© 2020 Wiley Periodicals, Inc.Obesity is strongly linked to male infertility. Testicular spermatogenic cell apoptosis plays an important role in obesity-related male infertility. Pituitary adenylate cyclase-activating peptide (PACAP) has been recently shown to exhibit antiapoptotic and antidiabetic effects. However, the effects of PACAP on obesity-related male infertility remain unknown. The purpose of the current study is to explore the role of PACAP in obesity-related male infertility. Here, C57BL/6 male mice were fed with a high-fat diet to induce obesity and then treated with PACAP. PACAP treatment ameliorated obesity characteristics, including body weight, epididymal adipose weight, testes/body weight, serum lipids levels, and reproductive hormone levels in vivo. Additionally, PACAP was shown to improve the reproductive function of the obese mice, which was characterized by improved testis morphology, sperm parameters, acrosome reaction, and embryo quality after in vitro fertilization via silent information regulator 1 (Sirt1) activation and p53 deacetylation. These beneficial effects of PACAP were abolished in obese mice with testis-specific knockdown of Sirt1. The mechanism studies showed that PACAP selectively binds to the PAC1 receptor to attenuate palmitic acid-induced mouse spermatogenic cell (GC-1) apoptosis via the PKA/CREB/Sirt1/p53 pathway. However, this mechanism was inhibited in GC-1 cells lacking Sirt1. Finally, human semen studies showed that the decline in sperm quality in obese infertile men was partly due to Sirt1 downregulation and p53 acetylation. Our data suggest that PACAP could ameliorate fertility in obese male mice and may be a promising candidate drug for obesity-induced male infertility. © 2020 Wiley Periodicals, Inc.Children with haematologic malignancies and haematopoietic stem cell transplant recipients are at high risk for invasive fungal diseases (IFD). There has been an increased number of at-risk children over the past two decades due to improvements in cancer therapies resulting in improved survival of children with high-risk and refractory malignancies. The predominant organisms that cause IFD include Candida spp., Aspergillus spp. and the Mucorales molds. Clinical presentations of IFD vary based on host immune status and the causative organism. Though serum biomarkers such as the galactomannan assay and beta-D-glucan assay have been validated in adults, there are limited data regarding their diagnostic value in children. Thus, the gold standard for IFD diagnosis remains tissue biopsy with histopathological and microbiological evaluation. Treatment of IFD is multimodal and involves antifungal drugs, correction of immune dysfunction and surgical resection when feasible. Paediatric practice regarding IFD is largely extrapolated from data generated in adult patients; in this review, we evaluate both primary paediatric studies and guidelines intended for adult patients that are applied to paediatric patients. There remain significant knowledge gaps with respect to the prevention, diagnosis and treatment of IFD in immunocompromised children, and further research is needed to help guide management decisions. © 2019 British Society for Haematology and John Wiley & Sons Ltd.BACKGROUND Antigenic drift of the hemagglutinin (HA) and neuraminidase (NA) proteins of influenza virus cause decrease in vaccine efficacy. Since the information about the evolution of these viruses in Saudi is deficient so we investigated the genetic diversity of circulating H1N1 viruses. METHODS Nasopharyngeal aspirates/swabs collected from 149 patients hospitalized with flu like symptoms during 2014 and 2015 were analyzed. Viral RNA extraction was followed by RT-PCR and genetic sequencing. We analyzed complete gene sequences of HA and NA from 80 positive isolates. RESULTS Phylogenetic analysis of HA and NA genes of 80 isolates showed similar topologies and co-circulation of clades 6b. Genetic diversity was observed among circulating viruses belonging to clade 6B.1A. The amino acid residues in the HA epitope domain were under purifying selection. Amino acid changes at key antigenic sites, such as position S101N, S179N (antigenic site-Sa), I233T (antigenic site-Sb) in the head domain might have resulted in antigenic drift and emergence of variant viruses. For NA protein, 36% isolates showed the presence of amino acid changes such as V13I (n=29), I314M (n=29) and 12% had I34V (n=10). However, H257Y mutation responsible for resistance to neuraminidase inhibitors was missing. CONCLUSIONS Presence of amino acid changes at key antigenic sites and their topologies with structural mapping of residues under purifying selection highlights the importance of antigenic drift and warrants further characterization of recently circulating viruses in view of vaccine effectiveness. The co-circulation of several clades and the predominance of clade 6B.1 suggest multiple introductions in Saudi. This article is protected by copyright. All rights reserved. ACBI1 manufacturer This article is protected by copyright. All rights reserved.In spite of the amount of research on fetal development of the human middle ear and ear ossicles, there has been no report showing a joint between the short limb of incus and the otic capsule or petrous part of the temporal bone. According to observations of serial histological sections from 65 embryos and fetuses at 7-17 weeks of development, the incudopetrosal joint exhibited a developmental sequence similar to the other joints of ossicles, with an appearance of an interzone followed by a trilaminar configuration at 7-12 weeks, a joint cavitation at 13-15 weeks and development of intraarticular and capsular ligaments at 16-17 weeks. These processes occurred at the same time or slightly later than any other joint. Thus, the joint development might coordinate with vibrating ossicles in utero. The growing short limb of incus appeared to accelerate an expansion of the epitympanic recess of the tympanic cavity. Additional observations of five late-stage fetuses demonstrated the incudopetrosal joint located in the fossa incudis joint changing to syndesmosis. Consequently, a real joint with a cavity existed transiently between the human neurocranium and the first pharyngeal arch derivative (i.e. incus) in contrast to the tympanostapedial joint or syndesmosis between the neurocranium and the second arch derivative. The newly described joint might have an effect on the widely accepted primary jaw concept the mammalian jaw should thus have been created within the first pharyngeal arch, although the connection with neurocranium by the stapes is of a different origin. © 2020 Anatomical Society.