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Many studies have shown that microbes, which share nearly identical 16S rRNA genes, can have highly divergent genomes. Microbes from distinct parts of the ocean also exhibit biogeographic patterning. Here we seek to better understand how certain microbes from the same species have adapted for growth under local conditions. The phenotypic and genomic heterogeneity of three strains of Colwellia psychrerythraea was investigated in order to understand adaptions to local environments. Colwellia are psychrophilic heterotrophic marine bacteria ubiquitous in cold marine ecosystems. We have recently isolated two Colwellia strains: ND2E from the Eastern Mediterranean and GAB14E from the Great Australian Bight. The 16S rRNA sequence of these two strains were greater than 98.2% identical to the well-characterized C. psychrerythraea 34H, which was isolated from arctic sediments. Salt tolerance, and carbon source utilization profiles for these strains were determined using Biolog Phenotype MicoArrays. These strains exhibited distinct salt tolerance, which was not associated with the salinity of sites of isolation. The carbon source utilization profiles were distinct with less than half of the tested carbon sources being metabolized by all three strains. Whole genome sequencing revealed that the genomes of these three strains were quite diverse with some genomes having up to 1600 strain-specific genes. Many genes involved in degrading strain-specific carbon sources were identified. There appears to be a link between carbon source utilization and location of isolation with distinctions observed between the Colwellia isolate recovered from sediment compared to water column isolates.

findings are presented from an investigation to improve understanding of the environmental risks associated with developing an unconventional-hydrocarbons industry in the UK. The EQUIPT4RISK project, funded by UK Research Councils, focused on investigations around Preston New Road (PNR), Fylde, Lancashire, and Kirby Misperton Site A (KMA), North Yorkshire, where operator licences to explore for shale gas by hydraulic fracturing (HF) were issued in 2016, although exploration only took place at PNR. EQUIPT4RISK considered atmospheric (greenhouse gases, air quality), water (groundwater quality) and solid-earth (seismicity) compartments to characterise and model local conditions and environmental responses to HF activities. Risk assessment was based on the source-pathway-receptor approach. Baseline monitoring of air around the two sites characterised the variability with meteorological conditions, and isotopic signatures were able to discriminate biogenic methane (cattle) from thermogenic (natural-gas) sources. Monitoring of a post-HF nitrogen-lift (well-cleaning) operation at PNR detected the release of atmospheric emissions of methane (4.2 ± 1.4 t CH 4 ). Groundwater monitoring around KMA identified high baseline methane concentrations and detected ethane and propane at some locations. Dissolved methane was inferred from stable-isotopic evidence as overwhelmingly of biogenic origin. Groundwater-quality monitoring around PNR found no evidence of HF-induced impacts. Two approaches for modelling induced seismicity and associated seismic risk were developed using observations of seismicity and operational parameters from PNR in 2018 and 2019. Novel methodologies developed for monitoring include use of machine learning to identify fugitive atmospheric methane, Bayesian statistics to assess changes to groundwater quality, a seismicity forecasting model seeded by the HF-fluid injection rate and high-resolution monitoring of soil-gas methane. The project developed a risk-assessment framework, aligned with ISO 31000 risk-management principles, to assess the theoretical combined and cumulative environmental risks from operations over time. This demonstrated the spatial and temporal evolution of risk profiles: seismic and atmospheric impacts from the shale-gas operations are modelled to be localised and short-lived, while risk to groundwater quality is longer-term., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Just Transition, an organizing and policy framework that has emerged from the climate justice movement, is a powerful upstream response to health disparities created by structural subordination. As the public health field pushes itself to address the "cause of causes" of unjust health disparities, Just Transition offers new possibilities for partnership and collective action. We introduce the Just Transition framework, explain its relevance to the concerns of health justice advocates, and provide some examples of how the two movements might work together.

Background: Indications for replantation following traumatic digit amputations are more liberal in the pediatric population than in adults, but delineation of patient selection within pediatrics and their outcomes have yet to be elucidated. This study uses a national pediatric database to evaluate patient characteristics and injury patterns involved in replantation and their outcomes. Methods: The Healthcare Cost and Utilization Project Kid's Inpatient Database was queried for traumatic amputations of the thumb and finger from 2000 to 2012. Participants were separated into those who underwent replantation and those who underwent amputation. Patients undergoing replantation were further divided into those requiring revision amputation and/or microvascular revision. Patient age, sex, insurance, digit(s) affected, charges, length of stay, and complications were extracted for each patient. Results: Traumatic digit amputations occurred in 3090 patients, with 1950 (63.1%) undergoing revision amputation and 1140 (36.9%) undergoing replantation. Younger patients, those with thumb injuries, females, and those covered under private insurance were significantly more likely to undergo replantation. Cost, length of stay, and in-hospital complications were significantly greater in replantation patients than in those who had undergone amputation. Following replantation, 237 patients (20.8%) underwent revision amputation and 209 (18.3%) underwent vascular revision, after which 58 required revision amputation. Risk of revision following replantation involved older patients, males, and procedures done recently. Conclusions: Pediatric patients who underwent replantation were significantly younger, female, had thumb injuries, and were covered by private insurance. Our findings demonstrate that in addition to injury factors, demographics play a significant role in the decision for finger replantation and its outcomes.

Background: Minimal clinically important difference (MCID) estimates are useful for gauging clinical relevance when interpreting changes or differences in patient-reported outcomes scores. These values are lacking in the setting of elbow trauma. Our primary purpose was to estimate the MCID of the Patient-Reported Outcomes Measurement Information System (PROMIS) physical function (PF) computer adaptive test (CAT), the PROMIS upper extremity (UE) CAT, and the QuickDASH using an anchor-based approach for patients recovering from elbow trauma and related surgeries. Secondarily, we aimed to estimate the MCID using the 1/2 standard deviation method., Materials & Methods: Adult patients undergoing treatment for isolated elbow injuries between July 2014 and April 2020 were identified at a single tertiary academic medical center. Outcomes, including the PROMIS PF CAT v1.2/2.0, PROMIS UE CAT v1.2, and QuickDASH, were collected via a tablet computer. For inclusion, baseline (6 months before injury up to 11 days postoperatively or after injury) and follow-up (11 to 150 days postoperative or after injury) PF or UE CAT scores were required, as well as a response to an anchor question querying improvement in physical function. The MCID was calculated using (1) an anchor-based approach using the difference in mean score change between anchor groups reporting "No change" and "Slightly Improved/Improved" and (2) the 1/2 standard deviation method., Results: Of the 146 included patients, the mean age was 46 ± 18 years and 67 (46%) were women. Most patients (129 of 146 or 88%) were recovering from surgery, and the remaining 12% were recovering from nonoperatively managed fractures and/or dislocations. The mean follow-up was 157 ± 192 days. Scores for each instrument improved significantly between baseline and follow-up. Anchor-based MCID values were calculated as follows: 5.7, 4.6, and 5.3 for the PROMIS PF CAT, PROMIS UE CAT, and QuickDASH, respectively. MCID values estimated using the 1/2 standard deviation method were 4.3, 4.8, and 11.7 for the PROMIS PF CAT, PROMIS UE CAT, and QuickDASH, respectively., Conclusions: In the setting of elbow trauma, we propose MCID ranges of 4.3 to 5.7 for the PROMIS PF CAT, 4.6 to 4.8 for the PROMIS UE CAT, and 5.3 to 11.7 for the QuickDASH. These values will provide a framework for clinical relevance when interpreting clinical outcomes studies, or powering clinical trials, for populations recovering from trauma., (© 2021 The Author(s).)

We have examined the reaction of Salmonella enterica serovar typhimurium tryptophan (Trp) synthase α 2 β 2 complex with l-Trp, d-Trp, oxindolyl-l-alanine (OIA), and dioxindolyl-l-alanine (DOA) in the presence of disodium (dl)-α-glycerol phosphate (GP), using stopped-flow spectrophotometry and X-ray crystallography. All structures contained the d-isomer of GP bound at the α-active site. (3 S )-OIA reacts with the pyridoxal-5'-phosphate (PLP) of Trp synthase to form a mixture of external aldimine and quinonoid complexes. The α-carboxylate of OIA rotates about 90° to become planar with the PLP when the quinonoid complex is formed, resulting in a conformational change in the loop of residues 110-115. The COMM domain of the Trp synthase-OIA complex is found as a mixture of two conformations. The (3 R )-diastereomer of DOA binds about 5-fold more tightly than (3 S )-OIA and also forms a mixture of aldimine and quinonoid complexes. DOA forms an additional H-bond between the 3-OH of DOA and βLys-87. l-Trp does not form a covalent complex with the PLP of Trp synthase. However, d-Trp forms a mixture of two external aldimine complexes which differ in the orientation of the α-carboxylate. In one conformation, the α-carboxylate is in the plane of the PLP, while in the other conformation, the α-carboxylate is perpendicular to the PLP plane. These results confirm that the stereochemistry of the transient indolenine quinonoid intermediate in the mechanism of Trp synthase is (3 S ) and demonstrate the linkage between aldimine and quinonoid reaction intermediates in the β-active site and allosteric communications with the α-active site.

Background: Traumatic digit amputations are common hand injuries in the United States. The primary aim of our study was to describe the relationship between season and mechanisms of amputation. Methods: The Emergency Department and Orthopaedic Surgery Billing Department databases of our level І institution in the Northeast were reviewed to identify patients with a traumatic digit amputation between January 2010 and December 2015. Inclusion criteria were defined as any patient presenting with a partial or complete amputation through Verdan zone I or II. All patient information was entered into a secure database, including date of injury, demographic information, digits amputated, mechanism of injury (crush, laceration, avulsion, bite, blast, saw, snow blower, or lawn mower), and Verdan zones of amputation. In addition to descriptive statistics, Fisher exact and χ 2 tests were used to compare the incidence of these traumatic digit amputation mechanisms between seasons. Results: For this 6-year period, an average of 24 patients presented each season for treatment of a traumatic digit amputation. Of all seasons, spring had the highest proportion of lawn mower amputations (62.5%; P < .0001), summer had the highest proportion of blast amputations (75.0%; P = .011), and winter had the highest proportion of snow blower amputations (90.9%; P < .0001). All other traumatic digit amputation mechanisms had no significant seasonal variation in incidence ( P > .30). Conclusions: Given that certain traumatic digit amputation mechanisms occur predictably during certain seasons, seasonal public education has the potential to prevent these debilitating injuries.

When stature estimation of incomplete skeletal remains is necessary, researchers select an estimation equation which will produce the most accurate estimates. The purpose of this study is to propose that, given prior information of a target sample, the Bayes factor can be a useful tool to quantitatively evaluate and compare performance of multiple equations in this regard. This study also explores the best-performing equations to reconstruct statures of Korean War casualties with a demonstration of equation comparisons by the Bayes factor. Thirty-three sets of stature estimates were generated using different equations based on the osteometric data of the Korean War casualties. The distribution of each set was compared to that of the population (i.e., Korean servicemen during the Korean War) using the Bayes factors and posterior probabilities generated by the R codes in the LearnBayes package. A higher Bayes factor indicates a closer similarity between the two distributions under comparison. The equation with the highest Bayes factor in this study was Choi et al.'s (1997) humerus equation (bf=9.84), followed by the femur equation of the same authors (bf=5.3). The Bayesian approach has advantages over the traditional frequentist approach primarily based on the p-value. Particularly, the Bayes factor can provide practical interpretations on the models under comparison, which allows for a quantitative prioritization of different models. Researchers can obtain more accurate stature estimates of a target sample by using the equation of the highest Bayes factor., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The objective of this study was to determine the comparative cost-effectiveness of performing initial revision finger amputation in the emergency department (ED) versus in the operating room (OR) accounting for need for unplanned secondary revision in the OR. Methods: We retrospectively examined patients presenting to the ED with traumatic finger and thumb amputations from January 2010 to December 2015. Only those treated with primarily revision amputation were included. Following initial management, the need for unplanned reoperation was assessed and associated with setting of initial management. A sensitivity analysis was used to determine the cost-effectiveness threshold for initial management in the ED versus the OR. Results: Five hundred thirty-seven patients had 677 fingertip amputations, of whom 91 digits were initially primarily revised in the OR, and 586 digits were primarily revised in the ED. Following initial revision, 91 digits required unplanned secondary revision. The unplanned secondary revision rates were similar between settings: 13.7% digits from the ED and 12.1% of digits from the OR ( P = .57). When accounting for direct costs, an incidence of unplanned revision above 77.0% after initial revision fingertip amputation in the ED would make initial revision fingertip amputation in the OR cost-effective. Therefore, based on the unplanned secondary revision rate, initial management in the ED is more cost-effective than in the OR. Conclusions: There is no significant difference in the incidence of unplanned/secondary revision of fingertip amputation rate after the initial procedure was performed in the ED versus the OR.

Background: Trapezium dislocations are rare injuries., Methods: A PubMed search of the term "trapezium dislocation" was conducted. Publications reporting a complete trapezium dislocation were included in the review., Results: The PubMed search resulted in 168 results. Fourteen publications reporting on 16 complete trapezium dislocations met inclusion criteria. A case of delayed diagnosis of a trapezium dislocation is presented. The literature is reviewed for pertinent clinically relevant information with respect to trapezium dislocations. A systematic method for radiographic analysis of trapezium dislocations and classification are described, and a treatment algorithm is presented., Conclusions: Trapezium dislocations are infrequent injuries with few cases reported in the literature. Given the rarity of this injury, diagnosis and appropriate treatment may be delayed due to difficulty in recognition. Using the described method of radiographic analysis, delayed diagnosis may be avoided with implementation of timely treatment.

Major depressive disorder (MDD) is a leading contributor to the global burden of disease. However, the causal relationship of risk factors, such as genetic predisposition or experience of augmented stress, remain unknown. Numerous studies in humans and rodents have implicated brain-derived neurotrophic factor (BDNF) in MDD pathology, as a genetic risk factor and a factor regulated by stress. Until now, the majority of preclinical studies have employed genetically modified mice as their model of choice. However, mice display a limited behavioural repertoire and lack expression of circulating BDNF, which is present in rats and humans. Therefore, heterozygous BDNF (BDNF +/- ) rats were tested for affective behaviours and accompanying expression of key genes associated with affective disorders in the brain. We found that BDNF +/- rats, which have reduced BDNF levels in brain and plasma, displayed symptoms of anhedonia, a core symptom of MDD, and anxiety-like behaviour, but no behavioural despair or cognitive impairments. This was accompanied by changes in the expression of genes that are implicated in modulation of the stress response and affective disorders. Hence, glucocorticoid receptor, neuregulin 1 and disrupted-in-schizophrenia 1 gene expression were upregulated in the prefrontal cortex of BDFN +/- rats, whereas FK506 binding protein 5 levels were decreased in the hippocampus. We conclude that a reduction in BDNF levels alters expression of genes associated with affective disorders, which may contribute to the development of depressive-like symptoms., (© 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

Diabetics have a much greater prevalence of trigger finger than nondiabetics and are more likely to have severe symptoms. Diabetic trigger finger may be more accurately described on a spectrum of diabetic hand pathology alongside carpal tunnel syndrome and cheiroarthropathy. Recent publications have called into question the current treatment algorithm for diabetic trigger finger. Although some evidence supports the use of corticosteroid injections, a recent cost analysis reported that immediate surgical release of the A1 pulley in the clinic is the most cost-effective management of diabetic trigger finger. In addition to traditional treatment with injection and open release, percutaneous release with or without simultaneous corticosteroid injection has shown promising results and may have a role in patient care. The appropriate treatment algorithm in terms of efficacy, safety, and cost remains controversial., (Copyright © 2019 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Lunate and perilunate dislocations are potentially devastating injuries that are often unrecognized at initial evaluation. Prompt recognition and treatment is necessary to prevent adverse sequelae, including median nerve dysfunction, carpal instability, posttraumatic arthritis, reduced functionality, and avascular necrosis. In patients who are surgical candidates, operative intervention is warranted to restore carpal kinematics and provide optimal outcomes. [Orthopedics. 2019; 42(1):e1-e6.]., (Copyright 2018, SLACK Incorporated.)

Purpose: Primary revision amputation is the most common treatment method for traumatic digit amputations in the United States. Few studies have reported secondary revision rates after primary revision amputation. The primary aim of our study was to identify risk factors for secondary revision within 1 year of the index procedure. Secondarily, we describe the incidence and timing of complications requiring secondary revision., Methods: Our institution's emergency department (ED) database was reviewed for traumatic digit amputations over a 6-year period. Patients were reviewed for demographic characteristics, comorbidities, site of treatment (ED versus operating room), and complications requiring secondary revision. Conditional Cox Proportional Hazard regression was used to model hazard of revision within 1 year of index procedure relative to site of initial management, mechanism of injury, injury characteristics, and patient demographics., Results: Five hundred and thirty-seven patients with 677 digits were managed with primary revision amputation. Five hundred and eighty-six digits (86.6%) were revised in the ED, and 91 (13.4%) in the operating room. Ninety-one digits required secondary revision, including 83 within 1 year. No increased risk of secondary revision amputation within 1 year of the index procedure was observed for patients treated in the ED compared with the operating room. Relative to crush injuries, bite and sharp laceration amputations had 4.8 times and 2.6 times increased risk of secondary revision, respectively. The index finger had a 5.3-fold increased risk of revision with the thumb as the reference digit. Work-related injuries had a 1.9-fold increased risk of secondary revision compared with non-work-related injuries., Conclusions: No evidence was found indicating that traumatic digit amputations primarily revised in the ED had an increased risk of secondary revision. Patients may be counseled on the risk of secondary procedures based on the mechanism of injury, injury characteristics and demographics, as well as the timing of complications., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Exposure to trichloroethylene (TCE) is linked to formation of congenital heart defects in humans and animals. Prior interactome analysis identified the transcription factor, Hepatocyte Nuclear Factor 4 alpha (HNF4a), as a potential target of TCE exposure. As a role for HNF4a is unknown in the heart, we examined developing avian hearts for HNF4a expression and for sensitivity to TCE and the HNF4a agonist, Benfluorex. In vitro analysis using a HNF4a reporter construct showed both TCE and HFN4a to be antagonists of HNF4a-mediated transcription at the concentrations tested. HNF4a mRNA is expressed transiently in the embryonic heart during valve formation and cardiac development. Embryos were examined for altered gene expression in the presence of TCE or Benfluorex. TCE altered expression of selected mRNAs including HNF4a, TRAF6 and CYP2C45. There was a transition between inhibition and induction of marker gene expression in embryos as TCE concentration increased. Benfluorex was largely inhibitory to selected markers. Echocardiography of exposed embryos showed reduced cardiac function with both TCE and Benfluorex. Cardiac contraction was reduced by 29% and 23%, respectively at 10 ppb. The effects of TCE and Benfluorex on autocrine regulation of HNF4a, selected markers and cardiac function argue for a functional interaction of TCE and HNF4a. Further, the dose-sensitive shift between inhibition and induction of marker expression may explain the nonmonotonic-like dose response observed with TCE exposure in the heart., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Chronic exposure to stress during midlife associates with subsequent age-related cognitive decline and may increase the vulnerability to develop psychiatric conditions. Increased hypothalamic-pituitary-adrenal (HPA) axis activity has been implicated in pathogenesis though any causative role for glucocorticoids is unestablished. This study investigated the contribution of local glucocorticoid regeneration by the intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), in persisting midlife stress-induced behavioral effects in mice. Middle-aged (10 months old) 11β-HSD1-deficient mice and wild-type congenic controls were randomly assigned to 28 days of chronic unpredictable stress or left undisturbed (non-stressed). All mice underwent behavioral testing at the end of the stress/non-stress period and again 6-7 months later. Chronic stress impaired spatial memory in middle-aged wild-type mice. The effects, involving a wide spectrum of behavioral modalities, persisted for 6-7 months after cessation of stress into early senescence. Enduring effects after midlife stress included impaired spatial memory, enhanced contextual fear memory, impaired fear extinction, heightened anxiety, depressive-like behavior, as well as reduced hippocampal glucocorticoid receptor mRNA expression. In contrast, 11β-HSD1 deficient mice resisted both immediate and enduring effects of chronic stress, despite similar stress-induced increases in systemic glucocorticoid activity during midlife stress. In conclusion, chronic stress in midlife exerts persisting effects leading to cognitive and affective dysfunction in old age via mechanisms that depend, at least in part, on brain glucocorticoids generated locally by 11β-HSD1. This finding supports selective 11β-HSD1 inhibition as a novel therapeutic target to ameliorate the long-term consequences of stress-related psychiatric disorders in midlife., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Update: This article was updated on February 26, 2018, because of a previous error. On pages 1 and 7, in the author byline section, the authors' names that had read "Andrew Harris" and "Brett Owens" now reads "Andrew P. Harris" and "Brett D. Owens."

Skiing and snowboarding have increased in popularity since the 1960s. Both sports are responsible for a substantial number of musculoskeletal injuries treated annually by orthopaedic surgeons. Specific injury patterns and mechanisms associated with skiing and snowboarding have been identified. No anatomic location is exempt from injury, including the head, spine, pelvis, and upper and lower extremities. In these sports, characteristic injury mechanisms often are related to the position of the limbs during injury, the athlete's expertise level, and equipment design. Controversy exists about the effectiveness of knee bracing and wrist guards in reducing the incidence of these injuries. Understanding these injury patterns, proper training, and the use of injury prevention measures, such as protective equipment, may reduce the overall incidence of these potentially debilitating injuries.

Background: Hand and finger injuries account for approximately 4.8 million visits to emergency departments each year. These injuries can cause a great deal of distress for both patients and providers and are often initially encountered in urgent care clinics, community hospitals, and level one trauma centers. Tip amputation injuries vary widely in mechanism, ranging from sharp lacerations to crush injuries that present with varying degrees of contamination. The severity of damage to soft tissue, bone, arteries and nerves is dependent upon the mechanism and guides treatment decision-making. The management algorithm can oftentimes be complex, as a wide variety of providers, including orthopedists, general surgeons, plastic surgeons and emergency physicians, may care for these injuries, depending on location and local culture. We review the common mechanisms for tip amputation and the optimal treatment in adults, based on the severity of the injury, degree of wound contamination, and the facilities available to the provider., Methods: Pubmed was searched using text words for articles related to management of fingertip injuries in adults. Bibliographies of matching articles were searched for additional relevant articles, which were then also reviewed. 107 articles were reviewed in total, and 61 were deemed relevant for inclusion. All clinical studies and reviews were included. Particular attention was paid to articles published within the past 15 years., Results: In the United States, up to 90% of fingertip amputations are treated with non-replant techniques. In comparison, the majority of amputations in Asian countries are replanted due to moral values and importance of body integrity. Tip amputation injuries can be managed with local debridement, complex reconstruction, or simply with irrigation and application of a sterile dressing., Conclusion: In the United States, most fingertip amputations in adults are treated with non-replant techniques. However, the precise management of a fingertip injury in adults depends on the degree of injury itself, and a number of operative and non-operative techniques may be successfully employed., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The musculoskeletal manifestations of hemophilia A and B are some of the most common presenting symptoms and continue to be challenging to practitioners. Hemophilic arthropathy, if not initially adequately treated and managed, may lead to debilitating disease and eventually require the consideration of major surgery, including total joint arthroplasty. Thorough comprehension of the pathophysiology, diagnosis, and both medical and surgical interventions is critical in establishing an appropriate treatment regimen for these patients. Furthermore, a true multidisciplinary approach involving hematology, orthopedics, and physical therapy is essential for a patient with hemophilic arthropathy. The authors present a comprehensive review of hemophilic arthropathy from an orthopedist's perspective. [Orthopedics. 2017; 40(6):e940-e946.]., (Copyright 2017, SLACK Incorporated.)

Pyogenic flexor tenosynovitis (PFT) is a well known infectious condition of the hand, involving the inoculation of the flexor tendon sheath with microorganisms. Many cases have been reported, common causes including direct inoculation by a puncture wound and deep lacerations extending into the flexor tendon sheath. In this report, we present a case of a 50 year old female with PFT resulting from autophagia (consuming one's own body parts, in our case, fingers) successfully treated with irrigation and debridement, amputation of the index finger at the metacarpophalangeal joint and antibiotic therapy.

Evidence from human studies suggests that high expression of brain mineralocorticoid receptors (MR) may promote resilience against negative consequences of stress exposure, including childhood trauma. We examined, in mice, whether brain MR overexpression can alleviate the effects of chronic early life stress (ELS) on contextual memory formation under low and high stress conditions, and neurogenesis and synaptic function of dentate gyrus granular cells. Male mice were exposed to ELS by housing the dam with limited nesting and bedding material from postnatal day (PND) 2 to 9. We investigated the moderating role of MRs by using forebrain-specific transgenic MR overexpression (MR-tg) mice. Low-stress contextual (i.e., object relocation) memory formation was hampered by ELS in wildtype but not MR-tg mice. Anxiety like behavior and high-stress contextual (i.e., fear) memory formation were unaffected by ELS and/or MR expression level. At the cellular level, an interaction effect was observed between ELS and MR overexpression on the number of doublecortin-positive cells, with a significant difference between the wildtype ELS and MR-tg ELS groups. No interaction was found regarding Ki-67 and BrdU staining. A significant interaction between ELS and MR expression was further observed with regard to mEPSCs and mIPSC frequency. The ratio of evoked EPSC/IPSC or NMDA/AMPA responses was unaffected. Overall, these results suggest that ELS affects contextual memory formation under low stress conditions as well as neurogenesis and synaptic transmission in dentate granule cells, an effect that can be alleviated by MR-overexpression.

Mice lacking the intracellular glucocorticoid-regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) are protected from age-related spatial memory deficits. 11β-HSD1 is expressed predominantly in the brain, liver and adipose tissue. Reduced glucocorticoid levels in the brain in the absence of 11β-HSD1 may underlie the improved memory in aged 11β-HSD1 deficient mice. However, the improved glucose tolerance, insulin sensitisation and cardioprotective lipid profile associated with reduced peripheral glucocorticoid regeneration may potentially contribute to the cognitive phenotype of aged 11β-HSD1 deficient mice. In the present study, transgenic mice with forebrain-specific overexpression of 11β-HSD1 (Tg) were intercrossed with global 11β-HSD1 knockout mice (HSD1KO) to examine the influence of forebrain and peripheral 11β-HSD1 activity on spatial memory in aged mice. Transgene-mediated delivery of 11β-HSD1 to the hippocampus and cortex of aged HSD1KO mice reversed the improved spatial memory retention in the Y-maze but not spatial learning in the watermaze. Brain-derived neurotrophic factor (BDNF) mRNA levels in the hippocampus of aged HSD1KO mice were increased compared to aged wild-type mice. Rescue of forebrain 11β-HSD1 reduced BDNF mRNA in aged HSD1KO mice to levels comparable to aged wild-type mice. These findings indicate that 11β-HSD1 regenerated glucocorticoids in the forebrain and decreased levels of BDNF mRNA in the hippocampus play a role in spatial memory deficits in aged wild-type mice, although 11β-HSD1 activity in peripheral tissues may also contribute to spatial learning impairments in aged mice., (© 2016 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

The midtarsal joint, also known as the Chopart or the transverse tarsal joint, is composed of the talonavicular and calcaneocuboid articulations. 1 Midtarsal joint dislocations are rare injuries given the strong periarticular ligamentous support.2, 3 Medial, lateral, dorsal, and rarely plantar dislocations have been reported from multiple high-energy mechanisms.4, 5 We describe the case of a 24-year-old male who sustained talonavicular and calcaneocuboid plantar dislocations associated with a middle and lateral intercuneiform dislocation, open proximal 5th metatarsal fracture, 2nd-4th metatarsal base fractures, and lateral cuneiform fracture. The mechanism of injury, diagnosis, management, operative intervention, and follow up are discussed.

Brain-derived neurotrophic factor (BDNF) signaling is implicated in the etiology of many psychiatric disorders associated with altered emotional processing. Altered peripheral (plasma) BDNF levels have been proposed as a biomarker for neuropsychiatric disease risk in humans. However, the relationship between peripheral and central BDNF levels and emotional brain activation is unknown. We used heterozygous BDNF knockdown rats (BDNF(+/-)) to examine the effects of genetic variation in the BDNF gene on peripheral and central BDNF levels and emotional brain activation as assessed by awake functional magnetic resonance imaging (fMRI). BDNF(+/-) and control rats were trained to associate a flashing light (conditioned stimulus; CS) with foot-shock, and brain activation in response to the CS was measured 24 h later in awake rats using fMRI. Central and peripheral BDNF levels were decreased in BDNF(+/-) rats compared with control rats. Activation of fear circuitry (amygdala, periaqueductal gray, granular insular) was seen in control animals; however, activation of this circuitry was absent in BDNF(+/-) animals. Behavioral experiments confirmed impaired conditioned fear responses in BDNF(+/-) rats, despite intact innate fear responses. These data confirm a positive correlation [r = 0.86, 95% confidence interval (0.55, 0.96); P = 0.0004] between peripheral and central BDNF levels and indicate a functional relationship between BDNF levels and emotional brain activation as assessed by fMRI. The results demonstrate the use of rodent fMRI as a sensitive tool for measuring brain function in preclinical translational studies using genetically modified rats and support the use of peripheral BDNF as a biomarker of central affective processing., (© 2015 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)

Early-life stress (ELS) is a risk factor for the development of psychopathology, particularly in women. Human studies have shown that certain haplotypes of NR3C2, encoding the mineralocorticoid receptor (MR), that result in gain of function, may protect against the consequences of stress exposure, including childhood trauma. Here, we tested the hypothesis that forebrain-specific overexpression of MR in female mice would ameliorate the effects of ELS on anxiety and memory in adulthood. We found that ELS increased anxiety, did not alter spatial discrimination and reduced contextual fear memory in adult female mice. Transgenic overexpression of MR did not alter anxiety but affected spatial memory performance and enhanced contextual fear memory formation. The effects of ELS on anxiety and contextual fear were not affected by transgenic overexpression of MR. Thus, MR overexpression in the forebrain does not represent a major resilience factor to early life adversity in female mice.

Exposure to chronic stress is a risk factor for cognitive decline and psychopathology in genetically predisposed individuals. Preliminary evidence in humans suggests that mineralocorticoid receptors (MRs) may confer resilience to these stress-related changes. We specifically tested this idea using a well-controlled mouse model for chronic stress in combination with transgenic MR overexpression in the forebrain. Exposure to unpredictable stressors for 21 days in adulthood reduced learning and memory formation in a low arousing hippocampus-dependent contextual learning task, but enhanced stressful contextual fear learning. We found support for a moderating effect of MR background on chronic stress only for contextual memory formation under low arousing conditions. In an attempt to understand potentially contributing factors, we studied structural plasticity. Chronic stress altered dendritic morphology in the hippocampal CA3 area and reduced the total number of doublecortin-positive immature neurons in the infrapyramidal blade of the dentate gyrus. The latter reduction was absent in MR overexpressing mice. We therefore provide partial support for the idea that overexpression of MRs may confer resilience to the effects of chronic stress on hippocampus-dependent function and structural plasticity.

Functional magnetic resonance imaging (fMRI) of learned behaviour in 'awake rodents' provides the opportunity for translational preclinical studies into the influence of pharmacological and genetic manipulations on brain function. fMRI has recently been employed to investigate learned behaviour in awake rats. Here, this methodology is translated to mice, so that future fMRI studies may exploit the vast number of genetically modified mouse lines that are available. One group of mice was conditioned to associate a flashing light (conditioned stimulus, CS) with foot shock (PG; paired group), and another group of mice received foot shock and flashing light explicitly unpaired (UG; unpaired group). The blood oxygen level-dependent signal (proxy for neuronal activation) in response to the CS was measured 24 h later in awake mice from the PG and UG using fMRI. The amygdala, implicated in fear processing, was activated to a greater degree in the PG than in the UG in response to the CS. Additionally, the nucleus accumbens was activated in the UG in response to the CS. Because the CS signalled an absence of foot shock in the UG, it is possible that this region is involved in processing the safety aspect of the CS. To conclude, the first use of fMRI to visualise brain activation in awake mice that are completing a learned emotional task is reported. This work paves the way for future preclinical fMRI studies to investigate genetic and environmental influences on brain function in transgenic mouse models of disease and aging., (© 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Mineralocorticoid receptors (MRs) have been implicated in behavioral adaptation and learning and memory. Since-at least in humans-MR function seems to be sex-dependent, we examined the behavioral relevance of MR in female mice exhibiting transgenic MR overexpression in the forebrain. Transgenic MR overexpression did not affect contextual fear memory or cued fear learning and memory. Moreover, MR overexpressing and control mice discriminated equally well between fear responses in a combined cue and context fear conditioning paradigm. Also context-memory in an object recognition task was unaffected in MR overexpressing mice. We conclude that MR overexpression in female animals does not affect fear conditioned responses and object recognition memory.

Adverse experiences during childhood are associated with the development of psychiatric disorders later in life. In particular, childhood abuse and neglect are risk factors for addictive disorders, such as substance misuse and pathological gambling. Impulsivity and compulsivity are key features of these disorders. Therefore, we investigated whether childhood adversity might increase vulnerability for addictive disorders through promotion of compulsive and impulsive behaviors. Rats were exposed to a brief, variable childhood or prepubertal stress protocol (Postnatal Days 25-27), and their behavior in a delay discounting task was compared with that of control animals in adulthood. Prepubertal stress produced compulsive-type behavior in females. Specifically, stressed females displayed inappropriate responses during a choice phase of the task, perseverating with nosepoke responding instead of choosing between 2 levers. Stressed females also showed learning impairments during task training. However, prepubertal stress was not associated with the development of impulsive behavior, as rates of delay discounting were not affected in either sex. Childhood adversity may contribute to the establishment and maintenance of addictive disorders by increasing perseveration in females. Perseverative behavior may therefore provide a viable therapeutic target for preventing the development of addictive disorders in individuals exposed to childhood adversity. These effects were not seen in males, highlighting sex differences in response to early life stress., ((c) 2015 APA, all rights reserved).)

Here, we report the draft genome of Pseudoalteromonas sp. strain ND6B, which is able to grow with crude oil as a carbon source. Strain ND6B was isolated from eastern Mediterranean Sea deep water at a depth of 1,210 m. The genome of strain ND6B provides insight into the oil-degrading ability of the Pseudoalteromonas species., (Copyright © 2014 Harris et al.)

An imbalance between central glucocorticoid (GR) and mineralocorticoid (MR) receptors is proposed to underlie the HPA axis dysregulation that associates with susceptibility to psychopathology (anxiety, PTSD). To test this 'balance hypothesis' we examined whether the impact of MR levels upon HPA-axis control and behaviour depended on the relative levels of GR and vice versa. Avoiding antenatal maternal 'programming' effects by using littermates, we generated mice with forebrain MR over-expression (MR(hi)) and/or simultaneous global GR under-expression (GR(lo)). We found a significant interaction between MR and GR in control of the HPA-axis under stressed but not basal conditions. With reduced GR levels, HPA-axis activity in response to restraint stress was enhanced, likely due to impaired negative feedback. However, high MR in concert with reduced GR minimised this HPA-axis overshoot in response to stress. MR:GR balance also played a role in determining strategies of spatial memory during a watermaze probe trial: when coupled with GR under-expression, MR(hi) show enhanced perseveration, suggesting enhanced spatial recall or reduced exploratory flexibility. Other alterations in cognitive functions were specific to a single receptor without interaction, with both MR(hi) and GR(lo) manipulations independently impairing reversal learning in spatial and fear memory tasks. Thus, MR and GR interact in specific domains of neuroendocrine and cognitive control, but for other limbic-associated behaviours each receptor mediates its own repertoire of responses. Since modulation of HPA-axis and behavioural dysfunction associated with high levels of MR, selective ligands or transcriptional regulators may afford novel therapeutic approaches to affective psychopathologies., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Tryptophan indole lyase (TIL), an enzyme found in Escherichia coli and related enterobacteria, produces indole from l-tryptophan (l-Trp). Indole is a signaling molecule in bacteria, affecting biofilm formation, pathogenicity and antibiotic resistance. β-(Benzimidazol-1-yl)-l-alanine (BZI-Ala), 2-amino-4-(benzimidazol-1-yl)butyric acid (homo-BZI-Ala) and 2-amino-5-(benzimidazol-1-yl)pentanoic acid (bishomo-BZI-Ala) were synthesized and tested as substrates and inhibitors of TIL. BZI-Ala is a good substrate of TIL, with Km = 300 μm, kcat = 5.6 s(-1) and kcat /Km = 1.9 × 10(4) , similar to l-Trp. BZI-Ala is also a good substrate for H463F mutant TIL, which has very low activity with l-Trp. In contrast, homo-BZI-Ala was found to be a potent competitive inhibitor of TIL, with a Ki of 13.4 μm. However, the higher homolog, bishomo-BZI-Ala, was inactive as an inhibitor of TIL at a concentration of 600 μm, and is thus a much weaker inhibitor. The reaction of TIL with BZI-Ala was too fast to be observed in the stopped-flow spectrophotometer, and shows an aldimine intermediate in the steady state. However, H463F TIL shows equilibrating mixtures of aldimine and quinonoid complexes in the steady state. The spectra of the reaction of TIL with homo-BZI-Ala show a rapidly formed intermediate absorbing at 340 nm, probably a gem-diamine, that decays slowly to form a quinonoid complex absorbing at 494 nm. The potent binding of homo-BZI-Ala may be due to it being a 'bi-product' analog of the indole-α-aminoacrylate complex. These results demonstrate that an amino acid substrate may be converted to a potent inhibitor of TIL simply by homologation, which may be useful in the design of other potent TIL inhibitors., (© 2013 The Authors Journal compilation © 2013 FEBS.)

Sara Shettleworth has played a defining role in the development of animal cognition and its integration into other parts of biology, especially behavioural ecology. Here we chart some of that progress in understanding the causes and importance of variation in cognitive ability and highlight how Tinbergen's levels of explanation provide a useful framework for this field. We also review how experimental design is crucial in investigating cognition and stress the need for naturalistic experiments and field studies. We focus particularly on the example of the relationship among food hoarding, spatial cognition and hippocampal structure, and review the conflicting evidence for sex differences in spatial cognition. We finish with speculation that a combination of Tinbergen and Shettleworth-style approaches would be the way to grapple with the as-yet unanswered questions of why birds mimic heterospecifics.

Cerebral vasodilatory responses evoked by activation of NMDA receptors and by hypercapnia are important factors in the integrated vascular response to perinatal cerebral ischemia. Cerebral vasodilation to NMDA is mediated by nitric oxide in adult and newborn animals, whereas vasodilation to hypercapnia is thought to become modulated by nitric oxide, at least in swine, after the newborn period. The developmental role of nitric oxide in the cerebral blood flow response to NMDA and hypercapnia was investigated at mid- and late gestation in fetal sheep. Superfusion of 300microM NMDA over the cerebral cortex through a closed cranial window on the exteriorized head of an anesthetized fetus increased laser-Doppler flow by 41+/-7% (+/-S.E.) at 0.65 gestation. The increase was reduced by superfusion of a nitric oxide synthase inhibitor (18+/-8%). At 0.9 gestation, the response to NMDA was augmented (85+/-24%) compared to that at 0.65 gestation and was reduced by a nitric oxide synthase inhibitor (32+/-6%). In unanesthetized fetal sheep, hypercapnic reactivity of microsphere-determined cerebral blood flow was not significantly attenuated by nitric oxide synthase inhibition at 0.65 gestation (4.6+/-0.7 to 3.7+/-1.0% change/mmHg pCO2) or at 0.9 gestation (4.0+/-0.7 to 3.5+/-0.9% change/mmHg pCO2). Therefore, nitric oxide-dependent cerebrovascular dilation to NMDA-receptor activation is present as early as 0.65 gestation in fetal sheep and increases further during the last trimester, whereas vasodilation to hypercapnia remains unchanged and independent of nitric oxide during the last trimester. Hence, cerebrovascular reactivities to different stimuli do not mature concurrently.

Galanin (GAL) impairs performance on cognitive tasks when administered centrally to rats. GAL transgenic (GAL-tg) mice overexpressing endogenous GAL show deficits on the probe trial of the Morris water maze spatial learning task, on the social transmission of food preference olfactory memory task, and on the trace cued fear conditioning emotional learning and memory task. Knockout mice deficient in the GAL-R1 receptor subtype were normal on most memory tasks, while showing a small deficit in trace cued fear conditioning, suggesting a selective role for the GAL-R1 in aversive memories, and implicating other GAL receptor subtypes in spatial learning and olfactory social memory. The growing body of rodent literature implicating excess GAL in cognitive impairment is relevant to the overexpression of GAL in the basal forebrain during the progression of Alzheimer's disease.

The neuropeptide galanin induces performance deficits in a wide range of cognitive tasks in rodents. Three G-protein-coupled galanin receptor subtypes, designated GAL-R1, GAL-R2 and GAL-R3, have been cloned. The present study examined the role of GAL-R1 in cognition by testing mice with a null mutation in Galr1 on several different types of learning and memory tasks. Assessments of general health, neurological reflexes, sensory abilities and motor functions were conducted as control measures. Mutant mice were unimpaired in social transmission of food preference and the Morris water maze. In tests of fear conditioning, mutant mice were unimpaired in a delay version of cued fear conditioning. However, mice homozygous for the null mutation were impaired in a trace version of cued fear conditioning. Mutant mice were unimpaired in contextual fear conditioning, whether training was by the delay or trace protocol. General health, neurological reflexes, sensory abilities and motor functions did not differ across genotypes, indicating that the trace fear conditioning deficit was not an artifact of procedural disabilities. The findings of normal performance on several cognitive tasks and a selective deficit in trace cued fear conditioning in homozygous GAL-R1 mutant mice are discussed in terms of hypothesized roles of the GAL-R1 subtype. The generally normal phenotype of GAL-R1 null mutants supports the use of this line for identification of the receptor subtypes that mediate the cognitive deficits produced by exogenous galanin.

Social transmission of food preference (STFP) is a test of olfactory memory that can be used in mice. Confounds in STFP that can lead to misinterpretation of an STFP deficit as a memory impairment include changes in social interaction and olfaction. The issue of changes in social interaction was addressed by evaluating an observer-centric and a demonstrator-centric method for scoring the interaction phase of STFP in mice. The demonstrator-centric method was applied to a line of STFP-impaired, galanin-overexpressing transgenic (GAL-tg). GAL-tg mice were impaired in STFP without deficits in social interaction. In tests of olfactory ability, GAL-tg mice were unimpaired on buried-food and habituation-dishabituation tasks. The current studies describe an expanded method for using STFP in mice and confirm a deficit in olfactory memory in GAL-tg mice.

Galanin inhibits the release of several neurotransmitters and produces performance deficits in a variety of spatial and aversive learning and memory tasks. The experiments in this study investigated the role galanin has in emotional learning and memory using a standard delay cued and contextual fear conditioning task. Rats were administered galanin into the lateral ventricles before training, and scored for freezing behavior in the same context and in a novel context with and without an auditory cue (CS) that had been paired previously with an aversive stimulus (US). Galanin-overexpressing transgenic mice were tested in an identical behavioral protocol. The galanin-administered rats and the transgenic mice were not significantly different from their respective controls on this task. A more challenging trace cued and contextual fear conditioning procedure was administered to separate groups of galanin-treated rats and galanin-overexpressing transgenic mice. Subjects were trained with the same CS and US, however, a 2.5-sec delay was inserted between CS offset and US onset. Following the trace conditioning, rats administered galanin and mice overexpressing galanin both exhibited significantly less freezing to the CS in the novel context as compared with their control groups. These results indicate that the observed disruption of cued fear conditioning was specific to the more difficult trace conditioning task. These findings are the first demonstration that galanin impairs performance on an emotional memory task and support the hypothesis that galanin-induced deficits are specific to more difficult cognitive tasks.

You can see that legislation can be affected at many levels, and advocacy can play a crucial role in the outcome. Next year, I hope that I will be able to write the conclusion of the BPQA sunset legislation story. In the meantime, please continue to advocate for physicians and our patients in Maryland. Our legislators need to hear from people like you who really understand how health care is being delivered in Maryland.