Early Hypophosphatemia as a Prognostic Marker in Acute Pancreatitis.

OBJECTIVES: Acute pancreatitis (AP) is a complex disease representing a significant portion of gastrointestinal-related hospitalizations in the U.S. Understanding risk factors of AP might provide attractive therapeutic targets. We evaluated hypophosphatemia as a risk factor for worse outcomes in AP. METHODS: We performed a retrospective review of electronic health records of patients with AP admissions from 01/01/2012-12/31/2021 at Cedars-Sinai Medical Center, evaluating patients with serum phosphate measured within 48 hours of admission. Multivariable logistic regression modeling was employed to evaluate associations with ICU admission, AP severity, and a multivariable log-linear model was employed to examine associations with length of stay (LOS). RESULTS: Of 1,526 patients admitted for AP, 33% (499) had a serum phosphate level measured within 48 hours. Patients with hypophosphatemia were more likely to have been admitted to the ICU (AOR = 4.57; 95% CI: 2.75-7.62; P < 0.001), have a longer hospital stay (log-LOS = 0.34; SE; 0.09; 95% CI: 0.17-0.52; P < 0.001), and were more likely to have moderate or severe AP (AOR = 1.80; 95% CI: 1.16-2.80; P < 0.001) compared to those without hypophosphatemia. CONCLUSION: Serum phosphate is infrequently measured in patients with AP and shows promise as a rapid, inexpensive, and early prognostic marker for worse outcomes of AP.

Decreased Effective Patellar Tendon Length following Distalization Tibial Tubercle Osteotomy without Patellar Tendon Tenodesis.

Background: Distalization tibial tubercle osteotomy (TTO) is an effective treatment for improving patellar height in patients with patella alta associated with patellofemoral instability and cartilage lesions. The addition of a patellar tendon tenodesis has been suggested; nonetheless, concerns exist regarding possible increased patellofemoral cartilage stresses. Purpose: To evaluate pre- and postoperative patellar tendon length and alignment parameters on magnetic resonance imaging (MRI), as well as patient-reported outcome measures (PROMs) after distalization TTO without patellar tendon tenodesis. Study Design: Case series; Level of evidence, 4. Methods: Twenty skeletally mature patients who underwent distalization TTO with or without anteromedialization at our institution between December 2014 and August 2021 were included. All patients underwent pre- and postoperative MRIs of the affected knee. The Caton-Deschamps index (CDI), the axial and sagittal tibial tubercle-trochlear groove (TT-TG) distances, the distances from the tibial plateau to the patellar tendon insertion and the tibial tubercle, and the patellar tendon length were assessed. PROMs included the International Knee Documentation Committee Subjective Knee Evaluation Form, the Knee injury and Osteoarthritis Outcome Score-Quality of Life subscale, the Kujala Anterior Knee Pain Scale, and the Veterans RAND 12-Item Health Survey mental and physical component scores. Results: The mean patient age at surgery was 27.4 years (range, 14-42 years). Radiographic parameters demonstrated improved patellar height (CDI decreased from 1.36 to 1.11; P < .001) after distalization TTO. The distance from the tibial plateau to the patellar tendon insertion significantly decreased from 20.1 mm preoperatively to 17.9 mm postoperatively (P < .020), and the patellar tendon length decreased from 53.4 mm preoperatively to 46.0 mm postoperatively (P < .001). The patellar tendon insertion was not distalized after distalization TTO, likely because of scarring of the patellar tendon proximal to the osteotomy site. Patients demonstrated significant pre- to postoperative improvements on all PROMs (P≤ .024 for all ). There were 4 (20%) complications-2 cases of arthrofibrosis, 1 postoperative infection, and 1 osteotomy delayed union. Conclusion: Distalization TTO without patellar tendon tenodesis was associated with improved radiographic outcomes and PROMs. It provides an additional tool for surgical management of patellofemoral pathology with associated patella alta.

Using Redox-Switchable Polymerization Catalysis to Synthesize a Chemically Recyclable Thermoplastic Elastomer.

In an effort to synthesize chemically recyclable thermoplastic elastomers, a redox-switchable catalytic system was developed to synthesize triblock copolymers containing stiff poly(lactic acid) (PLA) end blocks and a flexible poly(tetrahydrofuran-co-cyclohexene oxide) (poly(THF-co-CHO) copolymer as the mid-block. The orthogonal reactivity induced by changing the oxidation state of the iron-based catalyst enabled the synthesis of the triblock copolymers in a single reaction flask from a mixture of monomers. The triblock copolymers demonstrated improved flexibility compared to poly(l-lactic acid) (PLLA) and thermomechanical properties that resemble thermoplastic elastomers, including a rubbery plateau in the range of -60 to 40 °C. The triblock copolymers containing a higher percentage of THF versus CHO were more flexible, and a blend of triblock copolymers containing PLLA and poly(d-lactic acid) (PDLA) end-blocks resulted in a stereocomplex that further increased polymer flexibility. Besides the low cost of lactide and THF, the sustainability of this new class of triblock copolymers was also supported by their depolymerization, which was achieved by exposing the copolymers sequentially to FeCl3 and ZnCl2 /PEG under reactive distillation conditions.

Evidence of increasing juvenile white sharks' (Carcharodon carcharias) habitat use at the Northern Channel Islands.

Juvenile white sharks (Carcharodon carcharias) typically aggregate along coastal beaches; however, high levels of recruitment and shifting oceanographic conditions may be causing habitat use expansions. Telemetry data indicate increased habitat use at the Northern Channel Islands (California, USA) by juvenile white shark that may be in response to increased population density at aggregation locations, or anomalous oceanographic events that impact habitat use or expand available habitat. Findings illustrate the need for long-term movement monitoring and understanding drivers of habitat use shifts and expansion to improve ecosystem management.

A Simple, Selective, and General Catalyst for Ring Closing Depolymerization of Polyesters and Polycarbonates for Chemical Recycling.

The ability to efficiently and selectively process mixed polymer waste is important to address the growing plastic waste problem. Herein, we report that the combination of ZnCl2 and an additive amount of poly(ethylene glycol) under vacuum can readily and selectively depolymerize polyesters and polycarbonates with high ceiling temperatures (Tc >200 °C) back to their constitute monomers. Mechanistic experiments implicate a random chain scission mechanism and a catalyst structure containing one equivalent of ZnCl2 per ethylene glycol repeat unit in the poly(ethylene glycol). In addition to being general for a wide variety of polyesters and polycarbonates, the catalyst system could selectively depolymerize a polyester in the presence of other commodity plastics, demonstrating how reactive distillation using the ZnCl2 /PEG600 catalyst system can be used to separate mixed plastic waste.

Variable post-release mortality in common shark species captured in Texas shore-based recreational fisheries.

The practice of catch and release fishing is common among anglers but has been shown to cause unintended mortalities in some species. Current post-release mortality estimates used in coastal shark stock assessments are typically derived from boat-based shark fisheries, which differ from shore-based operations that expose sharks to potentially more stressful environmental and handling conditions. Recreational post-release mortality rates in shore-based fisheries must be quantified to improve stock assessment models and to create guidelines that protect species from overexploitation. Here, we partnered with experienced anglers acting as citizen scientists to deploy pop-up satellite archival transmitting tags (PSAT, n = 22) and acceleration data loggers (ADLs, n = 22). on four commonly caught sharks including the blacktip shark (Carcharhinus limbatus, n = 11), bull shark (Carcharhinus leucas, n = 14), tiger shark (Galeocerdo cuvier, n = 6), and great hammerheads (Sphyrna mokarran, n = 2). Mortality occurred within minutes to hours post-release. If evidence of mortality occurred after normal diving behavior had been re-established for 10 days, then the mortality was considered natural and not related to the catch-and-release process. Post-release mortality estimates ranged from 0% for bull and tiger sharks to 45.5% for blacktip sharks. Of the two great hammerheads, one died within 30 minutes post-release while the other exhibited mortality characteristics 14 days after release. Moribund blacktip sharks experienced on average 3.4-4.9°C warmer water compared with survivors. Recovery periods were estimated for survivors of each species and were highly variable, differing based on duration of tag deployment. High variability in responses to capture and release between species demonstrates the need for species-specific assessments of post-release mortality in shore-based recreational fisheries.

Critical Role for Macrophages in the Developmental Programming of Pancreatic ß-Cell Area in Offspring of Hypertensive Pregnancies.

Preeclampsia is a pregnancy-specific complication with long-term negative outcomes for offspring, including increased susceptibility to type 2 diabetes (T2D) in adulthood. In a rat reduced uteroplacental perfusion pressure (RUPP) model of chronic placental ischemia, maternal hypertension in conjunction with intrauterine growth restriction mimicked aspects of preeclampsia and resulted in female embryonic day 19 (e19) offspring with reduced ß-cell area and increased ß-cell apoptosis compared with offspring of sham pregnancies. Decreased pancreatic ß-cell area persisted to postnatal day 13 (PD13) in females and could influence whether T2D developed in adulthood. Macrophage changes also occurred in islets in T2D. Therefore, we hypothesized that macrophages are crucial to reduction in pancreatic ß-cell area in female offspring after chronic placental ischemia. Macrophage marker CD68 mRNA expression was significantly elevated in e19 and PD13 islets isolated from female RUPP offspring compared with sham. Postnatal injections of clodronate liposomes into female RUPP and sham offspring on PD2 and PD9 significantly depleted macrophages compared with injections of control liposomes. Depletion of macrophages rescued reduced ß-cell area and increased ß-cell proliferation and size in RUPP offspring. Our studies suggest that the presence of macrophages is important for reduced ß-cell area in female RUPP offspring and changes in macrophages could contribute to development of T2D in adulthood.

Characterizing the hypoxic performance of a fish using a new metric: PAAS-50.

The hypoxic constraint on peak oxygen uptake (MO2,peak) was characterized in rainbow trout over a range of ambient oxygen tensions with different testing protocols and statistical models. The best-fit model was selected using both statistical criteria (R2 and AIC) and the model's prediction of three anchor points for hypoxic performance: critical PO2 (Pcrit), maximum MO2 and a new metric, the minimum PO2 that supports 50% of absolute aerobic scope (PAAS-50). The best-fitting model was curvilinear using five strategically selected PO2 values. This model predicted PAAS-50 as 70 mmHg (coefficient of variation, CV=9%) for rainbow trout. Thus, while a five-point hypoxic performance curve can characterize the limiting effects of hypoxia in fish, as envisaged by Fry over 75 years ago, PAAS-50 is a promising metric to compare hypoxic constraints on performance in a standardized manner both within and across fish species.

A biologging database of juvenile white sharks from the northeast Pacific.

Species occurrence records are vital data streams in marine conservation with a wide range of important applications. From 2001-2020, the Monterey Bay Aquarium led an international research collaboration to understand the life cycle, ecology, and behavior of white sharks (Carcharodon carcharias) in the southern California Current. The collaboration was devoted to tagging juveniles with animal-borne sensors, also known as biologging. Here we report the full data records from 59 pop-up archival (PAT) and 20 smart position and temperature transmitting (SPOT) tags that variously recorded pressure, temperature, and light-level data, and computed depth and geolocations for 63 individuals. Whether transmitted or from recovered devices, raw data files from successful deployments (n = 70) were auto-ingested from the manufacturer into the United States (US) Animal Telemetry Network's (ATN) Data Assembly Center (DAC). There they have attributed a full suite of metadata, visualized within their public-facing data portal, compiled for permanent archive under the DataONE Research Workspace member node, and are accessible for download from the ATN data portal.

Emoqol 100, an ultra ultra-brief mood case-finding tool: A diagnostic accuracy study.

BACKGROUND: Case-finding for low mood in primary care can be time-consuming using current depression inventories. AIM: To assess the diagnostic accuracy, of a single verbally administered question on the emotional quality of life (Emoqol 100), for low mood in patients with symptoms of distress in an ambulatory care setting. DESIGN AND SETTING: Eligible patients were consecutive patients seen by one of the authors over 13 months with possible distress/low mood. The index test was the verbally asked Emoqol 100, which is the patient's emotional quality of life now, with 100 being perfect emotional health and 0 being the worst imaginable. The reference standard is the written version of the PHQ-9 with a cut point of ≥10. METHODS: A retrospective audit of consecutive consultations in a single primary care clinic. RESULTS: One hundred two patients were seen during the study period, of which 76 met the eligibility criteria for this audit, and there were 215 test results. For a cut point of <50 on the Emoqol 100 and the PHQ-9 ≥10 the sensitivity was 47% (95% CI 39-54), and the specificity was 93% (95% CI 86-100). The positive predictive value was 95%, and the negative predictive value was 37%. CONCLUSION: This is the first accuracy estimation of the Emoqol 100. It appears to have a high specificity which means when it is positive (<50) it is a good estimate of a high PHQ-9, i.e. a mood issue probably exists. The test will be helpful for busy primary care clinicians as it takes less than 15 seconds to verbally administer.

Methane removal and the proportional reductions in surface temperature and ozone.

Mitigating climate change requires a diverse portfolio of technologies and approaches, including negative emissions or removal of greenhouse gases. Previous literature focuses primarily on carbon dioxide removal, but methane removal may be an important complement to future efforts. Methane removal has at least two key benefits: reducing temperature more rapidly than carbon dioxide removal and improving air quality by reducing surface ozone concentration. While some removal technologies are being developed, modelling of their impacts is limited. Here, we conduct the first simulations using a methane emissions-driven Earth System Model to quantify the climate and air quality co-benefits of methane removal, including different rates and timings of removal. We define a novel metric, the effective cumulative removal, and use it to show that each effective petagram of methane removed causes a mean global surface temperature reduction of 0.21 ± 0.04°C and a mean global surface ozone reduction of 1.0 ± 0.2 parts per billion. Our results demonstrate the effectiveness of methane removal in delaying warming thresholds and reducing peak temperatures, and also allow for direct comparisons between the impacts of methane and carbon dioxide removal that could guide future research and climate policy. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 1)'.

Massive Iatrogenic Pediatric Ketamine Overdose With Serial Levels and Minimal Morbidity.

ABSTRACT: Ketamine is a dissociative anesthetic commonly used for procedural sedation owing to its perceived favorable safety profile. Despite its frequent use, overdoses of ketamine are rarely reported, and no cases with serum levels of ketamine or its metabolite have previously been reported. We report a case of an iatrogenic pediatric ketamine 20 mg/kg intramuscular overdose with serial ketamine and norketamine levels that resulted in minimal toxicity.

Iron-catalysed enantioconvergent Suzuki-Miyaura cross-coupling to afford enantioenriched 1,1-diarylalkanes.

The first stereoconvergent Suzuki-Miyaura cross-coupling reaction was developed to afford enantioenriched 1,1-diarylalkanes. An iron-based complex containing a chiral cyanobis(oxazoline) ligand framework was best to obtain enantioenriched 1,1-diarylalkanes from cross-coupling reactions between unactivated aryl boronic esters and benzylic chlorides. Enhanced yields were obtained when 1,3,5-trimethoxybenzene was used as an additive, which is hypothesized to extend the lifetime of the iron-based catalyst. Exceptional enantioselectivities were obtained with challenging ortho-substituted benzylic chlorides.

The denticle surface of thresher shark tails: Three-dimensional structure and comparison to other pelagic species.

Shark skin denticles (scales) are diverse in morphology both among species and across the body of single individuals, although the function of this diversity is poorly understood. The extremely elongate and highly flexible tail of thresher sharks provides an opportunity to characterize gradients in denticle surface characteristics along the length of the tail and assess correlations between denticle morphology and tail kinematics. We measured denticle morphology on the caudal fin of three mature and two embryo common thresher sharks (Alopias vulpinus), and we compared thresher tail denticles to those of eleven other shark species. Using surface profilometry, we quantified 3D-denticle patterning and texture along the tail of threshers (27 regions in adults, and 16 regions in embryos). We report that tails of thresher embryos have a membrane that covers the denticles and reduces surface roughness. In mature thresher tails, surfaces have an average roughness of 5.6 µm which is smoother than some other pelagic shark species, but similar in roughness to blacktip, porbeagle, and bonnethead shark tails. There is no gradient down the tail in roughness for the middle or trailing edge regions and hence no correlation with kinematic amplitude or inferred magnitude of flow separation along the tail during locomotion. Along the length of the tail there is a leading-to-trailing-edge gradient with larger leading edge denticles that lack ridges (average roughness = 9.6 µm), and smaller trailing edge denticles with 5 ridges (average roughness = 5.7 µm). Thresher shark tails have many missing denticles visible as gaps in the surface, and we present evidence that these denticles are being replaced by new denticles that emerge from the skin below.

Detecting HLA-infectious disease associations for multi-strain pathogens.

Human Leukocyte Antigen (HLA) molecules play a vital role helping our immune system to detect the presence of pathogens. Previous work to try and ascertain which HLA alleles offer advantages against particular pathogens has generated inconsistent results. We have constructed an epidemiological model to understand why this may occur. The model captures the epidemiology of a multi strain pathogen for which the host's ability to generate immunological memory responses to particular strains depends on that host's HLA genotype. We find that an HLA allele's ability to protect against infection, as measured in a case control study, depends on the population frequency of that HLA allele. Furthermore, our capability to detect associations between HLA alleles and infection with a multi strain pathogen may be affected by the properties of the pathogen itself (i.e R0 and length of infectious period). Both host and pathogen genetics must be considered in order to identify true HLA associations. However, in the absence of detailed pathogen genetic information, a negative correlation between the frequency of an HLA type and its apparent protectiveness against disease caused by multi strain pathogen is a strong indication that the HLA type in question is well adapted to a subset of strains of that pathogen.

Neuronal ablation of mt-AspRS in mice induces immune pathway activation prior to severe and progressive cortical and behavioral disruption.

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare, slowly progressive white matter disease caused by mutations in the mitochondrial aspartyl-tRNA synthetase (mt-AspRS, or DARS2). While patients show characteristic MRI T2 signal abnormalities throughout the cerebral white matter, brainstem, and spinal cord, the phenotypic spectrum is broad and a multitude of gene variants have been associated with the disease. Here, Dars2 disruption in CamKIIα-expressing cortical and hippocampal neurons results in slowly progressive increases in behavioral activity at five months, and culminating by nine months as severe brain atrophy, behavioral dysfunction, reduced corpus callosum thickness, and microglial morphology indicative of neuroinflammation. Interestingly, RNAseq based gene expression studies performed prior to the presentation of this severe phenotype reveal the upregulation of several pathways involved in immune activation, cytokine production and signaling, and defense response regulation. RNA transcript analysis demonstrates that activation of immune and cell stress pathways are initiated in advance of a behavioral phenotype and cerebral deficits. An understanding of these pathways and their contribution to significant neuronal loss in CamKII-Dars2 deficient mice may aid in deciphering mechanisms of LBSL pathology.

Role of B1 and B2 lymphocytes in placental ischemia-induced hypertension.

Preeclampsia is a prevalent pregnancy complication characterized by new-onset maternal hypertension and inflammation, with placental ischemia as the initiating event. Studies of others have provided evidence for the importance of lymphocytes in placental ischemia-induced hypertension; however, the contributions of B1 versus B2 lymphocytes are unknown. We hypothesized that peritoneal B1 lymphocytes are important for placental ischemia-induced hypertension. As an initial test of this hypothesis, the effect of anti-CD20 depletion on both B-cell populations was determined in a reduced utero-placental perfusion pressure (RUPP) model of preeclampsia. Anti-murine CD20 monoclonal antibody (5 mg/kg, Clone 5D2) or corresponding mu IgG2a isotype control was administered intraperitoneally to timed pregnant Sprague-Dawley rats on gestation day (GD)10 and 13. RUPP or sham control surgeries were performed on GD14, and mean arterial pressure (MAP) was measured on GD19 from a carotid catheter. As anticipated, RUPP surgery increased MAP and heart rate and decreased mean fetal and placental weight. However, anti-CD20 treatment did not affect these responses. On GD19, B-cell populations were enumerated in the blood, peritoneal cavity, spleen, and placenta with flow cytometry. B1 and B2 cells were not significantly increased following RUPP. Anti-CD20 depleted B1 and B2 cells in peritoneum and circulation but depleted only B2 lymphocytes in spleen and placenta, with no effect on circulating or peritoneal IgM. Overall, these data do not exclude a role for antibodies produced by B cells before depletion but indicate the presence of B lymphocytes in the last trimester of pregnancy is not critical for placental ischemia-induced hypertension.NEW & NOTEWORTHY The adaptive and innate immune systems are implicated in hypertension, including the pregnancy-specific hypertensive condition preeclampsia. However, the mechanism of immune system dysfunction leading to pregnancy-induced hypertension is unresolved. In contrast to previous reports, this study reveals that the presence of classic B2 lymphocytes and peritoneal and circulating B1 lymphocytes is not required for development of hypertension following third trimester placental ischemia in a rat model of pregnancy-induced hypertension.

Specific RITA Modification Produces Hyperselective Cytotoxicity While Maintaining In Vivo Antitumor Efficacy.

The preclinical antitumor agent RITA (2,5-bis[5-hydroxymethyl-2-thienyl] furan, NSC 652287), an analog of the natural product α-terthiophene, failed during the development phase due to acute pulmonary toxicity in animal models. A series of synthetic modifications to RITA's heterocyclic scaffold resulted in activity ranging from broadly cytotoxic to highly selective. In the NCI 60-cell line screen, these "hyperselective" agents (e.g., imatinib) are rare. A selectivity index (SI) was developed to quantify this desirable feature, which is 20 for imatinib, whereas RITA's SI is only 0.10. One of the described hyperselective RITA analogs (SI = 7.9) completely lost activity in the presence of a known SULT1A1 inhibitor. These results, coupled with previous evidence that RITA is a SULT1A1 substrate, suggest that carbinol modification by a sulfate leaving group and subsequent formation of a reactive carbocation may explain RITA's broad cytotoxicity. Although SULT1A1 expression is required for susceptibility, hyperselective analogs exhibited reduced association of activity with SULT1A1 mRNA expression compared with RITA, apparently requiring some additional target(s). In support of this hypothesis, there is a strong correlation (P < 0.01, r = 0.95) between quantum mechanically calculated energy barriers for carbocation formation from sulfonated analogs and SI, indicating that hyperselective RITA analogs generate reactive carbocations less readily after sulfate activation. Importantly, narrowing the cytotoxicity profile of RITA did not eliminate its analogs' in vivo antitumor activity, as several new hyperselective agents, NSC 773097 (1), 773392 (2), and 782846 (6), displayed impressive activity against A498 xenografts in mice.

Quantifying habitat selection and variability in habitat suitability for juvenile white sharks.

While adult white sharks (Carcharodon carcharias) are apex predators with a circumglobal distribution, juvenile white sharks (JWS) feed primarily on bottom dwelling fishes and tend to be coastally associated. Despite the assumedly easier access to juveniles compared to large, migratory adults, limited information is available on the movements, environments, and distributions of individuals during this life stage. To quantify movement and understand their distribution in the southern California Bight, JWS were captured and fitted with dorsal fin-mounted satellite transmitters (SPOT tags; n = 18). Nine individuals crossed the U.S. border into Baja California, Mexico. Individuals used shallow habitats (134.96 ± 191.1 m) close to shore (7.16 ± 5.65 km). A generalized linear model with a binomial distribution was used to predict the presence of individuals based on several environmental predictors from these areas. Juveniles were found to select shallow habitats (< 1000 m deep) close to land (< 30 km of the shoreline) in waters ranging from 14 to 24°C. Southern California was found to be suitable eight months of the year, while coastal habitats in Baja California were suitable year-round. The model predicted seasonal movement with sharks moving from southern California to Baja California during winter. Additionally, habitat distribution changed inter-annually with sharks having a more northerly distribution during years with a higher Pacific Decadal Oscillation index, suggesting sharks may forego their annual fall migrations to Baja California, Mexico, during El Niño years. Model predictions aligned with fishery-dependent catch data, with a greater number of sharks being captured during periods and/or areas of increased habitat suitability. Thus, habitat models could be useful for predicting the presence of JWS in other areas, and can be used as a tool for potentially reducing fishery interactions during seasons and locations where there is increased susceptibility of incidental catch.