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1.
Glob Chang Biol ; 30(6): e17340, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38840515

ABSTRACT

Grassy ecosystems cover more than 40% of the world's terrestrial surface, supporting crucial ecosystem services and unique biodiversity. These ecosystems have experienced major losses from conversion to agriculture with the remaining fragments threatened by global change. Woody plant encroachment, the increase in woody cover threatening grassy ecosystems, is a major global change symptom, shifting the composition, structure, and function of plant communities with concomitant effects on all biodiversity. To identify generalisable impacts of encroachment on biodiversity, we urgently need broad-scale studies on how species respond to woody cover change. Here, we make use of bird atlas, woody cover change data (between 2007 and 2016) and species traits, to assess: (1) population trends and woody cover responses using dynamic occupancy models; (2) how outcomes relate to habitat, diet and nesting traits; and (3) predictions of future occupancy trends, for 191 abundant, southern African bird species. We found that: (1) 63% (121) of species showed a decline in occupancy, with 18% (34) of species' declines correlated with increasing woody cover (i.e. losers). Only 2% (4) of species showed increasing population trends linked with increased woody cover (i.e. winners); (2) Open habitat specialist, invertivorous, ground nesting birds were the most frequent losers, however, we found no definitive evidence that the selected traits could predict outcomes; and (3) We predict open habitat loser species will take on average 52 years to experience 50% population declines with current rates of encroachment. Our results bring attention to concerning region-wide declining bird population trends and highlight woody plant encroachment as an important driver of bird population dynamics. Importantly, these findings should encourage improved management and restoration of our remaining grassy ecosystems. Furthermore, our findings show the importance of lands beyond protected areas for biodiversity, and the urgent need to mitigate the impacts of woody plant encroachment on bird biodiversity.


Subject(s)
Biodiversity , Birds , Ecosystem , Population Dynamics , Animals , Birds/physiology , Conservation of Natural Resources , South Africa
2.
J Vasc Surg Venous Lymphat Disord ; : 101925, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38914374

ABSTRACT

OBJECTIVE: Surgical decompression via transaxillary first rib resection (TFRR) is often performed in patients presenting with venous thoracic outlet syndrome (VTOS). We aimed to evaluate the outcomes of TFRR based on chronicity of completely occluded axillosubclavian veins in VTOS. METHODS: We performed a retrospective institutional review of all patients who underwent TFRR for VTOS and had a completely occluded axillosubclavian vein between 2003 and 2022. Patients were categorized into three groups based on the time of inciting VTOS event to TFRR acuity of their venous occlusion: <4 weeks, 4 to 12 weeks, and >12 weeks. We evaluated the association of TFRR timing with 1-year outcomes, including patency and symptomatic improvement. We used the χ2 test to compare baseline characteristics and postoperative outcomes. RESULTS: Overall, 103 patients underwent TFRR for VTOS with a completely occluded axillosubclavian vein (median age, 30.0 years; 42.7% female; 8.8% non-White), of whom 28 had occlusion at <4 weeks, 36 had occlusion at 4 to 12 weeks, and 39 had occlusion at >12 weeks. Postoperative venogram performed 2 to 3 weeks after TFRR demonstrated that 78.6% in the <4 weeks group, 72.2% in the 4- to 12-weeks group, and 61.5% in the >12 weeks group had some degree of recanalization (P = .76). Postoperative balloon angioplasty was successfully performed in 60 patients with stenosed or occluded axillosubclavian vein at the time of postoperative venogram. At the 10- to 14-month follow-up, 79.2% of the <4 weeks group, 73.3% of the 4- to 12-weeks group, and 73.3% of the >12 weeks group had patent axillosubclavian veins based on duplex ultrasound examination (P = .86). Among patients who underwent postoperative balloon angioplasty, 80.0%, 85.0% and 100% in the <4 weeks, 4- to 12-weeks, and >12 weeks groups respectively demonstrated patency at 10 to 14 months (P = .31). Symptomatic improvement was reported in 95.7% in the <4 weeks group, 96.7% in the 4- to 12-weeks group, and 93.5% in the >12 weeks group (P = .84). CONCLUSIONS: TFRR offers excellent postoperative outcomes for patients with symptomatic VTOS, even in cases of completely occluded axillosubclavian veins, regardless of the chronicity of the occlusion. By 14 months, 95.2% of patients experienced symptomatic improvement, and 75% attained venous patency.

3.
Am J Physiol Renal Physiol ; 326(4): F669-F679, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38450433

ABSTRACT

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to control noncompressible hemorrhage not addressed with traditional tourniquets. However, REBOA is associated with acute kidney injury (AKI) and subsequent mortality in severely injured trauma patients. Here, we investigated how the degree of aortic occlusion altered the extent of AKI in a porcine model. Female Yorkshire-cross swine (n = 16, 68.1 ± 0.7 kg) were anesthetized and had carotid and bilateral femoral arteries accessed for REBOA insertion and distal and proximal blood pressure monitoring. Through a laparotomy, a 6-cm liver laceration was performed and balloon inflation was performed in zone 1 of the aorta for 90 min, during which animals were randomized to target distal mean arterial pressures of 25 or 45 mmHg via balloon volume adjustment. Blood draws were taken at baseline, end of occlusion, and time of death, at which point renal tissues were harvested 6 h after balloon deflation for histological and molecular analyses. Renal blood flow was lower in the 25-mmHg group (48.5 ± 18.3 mL/min) than in the 45-mmHg group (177.9 ± 27.2 mL/min) during the occlusion phase, which recovered and was not different after balloon deflation. AKI was more severe in the 25-mmHg group, as evidenced by circulating creatinine, blood urea nitrogen, and urinary neutrophil gelatinase-associated lipocalin. The 25-mmHg group had increased tubular necrosis, lower renal citrate synthase activity, increased tissue and circulating syndecan-1, and elevated systemic inflammatory cytokines. The extent of renal ischemia-induced AKI is associated with the magnitude of mitochondrial biomass and systemic inflammation, highlighting potential mechanistic targets to combine with partial REBOA strategies to prevent AKI.NEW & NOTEWORTHY Large animal models of ischemia-reperfusion acute kidney injury (IR-AKI) are lacking. This report establishes a titratable IR-AKI model in swine in which a balloon catheter can be used to alter distal pressures experienced by the kidney, thus controlling renal blood flow. Lower blood flow results in greater renal dysfunction and structural damage, as well as lower mitochondrial biomass, elevated systemic inflammation, and vascular dysfunction.


Subject(s)
Acute Kidney Injury , Balloon Occlusion , Reperfusion Injury , Shock, Hemorrhagic , Humans , Swine , Female , Animals , Disease Models, Animal , Hemorrhage/prevention & control , Acute Kidney Injury/etiology , Ischemia , Inflammation , Balloon Occlusion/methods , Shock, Hemorrhagic/therapy
4.
New Phytol ; 242(2): 392-423, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38409806

ABSTRACT

A minuscule fraction of the Earth's paleobiological diversity is preserved in the geological record as fossils. What plant remnants have withstood taphonomic filtering, fragmentation, and alteration in their journey to become part of the fossil record provide unique information on how plants functioned in paleo-ecosystems through their traits. Plant traits are measurable morphological, anatomical, physiological, biochemical, or phenological characteristics that potentially affect their environment and fitness. Here, we review the rich literature of paleobotany, through the lens of contemporary trait-based ecology, to evaluate which well-established extant plant traits hold the greatest promise for application to fossils. In particular, we focus on fossil plant functional traits, those measurable properties of leaf, stem, reproductive, or whole plant fossils that offer insights into the functioning of the plant when alive. The limitations of a trait-based approach in paleobotany are considerable. However, in our critical assessment of over 30 extant traits we present an initial, semi-quantitative ranking of 26 paleo-functional traits based on taphonomic and methodological criteria on the potential of those traits to impact Earth system processes, and for that impact to be quantifiable. We demonstrate how valuable inferences on paleo-ecosystem processes (pollination biology, herbivory), past nutrient cycles, paleobiogeography, paleo-demography (life history), and Earth system history can be derived through the application of paleo-functional traits to fossil plants.


Subject(s)
Ecosystem , Fossils , Ecology , Plants , Phenotype
5.
Am J Case Rep ; 25: e942264, 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38258287

ABSTRACT

BACKGROUND Cystocerebral syndrome is delirium occurring in the elderly that results from urinary retention and acute bladder distension. Urinary retention can cause cerebral issues, such as altered mental status, without having an infection present. The pathophysiology is possibly due to increased catecholamine secretion while attempting to micturate. Due to its presenting symptoms, most physicians begin cerebrovascular workup, performing unnecessary and, often, invasive imaging studies. Although easily overlooked as a differential diagnosis, cystocerebral syndrome is an easily treatable cause of delirium and should be considered during treatment of elderly patients with delirium. CASE REPORT The patient was an 89-year-old man with a medical history of chronic obstructive airway disease, dementia, hypertensive disorder, and gastroesophageal reflux disease who presented with altered mental status secondary to urinary incontinence. The computed tomography scan without contrast showed a large volume of impacted stool in the cecum, with a distended urinary bladder. This case report describes his presentation, medical treatment, and outcome and discusses areas of gap improvement. CONCLUSIONS To date, there are only a handful of published articles on cystocerebral syndrome. This case report aims to add the awareness of bladder distention as an etiology of cystocerebral syndrome to the body of knowledge in the scientific community in the hope that patients will be identified and treated earlier, more safely, and at a reduced cost. Cystocerebral syndrome needs to be extensively addressed in research, and physicians should consider it one of the important differential diagnoses of delirium among elderly men.


Subject(s)
Delirium , Gastroesophageal Reflux , Urinary Retention , Aged, 80 and over , Humans , Male , Catecholamines , Diagnosis, Differential , Syndrome , Urinary Retention/etiology
6.
Mil Med ; 189(3-4): e612-e619, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-37632757

ABSTRACT

INTRODUCTION: Shock states that occur during, for example, profound hemorrhage can cause global tissue hypoperfusion leading to organ failure. There is an unmet need for a reliable marker of tissue perfusion during hemorrhage that can be followed longitudinally. Herein, we investigated whether longitudinal POMCO2 tracks changes in hemodynamics in a swine model of coagulopathic uncontrolled junctional hemorrhage. MATERIALS AND METHODS: Female Yorkshire-crossbreed swine (n = 7, 68.1 ± 0.7 kg) were anesthetized and instrumented for continuous measurement of mean arterial pressure (MAP). Coagulopathy was induced by the exchange of 50 to 60% of blood volume with 6% Hetastarch over 30 minutes to target a hematocrit of <15%. A 4.5-mm arteriotomy was made in the right common femoral artery with 30 seconds of free bleeding. POMCO2 was continuously measured from baseline through hemodilution, hemorrhage, and a subsequent 3-h intensive care unit period. Rotational thromboelastometry and blood gases were measured. RESULTS: POMCO2 and MAP showed no significant changes during the hemodilution phase of the experiment, which produced coagulopathy evidenced by prolonged clot formation times. However, POMCO2 increased because of the uncontrolled hemorrhage by 11.3 ± 3.1 mmHg and was inversely correlated with the drop (17.9 ± 5.9 mmHg) in MAP (Y = -0.4122*X + 2.649, P = .02, r2 = 0.686). In contrast, lactate did not significantly correlate with the changes in MAP (P = .35) or POMCO2 (P = .37). CONCLUSIONS: Despite the logical appeal of measuring noninvasive tissue CO2 measurement as a surrogate for gastrointestinal perfusion, prior studies have only reported snapshots of this readout. The present investigation shows real-time longitudinal measurement of POMCO2 to confirm that MAP inversely correlates to POMCO2 in the face of coagulopathy. The simplicity of measuring POMCO2 in real time can provide an additional practical option for military or civilian medics to monitor trends in hypoperfusion during hemorrhagic shock.


Subject(s)
Blood Coagulation Disorders , Shock, Hemorrhagic , Swine , Female , Animals , Blood Pressure/physiology , Carbon Dioxide , Hemorrhage , Hemodynamics/physiology , Blood Coagulation Disorders/etiology , Lactic Acid , Disease Models, Animal
8.
Endocrine ; 83(2): 349-352, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37821692

ABSTRACT

Paragangliomas are neuroendocrine tumors that have the potential to secrete catecholamines. They have been linked to genetic mutations in the mitochondrial succinate dehydrogenase (SDH) complex. Patients can experience both physical symptoms and psychiatric symptoms like anxiety, depression, and psychosis. These symptoms can occur as paroxysmal episodes with periods of increased catecholamine secretion. We describe a patient with SDHB gene mutation, who has been diagnosed with a jugular paraganglioma, and was brought to the hospital under Baker Act for threats made online. Since diagnosis this patient has been experiencing both anxiety and post-traumatic stress disorder (PTSD). The patient and a family member report increased emotional lability, and the patient reports multiple daily episodes of anxiousness. This case outlines the connection between paragangliomas and psychiatric symptoms, the impact they can have on patients' daily lives, and the importance of addressing the possibility of these symptoms and establishing a multispecialty healthcare team at the time of diagnosis.


Subject(s)
Adrenal Gland Neoplasms , Paraganglioma , Humans , Succinate Dehydrogenase/genetics , Paraganglioma/genetics , Mutation , Catecholamines , Anxiety , Adrenal Gland Neoplasms/genetics , Germ-Line Mutation
9.
Ann Surg Oncol ; 31(1): 376-381, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37936021

ABSTRACT

BACKGROUND: Approximately 20% of breast cancers express HER2-positive receptors in the USA. HER2 receptor immunohistochemistry (IHC) staining with equivocal (2+) results commonly undergoes fluorescence in-situ hybridization (FISH) for further classification. Current guidelines do not recommend routine FISH testing in IHC-negative (0 or 1+) cases. This study investigates an institution that performs both IHC and FISH testing on all cases to identify the true HER2-positive rate. PATIENTS AND METHODS: A retrospective chart review from 2015 to 2021 was conducted at an institution where both HER2 IHC and FISH testing were performed at the time of diagnosis for all invasive breast cancers. The rate of true HER2-positive patients was determined, and patient and tumor characteristics were further explored. RESULTS: A total of 1835 invasive breast cancer cases were primarily treated at this institution. A total of 289 cases were HER2 positive on IHC and FISH testing (15.7%). An additional 38 cases were identified as HER2 negative on IHC, but reclassified as HER2 positive on reflex FISH testing. Total HER2 positive cases increased from 289 (15.7%) to 327 cases (17.8%) with reflex FISH testing. CONCLUSIONS: The additional HER2-positive cases after completing FISH testing on IHC-negative tumors suggests there may be a role for routine FISH testing in addition to standard IHC staining to determine HER2 status for breast cancer. The ethical, prognostic and even  benefits of a correct diagnosis outweigh the added expense of FISH testing.


Subject(s)
Breast Neoplasms , Receptor, ErbB-2 , Humans , Female , Receptor, ErbB-2/genetics , Biomarkers, Tumor , Retrospective Studies , In Situ Hybridization, Fluorescence/methods , Immunohistochemistry , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast Neoplasms/pathology
10.
Diagn Microbiol Infect Dis ; 107(4): 116055, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37716218

ABSTRACT

A member of the Enterobacteriaceae family, Providencia alcalifaciens is typically recognized as a source of gastrointestinal illness. Although its pathogenicity is not well known, many studies have suggested its mechanism of action involves the invasion of the intestinal mucosal layer. Although P. alcalifaciens is a urease producing microorganism, it has not been associated with the formation of a staghorn calculus in the setting of a urinary tract infection. This organism is neither commonly pursued in research or investigation nor is it commonly tested for in the clinical setting. This is especially true when combined with other disease processes, such as calculus formation. The advancement of antibiotic resistance, such as carbapenemase-producing strains, should bring more attention and routine investigation to this organism in the acute stage of infection. In this case report we introduce a 43-year-old Cuban female, who presents with a left-sided staghorn calculi and urine culture positive for carbapenemase-producing P. alcalifaciens.


Subject(s)
Staghorn Calculi , Humans , Female , Adult , Providencia , Enterobacteriaceae
11.
J Surg Res ; 291: 116-123, 2023 11.
Article in English | MEDLINE | ID: mdl-37356340

ABSTRACT

INTRODUCTION: Vascular reconstruction requires technical expertise and is often time consuming. As a novel alternative to traditional hand-sewn vascular anastomoses, the VasoLock (VL), is a nonabsorbable, sutureless anastomosis device with traction anchors designed to hold free artery ends together. These anchors do not penetrate the vessel wall but adhere by leveraging the elasticity of the vessels to fasten blood vessels together. This pilot study assesses the performance and patency of this novel device in a porcine model of femoral artery injury. METHODS: Female swine (n = 7) underwent femoral artery exposure for a total of 10 VL implanted. Study animals underwent hemodilution to a target hematocrit of 15% and ROTEM was used to assess coagulopathy, followed by an arterial injury via transection. The VL was inserted without any sutures. Flow-probe monitors were positioned proximal and distal to the device and flow rates were measured continuously for a total of 90 min. Flow was analyzed and presented as a ratio of distal to proximal flow with the slope of this ratio across time subsequently determined. Angiographic assessment was completed to evaluate for patency and technical complications after 90 min of implant. RESULTS: The average animal weight was 44.1 ± 3.2 kg. The average mean arterial pressure at the time of implant was 51.2 ± 7.8 mmHg, median heart rate was 77.4 (IQR = 77.25-157.4) beats per minute, and average temperature was 36.1 ± 1.5°C. The baseline hematocrit was 13.5 ± 3.0%, average pH was 7.20 ± 0.1, average clotting time was 154.1 ± 58.7 s and average clot formation time was 103.4 ± 10.9 s all demonstrating the acidotic, hypothermic, and coagulopathic state of the swine at the time of insertion. During the 90-min observation period, the average flow gradient identified across the VL was 0.99 ± 0.24, indicating no significant change in flow across the VL. The average slope of the gradients was 0.0005 (P = 0.22), suggesting the ratio of proximal and distal flow did not change over the 90 min. Following 90 min of dwell time, all VL were patent without technical complication. Angiographic assessment at 90 min demonstrated no evidence of dissection, device migration, arterial extravasation, or thromboembolism with any of the 10 devices. CONCLUSIONS: This pilot study demonstrated technical feasibility of the novel VL device over a 90-min observation period. All VL were patent and no negative events or complications were identified. This technology demonstrated significant promise in a coagulopathic state: additional investigation, involving long-term survival, is warranted for further validation.


Subject(s)
Femoral Artery , Female , Animals , Swine , Proof of Concept Study , Pilot Projects , Vascular Patency , Anastomosis, Surgical , Femoral Artery/surgery
12.
J Trauma Acute Care Surg ; 95(2S Suppl 1): S144-S151, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37259206

ABSTRACT

BACKGROUND: Hemostatic dressings are used extensively in both military and civilian trauma to control lethal noncompressible hemorrhage. The ideal topical hemostatic agent would provide reliable hemostasis in patients with profound acidosis, coagulopathy, and shock. This study aimed to compare next-generation hemostatic agents against the current military standard in a translational swine model of vascular injury and coagulopathy. METHODS: Female Yorkshire swine were randomized to eight groups (total n = 63; control n = 14, per group n = 7) of hemostatic agents and included: QuikClot Combat Gauze (Teleflex, Morrisville, NC), which served as the control; BloodSTOP IX (LifeScience Plus, Mountain View, CA); Celox Rapid (Medtrade Product, Crewe, United Kingdom); ChitoSAM 100 (Sam Medical, Tualatin, OR); EVARREST Fibrin Sealant Patch (Ethicon, Raritan, NJ); TAC Wrapping Gauze (H&H Medical, Williamsburg, VA); ChitoGauze XR Pro (Tricol Biomedical, Portland, OR); and X-Stat 30 (RevMedX, Wilsonville, OR). Hemodilution via exchange transfusion of 6% hetastarch was performed to induce acidosis and coagulopathy. An arteriotomy was created, allowing 30 seconds of free bleeding followed by application of the hemostatic agent and compression via an external compression device. A total of three applications were allowed for continued/recurrent bleeding. All blood loss was collected, and hemostatic agents were weighed to calculate blood volume loss. Following a 180-minute observation period, angiography was completed to evaluate for technical complication and distal perfusion of the limb. Finally, the limb was ranged five times to assess for rebleeding and clot stability. RESULTS: All swine were confirmed coagulopathic with rotational thromboelastography and acidotic (pH 7.2 ± 0.02). BloodSTOP IX allowed a significant increase in blood loss and number of applications required to obtain hemostasis compared with all other groups. BloodSTOP IX demonstrated a decreased survival rate (29%, p = 0.02). All mortalities were directly attributed to exsanguination as a result of device failure. In surviving animals, there was no difference in extravasation. BloodSTOP IX had an increased rebleeding rate after ranging compared with QuikClot Combat Gauze ( p = 0.007). CONCLUSION: Most novel hemostatic agents demonstrated comparable efficacy compared with the currently military standard hemostatic dressing, CG.


Subject(s)
Acidosis , Blood Coagulation Disorders , Hemostatics , Animals , Female , Bandages , Blood Coagulation Disorders/therapy , Blood Coagulation Disorders/complications , Disease Models, Animal , Fibrin Tissue Adhesive/therapeutic use , Hemorrhage/therapy , Hemorrhage/etiology , Hemostatic Techniques , Hemostatics/therapeutic use , Swine
13.
Cell Rep ; 42(4): 112392, 2023 04 25.
Article in English | MEDLINE | ID: mdl-37058410

ABSTRACT

Inguinal white adipose tissue (iWAT) is essential for the beneficial effects of exercise training on metabolic health. The underlying mechanisms for these effects are not fully understood, and here, we test the hypothesis that exercise training results in a more favorable iWAT structural phenotype. Using biochemical, imaging, and multi-omics analyses, we find that 11 days of wheel running in male mice causes profound iWAT remodeling including decreased extracellular matrix (ECM) deposition and increased vascularization and innervation. We identify adipose stem cells as one of the main contributors to training-induced ECM remodeling, show that the PRDM16 transcriptional complex is necessary for iWAT remodeling and beiging, and discover neuronal growth regulator 1 (NEGR1) as a link between PRDM16 and neuritogenesis. Moreover, we find that training causes a shift from hypertrophic to insulin-sensitive adipocyte subpopulations. Exercise training leads to remarkable adaptations to iWAT structure and cell-type composition that can confer beneficial changes in tissue metabolism.


Subject(s)
Adipose Tissue, White , Motor Activity , Male , Mice , Animals , Adipose Tissue, White/metabolism , Adaptation, Physiological/physiology , Acclimatization/physiology , Transcription Factors/metabolism , Adipose Tissue, Brown/metabolism , Adipose Tissue/metabolism , Mice, Inbred C57BL , Cell Adhesion Molecules, Neuronal/metabolism
14.
Cureus ; 15(3): e36707, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36992814

ABSTRACT

Gout is the most common inflammatory arthritis which is caused by the buildup of uric acid crystals in the joints, that leads to severe pain, swelling, and stiffness. The condition typically affects the first metatarsophalangeal joint but it can impact other joints in the body. We present a case in which a 43-year-old male with a past medical history of obesity, hypertension, osteoarthritis, and gout presented with bilateral leg pain and the inability to walk for the last two years. Labs showed persistent leukocytosis, elevated ESR (erythrocyte sedimentation rate), normal uric acid levels, with physical exam findings of bilateral tender nodular leg lesions. Chest X-ray, head CT without contrast, left hip X-ray and ultrasound of left lower extremity were performed which were all negative. Biopsy of the tender skin nodules confirmed the diagnosis of tophaceous gout. Acute and prophylactic treatment of tophaceous gout resulted in resolved inflammation and leukocytosis without any complications.

15.
Sci Adv ; 9(1): eade1694, 2023 01 06.
Article in English | MEDLINE | ID: mdl-36608116

ABSTRACT

Spinal and bulbar muscular atrophy is caused by polyglutamine (polyQ) expansions in androgen receptor (AR), generating gain-of-function toxicity that may involve phosphorylation. Using cellular and animal models, we investigated what kinases and phosphatases target polyQ-expanded AR, whether polyQ expansions modify AR phosphorylation, and how this contributes to neurodegeneration. Mass spectrometry showed that polyQ expansions preserve native phosphorylation and increase phosphorylation at conserved sites controlling AR stability and transactivation. In small-molecule screening, we identified that CDC25/CDK2 signaling could enhance AR phosphorylation, and the calcium-sensitive phosphatase calcineurin had opposite effects. Pharmacologic and genetic manipulation of these kinases and phosphatases modified polyQ-expanded AR function and toxicity in cells, flies, and mice. Ablation of CDK2 reduced AR phosphorylation in the brainstem and restored expression of Myc and other genes involved in DNA damage, senescence, and apoptosis, indicating that the cell cycle-regulated kinase plays more than a bystander role in SBMA-vulnerable postmitotic cells.


Subject(s)
Calcium , Receptors, Androgen , Mice , Animals , Receptors, Androgen/chemistry , Gain of Function Mutation , Cyclin-Dependent Kinases/genetics , Phosphoric Monoester Hydrolases/genetics
16.
Vascular ; 31(4): 777-783, 2023 Aug.
Article in English | MEDLINE | ID: mdl-35430941

ABSTRACT

INTRODUCTION: The use of antiplatelet (AP) and anticoagulation (AC) therapy after autogenous vein repair of traumatic arterial injury is controversial. The hypothesis in this study was that there is no difference in early postoperative outcomes regardless of whether AC, AP, both, or neither are used. METHODS: The American Association for the Surgery of Trauma (AAST) PROspective Observational Vascular Injury Treatment (PROOVIT) registry was queried from November, 2013, to January, 2019, for arterial injuries repaired with a vein graft. Demographics and injury characteristics were compared. Need for in-hospital reoperation was the primary outcome in this four-arm study, assessed with two ordinal logistic regression models (1. no therapy vs. AC only vs. AC and AP; 2. no therapy vs. AP only vs. AC and AP). RESULTS: 373 patients (52 no therapy, 88 AP only, 77 AC only, 156 both) from 19 centers with recorded Injury Severity Scores (ISS) were identified. Patients who received no therapy were younger than those who received AP (27.0 vs. 34.2, p = 0.02), had higher transfusion requirement (p < 0.01 between all groups) and a different distribution of anatomic injury (p < 0.01). After controlling for age, sex, ISS, platelet count, hemoglobin, pH, lactate, INR, transfusion requirement and anatomic location, there was no association with postoperative medical therapy and in-hospital operative reintervention, or any secondary outcome, including thrombosis (p = 0.67, p = 0.22). CONCLUSIONS: Neither AC nor AP alone, nor in combination, impact complication rate after arterial repair with autologous vein. These patients can be safely treated with or without antithrombotics, recognizing that this study did not demonstrate a beneficial effect.


Subject(s)
Vascular System Injuries , Humans , Vascular System Injuries/surgery , Vascular Surgical Procedures , Arteries/surgery , Prospective Studies , Anticoagulants , Treatment Outcome , Retrospective Studies
17.
Mil Med ; 188(11-12): 3683-3686, 2023 11 03.
Article in English | MEDLINE | ID: mdl-35830418

ABSTRACT

Medical evacuation (MEDEVAC) from a combat zone requires complex decision-making and coordination of assets. A MEDEVAC helicopter team transports not only battle-injured patients but also patients with urgent non-battle-related medical diagnoses from extremely remote locations and are at the mercy of terrain, weather, and enemy contact. The military represents a young population particularly susceptible to venous thoracic outlet syndrome (vTOS) given the rigorous physical activity demands. Current literature supports immediate anticoagulation and surgical decompression within 14 days of diagnosis of vTOS to prevent long-term morbidity. Presented is a case of service member with vTOS presenting at an extremely remote military clinic who underwent a prompt evacuation ∼7,000 miles utilizing rotary-wing transport, followed by three to four more fixed-wing flights to a military treatment facility in the United States. Immediate recognition and ultrasound of this patient to confirm vTOS upon presentation and effective communication to non-medical military commanders and the receiving medical personnel at each Echelon was necessary to ensure an expedited evacuation. The surgeons treating this patient recommend prompt evacuation of deployed service members with suspected vTOS, venogram at the Role 3 if ultrasound is inconclusive, anticoagulation, and return to a Role 4 CONUS facility for definitive surgical management within 14 days. This case is an example of the efficiency of the military MEDEVAC system on a global scale, ensuring optimum medical care for all service members deployed.


Subject(s)
Military Personnel , Thoracic Outlet Syndrome , Humans , United States , Thoracic Outlet Syndrome/surgery , Decompression, Surgical , Anticoagulants/therapeutic use , Sorbitol
18.
Death Stud ; 47(2): 192-203, 2023.
Article in English | MEDLINE | ID: mdl-35266437

ABSTRACT

Psychologists may have a uniquely high risk for suicide. We examined whether, among 172 psychologists, factors predicting suicide risk among the general population (e.g., gender and mental illness), occupational factors (e.g., burnout and secondary traumatic stress), and past trauma predicted suicidality. We also tested whether resilience and meaning in life were negatively related to suicidality and whether resilience buffered relationships between risk factors and suicidality. Family history of mental illness, number of traumas, and lifetime depression/anxiety predicted higher suicidality, whereas resilience predicted lower suicidality. At higher levels of resilience, the relationship between family history of suicide and suicidality was stronger.


Subject(s)
Mental Disorders , Suicide , Humans , Suicidal Ideation , Risk Factors
19.
Autophagy ; 19(4): 1199-1220, 2023 04.
Article in English | MEDLINE | ID: mdl-36048753

ABSTRACT

ABBREVIATIONS: Atg5: Autophagy-related 5; Atg8a: Autophagy-related 8a; AL: autolysosome; AP: autophagosome; BAF1: bafilomycin A1; BDNF: brain derived neurotrophic factor; BMP: bone morphogenetic protein; Cyt-c-p: Cytochrome c proximal; CQ: chloroquine; DCTN1: dynactin 1; Dhc: dynein heavy chain; EE: early endosome; DYNC1I1: dynein cytoplasmic 1 intermediate chain 1; HD: Huntington disease; HIP1/Hip1: huntingtin interacting protein 1; HTT/htt: huntingtin; iNeuron: iPSC-derived human neurons; IP: immunoprecipitation; Khc: kinesin heavy chain; KIF5C: kinesin family member 5C; LAMP1/Lamp1: lysosomal associated membrane protein 1; LE: late endosome; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAP3K12/DLK: mitogen-activated protein kinase kinase kinase 12; MAPK8/JNK/bsk: mitogen-activated protein kinase 8/basket; MAPK8IP3/JIP3: mitogen-activated protein kinase 8 interacting protein 3; NGF: nerve growth factor; NMJ: neuromuscular junction; NTRK1/TRKA: neurotrophic receptor tyrosine kinase 1; NRTK2/TRKB: neurotrophic receptor tyrosine kinase 2; nuf: nuclear fallout; PG: phagophore; PtdIns3P: phosphatidylinositol-3-phosphate; puc: puckered; ref(2)P: refractory to sigma P; Rilpl: Rab interacting lysosomal protein like; Rip11: Rab11 interacting protein; RTN1: reticulon 1; syd: sunday driver; SYP: synaptophysin; SYT1/Syt1: synaptotagmin 1; STX17/Syx17: syntaxin 17; tkv: thickveins; VF: vesicle fraction; wit: wishful thinking; wnd: wallenda.


Subject(s)
Autophagy , Kinesins , Humans , Kinesins/metabolism , Mitogen-Activated Protein Kinase 8/metabolism , Axons/metabolism , Transcription Factors/metabolism , Carrier Proteins , Endosomes/metabolism , Huntingtin Protein/metabolism , Lysosomal Membrane Proteins/metabolism
20.
Article in English | MEDLINE | ID: mdl-36483443

ABSTRACT

Objective: To evaluate infectious pathogen transmission data visualizations in outbreak publications. Design: Scoping review. Methods: Medline was searched for outbreak investigations of infectious diseases within healthcare facilities that included ≥1 data visualization of transmission using data observable by an infection preventionist showing temporal and/or spatial relationships. Abstracted data included the nature of the cluster(s) (pathogen, scope of transmission, and individuals involved) and data visualization characteristics including visualization type, transmission elements, and software. Results: From 1,957 articles retrieved, we analyzed 30 articles including 37 data visualizations. The median cluster size was 20.5 individuals (range, 7-1,963) and lasted a median of 214 days (range, 12-5,204). Among the data visualization types, 10 (27%) were floor-plan transmission maps, 6 (16%) were timelines, 11 (30%) were transmission networks, 3 (8%) were Gantt charts, 4 (11%) were cluster map, and 4 (11%) were other types. In addition, 26 data visualizations (70%) contained spatial elements, 26 (70%) included person type, and 19 (51%) contained time elements. None of the data visualizations contained contagious periods and only 2 (5%) contained symptom-onset date. Conclusions: The data visualizations of healthcare-associated infectious disease outbreaks in the systematic review were diverse in type and visualization elements, though no data visualization contained all elements important to deriving hypotheses about transmission pathways. These findings aid in understanding the visualizing transmission pathways by describing essential elements of the data visualization and will inform the creation of a standardized mapping tool to aid in earlier initiation of interventions to prevent transmission.

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