E3 Ubiquitin Ligases in Gammaherpesviruses and HIV: A Review of Virus Adaptation and Exploitation.

For productive infection and replication to occur, viruses must control cellular machinery and counteract restriction factors and antiviral proteins. Viruses can accomplish this, in part, via the regulation of cellular gene expression and post-transcriptional and post-translational control. Many viruses co-opt and counteract cellular processes via modulation of the host post-translational modification machinery and encoding or hijacking kinases, SUMO ligases, deubiquitinases, and ubiquitin ligases, in addition to other modifiers. In this review, we focus on three oncoviruses, Epstein-Barr virus (EBV), Kaposi's sarcoma herpesvirus (KSHV), and human immunodeficiency virus (HIV) and their interactions with the ubiquitin-proteasome system via viral-encoded or cellular E3 ubiquitin ligase activity.

Changes in parrot diversity after human arrival to the Caribbean.

Humans did not arrive on most of the world's islands until relatively recently, making islands favorable places for disentangling the timing and magnitude of natural and anthropogenic impacts on species diversity and distributions. Here, we focus on Amazona parrots in the Caribbean, which have close relationships with humans (e.g., as pets as well as sources of meat and colorful feathers). Caribbean parrots also have substantial fossil and archaeological records that span the Holocene. We leverage this exemplary record to showcase how combining ancient and modern DNA, along with radiometric dating, can shed light on diversification and extinction dynamics and answer long-standing questions about the magnitude of human impacts in the region. Our results reveal a striking loss of parrot diversity, much of which took place during human occupation of the islands. The most widespread species, the Cuban Parrot, exhibits interisland divergences throughout the Pleistocene. Within this radiation, we identified an extinct, genetically distinct lineage that survived on the Turks and Caicos until Indigenous human settlement of the islands. We also found that the narrowly distributed Hispaniolan Parrot had a natural range that once included The Bahamas; it thus became "endemic" to Hispaniola during the late Holocene. The Hispaniolan Parrot also likely was introduced by Indigenous people to Grand Turk and Montserrat, two islands where it is now also extirpated. Our research demonstrates that genetic information spanning paleontological, archaeological, and modern contexts is essential to understand the role of humans in altering the diversity and distribution of biota.

Ancient DNA confirms diverse origins of early post-Columbian cattle in the Americas.

Before the arrival of Europeans, domestic cattle (Bos taurus) did not exist in the Americas, and most of our knowledge about how domestic bovines first arrived in the Western Hemisphere is based on historical documents. Sixteenth-century colonial accounts suggest that the first cattle were brought in small numbers from the southern Iberian Peninsula via the Canary archipelago to the Caribbean islands where they were bred locally and imported to other circum-Caribbean regions. Modern American heritage cattle genetics and limited ancient mtDNA data from archaeological colonial cattle suggest a more complex story of mixed ancestries from Europe and Africa. So far little information exists to understand the nature and timing of the arrival of these mixed-ancestry populations. In this study we combine ancient mitochondrial and nuclear DNA from a robust sample of some of the earliest archaeological specimens from Caribbean and Mesoamerican sites to clarify the origins and the dynamics of bovine introduction into the Americas. Our analyses support first arrival of cattle from diverse locales and potentially confirm the early arrival of African-sourced cattle in the Americas, followed by waves of later introductions from various sources over several centuries.

Genicular nerve block for emergency department patient: a successful management of subacute osteoarthritic knee pain.

The genicular nerve block (GNB) performed under ultrasound is a common procedure in the perioperative and outpatient setting for the treatment of surgical knee pain and osteoarthritis. It provides motor-sparing analgesia to the knee, making it a potential alternative to other modes of pain management in the emergency department (ED). We present an elderly woman with acute-on-chronic osteoarthritic knee pain which was relieved for a week after a GNB during her ED visit. In patients with knee pain, the ultrasound guided GNB has the potential to provide short-term analgesia for patients with pain refractory to other modes of analgesia. The GNB shows promise as a reliable contribution to a multimodal approach to pain management in the ED setting.

Wild mockingbirds distinguish among familiar humans.

Although individuals of some species appear able to distinguish among individuals of a second species, an alternative explanation is that individuals of the first species may simply be distinguishing between familiar and unfamiliar individuals of the second species. In that case, they would not be learning unique characteristics of any given heterospecific, as commonly assumed. Here we show that female Northern Mockingbirds (Mimus polyglottos) can quickly learn to distinguish among different familiar humans, flushing sooner from their nest when approached by people who pose increasingly greater threats. These results demonstrate that a common small songbird has surprising cognitive abilities, which likely facilitated its widespread success in human-dominated habitats. More generally, urban wildlife may be more perceptive of differences among humans than previously imagined.

Historical DNA from a rediscovered nineteenth-century paratype reveals genetic continuity of a Bahamian hutia (Geocapromys ingrahami) population.

Past and ongoing human activities have shaped the geographical ranges and diversity of species. New genomic techniques applied to degraded samples, such as those from natural history collections, can uncover the complex evolutionary consequences of human pressures and generate baselines for interpreting magnitudes of species loss or persistence relevant to conservation. Here we integrate mitogenomic data with historical records from a recently rediscovered Bahamian hutia (Geocapromys ingrahami; (FMP Z02816)) specimen at the Fairbanks Museum & Planetarium (Vermont, USA) to determine when and where the specimen was collected and to place it in a phylogenetic context with specimens that both predate (palaeontological) and postdate (archaeological) human arrival in The Bahamas. We determined that this specimen was part of the same population as the named holotype specimen in 1891 on East Plana Cay (EPC). Bahamian hutia populations were widely extirpated following European colonization. Today, EPC hosts the last remaining natural Bahamian hutia population. Mitogenomic data places the focal specimen within the southern Bahamian hutia population, which is now largely restricted to EPC. The results reveal previously undocumented genetic continuity among the EPC population for at least the past 500 years, highlighting how 'dark' museum specimens inform new conservation-relevant understandings of diversity.

Successful Glenohumeral Shoulder Reduction With Combined Suprascapular and Axillary Nerve Block.

BACKGROUND: Anterior glenohumeral dislocation is a common injury seen in the emergency department (ED) that sometimes requires procedural sedation for manual reduction. When compared with procedural sedation for dislocation reductions, peripheral nerve blocks provide similar patient satisfaction scores but have shorter ED length of stays. In this case report, we describe the first addition of an ultrasound-guided axillary nerve block to a suprascapular nerve block for reduction of an anterior shoulder dislocation in the ED. CASE REPORT: A 34-year-old man presented to the ED with an acute left shoulder dislocation. The patient was a fit rock climber with developed muscular build and tone. An attempt to reduce the shoulder with peripheral analgesia was unsuccessful. A combined suprascapular and axillary nerve block was performed with 0.5% bupivacaine, allowing appropriate relaxation of the patient's musculature while providing excellent pain control. The shoulder was then successfully reduced without procedural sedation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Procedural sedation for reduction of anterior shoulder dislocations is time consuming, resource intensive, and can be risky in some populations. The addition of an axillary nerve block to a suprascapular nerve block allows for more complete muscle relaxation to successfully reduce a shoulder dislocation without procedural sedation.

Cryoneurolysis of Intercostal Nerve for Rib Trauma and Intercostal Neuralgia in the Emergency Department: A Multidisciplinary Approach.

BACKGROUND: Management of pain from traumatic rib injury is very challenging. Both acute and chronic pain caused by rib injury can cause significant morbidity (pain-induced hypoventilation, pneumonia, respiratory failure) and functional hindrance. Traditional pain management strategies in the emergency department (ED) that target acute traumatic rib pain are limited by the side effects of medications or the temporary half-life of anesthetics used for a nerve block. Both treatment modalities fall short of addressing subsequent chronic sequelae. CASE REPORT: We present the first-time use of cryoneurolysis on an ED patient for the treatment of 10/10 severe traumatic intercostal neuralgia that resulted in the patient being discharged home pain free. The patient initially underwent a multilevel left-sided T5-T7 intercostal nerve block, followed by ultrasound-guided percutaneous cryoneurolysis of those intercostal nerves using two cycles of 2 min of cooling to a temperature of -70°C (nitrous oxide), with 30 s of thawing in between. The patient experienced 100% pain relief immediately post procedure that was sustained. He remained completely symptom free more than 6 months after the bedside procedure and returned to sports without restrictions. Why Should an Emergency Physician Be Aware of This? This case highlights the benefits of cross-departmental collaboration between the ED, Anesthesia, and Pain Management. We hope this model of multidisciplinary pain modulation can be replicated for other patients with similar pain and can herald a new paradigm of pain management in the ED.

Analysis of the earliest complete mtDNA genome of a Caribbean colonial horse (Equus caballus) from 16th-century Haiti.

Unlike other European domesticates introduced in the Americas after the European invasion, equids (Equidae) were previously in the Western Hemisphere but were extinct by the late Holocene era. The return of equids to the Americas through the introduction of the domestic horse (Equus caballus) is documented in the historical literature but is not explored fully either archaeologically or genetically. Historical documents suggest that the first domestic horses were brought from the Iberian Peninsula to the Caribbean in the late 15th century CE, but archaeological remains of these early introductions are rare. This paper presents the mitochondrial genome of a late 16th century horse from the Spanish colonial site of Puerto Real (northern Haiti). It represents the earliest complete mitogenome of a post-Columbian domestic horse in the Western Hemisphere offering a unique opportunity to clarify the phylogeographic history of this species in the Americas. Our data supports the hypothesis of an Iberian origin for this early translocated individual and clarifies its phylogenetic relationship with modern breeds in the Americas.

Peripheral Nerve Stimulation for Chronic Pain and Migraine: A Review.

Interventional pain procedures offer treatments for chronic pain conditions refractory to conservative measures. Neuromodulation, including peripheral nerve stimulation (PNS), applies electrical stimuli to neural structures to treat pain. Here we review the literature on PNS for various chronic pain conditions including neuropathic pain, postamputation pain, musculoskeletal pain, migraine, and pelvic pain.

Ultrasound-Guided Percutaneous Cryoneurolysis for Post-Thoracotomy Pain Syndrome: A Case Report.

Post-thoracotomy pain syndrome (PTPS) is a post-operative thoracotomy complication that is difficult to treat. We describe the first-time use of ultrasound-guided percutaneous cryoneurolysis of the intercostal nerves to successfully treat PTPS refractory to conventional medications and interventions. We report a case of a 40-year-old male with two years of severe PTPS sustained after undergoing a thoracotomy. Treatment with intercostal cryoneurolysis resulted in an immediate 75% improvement in pain for six weeks followed by sustained 50% pain relief for eight weeks. This highlights the potential of this intervention as a radiation-free, safe, and efficacious therapy for chronic PTPS.

Climate drivers of adult insect activity are conditioned by life history traits.

Insect phenological lability is key for determining which species will adapt under environmental change. However, little is known about when adult insect activity terminates and overall activity duration. We used community-science and museum specimen data to investigate the effects of climate and urbanisation on timing of adult insect activity for 101 species varying in life history traits. We found detritivores and species with aquatic larval stages extend activity periods most rapidly in response to increasing regional temperature. Conversely, species with subterranean larval stages have relatively constant durations regardless of regional temperature. Species extended their period of adult activity similarly in warmer conditions regardless of voltinism classification. Longer adult durations may represent a general response to warming, but voltinism data in subtropical environments are likely underreported. This effort provides a framework to address the drivers of adult insect phenology at continental scales and a basis for predicting species response to environmental change.

Ultrasound-Guided Caudal Epidural Steroid Injection for Back Pain: A Case Report of Successful Emergency Department Management of Radicular Low Back Pain Symptoms.

BACKGROUND: Radicular low back pain is difficult to treat and commonly encountered in the Emergency Department (ED). Pain associated with acute radiculopathy results in limited ability to work, function, and enjoy life, and is associated with increased risk of chronic opioid therapy. In this case report, we describe the first ED-delivered ultrasound-guided caudal epidural steroid injection (ESI) used to treat medication-refractory lumbar radiculopathy, which resulted in immediate and sustained resolution of pain. CASE REPORT: A 56-year old man with a past medical history of chronic lumbar radiculopathy presented to the ED with acute low back and right lower-extremity pain. Based on history and physical examination, a right L5 radiculopathy was suspected. His pain was poorly controlled despite multimodal analgesia, at which point he was offered admission or an ultrasound-guided caudal ESI. The procedure was performed using dexamethasone, preservative-free normal saline, and preservative-free 1% lidocaine solution, after which the patient reported 100% resolution of his pain and requested discharge from the ED. Why Should an Emergency Physician Be Aware of This? The safety and efficacy of ultrasound-guided caudal ESIs have been established, but there is a paucity of literature exploring their application in the ED. We present a case of a refractory lumbar radiculopathy successfully treated with an ultrasound-guided caudal ESI. ED-performed epidurals can be one additional tool in the emergency physician arsenal to treat acute or chronic lumbar radiculopathy.

Novel Use of 3-Point Genicular Nerve Block for Acute Knee Pain in the Emergency Department.

BACKGROUND: Ultrasound-guided genicular nerve blocks (GNBs) in the emergency department (ED) have easily identifiable anatomic targets and offer an opportunity to provide safe, effective, motor-sparing analgesia for acute knee pain. Case Report A 68-year-old woman presented with acute, 8/10 right knee pain due to an isolated right lateral tibial plateau fracture. After informed consent and with the ultrasound in the sagittal plane, the superior lateral (SLGN), superior medial (SMGN), and inferior medial (IMGN) genicular nerves were identified at the junction of their respective femoral or tibial epicondyle and femoral or tibial epiphysis. The skin was anesthetized and an echogenic needle was inserted under ultrasound guidance to inject 1.0 mL of 0.5% bupivacaine around the right SLGN, SMGN, and IMGN. Approximately 30 minutes after the GNBs, the patient reported 0/10 pain at rest and 1/10 pain with movement. She did not require opioids during her ED visit or upon discharge. Why Should an Emergency Physician Be Aware of This? GNBs show promise as a useful tool to provide acute and medium-term motor-sparing analgesia in a patient with acute knee pain. GNBs have easy-to-recognize anatomic targets on ultrasound and may be a suitable adjunct or alternative to a multimodal pain regimen in the emergency department.

Erector spinae plane block: a new option for managing acute axial low back pain in the emergency department.

Aim: To evaluate pain and length of stay outcomes in six patients who received an erector spinae plane block (ESPB) in the emergency department (ED) for low back pain. Materials & methods: A case series of six patients who received unilateral or bilateral ESPB after presenting to the ED for acute atraumatic axial low back pain. Results: The average visual analog scale pain score reduction was 81.8%, and length of stay after ESPB was 73.5 min. No postprocedure opiates in the ED or after discharge were required. Conclusion: The ESPB is a rapid, safe and opiate-sparing option for the treatment of acute low back pain.

Lay abstract Acute low back pain is one of the most common reasons patients present to the emergency department (ED), and it is often difficult to treat. The erector spinae plane block (ESPB) is a nerve block used to treat thoracic, rib, spine and abdominal wall pain. There is currently limited evidence to support its use in treating low back pain in the ED. This case series looks at outcomes of six patients who presented to the ED with low back pain who were treated with an ESPB that targets the low back muscles. Visual Analog Scale pain score reduction after the procedure ranged between 71 and 100%, with an average of 81.8%. The average length of stay (LOS) prior to the nerve block was 225 min, with a range of 107­480 min. Average LOS after the block was 73.5 min, with a range of 26­180 min. Five of six patients did not have any return ED visits for back pain. All six patients required no opiates after the procedure in the ED or after discharge. These cases show the ESPB is a promising technique that gives emergency physicians a rapid, safe and opiate-sparing option for the treatment of low back pain. ESPBs can result in decreased pain, decreased LOS, decreased opiate requirements and decreased admission for refractory pain.

Lasmiditan for the acute treatment of migraine.

Migraine is a leading cause of morbidity and disability worldwide. Triptans were the first migraine-specific drug class developed and have proven efficacy in treatment of this neurological disease. They are however contraindicated in patients with cardiovascular disease and possibly others, owning to their vasoconstrictive properties. This review will focus on lasmiditan, which has been called the first 'ditan' and 'neurally acting anti-migraine agent', designed to selectively agonize the serotonin 5-HT1F receptor subtype, providing anti-migraine effects without concomitant vasoconstriction. To date, lasmiditan has proven safe and effective for the acute treatment of migraine in two Phase II and four Phase III trials. Post hoc analysis revealed that the majority of treatment-emergent adverse events were CNS-related, mild-to-moderate in severity and self-limiting. The US FDA label recommends that patients not drive or operate machinery until at least 8 h after taking each dose of lasmiditan.

Lay abstract Migraine is a leading cause of pain and disability worldwide. Triptans (e.g., sumatriptan) were the first migraine-specific drug class developed and have proven to be effective treatments. Triptans are however contraindicated in patients with heart disease and possibly in some subsets of migraine, due to vasoconstriction concerns. This review will focus on lasmiditan, the first 5-HT_1F receptor agonist or 'ditan'. It does not carry vasoconstrictive concerns and is safe to use in patients who cannot take triptans. To date, lasmiditan has proven safe and effective for the acute treatment of migraine in multiple medical studies. Data from these studies indicates that the most common adverse effects from lasmiditan were dizziness, tingling and sleepiness. These symptoms were generally mild-to-moderate in severity and self-limiting. The US FDA label recommends that patients not drive or operate machinery until at least 8 h after taking each dose of lasmiditan.

Cannabinoids and Pain: The Highs and Lows.

The medicolegal landscape of cannabis continues to change, and with ever increasing access there has been a concurrent proliferation of research seeking to understand the utility of cannabinoids in treating innumerable conditions with pain at the forefront. This article seeks to summarize clinically relevant findings in cannabinoid research to better prepare clinicians in the utility of cannabis in the treatment of pain.

Ultrasound-Guided Hematoma Block for a Clavicular Fracture.

BACKGROUND: Clavicular fractures are commonly encountered in the emergency department (ED). Fracture pain is usually treated with nonsteroidal anti-inflammatory drugs (NSAID) and opioids; however, both of these drug classes have potentially significant side effects that limit their use in certain patient populations. Hematoma blocks are safe and effective alternatives for pain control. CASE REPORT: We present the case of a 39-year-old healthy man that presented to the ED with a clavicular fracture after a fall from a motorized scooter. He received minimal pain relief from hydrocodone-acetaminophen. A hematoma block was subsequently performed, with significant improvement in his pain. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Hematoma blocks are safe and effective treatments for clavicular fracture pain in the ED without the potentially significant side effects of NSAIDs and opioids.

Ancient DNA from the extinct Haitian cave-rail (Nesotrochis steganinos) suggests a biogeographic connection between the Caribbean and Old World.

Worldwide decline in biodiversity during the Holocene has impeded a comprehensive understanding of pre-human biodiversity and biogeography. This is especially true on islands, because many recently extinct island taxa were morphologically unique, complicating assessment of their evolutionary relationships using morphology alone. The Caribbean remains an avian hotspot but was more diverse before human arrival in the Holocene. Among the recently extinct lineages is the enigmatic genus Nesotrochis, comprising three flightless species. Based on morphology, Nesotrochis has been considered an aberrant rail (Rallidae) or related to flufftails (Sarothruridae). We recovered a nearly complete mitochondrial genome of Nesotrochis steganinos from fossils, discovering that it is not a rallid but instead is sister to Sarothruridae, volant birds now restricted to Africa and New Guinea, and the recently extinct, flightless Aptornithidae of New Zealand. This result suggests a widespread or highly dispersive most recent common ancestor of the group. Prior to human settlement, the Caribbean avifauna had a far more cosmopolitan origin than is evident from extant species.