Effects of a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic in an in vitro and in vivo model of CDKL5 deficiency disorder.

Background: Mutations in the X-linked CDKL5 gene underlie a severe epileptic encephalopathy, CDKL5 deficiency disorder (CDD), characterized by gross motor impairment, autistic features and intellectual disability. Absence of Cdkl5 negatively impacts neuronal proliferation, survival, and maturation in in vitro and in vivo models, resulting in behavioral deficits in the Cdkl5 KO mouse. While there is no targeted therapy for CDD, several studies showed that treatments enabling an increase in brain BDNF levels give rise to structural and behavioral improvements in Cdkl5 KO mice.

Engagement with Traditional Healers for Early Detection of Plague in Uganda.

In rural Uganda, many people who are ill consult traditional healers prior to visiting the formal healthcare system. Traditional healers provide supportive care for common illnesses, but their care may delay diagnosis and management of illnesses that can increase morbidity and mortality, hinder early detection of epidemic-prone diseases, and increase occupational risk to traditional healers. We conducted open-ended, semi-structured interviews with a convenience sample of 11 traditional healers in the plague-endemic West Nile region of northwestern Uganda to assess their knowledge, practices, and attitudes regarding plague and the local healthcare system.

Voluntary Running Improves Behavioral and Structural Abnormalities in a Mouse Model of CDKL5 Deficiency Disorder.

Cyclin-dependent kinase-like 5 () deficiency disorder (CDD) is a rare neurodevelopmental disease caused by mutations in the X-linked gene. CDD is characterized by a broad spectrum of clinical manifestations, including early-onset refractory epileptic seizures, intellectual disability, hypotonia, visual disturbances, and autism-like features. The knockout (KO) mouse recapitulates several features of CDD, including autistic-like behavior, impaired learning and memory, and motor stereotypies.

Early-onset brain alterations during postnatal development in a mouse model of CDKL5 deficiency disorder.

Mutations in the CDKL5 gene are the cause of CDKL5 deficiency disorder (CDD), a rare and severe neurodevelopmental condition characterized by early-onset epilepsy, motor impairment, intellectual disability, and autistic features. A mouse model of CDD, the Cdkl5 KO mouse, that recapitulates several aspects of CDD symptomology, has helped to highlight brain alterations leading to CDD neurological defects. Studies of brain morphogenesis in adult Cdkl5 KO mice showed defects in dendritic arborization of pyramidal neurons and in synaptic connectivity, a hypocellularity of the hippocampal dentate gyrus, and a generalized microglia over-activation.

Cardiac Functional and Structural Abnormalities in a Mouse Model of CDKL5 Deficiency Disorder.

CDKL5 (cyclin-dependent kinase-like 5) deficiency disorder (CDD) is a severe neurodevelopmental disease that mostly affects girls, who are heterozygous for mutations in the X-linked gene. Mutations in the gene lead to a lack of CDKL5 protein expression or function and cause numerous clinical features, including early-onset seizures, marked hypotonia, autistic features, gastrointestinal problems, and severe neurodevelopmental impairment. Mouse models of CDD recapitulate several aspects of CDD symptomology, including cognitive impairments, motor deficits, and autistic-like features, and have been useful to dissect the role of CDKL5 in brain development and function.

Expression of a Secretable, Cell-Penetrating CDKL5 Protein Enhances the Efficacy of Gene Therapy for CDKL5 Deficiency Disorder.

Although delivery of a wild-type copy of the mutated gene to cells represents the most effective approach for a monogenic disease, proof-of-concept studies highlight significant efficacy caveats for treatment of brain disorders. Herein, we develop a cross-correction-based strategy to enhance the efficiency of a gene therapy for CDKL5 deficiency disorder, a severe neurodevelopmental disorder caused by CDKL5 gene mutations. We created a gene therapy vector that produces an Igk-TATk-CDKL5 fusion protein that can be secreted via constitutive secretory pathways and, due to the cell-penetration property of the TATk peptide, internalized by cells.

Luteolin Treatment Ameliorates Brain Development and Behavioral Performance in a Mouse Model of CDKL5 Deficiency Disorder.

CDKL5 deficiency disorder (CDD), a rare and severe neurodevelopmental disease caused by mutations in the X-linked 5 gene, is characterized by early-onset epilepsy, intellectual disability, and autistic features. Although pharmacotherapy has shown promise in the CDD mouse model, safe and effective clinical treatments are still far off. Recently, we found increased microglial activation in the brain of a mouse model of CDD, the 5 KO mouse, suggesting that a neuroinflammatory state, known to be involved in brain maturation and neuronal dysfunctions, may contribute to the pathophysiology of CDD.

Intervention To Stop Transmission of Imported Pneumonic Plague - Uganda, 2019.

Plague, an acute zoonosis caused by Yersinia pestis, is endemic in the West Nile region of northwestern Uganda and neighboring northeastern Democratic Republic of the Congo (DRC) (1-4). The illness manifests in multiple clinical forms, including bubonic and pneumonic plague. Pneumonic plague is rare, rapidly fatal, and transmissible from person to person via respiratory droplets.

Knowledge and practices related to plague in an endemic area of Uganda.

Background: Plague is a virulent zoonosis reported most commonly from Sub-Saharan Africa. Early treatment with antibiotics is important to prevent mortality. Understanding knowledge gaps and common behaviors informs the development of educational efforts to reduce plague mortality.

Patterns of Human Plague in Uganda, 2008-2016.

Plague is a highly virulent fleaborne zoonosis that occurs throughout many parts of the world; most suspected human cases are reported from resource-poor settings in sub-Saharan Africa. During 2008-2016, a combination of active surveillance and laboratory testing in the plague-endemic West Nile region of Uganda yielded 255 suspected human plague cases; approximately one third were laboratory confirmed by bacterial culture or serology. Although the mortality rate was 7% among suspected cases, it was 26% among persons with laboratory-confirmed plague.

NOMAD spectrometer on the ExoMars trace gas orbiter mission: part 2-design, manufacturing, and testing of the ultraviolet and visible channel.

NOMAD is a spectrometer suite on board the ESA/Roscosmos ExoMars Trace Gas Orbiter, which launched in March 2016. NOMAD consists of two infrared channels and one ultraviolet and visible channel, allowing the instrument to perform observations quasi-constantly, by taking nadir measurements at the day- and night-side, and during solar occultations. Here, in part 2 of a linked study, we describe the design, manufacturing, and testing of the ultraviolet and visible spectrometer channel called UVIS.

Successful Treatment of Human Plague with Oral Ciprofloxacin.

The US Food and Drug Administration recently approved ciprofloxacin for treatment of plague (Yersina pestis infection) based on animal studies. Published evidence of efficacy in humans is sparse. We report 5 cases of culture-confirmed human plague treated successfully with oral ciprofloxacin, including 1 case of pneumonic plague.

NOMAD spectrometer on the ExoMars trace gas orbiter mission: part 1--design, manufacturing and testing of the infrared channels.

NOMAD is a spectrometer suite on board ESA's ExoMars trace gas orbiter due for launch in January 2016. NOMAD consists of two infrared channels and one ultraviolet and visible channel allowing the instrument to perform observations quasi-constantly, by taking nadir measurements at dayside and nightside, and during solar occultations. In this paper, the design, manufacturing, and testing of the two infrared channels are described.

Does Insulin Like Growth Factor-1 (IGF-1) Deficiency Have a "Protective" Role in the Development of Diabetic Retinopathy in Thalassamia Major Patients?

Rationale: Both insulin and IGF-1 have been implicated in the control of retinal endothelial cell growth, neovascularization and diabetic retinopathy. Recent findings have established an essential role for IGF-1 in angiogenesis and demonstrated a new target for control of retinopathy that explains why diabetic retinopathy initially increases with the onset of insulin treatment.

Objective: This cross-sectional study was designed to give insights into relationship between Insulin-Growth-Factor 1 (IGF-1) levels and diabetic retinopathy (DR) in a sample of thalassemia major (TM) patients with insulin dependent diabetes mellitus (IDDM).

Insulin-like Growth Factor-1 (IGF-1): Demographic, Clinical and Laboratory Data in 120 Consecutive Adult Patients with Thalassaemia Major.

Introduction: IGF-1 deficiency in TM patients in children and adolescents has been attributed to chronic anemia and hypoxia, chronic liver disease, iron overload and other associated endocrinopathies, e.g. growth hormone deficiency (GHD).

High prevalence of central hypothyroidism in adult patients with β-thalassemia major.

The commonest form of thyroid dysfunction seen in subjects with TM is primary hypothyroidism due to abnormalities of the thyroid gland. Central hypothyroidism (CH) has been reported as an uncommon clinical entity in TM patients although the anterior pituitary gland is particularly sensitive to free radical oxidative stresses. Diagnosis is usually made on a biochemical basis showing low circulating concentrations of thyroid hormone associated with an inappropriately low TSH levels.

Abnormal seminal parameters in patients with thalassemia intermedia and low serum folate levels.

Seminal parameters were evaluated in 16 fully mature patients with thalassemia intermedia. Their ages ranged from 19 to 54 years (mean age 27 yrs) and serum ferritin levels varied from 205 to 3400 ng/ml. Eleven patients (68.

Growth hormone and adrenal response to intramuscular glucagon test and its relationship to IGF-1 production and left ventricular ejection fraction in adult B-thalassemia major patients.

In patients with b-thalassemia major (TM), the anterior pituitary gland is particularly sensitive to free radical stresses. It has been reported that the GH deficiency (GHD) may be secondary to either pituitary or hypothalamic dysfunction. The duration of the disease, the patient's age and the severity of iron overload are the most important factors responsible for the defect of growth hormone (GH) secretion.

A practical method for the estimation of therapeutic activity in the treatment of Graves' hyperthyroidism.

Aim: To test the efficacy of a practical method which allows the calculation of personalized activity in Graves' disease.

Methods: The method is based on International Commission of Radiological Protection (ICRP) 53 data. The model allows the prediction of the activity administered in order to release 300 Gy to the thyroid, once its iodine uptake and mass are known.

Gamma ray dosimetry and mating capacity studies in the laboratory on Aedes albopictus males.

In Italy, Aedes albopictus Skuse is currently recognized as the most dangerous mosquito, and as currently applied conventional control methods gave unsatisfactory results, we are developing alternative strategies such as the sterile insect technique. To find the optimal sterilizing dose, male pupae were exposed to different doses of gamma rays in the range 20-80 Gy, generated by a Cesium-137 source. The effects of male pupal age at irradiation and gamma ray dose on adult male emergence, sterility level, longevity, and mating capacity were evaluated, and dose-response curves of residual fertility were calculated.

Assessment of cardiac and hepatic iron overload in thalassaemic patients by magnetic resonance: a four year observational study.

In this study, we present results of the determination of cardiac and hepatic iron overload in patients with thalassaemia by means of a non-invasive method based on magnetic resonance. The procedure was applied for a period of four years to a group of patients followed in the Thalassemia Centre of our hospital. The gathered data were stratified to indicate groups of patients with mild, moderate and severe hepatic iron overload.

A statistical method for the quantification of the learning index by means of multiple answer tests-Graduated Response Test.

In the fields of didactics and continuous professional development (CPD) plans, the increasing use of multiple answer tests for the evaluation of the level of knowledge in various kinds of subjects makes it increasingly important to have reliable and effective tools for data processing and for the evaluation of the results. The aim of the present work is to explore a new methodological approach based on a widely tested statistical analysis able to yield more information content when compared with the traditional methods. With this purpose we suggest a Graduated Response Test and the relative operating characteristic curve (ROC) for the evaluation of the results.