Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth.

The Hippo pathway and its nuclear effector Yap regulate organ size and cancer formation. While many modulators of Hippo activity have been identified, little is known about the Yap target genes that mediate these growth effects. Here, we show that yap-/- mutant zebrafish exhibit defects in hepatic progenitor potential and liver growth due to impaired glucose transport and nucleotide biosynthesis. Transcriptomic and metabolomic analyses reveal that Yap regulates expression of glucose transporter glut1, causing decreased glucose uptake and use for nucleotide biosynthesis in yap-/- mutants, and impaired glucose tolerance in adults. Nucleotide supplementation improves Yap deficiency phenotypes, indicating functional importance of glucose-fueled nucleotide biosynthesis. Yap-regulated glut1 expression and glucose uptake are conserved in mammals, suggesting that stimulation of anabolic glucose metabolism is an evolutionarily conserved mechanism by which the Hippo pathway controls organ growth. Together, our results reveal a central role for Hippo signaling in glucose metabolic homeostasis.

A novel corneal explant model system to evaluate antiviral drugs against feline herpesvirus type 1 (FHV-1).

Feline herpesvirus type-1 (FHV-1) is the most common viral cause of ocular surface disease in cats. Many antiviral drugs are used to treat FHV-1, but require frequent topical application and most lack well-controlled in vivo studies to justify their clinical use. Therefore, better validation of current and novel treatment options are urgently needed. Here, we report on the development of a feline whole corneal explant model that supports FHV-1 replication and thus can be used as a novel model system to evaluate the efficacy of antiviral drugs. The anti-herpes nucleoside analogues cidofovir and acyclovir, which are used clinically to treat ocular herpesvirus infection in cats and have previously been evaluated in traditional two-dimensional feline cell cultures in vitro, were evaluated in this explant model. Both drugs suppressed FHV-1 replication when given every 12 h, with cidofovir showing greater efficacy. In addition, the potential efficacy of the retroviral integrase inhibitor raltegravir against FHV-1 was evaluated in cell culture as well as in the explant model. Raltegravir was not toxic to feline cells or corneas, and most significantly, inhibited FHV-1 replication at 500 µM in both systems. Importantly, this drug was effective when given only once every 24 h. Taken together, our data indicate that the feline whole corneal explant model is a useful tool for the evaluation of antiviral drugs and, furthermore, that raltegravir appears a promising novel antiviral drug to treat ocular herpesvirus infection in cats.

Validation of the Clenched Fist View in Detecting Scapholunate Ligamentous Injury.

BACKGROUND: The purpose of this study was to determine the predictive value of the clenched fist stress views in identifying scapholunate ligament injuries. METHODS: An institutional review board-approved retrospective chart review was conducted of adult patients who underwent diagnostic arthroscopy with a ligamentous wrist injury from 2015 to 2020. Standard posteroanterior, lateral, and clenched fist stress radiographs were reviewed and scapholunate ligament gaps recorded. RESULTS: A total of 124 patients were included, of which 88 had normal standard radiographs and clenched fist radiographs. The positive predictive value of the clenched fist view was 69%, whereas the negative predictive value was 58%. The sensitivity of the clenched fist view was 40%, while the specificity was 82%. Of those patients with a negative clenched fist view, 42% were found to have an arthroscopic Geissler classification of 3 or higher scapholunate ligament injury. CONCLUSIONS: Despite the emphasis on stress radiographic views, a normal stress clenched fist view does not preclude arthroscopic findings of a Geissler class 3 or greater injury in symptomatic patients. The sensitivity of a clenched fist view is only 40%. These findings question the utility of stress radiographs when assessing for scapholunate ligament injuries.

Shoulder Arthroplasty for Patients With Proximal Humeral Paget's Disease.

Poorly controlled Paget's disease leads to excessive blood loss following total hip arthroplasty. The effect in shoulder arthroplasty is unknown. The authors reviewed 3 patients with Paget's disease involving the proximal humerus, comparing them with 17 patients with Paget's disease but no humeral involvement. The 3 patients had an estimated blood loss of 1400 mL, 1100 mL, and 350 mL, compared with an average of 280 mL in the control group. The first 2 cases required 4 units of packed red blood cells intraoperatively, and both were not managed with bisphosphonates. Paget's disease of the humerus leads to more intraoperative blood loss and higher blood transfusion requirements, particularly in cases not managed with bisphosphonates. [Orthopedics. 2021;44(4):e614-e619.].

Outcomes of Revision Total Wrist Arthroplasty.

LEVEL OF EVIDENCE: IV.

The Effects of Fault-Zone Cementation on Groundwater Flow at the Field Scale.

Fault zones are an important control on fluid flow, affecting groundwater supply, contaminant migration, and carbon storage. However, most models of fault seal do not consider fault zone cementation, despite the recognition that it is common and can dramatically reduce permeability. In order to study the field-scale hydrogeologic effects of fault zone cementation, we conducted a series of aquifer pumping tests in wells installed within tens of meters of the variably cemented Loma Blanca Fault, a normal fault in the Rio Grande Rift. In the southern half of the study area, the fault zone is cemented by calcite; the cemented zone is 2-8 m wide. In the center of the study area, the cemented fault zone is truncated at a buttress unconformity that laterally separates hydrostratigraphic units with a ∼40X difference in permeability. The fault zone north of the unconformity is not cemented. Constant rate pumping tests indicate that where the fault is cemented, it is a barrier to groundwater flow. This is an important demonstration that a fault with no clay in its core and similar sediment on both sides can be a barrier to groundwater flow by virtue of its cementation; most conceptual models for the hydrogeology of faults would predict that it would not be a barrier to groundwater flow. Additionally, the lateral permeability heterogeneity across the unconformity imposes another important control on the local flow field. This permeability discontinuity acts as either a no-flow boundary or a constant head boundary, depending on the location of pumping.

Management of Epiphrenic Diverticula and Short-term Outcomes.

Epiphrenic diverticulum is a rare and benign condition with significant surgical morbidity and evolving surgical management. The objective of this study was to analyze short-term clinical outcomes after surgery for epiphrenic diverticula. We conducted a retrospective cohort study in a single tertiary care center of all patients who underwent treatment for epiphrenic esophageal diverticula from June 1990 to December 2016. Data collection included demographics, operative details and short-term outcomes (esophageal leak, other complications, 30-day mortality). In addition, all preoperative imaging was reviewed by an esophageal radiologist in order to describe epiphrenic diverticula characteristics in a uniform and blinded manner. Of the 94 patients in the study, 84 patients were managed with an open surgical approach and 10 with minimally invasive techniques. Median size of diverticula was 5.5 cm and mean height above gastroesophageal junction was 4 cm. A myotomy was completed in 95% of patients and a fundoplication in 58%. The MIS group had a shorter length of stay (4 vs 6 days). Overall complication rate was 27% with an esophageal leak rate of 7% with 60% grade I leaks that sealed with conservative management. Complete resection of the diverticulum, closure of the muscle over the resection, contralateral myotomy, and consideration for partial fundoplication are common strategies utilized to surgically treat patients with epiphrenic diverticulum. Minimally invasive approaches are increasingly utilized.

Results of proximal interphalangeal arthroplasty: border digits versus middle digits.

This investigation assessed 106 consecutive primary proximal interphalangeal joint arthroplasties performed on border digits: 73 index or 33 little fingers. This was compared with 193 arthroplasties performed in non-border digits: 121 middle or 72 ring fingers. There were 20 proximal interphalangeal joint arthroplasties in the border digits that required revision surgery for pain and stiffness (10 digits), dislocation (six digits), implant fracture (one digit), and infection (three digits). Risk of revision surgery was not associated with border digit. The 5-year implant survival rate for the border digits was 81%. There was no significant difference in implant revision rate or joint dislocations between border and non-border digits. We conclude that proximal interphalangeal joint arthroplasties performed in border digits had similar pain relief, survivorship, complications, and reoperation rates compared with those performed in non-border digits.Level of evidence: IV.

Understanding the Geometry of Connected Fracture Flow with Multiperiod Oscillatory Hydraulic Tests.

An understanding of the spatial and hydraulic properties of fast preferential flow pathways in the subsurface is necessary in applications ranging from contaminant fate and transport modeling to design of energy extraction systems. One method for the characterization of fracture properties over interwellbore scales is Multiperiod Oscillatory Hydraulic (MOH) testing, in which the aquifer response to oscillatory pressure stimulations is observed. MOH tests were conducted on isolated intervals of wells in siliciclastic and carbonate aquifers in southern Wisconsin. The goal was to characterize the spatial properties of discrete fractures over interwellbore scales. MOH tests were conducted on two discrete fractured intervals intersecting two boreholes at one field site, and a nest of three piezometers at another field site. Fracture diffusivity estimates were obtained using analytical solutions that relate diffusivity to observed phase lag and amplitude decay. In addition, MOH tests were used to investigate the spatial extent of flow using different conceptual models of fracture geometry. Results indicated that fracture geometry at both field sites can be approximated by permeable two-dimensional fracture planes, oriented near-horizontally at one site, and near-vertically at the other. The technique used on MOH field data to characterize fracture geometry shows promise in revealing fracture network characteristics important to groundwater flow and transport.