A Biochemical and Biophysical Analysis of the Interaction of nsp9 with nsp12 from SARS-CoV-2-Implications for Future Drug Discovery Efforts.

The ongoing global pandemic of the coronavirus 2019 (COVID-19) disease is caused by the virus SARS-CoV-2, with very few highly effective antiviral treatments currently available. The machinery responsible for the replication and transcription of viral RNA during infection is made up of several important proteins. Two of these are nsp12, the catalytic subunit of the viral polymerase, and nsp9, a cofactor of nsp12 involved in the capping and priming of viral RNA.

A structural analysis of the nsp9 protein from the coronavirus MERS CoV reveals a conserved RNA binding interface.

Middle East respiratory syndrome coronavirus (MERS CoV) and severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) are RNA viruses from the Betacoronavirus family that cause serious respiratory illness in humans. One of the conserved non-structural proteins encoded for by the coronavirus family is non-structural protein 9 (nsp9). Nsp9 plays an important role in the RNA capping process of the viral genome, where it is covalently linked to viral RNA (known as RNAylation) by the conserved viral polymerase, nsp12.

Non-insulinoma pancreatogenous hypoglycemia syndrome due to nesidioblastosis following bariatric Roux-en-Y gastric bypass.

A 56-year-old woman with past medical history significant for bariatric Roux-en-Y gastric bypass 3 years prior presented for evaluation of an 8-month history of severe hypoglycemia relieved by intake of carbohydrates associated with syncopal episodes. Inpatient workup revealed endogenous hyperinsulinemia concerning for insulinoma vs. nesidioblastosis.

Rapidly Progressive Bilateral Vitreoretinal Lymphoma.

A 56-year-old male who presented with unilateral localized sub-retinal lesions suspicious for primary vitreoretinal lymphoma (PVRL) developed florid bilateral ocular involvement and was found to have lesions on MRI of the brain in a five-week period despite the absence of vitreous involvement during the entire course of his disease. His ocular lesions were monitored while on systemic treatment and an excellent clinical response was achieved. His central nervous system (CNS) lesions, however, continued to progress despite chemotherapy and whole-brain radiation.

Surgical Treatment of Propriospinal Myoclonus: A Case Report.

Propriospinal myoclonus (PSM) is a rare segmental movement disorder characterized by repetitive irregular myoclonic jerks of the trunk and/or axial limbs at the resting state. It is imperative to make a correct diagnosis as other movement disorders can be mistaken for or mask PSM. Therefore, a battery of neuroimaging and neurophysiological testing must be undertaken.

MIBG avidity correlates with clinical features, tumor biology, and outcomes in neuroblastoma: A report from the Children's Oncology Group.

Background: Prior studies suggest that neuroblastomas that do not accumulate metaiodobenzylguanidine (MIBG) on diagnostic imaging (MIBG non-avid) may have more favorable features compared with MIBG avid tumors. We compared clinical features, biologic features, and clinical outcomes between patients with MIBG nonavid and MIBG avid neuroblastoma.

Procedure: Patients had metastatic high- or intermediate-risk neuroblastoma and were treated on Children's Oncology Group protocols A3973 or A3961.

Medulloblastoma Down Under 2013: a report from the third annual meeting of the International Medulloblastoma Working Group.

Medulloblastoma is curable in approximately 70% of patients. Over the past decade, progress in improving survival using conventional therapies has stalled, resulting in reduced quality of life due to treatment-related side effects, which are a major concern in survivors. The vast amount of genomic and molecular data generated over the last 5-10 years encourages optimism that improved risk stratification and new molecular targets will improve outcomes.

Do bib clips pose a cross-contamination risk at the dental clinic?

Although multiple-use dental napkin holders have a relatively low risk of transmitting infection, they do require disinfection between patients. This study sought to: 1) determine the presence of bacterial load on two types of clips of reusable bib chains after dental procedures at the Endodontics and Orthodontics clinics at Tufts University School of Dental Medicine; and 2) evaluate the effectiveness of disinfecting the clips. These specialty clinics represent a wide spectrum of patients, procedures, and appointment times.

Outcome after reduced chemotherapy for intermediate-risk neuroblastoma.

Background: The survival rate among patients with intermediate-risk neuroblastoma who receive dose-intensive chemotherapy is excellent, but the survival rate among patients who receive reduced doses of chemotherapy for shorter periods of time is not known.

Methods: We conducted a prospective, phase 3, nonrandomized trial to determine whether a 3-year estimated overall survival of more than 90% could be maintained with reductions in the duration of therapy and drug doses, using a tumor biology-based therapy assignment. Eligible patients had newly diagnosed, intermediate-risk neuroblastoma without MYCN amplification; these patients included infants (<365 days of age) who had stage 3 or 4 disease, children (≥365 days of age) who had stage 3 tumors with favorable histopathological features, and infants who had stage 4S disease with a diploid DNA index or unfavorable histopathological features.

Gene-based outcome prediction in multiple cohorts of pediatric T-cell acute lymphoblastic leukemia: a Children's Oncology Group study.

Background: Continuous complete clinical remission in T-cell acute lymphoblastic leukemia (T-ALL) is now approaching 80% due to the implementation of aggressive chemotherapy protocols but patients that relapse continue to have a poor prognosis. Such patients could benefit from augmented therapy if their clinical outcome could be more accurately predicted at the time of diagnosis. Gene expression profiling offers the potential to identify additional prognostic markers but has had limited success in generating robust signatures that predict outcome across multiple patient cohorts.

Classic and desmoplastic medulloblastoma: complete case reports and characterizations of two new cell lines.

Medulloblastoma (MB) is the most common type of brain tumor affecting children. These tumors are a significant cause of childhood mortality and morbidity, and more effective and less invasive treatment options are urgently required. To achieve these aims, it will be critical to develop a more comprehensive understanding of the molecular pathogenesis of MB.

Prediction of relapse in paediatric pre-B acute lymphoblastic leukaemia using a three-gene risk index.

Despite high cure rates 25% of children with acute lymphoblastic leukaemia (ALL) relapse and have dismal outcome. Crucially, many are currently stratified as standard risk (SR) and additional markers to improve patient stratification are required. Here we have used diagnostic bone marrow specimens from 101 children with pre-B ALL to examine the use of gene expression profiles (GEP) as predictors of long-term clinical outcome.

Identification of novel molecular prognostic markers for paediatric T-cell acute lymphoblastic leukaemia.

In the last four decades the survival of patients with newly diagnosed childhood T-cell acute lymphoblastic leukaemia (T-ALL) has improved dramatically. In sharp contrast, relapsed T-ALL continues to confer a dismal prognosis. We sought to determine if gene expression profiling could uncover a signature of outcome for children with T-ALL.

Relapse in children with acute lymphoblastic leukemia involving selection of a preexisting drug-resistant subclone.

Relapse following remission induction chemotherapy remains a barrier to survival in approximately 20% of children suffering from acute lymphoblastic leukemia (ALL). To investigate the mechanism of relapse, 27 matched diagnosis and relapse ALL samples were analyzed for clonal populations using polymerase chain reaction (PCR)-based detection of multiple antigen receptor gene rearrangements. These clonal markers revealed the emergence of apparently new populations at relapse in 13 patients.

Fibrin clot adhesion to dentin conditioned with protein constructs: an in vitro proof-of-principle study.

Objectives: Periodontal regeneration is contingent on the adsorption, uninterrupted adhesion, and maturation of a fibrin clot to a periodontally compromised root surface. Clot adhesion appears vitally dependent on the formation of a resilient union between the clot and the root surface. Root surface demineralization will remove a root surface smear layer exposing dentin tubules and collagen matrix for enhanced clot adhesion.

Detection of hemizygous deletions in genomic DNA from leukaemia specimens for the diagnosis of patients.

Hemizygous deletions in genomic DNA appear to play an important role in tumorigenesis. The loss or inactivation of tumour suppressor genes (TSGs) is of critical importance in most malignancies, and has been shown to affect response to therapy. Here, we report a quantitative real-time polymerase chain reaction (qPCR) designed to detect two TSGs at the CDKN2A locus, p16(INK4A) and p14(ARF) that allows the detection of hemizygous deletions.

Deletion of one copy of the p16INK4A tumor suppressor gene is implicated as a predisposing factor in pediatric leukemia.

The p16INK4A tumor suppressor gene is frequently disrupted by mutation or deletion in a wide range of cancer types, ranging from leukemia to cancers of the bladder, skin, lung, liver, and spleen. We have previously shown that deletion of at least one copy of the p16INK4A gene is associated with an increased risk of relapse in pediatric leukemia. Our data suggest that hemizygous p16INK4A deletion may be constitutional, conferring susceptibility to leukemia.

Utilization of research methodology in designing and developing an interdisciplinary course in ethics.

Development research methodology was utilized to design an interdisciplinary ethics course for students from seven disciplines: dental hygiene, nursing, nurse anesthesia, occupational therapy, physician assistant, physical therapy, and social work. Two research questions, 'What content areas should be considered for inclusion in an interdisciplinary course in Ethics?' and 'What design framework, format, or structure would best fit the content chosen?' guided the study. An interdisciplinary faculty design team conducted a comparative analysis of each of the seven discipline's codes of ethics to find common topics of interest.

Successful induction and maintenance of long-term remission in a child with chronic relapsing autoimmune hemolytic anemia using rituximab.

Childhood autoimmune hemolytic anemia (AIHA) of the warm type is usually successfully managed with corticosteroids and/or immunoglobulin infusions. In a small proportion of patients AIHA follows a more severe and protracted pathway resulting in the use of immunosuppressive therapy and frequently culminating with the need for splenectomy. Rituximab is an anti-CD20 (B-cell) monoclonal antibody used for the treatment of patients with relapsed or refractory low-grade or follicular, CD20 positive, B-cell non-Hodgkin's lymphoma.

Customization of a standard practice management software program to satisfy the needs of a dental hygiene program.

The University of New England (UNE) Dental Hygiene Program converted from a paper format to a digital format to manage the daily, dental hygiene clinic transactions. The use of this practice management software created new opportunities to enhance the program's teaching mission, monitor the progress of individual students, and facilitate the data collection necessary to meet accreditation standards. This report will describe how this dental hygiene program customized a standard practice management software program to enhance the specific requirements of a clinical teaching institution.

A rare case of adenoviral fulminant hepatic necrosis after chemotherapy.

The authors report a rare case of fulminant adenoviral hepatic necrosis occurring after chemotherapy in a patient with a second relapse of acute myeloid leukemia. The literature is reviewed and the role of rapid viral diagnosis in the clinical management of this complication is discussed. A 10-year-old girl with relapsed acute myeloid leukemia after allogeneic bone marrow transplant underwent re-induction chemotherapy with high-dose cytosine arabinoside and amsacrine.