Background Loss of function mutations in SGPL1 are associated with Sphingosine-1-phosphate lyase insufficiency syndrome, comprising steroid resistant nephrotic syndrome, and primary adrenal insufficiency (PAI) in the majority of cases. SGPL1 encodes sphingosine-1-phosphate lyase (SGPL1) which is a major modulator of sphingolipid signaling. Case Presentation A Pakistani male infant presented at 5 months of age with failure to thrive, nephrotic syndrome, primary adrenal insufficiency, hypothyroidism, and hypogonadism. Other systemic manifestations included persistent lymphopenia, ichthyosis, and motor developmental delay. Aged 9 months, he progressed rapidly into end stage oligo-anuric renal failure and subsequently died. Sanger sequencing of the entire coding region of SGPL1 revealed the novel association of a rare homozygous mutation (chr1072619152, c.511A>G, p.N171D; MAF-1.701e-05) with the condition. Protein expression of the p.N171D mutant was markedly reduced compared to SGPL1 wild type when overexpressed in an SGPL1 knockout cell line, and associated with a severe clinical phenotype. Conclusions The case further highlights the emerging phenotype of patients with loss-of-function SGPL1 mutations. Whilst nephrotic syndrome is a recognized feature of other disorders of sphingolipid metabolism, sphingosine-1-phosphate lyase insufficiency syndrome is unique amongst the sphingolipidoses in presenting with multiple endocrinopathies. Given the multi-systemic and progressive nature of this form of PAI/ nephrotic syndrome, a genetic diagnosis is crucial for optimal management and appropriate screening for comorbidities in these patients. Copyright © 2020 Maharaj, Theodorou, Banerjee, Metherell, Prasad and Wallace.Objective To investigate voice characteristics and exercise related respiratory symptoms in extremely preterm born 11-year-old children, focusing particularly on associations with management of a patent ductus arteriosus (PDA). read more Study design Prospective follow-up of all children born in Norway during 1999-2000 at gestational age less then 28 weeks or with birthweight less then 1,000 g. Neonatal data were obtained prospectively on custom-made registration forms completed by neonatologists. Voice characteristics and exercise related respiratory symptoms were obtained at 11 years by parental questionnaires. Result Questionnaires were returned for 228/372 (61%) eligible children, of whom 137 had no history of PDA. PDA had been noted in 91 participants, of whom 36 had been treated conservatively, 21 with indomethacin, and 34 with surgery. Compared to the children treated with indomethacin or conservatively, the odds ratio (95% confidence interval) for the surgically treated children were 3.4 (1.3; 9.2) for having breathing problems during exercise, 16.9 (2.0; 143.0) for having a hoarse voice, 4.7 (1.3; 16.7) for a voice that breaks when shouting, 4.6 (1.1; 19.1) for a voice that disturbs singing, and 3.7 (1.1; 12.3) for problems shouting or speaking loudly. The significance of surgery per se was uncertain since the duration of mechanical ventilation was associated with the same outcomes. Conclusion Extremely preterm born children with a neonatal history of PDA surgery had more problems with voice and breathing during exercise in mid-childhood than those whose PDA had been handled otherwise. The study underlines the causal heterogeneity of exercise related respiratory symptoms in preterm born children. Copyright © 2020 Engeseth, Engan, Clemm, Vollsæter, Nilsen, Markestad, Halvorsen and Røksund.P63, and in particular the most expressed ΔNp63α isoform, seems to have a critical role in the outcome of head and neck cancer. Many studies have been conducted to assess the possible use of p63 as a prognostic marker in squamous cell carcinoma cancers, but the results are still not well-defined. Moreover, a clear relationship between the expression of ΔNp63α and the presence of high-risk HPV E6 and E7 oncoproteins has been delineated. Here we describe how ΔNp63α is mostly expressed in HPV-positive compared to HPV-negative head and neck cancer cell lines, with a very good correlation between ΔNp63α mRNA and protein levels. Copyright © 2020 Citro, Bellini, Medda, Sabatini, Tagliabue, Chu and Chiocca.The deer tick Ixodes scapularis transmits a variety of disease agents in the United States, spreading the bacteria that causes Lyme borreliosis, the protozoan agent of babesiosis, and viruses such as Powassan. However, a variety of other organisms have also evolved symbiotic relationships with this tick species, and it seems likely that some of these microbes have simultaneously coevolved mechanisms to impact each other and their tick host. The number of organisms identified as I. scapularis symbionts has increased seemingly exponentially with the advent of PCR and next generation sequencing technologies, but convincing arguments have proposed that some of these are of environmental origin, unadapted to surviving the physiological conditions of the tick or that they are artifacts of ultrasensitive detection methods. In this review, we examine the diversity of the known microbes occurring within the I. scapularis microbiome, the evidence for interactions between microbes, and discuss whether some organisms reported to be symbionts of I. scapularis are experimental artifacts. Copyright © 2020 Stewart and Bloom.Universal approaches to the prevention and treatment of human diseases fail to take into account profound immune diversity resulting from genetic variations across populations. Personalized or precision medicine takes into account individual lifestyle, environment, and biology (genetics and immune status) and is being adopted in several disease intervention strategies such as cancer and heart disease. However, its application in infectious diseases, particularly global diseases such as tuberculosis (TB), is far more complex and in a state of infancy. Here, we discuss the impact of human genetic variations on immune responses and how they relate to failures seen in current TB diagnostic, therapy, and vaccine approaches across populations. We offer our perspective on the challenges and potential for more refined approaches going forward. Copyright © 2020 Azad, Lloyd, Sadee and Schlesinger.