Audiogenic epileptic DBA/2 mice strain as a model of genetic reflex seizures and SUDEP

Epilepsy is a chronic neurological disease characterized by abnormal brain activity, which results in repeated spontaneous seizures. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of seizure-related premature death, particularly in drug-resistant epilepsy patients. The etiology of SUDEP is a structural injury to the brain that is not fully understood, but it is frequently associated with poorly controlled and repeated generalized tonic–clonic seizures (GTCSs) that cause cardiorespiratory and autonomic dysfunctions, indicating the involvement of the brainstem. Both respiratory and cardiac abnormalities have been observed in SUDEP, but not much progress has been made in their prevention. Owing to the complexity of SUDEP, experimental animal models have been used to investigate cardiac and/or respiratory dysregulation due to or associated with epileptic seizures that may contribute to death in humans. Numerous rodent models, especially mouse models, have been developed to better understand epilepsy and SUDEP physiopathology. This review synthesizes the current knowledge about dilute brown agouti coat color (DBA/2) mice as a possible SUDEP model because respiratory arrest (RA) and sudden death induced by audiogenic generalized seizures (AGSs) have been observed in these animals. Respiratory/cardiac dysfunction, brainstem arousal system dysfunction, and alteration of the neurotransmitter systems, which are observed in human SUDEP, have also been observed in these mice. In particular, serotonin (5-HT) alteration and adenosine neurotransmission appear to contribute to not only the pathophysiological mechanisms of medication but also seizure-related respiratory dysfunctions in this animal model. These neurotransmitter systems could be the relevant targets for medication development for chronic epilepsy and SUDEP prevention. We reviewed data on AGSs in DBA/2 mice and the relevance of this model of generalized tonic–clonic epilepsy to human SUDEP. Furthermore, the advantages of using this strain prone to AGSs for the identification of possible new therapeutic targets and treatment options have also been assessed

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Nutrition and pubertal development

Nutrition is one of the most important factors affecting pubertal development. Puberty entails a progressive nonlinear process starting from prepubescent to full sexual maturity through the interaction and cooperation of biological, physical, and psychological changes. Consuming an adequate and balanced healthy diet during all phases of growth (infancy, childhood and puberty) appears necessary both for proper growth and normal pubertal development. Girls begin puberty at an earlier age compared to past decades. Excessive eating of many processed, high-fat foods, may be the cause of this phenomenon. Overweight or obese children are more likely to enter puberty early. Some evidence suggests that obesity can accelerate the onset of puberty in girls and may delay the onset of puberty in boys. Moreover, the progression of puberty is affected by nutrition. On the other hand, puberty triggers a growth spurt, which increases nutritional needs including macro and micronutrients. Increased caloric, protein, iron, calcium, zinc and folate needs have to be provided during this critical period of rapid growth. Severe primary or secondary malnutrition also can delay the onset and progression of puberty. The higher incidence of anorexia nervosa and bulimia in adolescents imposes a nutritional risk on pubertal development. Moreover, many environmental endocrine disruptors (EDs) have been identified that can significantly impair the normal course of puberty. This mini-review sums up some important findings in this important complex that link nutrition and pubertal development

Advances in pubertal growth and factors influencing it: Can we increase pubertal growth?

Puberty is a period of development characterized by partially concurrent changes which includes growth acceleration, alteration in body composition and appearance of secondary sex characteristics. Puberty is characterized by an acceleration and then deceleration in skeletal growth. The initiation, duration and amount of growth vary considerably during the growth spurt. Pubertal growth and biological maturation are dynamic processes regulated by a variety of genetic and environmental factors. Changes in skeletal maturation and bone mineral accretion concomitant with the stage of pubertal development constitute essential components in the evaluation of growth during this pubertal period. Genetic, endocrine and nutritional factors and ethnicity contribute variably to the amount of growth gained during this important period of rapid changes. Many studies investigated the possibility of increasing pubertal growth to gain taller final adult height in adolescents with idiopathic short stature (ISS). The pattern of pubertal growth, its relation to sex maturity rating and factors affecting them has been addressed in this review. The results of different trials to increase final adult height of adolescents using different hormones have been summarized. These data enables Endocrinologists to give in-depth explanations to patients and families about the efficacy and clinical significance as well as the safety of using these therapies in the treatment of adolescents with ISS

Insulin-like growth factor- I and factors affecting it in thalassemia major

Despite improvement of blood transfusion regimens and iron chelation therapy growth and maturational delay, cardiomyopathy, endocrinopathies and osteoporosis still occur in good number of thalassemic patients. Decreased IGF-1 secretion occurs in the majority of the thalassemic patients particularly those with growth and pubertal delay. Many factors contribute to this decreased synthesis of IGF-I including disturbed growth hormone (GH) - insulin-like growth factor - I (IGF-I) axis. The possible factors contributing to low IGF-I synthesis in thalassemia and the possible interaction between low IGF-I secretion and the occurrence of these complications is discussed in this mini-review. Improvement of IGF-I secretion in thalassemic patients should be intended to improve linear growth and bone mineral accretion in thalassemic patients. This can be attained through adequate correction of anemia and proper chelation, nutritional supplementation (increasing caloric intake), correction of vitamin D and zinc deficiencies, induction of puberty and correction of hypogonadism at the proper time and treating GH deficiency. This review paper provides a summary of the current state of knowledge regarding IGF-I and factors affecting it in patients with thalassaemia major (TM). Search on PubMed and reference lists of articles with the term ′IGF-I, GH, growth, thalassemia, thyroxine, anemia, vitamin D, and zinc′ was carried out. A hundred and forty-eight articles were found and used in the write up and the data analyzed was included in this report

Vitamin D deficiency in adolescents

The prevalence of severe vitamin D deficiency (VDD) in adolescents is variable but considerably high in many countries, especially in Middle-east and Southeast Asia. Different factors attribute to this deficiency including lack of sunlight exposure due to cultural dress codes and veiling or due to pigmented skin, and less time spent outdoors, because of hot weather, and lower vitamin D intake. A potent adaptation process significantly modifies the clinical presentation and therefore clinical presentations may be subtle and go unnoticed, thus making true prevalence studies difficult. Adolescents with severe VDD may present with vague manifestations including pain in weight-bearing joints, back, thighs and/or calves, difficulty in walking and/or climbing stairs, or running and muscle cramps. Adaptation includes increased parathormone (PTH) and deceased insulin-like growth factor-I (IGF-I) secretion. PTH enhances the tubular reabsorption of Ca and stimulates the kidneys to produce 1, 25-(OH) 2D3 that increases intestinal calcium absorption and dissolves the mineralized collagen matrix in bone, causing osteopenia and osteoporosis to provide enough Ca to prevent hypocalcaemia. Decreased insulin like growth factor-I (IGF-I) delays bone growth to economize calcium consumption. Radiological changes are not uncommon and include osteoporosis/osteopenia affecting long bones as well as vertebrae and ribs, bone cysts, decalcification of the metaphysis of the long bones and pseudo fractures. In severe cases pathological fractures and deformities may occur. Vitamin D treatment of adolescents with VDD differs considerably in different studies and proved to be effective in treating all clinical, biochemical, and radiological manifestations. Different treatment regiments for VDD have been discussed and presented in this mini-review for practical use. Adequate vitamin D replacement after treating VDD, improving calcium intake (milk and dairy products), encouraging adequate exposure to the sun and possible enrichment of the stable food with vitamin D in areas with high prevalence of VDD are important measures to prevent the harmful consequences of VDD

Metalloproteases in Pain Generation and Persistence: A Possible Target?

Matrix metalloproteinases (MMPs) are a large family of zinc-dependent proteolytic enzymes associated with extracellular matrix protein turnover and tissue degradation. They participate to many different physiological reactions but are also hyperactivated in several diseases. Various literature studies have documented that MMPs play a role in the modulation of neuropathic and nociceptive pain. The heterogeneity of clinical and pre-clinical data is an important issue in this experimental context. Despite the presence of a good number of studies on MMP inhibitors, these drugs showed scarce efficacy and relevant side effects. In the present manuscript, we reviewed studies in the literature that define a possible role of MMPs in pain and the effects of their modulation

Metalloproteases in Pain Generation and Persistence: A Possible Target?

Matrix metalloproteinases (MMPs) are a large family of zinc-dependent proteolytic enzymes associated with extracellular matrix protein turnover and tissue degradation. They participate to many different physiological reactions but are also hyperactivated in several diseases. Various literature studies have documented that MMPs play a role in the modulation of neuropathic and nociceptive pain. The heterogeneity of clinical and pre-clinical data is an important issue in this experimental context. Despite the presence of a good number of studies on MMP inhibitors, these drugs showed scarce efficacy and relevant side effects. In the present manuscript, we reviewed studies in the literature that define a possible role of MMPs in pain and the effects of their modulation

A Preliminary Investigation of Special Types of Honey Marketed in Morocco

Background: This work aimed to perform a comprehensive investigation of organic Moroccan honeys obtained from plants of euphorbia, arbutus, and carob, based on the determination of physico-chemical profiles and volatile fingerprints. Methods: The selected analytical approach involved different techniques, including physico-chemical procedures for determination of humidity, acidity, diastase activity; solid-phase microextraction (SPME) coupled to GC-MS for aromatic fraction exploration; and ICP-MS for multi-element analysis. Results: The results obtained from the physico-chemical analyses were highly comparable to those of other commercial honeys. In 50% of samples investigated, the diastase number was just above the legal limit fixed by Honey Quality Standards. The analysis of the volatile fraction highlighted the presence of numerous compounds from the terpenoid group along with characteristic molecules such as furfural, isophorone, and derivatives. In most cases, VOCs were distinct markers of origin; in others, it was not possible to assess an exclusive source for bees to produce honey. Conclusion: The results contributed to place the three varieties of honey investigated among the commercial products available in the market. Many variables determined returned positive indications about quality and safety of these special honeys

Hand X-ray in pediatric endocrinology: Skeletal age assessment and beyond

Skeletal age assessment (SAA) is a clinical procedure which is used in determining the SA of children and adolescents. Bone development is influenced by a number of factors, including nutrition, hormonal secretions, and genetics. There are several factors to be borne in mind when using methods of assessing skeletal maturity. These include: Variability among methods, degree of variability in the estimation of skeletal maturation, sources of low accuracy, and dispersion of the values of skeletal maturation. Currently, the main clinical methods for SAA are the Greulich and Pyle (GP) and Tanner and Whitehouse (TW) methods. The GP method has the advantage of being quick and easy to use. A well-trained radiologist takes few minutes to determine the bone age (BA) from a single hand radiograph. The method of TW, however, seems to be more reliable than the GP method. In recent years, the increasing speed in computer sciences and reduction of their cost has given the opportunity to create and use computerized BA estimation system. Despite the fact that the number of automated systems for BAA have increased, most are still within the experimental phase. The use of automated BA determination system, cleared for clinical use in Europe (BoneXpert), has been validated for various ethnicities and children with endocrine disorders. Ultrasound imaging has some limitations that include operator dependence, lower intra-rater and inter-rater reliability of assessment and difficulties with standardization of documentation and imaging transfer. Magnetic resonance imaging (MRI) is noninvasive alternative tool for SA assessment in children. However, few studies have been reported on this topic, and further research is needed to evaluate the reliability and validity of MRI BAAs. In conclusion, at present radiographic methods for the assessment of BA remain the gold standards. Whatever method one adopts, it is essential to minimize the causes of imprecision by taking care to consider the quality of the X-ray. Moreover, it is imperative to assume a correct hand positioning because poor positioning can change the appearance of some bones. It is also preferable to employ scoring methods to these techniques and percentiles rather than BA in years and months. In addition, the possible differences in maturation among different population should be kept in mind