at 5 years is 10-15%. BD uveitis has several ophthalmological features that distinguish it from other uveitis. The main goals in the management of patients are the rapid resolution of intraocular inflammation, prevention of recurrent attacks, achievement of complete remission, and preservation of vision. Biologic therapies have changed the management of intraocular inflammation. The aim of this review is to provide an update previous article by our team on pathogenesis, diagnostic approaches, identification of factors associated with relapse and the therapeutic strategy of BD uveitis.

NOTCH2 related disorders: Description and review of the fetal presentation.

Signs of skeletal dysplasias are relatively common in fetuses with abnormal ultrasound (US) findings. The diversity of congenital skeletal disorders, the possibility of late-onset severe phenotypes and overlapping syndromes can be a challenge in the way of diagnosis, even if prenatal high-throuput sequencing allows for a better diagnosis, prognosis and genetic counseling. Hajdu-Cheney spectrum pathologies are rarely described in prenatal, and the signs associated remain poorly known, and do not include specific postnatal signs as acro-osteolysis and premature osteoporosis. We hereby report a couple for whom a medical termination of pregnancy was performed because a severe polymalformative syndrome associating severely short limbs with bowed long bones, severe cardiopathy, hyperechogenic kidneys and dysmorphism. After fetopathological and radiological examinations, Exome Sequencing (ES) was performed and revealed a de novo truncating mutation in the last exon of NOTCH2, responsible for Hajdu-Cheney or Serpentine Fibula Polycystic Kidney syndromes.

Design of a prospective, longitudinal cohort of people living with type 1 diabetes exploring factors associated with the residual cardiovascular risk and other diabetes-related complications: The SFDT1 study.

Type 1 diabetes mellitus (T1DM) is associated with a high risk of cardiovascular (CV) complications, even after controlling for traditional CV risk factors. Therefore, determinants of the residual increased CV morbidity and mortality remain to be discovered. This prospective cohort of people living with T1DM in France (SFDT1) will include adults and children aged over six years living with T1DM, recruited throughout metropolitan France and overseas French departments and territories. The primary objective is to better understand the parameters associated with CV complications in T1DM. Clinical data and biobank samples will be collected during routine visits every three years. Data from connected tools, including continuous glucose monitoring, will be available during the 10-year active follow-up. Patient-reported outcomes, psychological and socioeconomic information will also be collected either at visits or through web questionnaires accessible via the internet. Additionally, access to the national health data system (Health Data Hub) will provide information on healthcare and a passive 20-year medico-administrative follow-up. Using Health Data Hub, SFDT1 participants will be compared to non-diabetic individuals matched on age, gender, and residency area. The cohort is sponsored by the French-speaking Foundation for Diabetes Research (FFRD) and aims to include 15,000 participants.

Early continuous glucose monitoring for predicting remission of type 2 diabetes 1 year after bariatric surgery.

BACKGROUND: Bariatric surgery in obese subjects can result in remission of type 2 diabetes (T2D) at a distant time post-surgery. The aim of our observational prospective single-centre study was to examine glycaemic patterns in adult T2D candidates for bariatric surgery using a continuous glucose monitoring (CGM) sensor for 14 days after surgery to search for indicators predictive of T2D remission 1 year later. METHODS: Patients underwent CGM preoperatively and for 14 days postoperatively. Thereafter, body weight and glycated haemoglobin (HbA1c) levels were monitored at 3, 6 and 12 months after surgery. RESULTS: A total of 31 patients (mean age 47±2 years) were analyzed. After surgery, mean interstitial glucose levels fell rapidly from 157±31mg/dL preoperatively to 109±35mg/dL postoperatively (P<0.001), reaching nadir levels from day 3 after surgery. Successful bariatric surgery (loss of excess weight ≥50%) was observed in 28 (90%) patients, and diabetes remission (HbA1c≤6% with no antidiabetic treatment) 1 year after surgery was noted in 21 (68%) patients. CGM for 14 days post-surgery allowed prediction of diabetes remission 1 year after surgery: time spent above range <14% and standard deviation (SD) of glucose levels <33mg/dL were both strong predictors of T2D remission. Indeed, the association of these two criteria predicted diabetes remission with a 100% positive predictive value, 81% sensitivity and 100% specificity and, when combined with the advanced Diabetes Remission (Ad-DiaRem) score, further increased predictive accuracy. CONCLUSION: The use of 14-day postoperative CGM recordings together with presurgical clinical scores can help to predict diabetes remission 1 year after bariatric surgery.

Practical implementation of automated closed-loop insulin delivery: A French position statement.

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.

Diabetes-related cardiomyopathy: The sweet story of glucose overload from epidemiology to cellular pathways.

Type 2 diabetes (T2D) is a major risk factor for heart failure (HF). Although the number of cases of myocardial infarction in the T2D population has been reduced by 25% over the last 10 years, the incidence of HF is continuously increasing, making it the most worrying diabetes complication. This strongly reinforces the urgent need for innovative therapeutic interventions to prevent cardiac dysfunction in T2D patients. To this end, epidemiological, imaging and animal studies have aimed to highlight the mechanisms involved in the development of diabetic cardiomyopathy. Epidemiological observations clearly show that hyperglycaemia correlates with severity of cardiac dysfunction and mortality in T2D patients. Both animal and cellular studies have demonstrated that, in the context of diabetes, the heart loses its ability to utilize glucose, therefore leading to glucose overload in cardiomyocytes that, in turn, promotes oxidative stress, accumulation of advanced glycation end-products (AGEs) and chronic activation of the hexosamine pathway. These have all been found to activate apoptosis and to alter heart contractility, calcium signalling and mitochondrial function. Although, in the past, tight glycaemic control has failed to improve cardiac function in T2D patients, recent clinical trials have reported cardiovascular benefit with hypoglycaemic antidiabetic drugs of the SGLT2-inhibitor family. This review, based on clinical evidence from mechanistic studies as well as several large clinical trials, covers 15 years of research, and strongly supports the idea that hyperglycaemia and glucose overload play a central role in the pathophysiology of diabetic cardiomyopathy.

Practical implementation, education and interpretation guidelines for continuous glucose monitoring: A French position statement.

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.

Use of GLP-1 receptor agonists for type 2 diabetes treatment intensification after basal insulin failure.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are part of the armamentarium for the treatment of type 2 diabetes (T2D), although recent guidelines have mainly recommended their use on top of oral treatments when a single or combination of two or three oral hypoglycaemic agents has failed to lower HbA1c levels below the individualized target range. In such situations, the decision to use GLP-1RAs is mostly driven by their high level of efficacy, their effect on body weight balance and their safety considerations, such as low hypoglycaemic risk. According to the current guidelines, GLP-1RAs may also be used in T2D patients in addition to basal insulin, following specialist-care advice, in patients who are more severely obese or who may not have the capacity to handle the complexities of a multiple daily injection (MDI) insulin regimen. The present review looks at the scientific evaluations performed in this context as well as the clinical trials assessing the use of GLP-1RAs in combination with intensive insulin therapy as further step-up therapy.

Burden, genotype and phenotype profiles of adult patients with sickle cell disease in Cape Town, South Africa.

BACKGROUND: An exponential increase in the number of sickle cell disease (SCD) patients in paediatric services in Cape Town, South Africa, has been reported. The trend in adult/adolescent services has not been investigated. OBJECTIVES: To evaluate epidemiological trends of SCD and the profile of patients affected by SCD attending the Haematology Clinic at Groote Schuur Hospital (GSH), Cape Town. METHODS: (i) A retrospective review of the number of SCD patients over the past 20 years; (ii) a cross-sectional analysis of clinical and haematological characteristics of SCD patients; and (iii) molecular analysis of the haemoglobin S mutation, the haplotype in the ß-globin-like genes cluster, the 3.7 kb α-thalassaemia gene deletion and 19 selected single-nucleotide polymorphisms (SNPs) associated with fetal haemoglobin (HbF) levels. RESULTS: From 1995 to 2016, 81 adolescent/adult patients with SCD were registered, mostly originating from other African countries (n=61, 75.3%). There was an increase of over 200% in new cases (n=47) during the last quarter of the two decades investigated. Data from 34 of 58 regular attendees (58.6%) were analysed. The mean age of the patients was 26.1 years (standard deviation (SD) 9.8), and 70.6% were male. With the exception of four patients with sickle/ß-thalassaemia, all the patients had SCD (haemoglobin SS). The co-inheritance of a single 3.7 kb α-globin deletion was found in 42.3% of cases (n=11). The Bantu haplotype was the most observed (65.4% of chromosomes). Most HbF-promoting SNPs were not associated with variable levels of haematological indices. CONCLUSIONS: There is an increasing burden of adult SCD patients at GSH. National health and academic institutions need to adapt policies and healthcare professional training accordingly.

Seipin deficiency alters brown adipose tissue thermogenesis and insulin sensitivity in a non-cell autonomous mode.

Loss-of-function mutations in BSCL2 are responsible for Berardinelli-Seip congenital lipodystrophy, a rare disorder characterized by near absence of adipose tissue associated with insulin resistance. Seipin-deficient (Bscl2-/-) mice display an almost total loss of white adipose tissue (WAT) with residual brown adipose tissue (BAT). Previous cellular studies have shown that seipin deficiency alters white adipocyte differentiation. In this study, we aimed to decipher the consequences of seipin deficiency in BAT. Using a brown adipocyte cell-line, we show that seipin knockdown had very little effect on adipocyte differentiation without affecting insulin sensitivity and oxygen consumption. However, when submitted to cold acclimation or chronic ß3 agonist treatment, Bscl2-/- mice displayed altered thermogenic capacity, despite several signs of BAT remodeling. Under cold activation, Bscl2-/- mice were able to maintain their body temperature when fed ad libitum, but not under short fasting. At control temperature (i.e. 21 °C), fasting worsened Bscl2-/- BAT properties. Finally, Bscl2-/- BAT displayed obvious signs of insulin resistance. Our results in these lipodystrophic mice strongly suggest that BAT activity relies on WAT as an energetic substrate provider and adipokine-producing organ. Therefore, the WAT/BAT dialogue is a key component of BAT integrity in guaranteeing its response to insulin and cold-activated adrenergic signals.

Effects of glycaemic variability on cardiac remodelling after reperfused myocardial infarction: Evaluation of streptozotocin-induced diabetic Wistar rats using cardiac magnetic resonance imaging.

AIMS: In addition to hyperglycaemia, glycaemic variability seems to be associated with poor outcomes after acute myocardial infarction. This study explored the impact of glycaemic variability in diabetic Wistar rats subjected to myocardial ischaemia/reperfusion. METHODS: Animals with streptozotocin-induced diabetes received insulin either to maintain stable hyperglycaemia (Dh group) or to generate glycaemic variability (Dv). After experimental myocardial ischaemia/reperfusion was surgically induced, 7T cardiac magnetic resonance imaging (CMR) was performed at weeks 1 (w1) and 3 (w3). RESULTS: Twenty-six rats were randomized [sham group (S): n=5; control group (C): n=7; Dh group: n=6; and Dv group: n=8]. The mean amplitude of glucose reflecting glycaemic variability was higher in the Dv than in the Dh group (9.1±2.7mmol/L vs 5.9±1.9mmol/L; P<0.05). CMR assessment at w3 revealed ventricular enlargement in both Dh and Dv groups compared with the C and S groups (end-diastolic volume: 1.60±0.22 and 1.36±0.30mL/kg compared with 1.11±0.13 and 0.87±0.11mL/kg, respectively; P<0.05). Circumferential strain was altered between w1 and w3 in the remote area only in the Dv group, resulting in a lower value in this group than in the S, C and Dh groups (-0.11±0.01 vs -0.17±0.05, -0.15±0.03 and -0.16±0.03, respectively; P<0.05). In addition, at w3, oedema was also higher in the remote area in the Dv than in the C group (18.3±4.9ms vs 14.5±1.7ms, respectively; P<0.05). CONCLUSION: In the context of experimental myocardial ischaemia/reperfusion, our results suggest that glycaemic variability might have a potentially deleterious impact on myocardial outcomes beyond the classical glucose metrics.

Cervicofacial non-tuberculous mycobacteria: A report of 30 cases.

BACKGROUND: Mycobacterial infection is the most common cause of cervical granuloma, implicating either a tuberculous or a non-tuberculous mycobacterium (NTM). NTM is a ubiquitous organism, found in soil, water, food, etc. The most frequently implicated is Mycobacterium avium-intracellular. Most authors agree that NTM is increasingly isolated, due to a decrease in vaccination rates. Initial diagnosis is difficult and management is not clearly codified. METHODS: A retrospective study conducted in the University Hospital of Nantes, France, between 2005 and 2014, included all patients treated for head and neck NTM lymphadenitis. The research was conducted on the database of the institution's bacteriology department. Population, history, symptoms and diagnostic features were noted. Treatment, surgical complications, adverse reactions to antibiotics, patient adherence, antibiotic therapy duration, time to remission and prognosis were analyzed. RESULTS: Between 2005 and 2014, 30 patients were diagnosed with head and neck NTM lymphadenitis: 17 female, 13 male; mean age at diagnosis, 4.5 years. Locations were submandibular (n=16), parotid, (n=7), cervical (n=5), parapharyngeal (n=4) and, for 1 patient, in the auricle concha. Eight patients received first-line surgical treatment, which was effective in 75% of cases, 2 patients requiring additional antibiotic therapy. Twenty-two patients were treated with first-line antibiotherapy, which was effective in 90% of cases. There were no relapses at a mean 32 weeks' follow-up. CONCLUSIONS: Total resection of all affected nodes and infiltrated subcutaneous fatty tissue is the treatment of choice. Drug therapy (including at least a macrolide) seems indicated only in case of incomplete resection or if surgery would entail functional and/or esthetic risk. Increased incidence, since BCG vaccination was stopped, will continue to confront the practitioner with an infantile disease in which management must be multidisciplinary.

[Cytomegalovirus infection in pregnancy: A fourteen-year review in a pluridisciplinary prenatal center]. / Infection materno-fœtale à CMV : étude rétrospective dans un CPDPN sur une période de 14ans.

BACKGROUND: Cytomegalovirus (CMV) is the most frequent cause of congenital infection. The aim of this research was to describe the decision-process for parents to pursue gestation or to ask medical abortion after materno-fetal CMV infection. OBJECTIVES: The primary objective of this study is to analyze the decision-process for parents after materno-fetal infection with positive PCR after amniocentesis, to ask or not a medical termination of pregnancy (TOP). The secondary objectives are to compare ours results with literature review (pronostics factors, ultrasonographic signs and neonatal symptomatology). MATERIALS AND METHODS: This is a retrospective study, focused with a pluridisciplinary materno-fetal prenatal medical center, during a 14-year long period. Only 15 patients have been included in the study. They have been divided in 2 groups (the first group who decided to ask a TOP [n=8] and the second group who pursued the gestation [n=7]). We compare respectively their clinical, ultrasonographic, or other imagery and biological paths, before and after the birth. RESULTS: A total of 15/16 patients had a CMV seroconversion before 20weeks of gestation. The only infection after 20SA did not have any sequelae. The ultrasonography and the cerebral fetal MRI appeared to be very complementary for the assesment of brain injury, which is more frequent in the group with a TOP (7/8 versus 4/7). Three neonates out of 4 who had a cord positive viral blood load at birth are presenting neonatal symptoms, 2 of them will have severe brain and hearing injuries, the fourth one had no sequelae after 6months of life. CONCLUSION: Only the presence of ultrasonographic major brain damages, and confirmation with MRI, had a pejorative value as prognosis factor suggesting to patients to choose a TOP. Nevertheless, other ways of research are possible to assess the prognostic value in this difficult prenatal diagnosis process.

Preoperative localization of an insulinoma: selective arterial calcium stimulation test performance.

PURPOSE: Preoperative localization of an insulinoma is recommended to improve the cure rate, but non-invasive procedures can fail to detect the tumour. The objective of the study was to assess the performance of a selective arterial calcium stimulation test in the preoperative localization of insulinomas that were not detected by conventional imaging procedures. METHODS: We conducted a monocenter retrospective case review of 13 patients who had endogenous hyperinsulinism and were treated between 1994 and 2013. Patients were selected on the basis of negative or doubtful non-invasive preoperative imaging. A selective arterial calcium stimulation test was performed by pancreatic and hepatic arteriography with selective intra-arterial calcium stimulation and hepatic venous sampling in order to obtain the plasma insulin measurement. We evaluated the efficacy of the test by comparing the results with an endoscopic ultrasound. RESULTS: Twelve of the 13 patients underwent surgery, and the presence of an insulinoma was proven in 11 patients by pathological analysis of the tumour. An endoscopic ultrasound was consistent with surgery in 71.4 % of cases, while selective arterial calcium stimulation was consistent with surgery in 90.9 % and allowed detection of an insulinoma in two additional patients with a negative endoscopic ultrasound. One false-negative and one false-positive arterial calcium test were observed. No adverse events were recorded except transient skin flush following calcium injection in one patient. CONCLUSION: The selective arterial calcium stimulation test is a sensitive diagnostic procedure for localizing insulinomas and may be considered when non-invasive radiological imaging does not allow the detection of an occult insulinoma.

Indication, organization, practical implementation and interpretation guidelines for retrospective CGM recording: A French position statement.

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.