Structural determinants for naturally evolving H5N1 hemagglutinin to switch its receptor specificity.

Of the factors governing human-to-human transmission of the highly pathogenic avian-adapted H5N1 virus, the most critical is the acquisition of mutations on the viral hemagglutinin (HA) to "quantitatively switch" its binding from avian to human glycan receptors. Here, we describe a structural framework that outlines a necessary set of H5 HA receptor-binding site (RBS) features required for the H5 HA to quantitatively switch its preference to human receptors. We show here that the same RBS HA mutations that lead to aerosol transmission of A/Vietnam/1203/04 and A/Indonesia/5/05 viruses, when introduced in currently circulating H5N1, do not lead to a quantitative switch in receptor preference. We demonstrate that HAs from circulating clades require as few as a single base pair mutation to quantitatively switch their binding to human receptors. The mutations identified by this study can be used to monitor the emergence of strains having human-to-human transmission potential.

Extramammary Paget's disease: what do we know and how do we treat?

INTRODUCTION: Extramammary Paget's disease (EMPD) is a rare and complex condition, for which no established guidelines exist regarding diagnosis and management. There have been recent improvements in the diagnosis and management in EMPD, largely due to an enhanced understanding of its underlying pathogenesis. MATERIALS AND METHODS: A literature search on PubMed including articles that describe pathogenesis, clinical diagnosis, treatment modalities, and future treatment were selected and included to build this review. RESULTS: Recent studies would suggest the expression of HER2 and androgen receptors which could be useful targets for future treatment strategies. Carcinoembryonic antigen as a biomarker for EMPD has shown the potential to aid in the detection of metastatic EMPD and assessment of treatment response. Studies have also demonstrated the initial site of EMPD can be predictive of secondary malignancies, which helps guide initial work up and evaluation. CONCLUSIONS: Significant developments in understanding the pathogenesis of EMPD have been made, especially of the genomic aberrations associated with EMPD. This has allowed for the development and use of therapeutic options which may improve outcomes for patients with EMPD.

Juxtaglomerular cell tumor in a young male presenting with new onset congestive heart failure.

Renin secreting juxtaglomerular cell tumors are extremely rare benign tumors of the kidney. In this case, we highlight the atypical presentation of a young male patient presenting with vague complaints of worsening dyspnea, shortness of breath and anxiety. Initial workup of troponinemia and elevated BNP was initially most suggestive of a major cardiac event. An ejection fraction of 20% confirmed that this patient presented with heart failure. However, only further workup with imaging and renin and aldosterone labs revealed a functional renal mass as the cause. Timely intervention was pursued and pathology of the tumor was consistent with a juxtaglomerular cell tumor.

Acute Foreskin Strangulation Injury due to Bathing Suit Mesh Entrapment.

Genital injury can occur at any age of life but is most common in the pediatric population. Hair-tourniquets and circumcision procedures are the most common causes of penile injury in children. Foreskin trauma, aside from zipper related injuries, is sparsely reported. We describe the case of an 8-year-old male who presented with foreskin entrapment caused by bathing suit mesh. Management and literature review are discussed.

Preoperative Testosterone Therapy Prior to Surgical Correction of Hypospadias: A Review of the Literature.

Hypospadias is a congenital anomaly of the male urethra that causes significant morbidity in the pediatric male population. The mainstay of treatment is hypospadias repair surgery. However, given the common co-occurrence of microphallus in these patients, surgery remains difficult without adequate tissue for proper reconstruction of the urethra. The use of preoperative testosterone therapy, parenterally or topically, has been a topic of study for several years in urologic literature. This literature review aims to summarize the different studies that have been conducted to address whether preoperative testosterone therapy is beneficial, inconsequential, or detrimental to the surgical and cosmetic outcomes of hypospadias repair as well as to address the differences in routes of administration.

Torsion of the Appendix Testis in a Neonate.

Torsion of the appendix testis is a rare cause of scrotal swelling in the neonatal period. We present a case of torsion of the appendix testis in a one-day-old male. We discuss the physical examination and radiologic studies used to make the diagnosis. Nonoperative therapy was recommended and the patient has done well. Recognition of this condition in the neonatal period can prevent surgical intervention and its associated risks.

Structural basis for molecular interactions involving MRG domains: implications in chromatin biology.

MRG15 is a member of the mortality family of transcription factors that targets a wide variety of multiprotein complexes involved in transcription regulation, DNA repair, and alternative splicing to chromatin. The structure of the apo-MRG15 MRG domain implicated in interactions with diverse proteins has been described, but not in complex with any of its targets. Here, we structurally and functionally characterize the interaction between MRG15 and Pf1, two constitutively associated subunits of the histone deacetylase-associated Rpd3S/Sin3S corepressor complex. The MRG domain adopts a structure reminiscent of the apo state, whereas the Pf1 MRG-binding domain engages two discrete hydrophobic surfaces on the MRG domain via a bipartite motif comprising an α-helix and a segment in an extended conformation, both of which are critical for high-affinity interactions. Multiple MRG15 interactors share an FxLP motif in the extended segment, but equivalent sequence/helical motifs are not readily evident, implying potential diversity in MRG-recognition mechanisms.