Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic Encephalopathies.

The identification of factors that affect cannabidiol (CBD) systemic exposure may aid in optimizing treatment efficacy and safety in clinical practice. In this study, we aimed to correlate CBD plasma concentrations at a steady state to demographic, clinical, and pharmacological characteristics as well as seizure frequency after the administration of a purified CBD oil solution in a real-world setting of children with drug-resistant developmental and epileptic encephalopathies (DEEs). Patients receiving oral CBD pharmaceutical products at maintenance were enrolled.

Pharmacokinetics of cannabidiol in children with refractory epileptic encephalopathy.

Growing interest in the clinical use of cannabidiol (CBD) as adjuvant therapy for pediatric refractory epileptic encephalopathy emphasizes the need for drug treatment optimization. The aim of this study was to characterize the pharmacokinetics of CBD in pediatric patients with refractory epileptic encephalopathy receiving an oil-based oral solution. To evaluate CBD concentrations, six serial blood samples per patient were collected after the morning dose of CBD, at least 21 days after the beginning of treatment.

Exome sequencing reveals novel causes as well as new candidate genes for human globozoospermia.

Study Question: Can exome sequencing identify new genetic causes of globozoospermia?

Summary Answer: Exome sequencing in 15 cases of unexplained globozoospermia revealed deleterious mutations in seven new genes, of which two have been validated as causing globozoospermia when knocked out in mouse models.

What Is Known Already: Globozoospermia is a rare form of male infertility characterised by round-headed sperm and malformation of the acrosome. Although pathogenic variants in DPY19L2 and SPATA16 are known causes of globozoospermia and explain up to 70% of all cases, genetic causality remains unexplained in the remaining patients.

Estimation of the real burden of invasive meningococcal disease in Argentina.

Among the different existing types of bacterial meningitis, the one caused by Neisseria meningitidis is the main presentation of invasive meningococcal disease (IMD). IMD is a significant public health concern and has a reported incidence rate in Argentina of 0.44 cases per 100 000 inhabitants in 2015.

Dried Blood Spot Technique-Based Liquid Chromatography-Tandem Mass Spectrometry Method as a Simple Alternative for Benznidazole Pharmacokinetic Assessment.

Chagas disease (CD) is recognized as one of the major neglected global tropical diseases. Benznidazole (BNZ) is the drug of choice for the treatment of adults, young infants, and newborns with CD. However, the pharmacokinetics (PK) of BNZ have been poorly evaluated in all age groups, with consequent gaps in knowledge about PK-pharmacodynamic relationships in CD.

The axoneme: the propulsive engine of spermatozoa and cilia and associated ciliopathies leading to infertility.

This review article provides a critical analysis of the structure and molecular mechanisms of the microtubule axoneme of cilia and sperm flagella and their associated elements required for male fertility.A broad range of genetic and molecular defects (ciliopathies) are considered in the context of human diseases involving impaired motility in cilia and sperm flagella, providing provocative thought for future research in the area of male infertility.

Limited infant exposure to benznidazole through breast milk during maternal treatment for Chagas disease.

Background: Benznidazole (BNZ) is safe and effective for the treatment of paediatric Chagas disease. Treatment of adults is also effective in many cases, but discouraged in breastfeeding women because no information on BNZ transfer into breast milk is available. We aimed to evaluate the degree of BNZ transfer into breast milk in lactating women with Chagas disease.

Ultrastructural analysis of testicular tissue and sperm by transmission and scanning electron microscopy.

Transmission electron microscopy (TEM) studies have provided the basis for an in-depth understanding of the cell biology and normal functioning of the testis and male gametes and have opened the way to characterize the functional role played by specific organelles in spermatogenesis and sperm function. The development of the scanning electron microscope (SEM) extended these boundaries to the recognition of cell and organ surface features and the architectural array of cells and tissues. The merging of immunocytochemical and histochemical approaches with electron microscopy has completed a series of technical improvements that integrate structural and functional features to provide a broad understanding of cell biology in health and disease.

Acrosomal biogenesis in human globozoospermia: immunocytochemical, ultrastructural and proteomic studies.

Background: Acrosome biogenesis is a key event in sperm differentiation that depends on the proper interaction between the Golgi complex and the nuclear envelope of early spermatids. We studied the development, structure and biochemical characteristics of human acrosomes in germ cells and spermatozoa from testicular biopsies and semen samples of fertile men and patients with acrosomeless spermatozoa (globozoospermia). A set of proteins collectively known as the perinuclear theca (PT), which has been related to acrosomal development in many mammalian species, were also investigated.

Tales of the tail and sperm head aches: changing concepts on the prognostic significance of sperm pathologies affecting the head, neck and tail.

This article presents an update on the variable prognostic significance of different sperm pathologies in patients with severe male factor infertility due to morphology and motility disorders. Severe asthenozoospermia is one of the leading causes of male infertility as spermatozoa cannot reach the oocyte and/or penetrate normally. Identifying structural causes of sperm immotility was of great concern before the advent of intracytoplasmic sperm injection (ICSI), because immotility was the limiting factor in the treatment of these patients.

The making of abnormal spermatozoa: cellular and molecular mechanisms underlying pathological spermiogenesis.

Fertilization in mammals occurs via a series of well-defined events in the secluded environment of the female reproductive tract. The mode of selection of the fertilizing spermatozoon nevertheless remains unknown. As has become evident during in vitro fertilization by sperm microinjection into the oocyte, abnormal spermatozoa can successfully fertilize oocytes.

Origin and evolution of somatic cell testicular tumours in transgenic mice.

Transgenic mice bearing a construct in which the expression of the SV40 oncogene is directed by the AMH promoter (AT mice) develop testicular tumours in adult life. We aimed to study early steps of tumour development and characterize tumours at different ages by histological, morphometric, and immunohistochemical techniques. One- to 3-month-old AT mice depicted multifocal Leydig cell hyperplasia.

Biogenesis of the sperm head perinuclear theca during human spermiogenesis.

We analyzed the appearance and localization of the sub-acrosomal perinuclear theca (PT) during human spermiogenesis. The PT is tightly associated with acrosomal biogenesis.

Sperm pathology: a step beyond descriptive morphology. Origin, characterization and fertility potential of abnormal sperm phenotypes in infertile men.

Sperm pathology is presented as the discipline of characterizing structural and functional deficiencies in abnormal spermatozoa. This concept complements that of sperm morphology mainly concerned with the appearance of spermatozoa. These two notions collaborate in providing correlations of prognostic value with sperm fertilizing capacity, explaining the mechanisms of sperm inefficiency, suggesting strategies to improve fertilization and opening a door to molecular genetic studies.

Early manifestations of testicular dysgenesis in children: pathological phenotypes, karyotype correlations and precursor stages of tumour development.

Testicular dysgenesis derives from abnormal gonadal development caused by chromosome aberrations/mosaicisms or mutations/deletions in SRY or other genes responsible for testicular differentiation. Dysgenetic male pseudohaermaphroditism has bilateral dysgenetic testes characterized by a cortical network of anastomosing seminiferous cords that penetrate a thin albuginea. In asymmetric gonadal differentiation (or Mixed Gonadal Dysgenesis) a dysgenetic testis associates with a streak gonad with primitive sex cords embedded in an ovarian-like stroma.

Oral montelukast versus inhaled beclomethasone in 6- to 11-year-old children with asthma: results of an open-label extension study evaluating long-term safety, satisfaction, and adherence with therapy.

This 6-month, open-label extension study of a previously described base study compared oral montelukast with inhaled beclomethasone in terms of safety, forced expiratory volume in one second (FEV1) measurements, parent and patient satisfaction with treatment, asthma-related medical resource utilization, school absenteeism, and parental work loss in children with asthma. A total of 124 of 266 asthmatic children, 6 to 11 years of age, who enrolled in the base study entered a 6-month open-label extension study (74 boys, 50 girls) and were re-randomized (2:1 ratio) to receive once-daily oral montelukast (n = 83) or inhaled beclomethasone 100 mcg three times daily (n = 41). Children were evaluated in the clinic prior to re-randomization (Month 0) and at regular visits at 1, 3, and 6 months.

Infancy is not a quiescent period of testicular development.

Postnatal evolution of the testis in most laboratory animals is characterized by the close continuity between neonatal activation and pubertal development. In higher primates, infancy, a long period of variable duration, separates birth from the beginning of puberty. This period has been classically considered as a quiescent phase of testicular development, but is actually characterized by intense, yet inapparent activity.

Acephalic spermatozoa and abnormal development of the head-neck attachment: a human syndrome of genetic origin.

A series of 10 young sterile men with acephalic spermatozoa or abnormal head-mid-piece attachments is presented. Nine of these patients had 75-100% spermatozoa with minute cephalic ends and 0-25% abnormal head-middle piece attachments. Loose heads ranged between 0-35 for each 100 spermatozoa and normal forms were rare.

Ultrastructural pathology of the sperm flagellum: association between flagellar pathology and fertility prognosis in severely asthenozoospermic men.

An ultrastructural study of spermatozoa in a series of 247 severely asthenozoospermic patients disclosed two kinds of anomalies. The first was dysplasia of the fibrous sheath, a primary defect of spermatozoa with hypertrophy and hyperplasia of the fibrous sheath, associated axonemal anomalies, familial incidence and chronic respiratory disease. The patients could be divided into two subgroups: the complete form (all spermatozoa affected) and the incomplete form (alterations in 70-80% spermatozoa).

Presence and integration of human papillomavirus type 6 in a tonsillar carcinoma.

Human papillomavirus type 6 subtype a (HPV-6a) was detected in a human invasive tonsillar carcinoma. Southern blot hybridization analysis showed the presence of additional bands when using non-cutting and single-cut restriction enzymes. Molecular cloning yielded two recombinant clones of 8.

Phase II study of ifosfamide as a single drug for relapsed paediatric patients.

A total of 22 patients with different solid tumours refractory to previous chemotherapy were treated between May 1985 and December 1986 (osteosarcoma, 7; Wilms' tumour, 6; rhabdomyosarcoma, 2; Ewing's sarcoma, 2; non-Hodgkin's lymphoma, 2; retinoblastoma, 1; cavum lymphoepithelioma, 1; dyktioma, 1). Patients were aged between 3 and 20 years (mean, 10.6 years).

Spermatogenic onset. II. FSH modulates mitotic activity of germ and Sertoli cells in immature rats.

By using high doses of testosterone propionate (TP) endogenous FSH was lowered to non-detectable levels in immature rats of different ages. Combined administration of TP and human menopausal gonadotrophin (hMG) or purified human FSH (hFSH) restored circulating FSH to normal or supranormal levels. This experimental model was used to investigate the influences of hormones on the proliferation of Sertoli and germ cells.

Dysplasia of the fibrous sheath: an ultrastructural defect of human spermatozoa associated with sperm immotility and primary sterility.

A study of a group of five patients presenting with primary sterility and showing severe sperm immotility is presented. Most spermatozoa in these patients showed rigid, short, thick, and/or irregular tails and 95 to 100% were immotile. Electron-microscopy disclosed a common pattern of flagellar abnormalities.