Molecular Biophysics
It’s not Just Dentistry, It’s Dentistry and Oral Surgery!
When I completed my residency at the University of Pennsylvania School of Veterinary Medicine (Penn Vet) in 2000, I felt comfortable performing a number of dental and oral surgical diagnostic and therapeutic procedures in dogs and cats. They included oral examination, dental radiography, nerve blocks, dental cleaning, periodontal surgery, tooth extraction, endodontic treatment, restorations and prosthodontic crowns, oral tumor resections, jaw fracture repair, palate defect surgery, temporomandibular joint procedures, and regional lymph node and salivary gland resections.Bladder Cancer in a Long-term Survivor of the Prune Belly Syndrome
Prune belly syndrome (PBS) is a rare but morbid complexity of congenital anomalies that consists of abdominal wall defect, bilateral cryptorchidism, and urinary tract dilation. With the recent advances in perinatal care, the life expectancy of patients with PBS has improved. Although renal and sexual outcomes are frequently discussed in the literature, little is known about urinary tract malignancies in adulthood. Herein, we present a case of advanced bladder cancer in a 38-year-old man with PBS.Ovotesticular Disorder Mimicking Acute Spermatic Cord Torsion
Ovotesticular disorder is a rare form of sexual development in which a patient may have one ovary and one testis, or more commonly a gonad or gonads containing both ovarian and testicular tissue. Patients with this condition typically present in infancy with ambiguous genitalia. Delayed presentations of clinically symptomatic, older patients with normal external genitalia are extremely rare. We present a case of a 14-year-old male with normal external genitalia who presented with symptoms and signs consistent with spermatic cord torsion but found to have ovotesticular disorder on evaluation.Persistent Anhydramnios and Lower Urinary Tract Obstruction in a Patient With a Vesicoamniotic Shunt
Persistent anhydramnios after placement of a vesicoamniotic shunt is a rare but potentially serious concern in a patient in utero. We present the case a male fetus who at 32-week gestation had bilateral hydroureteronephrosis, a distended bladder, and anhydramnios. A vesicoamniotic shunt was placed, but the anhydramnios persisted. Postnatally, the child was found to have a migrated shunt, left grade V vesicoureteral reflux and posterior urethral valves. He underwent a posterior urethral valves ablation and removal of the migrated shunt.Bedside Intervention for Neonatal Hydrometrocolpos and Imperforate Hymen
Low complexity cases of neonatal hydrometrocolpos from imperforate hymen are typically treated with hymenotomy or hymenectomy. Although this is commonly performed in the operating room, bedside management is also safe and effective. We present a case of prenatally diagnosed, simple hydrometrocolpos treated via bedside hymenotomy on the first day of life. The patient received periprocedural antibiotics prior to the procedure and had full resolution of hydrometrocolpos without any complication or need for further intervention.Nephron-Sparing Approach For Familial Bilateral Synchronous Wilms Tumors
Wilms tumors are the most common renal malignancy of childhood, often presenting as asymptomatic abdominal masses. These tumors can occur either in a unilateral or bilateral fashion, with bilateral tumors more commonly associated with various genetic syndromes and familial inheritance with some known loci. Bilateral tumors present challenges with regards to balancing oncologic control with renal function. Here, we present an unusual case of a young female patient diagnosed with bilateral Wilms tumors on the background of a strong family history and unknown genetic loci.Congenital Giant Megaureter in a 16-Year-Old Female Presenting With Abdominal Pain: A Case Report and Review of Literature
We describe a case of congenital giant megaureter in a 16-year-old female. She presented with a 5-day history of abdominal distention, right flank pain and tenderness. Right pyelonephritis was suspected. Computerized tomography showed a large cystic abdominal mass with no appreciably functioning left kidney causing secondary compression of the contralateral right ureter. A left upper nephroureterectomy was performed, draining over 3.5 L of fluid. Our experience suggests that congenital giant megaureter should be considered in the differential for pediatric patients presenting with a cystic abdominal mass.Whole Exome Sequencing Identifies a Rare Mutation in NACAD as a Possible Cause of COVID Orchitis in Brothers
COVID orchitis (testicular pain) is reported in 10-15% of men with long COVID. We identified 2 siblings with COVID orchitis and hypothesized that genetic mutations are associated with susceptibility. Blood samples from 5 COVID-19 (+) men, three of whom had orchitis were evaluated by whole-exome-sequencing. A rare deletion on chromosome 7 was found in NACAD among the 3 men with orchitis. Interestingly, circulating ACE2 levels was decreased in men with COVID orchitis. This pilot study generated the hypothesis that men who develop COVID orchitis could have underlying genetic variants and altered levels in circulating ACE2 that may increase their risk.Preface
This issue of Veterinary Clinics of North America: Equine Practice builds on the foundation started in earlier issues of Veterinary Clinics of North America: Equine Practice that were topical on laminitis. This issue is an expanded and thoroughly updated issue that provides our fellow colleagues with a comprehensive and thorough resource for the “common” and “less common” problems of the equine foot and not just focused on laminitis. The information is the most exhaustive of any of the previous publications on the equine foot, while offering a point-by-point discussion of best practices when caring for the foot.Pediatric Penile Non-Involuting Congenital Hemangioma With an Associated Pyogenic Granuloma: Surgical Management of a Rare Vascular Anomaly
Vascular anomalies include both tumors and malformations. Infantile hemangiomas are the most common benign vascular tumor of infancy that proliferate after birth and eventually involute. By contrast, congenital hemangiomas are formed at birth and are categorized into three groups: rapidly involuting, partially-involuting, and non-involuting congenital hemangiomas (NICH). NICH do not regress and grow with age. Pyogenic granulomas, another acquired vascular tumor, develop over vascular lesions and cause bleeding.Misdiagnosis of Congenital Posterior Urethroperineal Fistula and Comparison With Urethral Duplications and Rectourethral Fistula
Congenital posterior urethroperineal fistula (CUPF) is a urothelium-lined tract between the posterior urethra and perineum. This condition is rare and has been proposed to be a urethral duplication variant. A case of CUPF that was misdiagnosed and surgically treated as a rectourethral fistula is presented. The clinical presentation, diagnosis, and treatment of CUPF are discussed and compared with those of Y-type urethral duplications and H-type rectourethral fistulas.Fluorescent Guided Lymph Node Harvest in Laparoscopic Wilms Nephroureterectomy
Lymph node harvest is an integral part of Wilms tumor surgery with both SIOP and COG protocols asking for more than 6 lymph nodes to best evaluate for nodal spread and a subsequent need for intensification of treatment. The majority of studies show that in both open and minimally invasive resections the median number of nodes removed is 4. Indocyanine green and near infrared fluorescence may be the key to solving this problem. In adult gynaecology, colorectal and breast cancers, ICG is used to identify sentinel nodes and facilitate nodal retrieval.Point-of-Care Ultrasound: —The Awakening of a Sleeping Giant
In 1999, as a general practitioner, I declared my first attempt at learning ultrasound a failure after taking an abdominal ultrasound course. Thus, 7 years later as a resident in emergency and critical care (2005-2007), I was resistant to making FAST ultrasound part of my clinical research requirement. The phrase by my Intern Director (1991), the late Dr Michael Garvey, has always been part of my daily practice since: “never send a patient out the door (home) with something you could easily have diagnosed.” Shortly after learning and routinely applying AFAST and TFAST as an extension of the physical exam in 2005 (and later Vet BLUE, 2010), these FAST ultrasound examinations became part of my quick assessment tests.Consent, Cryopreserved Sperm, and Posthumous Conception: Navigating the Ethical Maze
Recent years have borne witness to 2 ongoing, interrelated phenomena: an oft-publicized decline in male fertility and mounting interest in sperm cryopreservation.1 With heavier utilization of sperm freezing and banking services, a slew of scarcely explored legal-ethical issues rise to the forefront. Chief among these is the question of posthumous conception: what happens to frozen sperm after its donor has died? This is no mere academic point; it implicates parenthood, bodily autonomy, a partner's grieving process, estate distribution, and entitlement to Social Security benefits, among myriad others.Mapping invisible epitopes by NMR spectroscopy
Defining discontinuous antigenic epitopes remains a substantial challenge, as exemplified by the case of lipid transfer polyproteins, which are common pollen allergens. Hydrogen/deuterium exchange monitored by NMR can be used to map epitopes onto folded protein surfaces, but only if the complex rapidly dissociates. Modifying the standard NMR-exchange measurement to detect substoichiometric complexes overcomes this time scale limitation and provides new insights into recognition of lipid transfer polyprotein by antibodies.Shining light on rhodopsin selectivity: How do proteins decide whether to transport H+ or Cl–?
The versatile microbial rhodopsin family performs a variety of biological tasks using a highly conserved architecture, making it difficult to understand the mechanistic basis for different functions. Besaw et al. now report structures of a recently discovered cyanobacterial Cl−-pumping rhodopsin and its functionally divergent mutant that reveal how these transmembrane proteins create a gradient of activity with subtle changes. These insights are paralleled by a second recent report, which in combination answers long-standing questions about rhodopsin selectivity and will facilitate future engineering efforts.PSI relieves the pressure of membrane fusion
Some plant proteases contain a latent sequence known as the plant-specific insert (PSI) that, upon release from the full protease sequence, initiates membrane fusion to defend from pathogens. However, the mechanism by which it exerts its effects has been unclear. Zhao et al. report an elegant integration of biophysical experiments and molecular dynamics simulations to reveal events leading up to PSI-mediated membrane fusion. Their results demonstrate a pH-dependent monomer-to-dimer transition, clear evidence of membrane association, and probable structures of prefusion intermediates.Entropy provides an unexpected shield in photosynthesis
Vascular plants combat the excess photon bombarding of high-light conditions with several protective mechanisms. Despite decades of extensive research, new regulatory mech-anisms for photoprotection may remain unknown. Kim et al. now report that the monomeric disordered form of photosystem II (PSII), which is present in higher abundance in the native thylakoid membrane in response to high light, possesses an energy-quenching capability superior to that of the multimeric ordered phase, suggesting a new shielding strategy against high-light stress by altering the macro-organization of PSII supercomplexes.A protein folding intermediate pulls its weight
Proteins must acquire and maintain a specific fold to execute their biochemical function(s). In solution, unfolded proteins typically find this native structure through a biased sampling of preferred intermediate conformations. However, the initial search for these structures begins during protein synthesis, and it is unclear how much interactions between the ribosome and nascent polypeptide skew folding pathways. In this issue, Jensen and colleagues use a ribosomal force–profiling assay to show that RNase H forms a similar folding intermediate on and off the ribosome.Forcing the ribosome to change its message
Mechanical forces can be generated when nascent protein segments are integrated into a membrane. These forces are then transmitted through the nascent protein to the ribosome's catalytic core, but only a few biological consequences of this process have been identified to date. In this issue, Harrington et al. present evidence that these forces form a conserved mechanism to influence the efficiency of ribosomal frameshifting during translation of viral RNA, indicating that mechanical forces may play a broader regulatory role in translation than previously appreciated.Driving tau into phase-separated liquid droplets
Liquid–liquid phase separation of tau protein has been implicated in normal biological function as well as neurodegenerative diseases, including Alzheimer's. However, knowledge about these links is still scant, and the mechanisms driving tau into liquid droplets are poorly understood. A simplified in vitro system that uses unmodified human tau protein now suggests electrostatic interactions provide the basic instructions underlying liquid droplet formation.How a fortuitous collaboration helped catalyze new insights into helper proteins
What a way to begin a scientific career: Two newly independent researchers are brought together at a conference that was only possible because their country has just been reunified. In discussing their work, they discover that each holds half of a research project in their hands: The East German, Matthias Gaestel, can provide the critical protein for West German Johannes Buchner's robust assays. In their cross-country collaboration, they get clear and compelling data defining the previously enigmatic small heat shock proteins as molecular chaperones.
