Transitioning preclinical students into clerkships amidst curricular disruptions from the COVID-19 pandemic.

The COVID-19 pandemic resulted in significant disruptions to medical education. The patient care space was unavailable as a learning environment, which compounded the complexity of preparing students for clerkships with a traditional transition to clerkship (TTC) curriculum. We developed a multimodal, structured approach to re-introduce students to the clinical space prior to the start of clerkships.

AAIM Recommendations for the 2020-2021 Internal Medicine Residency Application Cycle in Response to the COVID-19 Pandemic.

This statement was released in June 2020 by the Alliance for Academic Internal Medicine to provide guidance for the 2020-2021 residency application cycle in light of the COVID-19 pandemic. While many of the recommendations are specific to this cycle, others, such as the Department Summary Letter of Evaluation, are meant to be an enduring change to the internal medicine residency application process. AAIM realizes that some schools may not yet have the tools or resources to implement the template fully this cycle and look toward collaboration within the internal medicine education community to facilitate adoption in the cycles to come.

Impact of diagnostic bone biopsies on the management of non-vertebral osteomyelitis: A retrospective cohort study.

Optimal antibiotic management of patients with osteomyelitis remains a challenge for many clinicians. Although image-guided bone biopsy (IGB) remains the gold standard, its role in confirming diagnosis and guiding antibiotic management is not clear in patients with non-vertebral osteomyelitis.To determine the diagnostic yield of IGB and its impact on antibiotic management in non-vertebral osteomyelitis.

Top Qualifications Hospitalist Leaders Seek in Candidates: Results from a National Survey.

Despite rapidly growing interest in Hospital Medicine (HM), no prior research has examined the factors that may be most beneficial or detrimental to candidates during the HM hiring process. We developed a survey instrument to assess how those involved in the HM hiring process assess HM candidate attributes, skills and behaviors. The survey was distributed electronically to nontrainee physician Society of Hospital Medicine members.

Increased lysosomal proteolysis counteracts protein accumulation in the proximal tubule during focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a prevalent cause of end-stage renal disease, but the mechanisms underlying progression are unresolved. Lysosomal protein accumulation in the proximal tubule, mediated by megalin and cubilin endocytosis of increased amounts of filtered protein, is thought to result in inflammation and fibrosis. Here we determine whether release of inflammatory and fibrotic mediators in response to protein overload in the proximal tubule is caused by lysosomal enzyme deficits and insufficient proteolysis.

Podocin inactivation in mature kidneys causes focal segmental glomerulosclerosis and nephrotic syndrome.

Podocin is a critical component of the glomerular slit diaphragm, and genetic mutations lead to both familial and sporadic forms of steroid-resistant nephrotic syndrome. In mice, constitutive absence of podocin leads to rapidly progressive renal disease characterized by mesangiolysis and/or mesangial sclerosis and nephrotic syndrome. Using established Cre-loxP technology, we inactivated podocin in the adult mouse kidney in a podocyte-specific manner.

Nephrin mutations can cause childhood-onset steroid-resistant nephrotic syndrome.

Classically, infants with mutations in NPHS1, which encodes nephrin, present with nephrotic syndrome within the first 3 mo of life (congenital nephrotic syndrome of the Finnish-type), and children with mutations in NPHS2, which encodes podocin, present later with steroid-resistant nephrotic syndrome. Recently, however, NPHS2 mutations have been identified in children with congenital nephrotic syndrome. Whether NPHS1 mutations similarly account for some cases of childhood steroid-resistant nephrotic syndrome is unknown.

Maternal environment interacts with modifier genes to influence progression of nephrotic syndrome.

Mutations in the NPHS2 gene, which encodes podocin, are responsible for some cases of sporadic and familial autosomal recessive steroid-resistant nephrotic syndrome. Inter- and intrafamilial variability in the progression of renal disease among patients bearing NPHS2 mutations suggests a potential role for modifier genes. Using a mouse model in which the podocin gene is constitutively inactivated, we sought to identify genetic determinants of the development and progression of renal disease as a result of the nephrotic syndrome.

Biliary and pancreatic dysgenesis in mice harboring a mutation in Pkhd1.

Autosomal recessive polycystic kidney disease is a hereditary fibrocystic disease that involves the kidneys and the biliary tract. Mutations in the PKHD1 gene are responsible for typical forms of autosomal recessive polycystic kidney disease. We have generated a mouse model with targeted mutation of Pkhd1 by disrupting exon 4, resulting in a mutant transcript with deletion of 66 codons and expression at approximately 30% of wild-type levels.

NPHS2 mutation analysis shows genetic heterogeneity of steroid-resistant nephrotic syndrome and low post-transplant recurrence.

Background: Mutations of NPHS2 are causative in familial autosomal-recessive (AR) and sporadic steroid-resistant nephrotic syndrome (SRNS). This study aimed to determine the spectrum of NPHS2 mutations and to establish genotype-phenotype correlations.

Methods: NPHS2 mutation analysis was performed in 338 patients from 272 families with SRNS: 81 families with AR SRNS, 172 patients with sporadic SRNS, and 19 patients with diffuse mesangial sclerosis (DMS).

Milder presentation of recessive polycystic kidney disease requires presence of amino acid substitution mutations.

Autosomal recessive polycystic kidney disease (ARPKD; MIM 263200) is a hereditary and severe form of polycystic disease affecting the kidneys and biliary tract with an estimated incidence of 1 in 20,000 live births. The clinical spectrum is widely variable: up to 50% of affected neonates die shortly after birth, whereas others survive to adulthood. Mutations at a single locus, polycystic kidney and hepatic disease 1 (PKHD1), are responsible for all typical forms of ARPKD.

Identification and characterization of Pkhd1, the mouse orthologue of the human ARPKD gene.

PKHD1, the gene mutated in human autosomal recessive polycystic kidney disease has recently been identified. Its translation products are predicted to belong to a superfamily of proteins involved in the regulation of cellular adhesion and repulsion. One notable aspect of the gene is its unusually complex pattern of splicing.

PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats.

Autosomal recessive polycystic kidney disease (ARPKD) is a severe form of polycystic kidney disease that presents primarily in infancy and childhood and that is characterized by enlarged kidneys and congenital hepatic fibrosis. We have identified PKHD1, the gene mutated in ARPKD. PKHD1 extends over > or =469 kb, is primarily expressed in human fetal and adult kidney, and includes a minimum of 86 exons that are variably assembled into a number of alternatively spliced transcripts.