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Bibliometric rankings of researchers are increasingly important for academic hiring and for making grant application decisions in the biomedical sciences. As a case study, we performed a comprehensive bibliometric analysis of German pharmacology and toxicology. The 42 members of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) represented in the German 'best scientist' ranking in biology and biochemistry on www.research.com for the year 2022 were analyzed according to various aspects. The scientist ranking on Research.com is based on the Hirsch Index (h-Index). In the comparatively small field of pharmacology, which accounts for only 4.2% of the scientists in the ranking on Research.com, there are only two women. This shows that female pharmacologists are highly underrepresented in elite pharmacology. To achieve a high h-Index, a pharmacologist must publish more papers than a biochemist or biologist. Furthermore, German elite pharmacology was compared in the three sub-societies of the DGPT. There are no significant differences between elite pharmacologists and toxicologists in terms of productivity. Two large German pharmacology schools (Günter Schultz and Franz Hofmann) are similar in all bibliometric parameters except for number of total publications. Age-specific factors were also defined for the analysis: 'academic age' and the quotient of the h-Index by 'academic age'. Any given bibliometric parameter (or combination of parameters) yielded different ranking results. This became even more evident when additionally considering the highly popular and widely used Laborjournal ranking of top pharmacology and toxicology researchers with only very few DGPT members listed. We unmasked 7 types of publication patterns of pharmacologists, an age-dependent publication peak at around 55 years and different trajectories for high- and low-volume publishing pharmacologists. In the future, less emphasis should be paid to bibliometric parameters in academic hiring and grant decisions than to the authentic societal and scientific impact of the research. Bibliometric parameters are very arbitrary within a very large segment of pharmacologists. Studies according to the paradigm of this account should be made for other countries, other learned societies, and other scientific fields. The different cultures among related scientific fields must be considered in bibliometric analyses as exemplified here for pharmacology versus biochemistry. Conversely, the bibliometric similarities between pharmacology and toxicology show that both fields belong together and have a very similar culture., (© 2024. The Author(s).)

The US population suffers 1.5 million head injuries annually, of which mild traumatic brain injuries (mTBI) comprise 75%. Many individuals subsequently experience long-lasting negative symptoms, including anxiety. Previous rat-based work in our laboratory has shown that mTBI changes neuronal counts in the hippocampus and amygdala, regions associated with anxiety. Specifically, mTBI increased neuronal death in the dorsal CA1 sub-region of the hippocampus, but attenuated it in the medial (MeA) and the basolateral nuclei of the amygdala nine days following injury, which was associated with greater anxiety. We have also shown that glucocorticoid receptor (GR) antagonism prior to concomitant stress and mTBI extinguishes anxiety-like behaviors. Using immunohistochemistry, this study examines the expression of brain-derived neurotrophic factor (BDNF) following social defeat and mTBI, and whether this is affected by prior glucocorticoid receptor antagonism as a potential mechanism behind these anxiety and neuronal differences. Here, stress and mTBI upregulate BDNF in the MeA, and both GR and mineralocorticoid receptor antagonism downregulate BDNF in the dorsal hippocampal CA1 and dentate gyrus, as well as the central nucleus of the amygdala. These findings suggest BDNF plays a role in the mechanism underlying neuronal changes following mTBI in amygdalar and hippocampal subregions, and may participate in stress elicited changes to neural plasticity in these regions. Taken together, these results suggest an essential role for BDNF in the development of anxiety behaviors following concurrent stress and mTBI., Competing Interests: 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., (© 2023 The Authors.)

The bone marrow failure syndromes (BMFS) are a diverse group of acquired and inherited diseases which may manifest in cytopenias, haematological malignancy and/or syndromic multisystem disease. Patients with BMFS frequently experience poor outcomes, and improved treatment strategies are needed. Collation of clinical characteristics and patient outcomes in a national disease-specific registry represents a powerful tool to identify areas of need and support clinical and research collaboration. Novel treatment strategies such as gene therapy, particularly in rare diseases, will depend on the ability to identify eligible patients alongside the molecular genetic features of their disease that may be amenable to novel therapy. The Australian Aplastic Anaemia and other Bone Marrow Failure Syndromes Registry (AAR) aims to improve outcomes for all paediatric and adult patients with BMFS in Australia by describing the demographics, treatments (including supportive care) and outcomes, and serving as a resource for research and practice improvement., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Individuals with germ line variants associated with hereditary hematopoietic malignancies (HHMs) have a highly variable risk for leukemogenesis. Gaps in our understanding of premalignant states in HHMs have hampered efforts to design effective clinical surveillance programs, provide personalized preemptive treatments, and inform appropriate counseling for patients. We used the largest known comparative international cohort of germline RUNX1, GATA2, or DDX41 variant carriers without and with hematopoietic malignancies (HMs) to identify patterns of genetic drivers that are unique to each HHM syndrome before and after leukemogenesis. These patterns included striking heterogeneity in rates of early-onset clonal hematopoiesis (CH), with a high prevalence of CH in RUNX1 and GATA2 variant carriers who did not have malignancies (carriers-without HM). We observed a paucity of CH in DDX41 carriers-without HM. In RUNX1 carriers-without HM with CH, we detected variants in TET2, PHF6, and, most frequently, BCOR. These genes were recurrently mutated in RUNX1-driven malignancies, suggesting CH is a direct precursor to malignancy in RUNX1-driven HHMs. Leukemogenesis in RUNX1 and DDX41 carriers was often driven by second hits in RUNX1 and DDX41, respectively. This study may inform the development of HHM-specific clinical trials and gene-specific approaches to clinical monitoring. For example, trials investigating the potential benefits of monitoring DDX41 carriers-without HM for low-frequency second hits in DDX41 may now be beneficial. Similarly, trials monitoring carriers-without HM with RUNX1 germ line variants for the acquisition of somatic variants in BCOR, PHF6, and TET2 and second hits in RUNX1 are warranted., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)

Mild traumatic brain injuries (mild TBIs) commonly occur in young adults of both sexes, oftentimes in high-stress environments. In humans, sex differences have been observed in the development of post-concussive anxiety and PTSD-like behaviors. Progesterone, a sex steroid that has neuroprotective properties, restores cognitive function in animal models following more severe TBI, but its effectiveness in preventing the psychological symptoms associated with mild TBI has not been evaluated. Using a model of mild TBI that pairs a social stressor (social defeat) with weight drop, male and naturally estrous-cycling female rats were treated with 4 mg/kg progesterone or vehicle once daily for 5 days after injury. Behavioral measures, including elevated plus maze (EPM), contextual fear conditioning, and novel object recognition (NOR) were assessed following progesterone treatment. Anxiety-like behavior was increased by mild TBI in male rats, with a smaller effect seen in female rats in the diestrus phase at the time of EPM testing. In contrast, mild TBI impaired fear learning in female rats in estrus at the time of fear acquisition. Progesterone treatment failed to attenuate post-mild TBI anxiety-like behavior in either sex. Furthermore, progesterone increased fear conditioning and impaired NOR discrimination in male rats, independent of TBI status. Overall, both sex and estrous cycle contributed to psychological outcomes following mild TBI, which were not ameliorated by post-TBI progesterone. This suggests sex steroids play an important role as a moderator of the expression of mild TBI-induced psychological symptoms, rather than as a potential treatment for their underlying etiology., 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 © 2023 Elsevier Inc. All rights reserved.)

Because germ line genetic testing is increasingly integrated into the clinical care of patients with hematologic malignancies, it is important for hematologists to effectively communicate with patients and their families about the genetic testing process and to relay the results in a concise and understandable manner. Effective communication facilitates trust between patients and providers and allows patients to feel empowered to ask questions and actively participate in their health care. Especially for inherited conditions, the patient's understanding of germ line genetic information is critical because it enables them to share this information with relatives who are at risk, thereby promoting cascade testing and providing potentially life-saving information to family members who may be similarly affected. Accordingly, a hematologist's skills in understanding the importance and implications of germ line genetic information and the ability to convey this information in patient-friendly language is a critical first step and can have a far-reaching impact. In this article, we outline a straightforward approach to discussing genetic information and provide the reader with practical tips that can be used when consenting patients to germ line genetic testing and disclosing subsequent test results. We also review special considerations and ethical concerns arising when offering genetic evaluation and germ line testing to patients and related donors for allogeneic hematopoietic stem cell transplantation., (© 2023 by The American Society of Hematology.)

In 2001, the primary and secondary syphilis incidence rate in rural Columbus County, North Carolina was the highest in the nation. To understand the development of syphilis outbreaks in rural areas, we developed and used the Bayesian Maximum Entropy Graphical User Interface (BMEGUI) to map syphilis incidence rates from 1999-2004 in seven adjacent counties in North Carolina. Using BMEGUI, incidence rate maps were constructed for two aggregation scales (ZIP code and census tract) with two approaches (Poisson and simple kriging). The BME maps revealed the outbreak was initially localized in Robeson County and possibly connected to more urban endemic cases in adjacent Cumberland County. The outbreak spread to rural Columbus County in a leapfrog pattern with the subsequent development of a visible low incidence spatial corridor linking Roberson County with the rural areas of Columbus County. Though the data are from the early 2000s, they remain pertinent, as the combination of spatial data with the extensive sexual network analyses, particularly in rural areas gives thorough insights which have not been replicated in the past two decades. These observations support an important role for the connection of micropolitan areas with neighboring rural areas in the spread of syphilis. Public health interventions focusing on urban and micropolitan areas may effectively limit syphilis indirectly in nearby rural areas., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fox et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mild traumatic brain injuries (mild TBIs) can affect both males and females, but females are more likely to report long-term psychological complications, including changes in mood and generalized anxiety. Additionally, reproductive cycle phase has been shown to affect mild TBI symptom expression within females. These variances may result from sex differences in mild TBI-induced alterations to neurotransmission in brain regions that influence mood and emotion, possibly mediated by sex steroids. The hippocampus and amygdala are implicated in stress responses and anxiety, and within these regions, gamma-aminobutyric acid (GABA) and serotonin modulate output and behavioral expression. Metabolites of progesterone can allosterically enhance GABAergic signaling, and sex steroids are suggested to regulate the expression of the serotonin transporter (SERT). To determine how mild TBI might alter GABA receptor and SERT expression in males and females, immunocytochemistry was used to quantify expression of the alpha-1 subunit of the GABA A receptor (α1-GABA A ), SERT, and a neuronal marker (NeuN) in the brains of adult male and naturally-cycling female rats, both with and without mild TBI, 17 days after injury. Mild TBI altered the expression of α1-GABA A in the amygdala and hippocampus in both sexes, but the direction of change observed depended on sex and reproductive cycle phase. In contrast, mild TBI had little effect on SERT expression. However, SERT expression differed between sexes and varied with the cycle phase. These findings demonstrate that regulation of neurotransmission following mild TBI differs between males and females, with implications for behavioral outcomes and the efficacy of therapeutic strategies., (Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.)

Telomere biology disorders (TBDs) are a spectrum of multisystem inherited disorders characterized by bone marrow failure, resulting from mutations in the genes encoding telomerase or other proteins involved in maintaining telomere length and integrity. Pathogenicity of variants in these genes can be hard to evaluate, because TBD mutations show highly variable penetrance and genetic anticipation related to inheritance of shorter telomeres with each generation. Thus, detailed functional analysis of newly identified variants is often essential. Herein, we describe a patient with compound heterozygous variants in the TERT gene, which encodes the catalytic subunit of telomerase, hTERT. This patient had the extremely severe Hoyeraal-Hreidarsson form of TBD, although his heterozygous parents were clinically unaffected. Molecular dynamic modeling and detailed biochemical analyses demonstrate that one allele (L557P) affects association of hTERT with its cognate RNA component hTR, whereas the other (K1050E) affects the binding of telomerase to its DNA substrate and enzyme processivity. Unexpectedly, the data demonstrate a functional interaction between the proteins encoded by the two alleles, with wild-type hTERT rescuing the effect of K1050E on processivity, whereas L557P hTERT does not. These data contribute to the mechanistic understanding of telomerase, indicating that RNA binding in one hTERT molecule affects the processivity of telomere addition by the other molecule. This work emphasizes the importance of functional characterization of TERT variants to reach a definitive molecular diagnosis for patients with TBD, and, in particular, it illustrates the importance of analyzing the effects of compound heterozygous variants in combination, to reveal interallelic effects., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Zebrafish are an important model for studying phagocyte function, but rigorous experimental systems to distinguish whether phagocyte-dependent effects are neutrophil or macrophage specific have been lacking. We have developed and validated transgenic lines that enable superior demonstration of cell-autonomous neutrophil and macrophage genetic requirements. We coupled well-characterized neutrophil- and macrophage-specific Gal4 driver lines with UAS:Cas9 transgenes for selective expression of Cas9 in either neutrophils or macrophages. Efficient gene editing, confirmed by both Sanger and next-generation sequencing, occurred in both lineages following microinjection of efficacious synthetic guide RNAs into zebrafish embryos. In proof-of-principle experiments, we demonstrated molecular and/or functional evidence of on-target gene editing for several genes (mCherry, lamin B receptor, trim33) in either neutrophils or macrophages as intended. These new UAS:Cas9 tools provide an improved resource for assessing individual contributions of neutrophil- and macrophage-expressed genes to the many physiological processes and diseases modelled in zebrafish. Furthermore, this gene-editing functionality can be exploited in any cell lineage for which a lineage-specific Gal4 driver is available. This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Background: Canine sudden acquired retinal degeneration syndrome (SARDS) causes blindness for which there are no proven effective treatments. We aimed to clarify the time to vision loss, treatment response/side effects, and prognosis for life in dogs with SARDS., Methods: An online questionnaire was administered to owners of dogs with a historical diagnosis of SARDS. Mortality data were compared with a published purebred reference population. Select parameters were analyzed statistically using general linear model with least square means, two-sample t tests, and chi-squared or Fisher's exact tests., Results: Responses from owners that stated that their dog visited an ophthalmologist and had electroretinography performed (n = 434) were analyzed. The majority of owners (65.4%) reported the time from vision disturbance to complete vision loss as <2 weeks; 19.4% reported >4 weeks. Onset of systemic clinical signs to complete vision loss was >4 weeks in 44.5% of responses. A higher proportion of owners reported some vision recovery with combination treatment (14.4%) compared with monotherapy (3.2%, P = .0004). Side effects of treatment were commonly reported. Dogs with SARDS did not have a shorter lifespan than the reference population but had higher incidence of kidney disease (P = .0001) and respiratory disease (P = .0004) at death., Conclusions: Dogs with SARDS have a rapid onset of vision loss. In the owner's opinion, treatment is unlikely to restore vision and is associated with systemic side effects. The potential for systemic pathologies that arise after SARDS diagnosis warrants further study., (© 2020 American College of Veterinary Ophthalmologists.)

Hypocellular bone marrow failure (BMF) has myriad differential diagnoses, most simply considered as acquired and inherited disorders, which are frequently indistinguishable upon morphologic examination of the blood and bone marrow. Accurate diagnosis is critical to optimization of management and begins with a detailed history (including family history) and physical examination. Next-generation sequencing technologies complement traditional testing techniques (such as chromosomal fragility and telomere length assessment) and have a broad application in the diagnosis and prognostication of BMF, with the importance of detection of both germline changes and also somatic variants increasingly well understood and appreciated. There is increasing awareness of germline predisposition to haematological malignancy, which incorporates but is not limited to the traditional inherited BMF syndromes and which raises challenges for counselling, monitoring and treatment of people who harbour a germline lesion. There are many benefits to both patients and their kindred of accurate determination of the precise germline change underlying heritable bone marrow diseases, along with its associated mode of inheritance. While individually, these diseases are rare, collectively they are not so and there are many collaborative efforts underway to document the natural history of these disorders, the associated phenotypes and the ever-increasing list of variants which have sufficient evidence to warrant the ascription of a pathogenic classification. We describe the many diagnostic considerations when evaluating newly presenting patients with hypocellular BMF, with a focus on genomic assessment, which is relevant in both germline and acquired diseases., (© 2020 John Wiley & Sons Ltd.)

The use of animal models for behavioral and pharmaceutical testing is employed in many different fields of research but often relies solely on male animals. When females are included, the existing literature frequently offers inconsistent results regarding the effects of sex and/or estrous cycle on anxiety-like behaviors. Our current study sought to establish baseline or normative behaviors in three commonly employed tests of anxiety-like behavior, and determine any sex or cycle differences. Anxiety-like behaviors in male and naturally-cycling female Sprague-Dawley rats were assessed using elevated plus maze, open field, and a social interaction/avoidance paradigm. Female rats were examined once daily to determine their stage of estrous. Results from the elevated plus maze but not the open field showed that female rats spent significantly more time in open areas than did male rats; however, there was no effect of estrous cycle stage. The social avoidance test revealed that female rats spent significantly more time in the interaction zone with an empty wire mesh cage (novel object), but there was no sex difference in time spent with an age- and sex- matched target rat. Females often exhibited greater locomotion as compared to males in social and non-social tests, but this was not related to primary anxiety measures in these tests. Overall, our findings indicate that outcomes differ in tests of anxiety-like behaviors, highlighting sex differences in the expression of anxiety-like behaviors that depend on the test employed. Importantly, the lack of estrous cycle effects suggest that for these anxiety-based tests, female Sprague-Dawley rats could be collapsed across the cycle phases to facilitate the inclusion of females in future behavioral experiments., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Bone marrow biopsy (BMB) is an accepted investigation in fever of unknown origin (FUO) to uncover haematological malignancies, such as lymphoma, and sometimes infections. With the advance in imaging modalities, such as 18-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) to identify the focus of lymphoma, BMB may not contribute to the diagnosis when there are no other clinical features to suggest an underlying haematological disease., Aim: To investigate the utility of BMB in determining the cause of FUO, when there are no other indications for BMB., Methods: Medical records of adult patients who had BMB performed for FUO or febrile illness from 1 January 2005 to 31 December 2014 in four metropolitan tertiary hospitals in Melbourne, Australia were reviewed. Patients with other concurrent indications for BMB, known human immunodeficiency virus infection and previously diagnosed connective tissue diseases were excluded., Results: Seventy-three patients were included in the study. Fifty-one patients had a final diagnosis for fever (systemic inflammatory diseases, infective, malignancy or other) while 22 patients had no diagnoses. In only 10 patients (13.7%) did BMB contribute to the diagnosis, finding either malignancy or granulomata. However, all these diagnoses could have been made without BMB. Two patients with diffuse large B-cell lymphoma had normal BMB. FDG-PET was helpful in making a diagnosis in eight (25%) out of 32 patients., Conclusion: Performing BMB in patients with FUO and no other haematological abnormalities is of very limited value, and other investigations, such as FDG-PET, may be more likely to help establish a definitive diagnosis., (© 2019 Royal Australasian College of Physicians.)

Acquired aplastic anaemia is a rare, serious, immunologically mediated bone marrow failure syndrome, characterised by marrow hypoplasia of varying severity and significant pancytopenia. Careful attention and investigation, including molecular testing, is required to confirm the diagnosis and exclude other mimicking conditions, such as inherited bone marrow failure syndromes. In a proportion of patients, the disease evolves to myelodysplasia or acute myeloid leukaemia and in some there is an association with paroxysmal nocturnal haemoglobinuria. The disease has a major impact on patient quality of life. Haemopoietic stem/progenitor cell transplantation for eligible patients with an available donor is the only current curative therapy. Other patients may receive immunosuppression, most commonly with anti-thymocyte globulin and cyclosporin. An initial response to immunosuppression is often encouraging, but relapse is common. Supportive care, including management of transfusion requirements and infections, is central to management. Promising new diagnostic tools and emerging therapies will likely transform approaches to this important, chronic and life-threatening condition., (© 2018 Royal Australasian College of Physicians.)

Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. While TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 activity (a disintegrin and metalloprotease thrombospondin, number 13). A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. While early confirmation of aHUS is often not possible, except in the minority of patients in whom autoantibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA., (© 2018 Asian Pacific Society of Nephrology.)

Dasatinib has shown superiority over imatinib in achieving molecular responses (MRs) in chronic phase chronic myeloid leukemia but with a different toxicity profile, which may impact its overall benefit. Reported toxicities include pleural effusions and pulmonary hypertension, and although the incidence of these events is well described, response to therapy and impact of dose modifications on toxicity has not been comprehensively characterized in a real-world setting. We retrospectively reviewed the incidence of dasatinib adverse events in 212 chronic phase chronic myeloid leukemia patients at 17 Australian institutions. Adverse events were reported in 116 patients (55%), most commonly pleural effusions (53 patients, 25%), which was the predominant cause of permanent drug cessation. Age and dose were risk factors for pleural effusion ( P < .01 and .047, respectively). Recurrence rates were higher in those who remained on 100 mg compared with those who dose reduced ( P = .041); however, recurrence still occurred at 50 mg. Patients who developed pleural effusions were more likely to have achieved MR4.5 after 6 months of dasatinib than those without effusions ( P = .008). Pulmonary hypertension occurred in 5% of patients, frequently in association with pleural effusion, and was reversible upon dasatinib cessation in 6 of 7 patients. Dose reductions and temporary cessations had minimal impact on MR rates. Our observations suggest that by using the lowest effective dose in older patients to minimize the effusion risk, dose modification for cytopenias, and care with concomitant antiplatelet therapy, the necessity for permanent dasatinib cessation due to toxicity is likely to be minimal in immunologically competent patients., Competing Interests: Conflict-of-interest disclosure: J.S. and D.Y. have received honoraria from Novartis and Bristol-Myers Squibb (BMS) and research funding from BMS and participated in Advisory Boards for Novartis. S.F. has received honoraria from BMS and research funding from BMS and participated in Advisory Boards for Ariad. C.F. has received a travel grant from BMS. A.G. has participated in Advisory Boards for Novartis and BMS. The remaining authors declare no competing financial interests.

Mild traumatic brain injuries (TBIs) comprise three-quarters of all TBIs occurring in the United States annually, and psychological symptoms arising from them can last years after injury. One commonly observed symptom following mild TBI is generalized anxiety. Most mild TBIs happen in stressful situations (sports, war, domestic violence, etc.) when glucocorticoids are elevated in the brain at the time of impact, and glucocorticoids have negative effects on neuronal health following TBI. Therefore, blocking glucocorticoid receptors might prevent emergence of anxiety symptoms post-injury. Adult male rats received mifepristone (20mg/kg) or spironolactone (50mg/kg) to block glucocorticoid and mineralocorticoid receptors, respectively, 40min prior to being exposed to acute social defeat stress followed immediately by mild TBI. In defeated rats with concomitant mild TBI, mifepristone restored time spent in the open arms of an elevated plus maze to control levels, demonstrating for the first time that glucocorticoid receptors play a critical role in the development of anxiety after mild TBI. Future treatments could target these receptors, alleviating anxiety as a major side effect in victims of mild TBI sustained in stressful situations., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Opioids are an important component of pain management strategies for many patients, but their use is associated with serious life-threatening adverse drug responses, such as respiratory depression, as well as a potential for abuse and dependence. This paper presents an overview of opioid pharmacology, pharmacokinetics and toxicology, as well as approaches to maintain or treat opioid dependence., (Copyright© South Dakota Medicine.)

Background: High-dose chemotherapy and autologous haematopoietic stem cell transplantation is an important therapeutic modality in the treatment of many haematological malignancies. Generally, stem cells are collected close to the time of the transplant, but an alternative is to collect and cryopreserve cells at an early stage of the illness so they are available for later use ('rainy day harvesting'). Although this practice has been commonplace in Australia, there is little evidence to document eventual use of cells collected in this manner., Methods: We conducted an audit of indications for and eventual transplantation of 'rainy day' harvests performed at our institution over a 10-year period., Results: Although there was some variation across different disease groups, we found that only 14% of cells were transplanted. The median delay to transplantation was 19 months., Conclusion: Together with recent advances in stem cell mobilisation techniques, results from this audit suggest that the practice may not be an effective use of limited health resources., (© 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.)

Rodents rely heavily on odor detection, discrimination, and memory to locate food, find mates, care for pups, and avoid predators. Estrogens have been shown to increase memory retention in rodents performing spatial memory and object placement tasks. Here we evaluate the extent to which 17β-estradiol modulates memory formation and duration in the olfactory system. Adult CD-1 mice were gonadectomized and given either systemic 17β-estradiol replacement, local 17β-estradiol in the main olfactory bulb, or no replacement. Before performing the behavioral task the mice were given saline or PHTPP (an estrogen receptor β [ER-β] antagonist) via bilateral infusion into the main olfactory bulb. As the beta-type estrogen receptor (ER-β) is more abundant than the alpha-type estrogen receptor in the murine main olfactory bulb, the current study focuses on 17β-estradiol and its interactions with ERβ. Habituation, a simple, nonassociative learning task in which an animal is exposed to the same odor over successive presentations, was used to evaluate the animals' ability to detect odors and form an olfactory memory. To evaluate memory duration, we added a final trial of intertrial interval time (30 or 60 min) in which we presented the habituated odor. Neither surgical nor drug manipulation affected the ability of mice to detect or habituate to an odor. After habituation, gonadectomized 17β-estradiol-treated mice retained memory of an odor for 30 min, whereas non-estradiol-treated, 17β-estradiol+ERβ antagonist (PHTPP), and untreated male mice did not remember an odor 30 min after habituation. The results show that both systemic and local bulbar infusions of 17β-estradiol enhance odor memory duration in mice.

Management of traumatic lower-limb vascular injury can offer special challenges even to experienced surgeons. Recent U.S. conflicts have advanced the practice of vascular trauma surgery on the battlefield and offer important lessons learned for management of similar injury in urban trauma centers. Damage control techniques for complex injuries when associated with hemodynamic instability may provide an opportunity to save both life and limb. This article provides an overview of damage control principles in the management of high-energy traumatic vascular injuries of the lower limb during recent U.S. military combat operations.

Current research has shown that neurofeedback, or EEG biofeedback as it is sometimes called, is a viable alternative treatment for Attention Deficit Hyperactivity Disorder (ADHD). The aim of this article is to illustrate current treatment modalities(s), compare them to neurofeedback, and present the benefits of utilizing this method of treatment to control and potentially alleviate the symptoms of ADHD. In addition, this article examines the prevalence rates and possible etiology of ADHD, the factors associated with ADHD and brain dysfunction, the current pharmacological treatments of ADHD, Ritalin, and the potential risks and side effects. Behavior modification and cognitive behavioral treatment for ADHD is discussed as well. Lastly, a brief history of the study of neurofeedback, treatment successes and clinical benefits, comparisons to medication, and limitations are presented.

This study examined gender differences in prospective within-day assessments of pain, pain coping, and mood in men and women having OA, and analyzed gender differences in dynamic relations between pain, mood, and pain coping. A sample of 64 women and 36 men diagnosed as having pain due to osteoarthritis of the knee(s) rated their pain, pain coping, and mood two times each day (once in the afternoon and once in the evening) for 30 days using a booklet format. Two gender differences were found in between person-analyses: women used more problem focused coping than men, and women who catastrophized were less likely than men to report negative mood. Several within-day and across-day gender differences were noted. First, women were much more likely to show a significant increase in pain over the day. Second, men were more likely than women to experience an increase in coping efficacy over the day. Third, men were more likely than women to use emotion-focused coping when their mood was more negative. Finally, men were more likely than women to experience an increase in negative mood and a decrease in positive mood in the morning after an evening of increased pain. Taken together, these findings underscore the importance of obtaining multiple daily assessments when studying gender differences in the pain experience.