Noninferiority of Multiplex Polymerase Chain Reaction Compared to Standard Urine Culture for Urinary Tract Infection Diagnosis in Pediatric Patients at Hackensack Meridian Health Children's Hospital Emergency Department.

Objective: To establish the noninferiority of the rapid and sensitive multiplex polymerase chain reaction (M-PCR) method versus standard urine culture (SUC) in pediatric urinary tract infection (UTI) diagnostic testing.

Methods: A United States of America (USA)-based single-center prospective observational study of 44 female and four male patients aged 3-21 years old presenting to a Pediatric Emergency Department in New Jersey with clinically suspected UTI. Urine specimens were primarily collected via midstream voiding.

The Expanding Role of United States Healthcare Chaplains in Clinical Ethics.

Healthcare chaplains in the United States increasingly report being tasked by their organizations to participate in the formal work of clinical ethics, by serving on ethics committees, performing clinical ethics consultations, or leading clinical ethics programs. This mapping study documents that professionally-trained chaplains possess a number of skills and attributes that enhance their capability for this work; however, they often lack certain knowledge specific to the discipline of clinical ethics that is needed for roles they are being asked to perform. The professional associations of both chaplaincy and clinical ethics are encouraged to address this educational gap for the benefit of both disciplines.

COL4A gene variants are common in children with hematuria and a family history of kidney disease.

Background: Inherited kidney diseases are a common cause of chronic kidney disease (CKD) in children. Identification of a monogenic cause of CKD is more common in children than in adults. This study evaluated the diagnostic yield and phenotypic spectrum of children who received genetic testing through the KIDNEYCODE sponsored genetic testing program.

CMV-associated collapsing focal segmental glomerulosclerosis after kidney transplant in a pediatric patient.

Background: Cytomegalovirus (CMV) is a significant cause of morbidity among immunocompromised patients who have undergone kidney transplantation and is known to rarely induce collapsing focal segmental glomerulosclerosis (FSGS) among adults.

Methods: We present the first reported case of CMV-induced collapsing FSGS in a pediatric patient after kidney transplant.

Results: Our patient underwent a deceased donor kidney transplant due to end-stage renal disease secondary to lupus nephritis.

The KIDNEYCODE Program: Diagnostic Yield and Clinical Features of Individuals with CKD.

Background: Despite increasing recognition that CKD may have underlyi ng genetic causes, genetic testing remains limited. This study evaluated the diagnostic yield and phenotypic spectrum of CKD in individuals tested through the KIDNEYCODE sponsored genetic testing program.

Methods: Unrelated individuals who received panel testing (17 genes) through the KIDNEYCODE sponsored genetic testing program were included.

Control of division in Chlamydomonas by cyclin B/CDKB1 and the anaphase-promoting complex.

In yeast and animals, cyclin B binds and activates the cyclin-dependent kinase ('CDK') CDK1 to drive entry into mitosis. We show that CYCB1, the sole cyclin B in Chlamydomonas, activates the plant-specific CDKB1 rather than the CDK1 ortholog CDKA1, confirming and extending previous results. Time-lapse microscopy shows that CYCB1 is synthesized before each division in the multiple fission cycle, then is rapidly degraded 3-5 minutes before division occurs.

A mixed methods evaluation of an intervention to prevent perinatal depression among Latina immigrants.

: The effectiveness of a cognitive behavioural intervention to prevent perinatal depression in low-income Latina immigrant pregnant women and mothers receiving WIC services was evaluated in a mixed methods study using a community based observational design.: The Mothers and Babies Course is a preventive intervention for perinatal depression that is based on cognitive behavioural theory (CBT). CBT is an evidence-based treatment and preventive intervention for perinatal depression.

DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS.

Background: We evaluated and compared the effects of sparsentan, a dual endothelin type A (ET) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS.

Methods: In this phase 2, randomized, double-blind, active-control Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Randomized, Double-blind, Active-Control, Dose-Escalation Study (DUET), patients aged 8-75 years with biopsy-proven FSGS, eGFR>30 ml/min per 1.73 m, and urinary protein-to-creatinine ratio (UP/C) ≥1.

Comprehensive Discovery of Cell-Cycle-Essential Pathways in .

We generated a large collection of temperature-sensitive lethal mutants in the unicellular green alga , focusing on mutations specifically affecting cell cycle regulation. We used UV mutagenesis and robotically assisted phenotypic screening to isolate candidates. To overcome the bottleneck at the critical step of molecular identification of the causative mutation ("driver"), we developed MAPS-SEQ (meiosis-assisted purifying selection sequencing), a multiplexed genetic/bioinformatics strategy.

High-Throughput Robotically Assisted Isolation of Temperature-sensitive Lethal Mutants in Chlamydomonas reinhardtii.

Systematic identification and characterization of genetic perturbations have proven useful to decipher gene function and cellular pathways. However, the conventional approaches of permanent gene deletion cannot be applied to essential genes. We have pioneered a unique collection of ~70 temperature-sensitive (ts) lethal mutants for studying cell cycle regulation in the unicellular green algae Chlamydomonas reinhardtii.

Loss-of-Function Mutations in YY1AP1 Lead to Grange Syndrome and a Fibromuscular Dysplasia-Like Vascular Disease.

Fibromuscular dysplasia (FMD) is a heterogeneous group of non-atherosclerotic and non-inflammatory arterial diseases that primarily involves the renal and cerebrovascular arteries. Grange syndrome is an autosomal-recessive condition characterized by severe and early-onset vascular disease similar to FMD and variable penetrance of brachydactyly, syndactyly, bone fragility, and learning disabilities. Exome-sequencing analysis of DNA from three affected siblings with Grange syndrome identified compound heterozygous nonsense variants in YY1AP1, and homozygous nonsense or frameshift YY1AP1 variants were subsequently identified in additional unrelated probands with Grange syndrome.

Adrenocorticotropic hormone therapy for the treatment of idiopathic nephrotic syndrome in children and young adults: a systematic review of early clinical studies with contemporary relevance.

Adrenocorticotropic hormone (ACTH) as a treatment for proteinuria due to nephrotic syndrome (NS) has re-emerged over the last decade. Current clinical data are primarily limited to adults with treatment-resistant NS. Largely unknown to today's clinicians is the existence of early clinical studies, following ACTH's introduction in the late 1940s, showing sustained proteinuria response in idiopathic NS in predominantly pediatric, treatment-naïve patients.

Analysis of mechanical grooming at various frequencies on a large scale test panel coated with a fouling-release coating.

A mechanical grooming test was performed on large scale steel test panels coated with a fouling-release (FR) coating (International Intersleek 900), at four different frequencies, during the high fouling season in Port Canaveral, Florida. Grooming at frequencies of three or two times per week was effective at removing heavy biofilm growth and significantly reduced macrofouling settlement. Mechanical grooming at lower frequencies of weekly or bi-weekly removed heavy biofilm growth but was much less effective at reducing macrofouling settlement.

The Need to Be Seen.

When we recognize our common humanity, suspend judgment and embrace the intrinsic value and worth of every individual, we elevate those we serve, and we elevate ourselves. Whether or not we are able to offer cure, we are always capable of fulfilling our mission to heal.

Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study.

Modulation of DNA Polymerase Noncovalent Kinetic Transitions by Divalent Cations.

Replicative DNA polymerases (DNAPs) require divalent metal cations for phosphodiester bond formation in the polymerase site and for hydrolytic editing in the exonuclease site. Me(2+) ions are intimate architectural components of each active site, where they are coordinated by a conserved set of amino acids and functional groups of the reaction substrates. Therefore Me(2+) ions can influence the noncovalent transitions that occur during each nucleotide addition cycle.

Analysis of long-term mechanical grooming on large-scale test panels coated with an antifouling and a fouling-release coating.

Long-term grooming tests were conducted on two large-scale test panels, one coated with a fluorosilicone fouling-release (FR) coating, and one coated with a copper based ablative antifouling (AF) coating. Mechanical grooming was performed weekly or bi-weekly using a hand operated, electrically powered, rotating brush tool. The results indicate that weekly grooming was effective at removing loose or heavy biofilm settlement from both coatings, but could not prevent the permanent establishment of low-profile tenacious biofilms.

Kinetic mechanisms governing stable ribonucleotide incorporation in individual DNA polymerase complexes.

Ribonucleoside triphosphates (rNTPs) are frequently incorporated during DNA synthesis by replicative DNA polymerases (DNAPs), and once incorporated are not efficiently edited by the DNAP exonucleolytic function. We examined the kinetic mechanisms that govern selection of complementary deoxyribonucleoside triphosphates (dNTPs) over complementary rNTPs and that govern the probability of a complementary ribonucleotide at the primer terminus escaping exonucleolytic editing and becoming stably incorporated. We studied the quantitative responses of individual Φ29 DNAP complexes to ribonucleotides using a kinetic framework, based on our prior work, in which transfer of the primer strand from the polymerase to exonuclease site occurs prior to translocation, and translocation precedes dNTP binding.

A systematic review of perinatal depression interventions for adolescent mothers.

Poor, adolescent, racial/ethnic minority women are at great risk for developing perinatal depression. However, little research has been conducted evaluating interventions for this population. We conducted a systematic review of preventive and treatment interventions for perinatal depression tested with adolescents, with a focus on low income, minority populations.

Kinetic mechanism at the branchpoint between the DNA synthesis and editing pathways in individual DNA polymerase complexes.

Exonucleolytic editing of incorrectly incorporated nucleotides by replicative DNA polymerases (DNAPs) plays an essential role in the fidelity of DNA replication. Editing requires that the primer strand of the DNA substrate be transferred between the DNAP polymerase and exonuclease sites, separated by a distance that is typically on the order of ~30 Å. Dynamic transitions between functional states can be quantified with single-nucleotide spatial precision and submillisecond temporal resolution from ionic current time traces recorded when individual DNAP complexes are held atop a nanoscale pore in an electric field.

Dynamics of translocation and substrate binding in individual complexes formed with active site mutants of {phi}29 DNA polymerase.

The Φ29 DNA polymerase (DNAP) is a processive B-family replicative DNAP. Fluctuations between the pre-translocation and post-translocation states can be quantified from ionic current traces, when individual Φ29 DNAP-DNA complexes are held atop a nanopore in an electric field. Based upon crystal structures of the Φ29 DNAP-DNA binary complex and the Φ29 DNAP-DNA-dNTP ternary complex, residues Tyr-226 and Tyr-390 in the polymerase active site were implicated in the structural basis of translocation.

Kinetic mechanism of translocation and dNTP binding in individual DNA polymerase complexes.

Complexes formed between phi29 DNA polymerase (DNAP) and DNA fluctuate discretely between the pre-translocation and post-translocation states on the millisecond time scale. The translocation fluctuations can be observed in ionic current traces when individual complexes are captured atop the α-hemolysin nanopore in an electric field. The presence of complementary 2'-deoxynucleoside triphosphate (dNTP) shifts the equilibrium across the translocation step toward the post-translocation state.

Dynamics of the translocation step measured in individual DNA polymerase complexes.

Complexes formed between the bacteriophage phi29 DNA polymerase (DNAP) and DNA fluctuate between the pre-translocation and post-translocation states on the millisecond time scale. These fluctuations can be directly observed with single-nucleotide precision in real-time ionic current traces when individual complexes are captured atop the α-hemolysin nanopore in an applied electric field. We recently quantified the equilibrium across the translocation step as a function of applied force (voltage), active-site proximal DNA sequences, and the binding of complementary dNTP.