-
Anaesthesia Jan 2015Over the last 10 years, the management of major haemorrhage in trauma patients has changed radically. This is mainly due to the recognition that many patients who are... (Review)
Review
Over the last 10 years, the management of major haemorrhage in trauma patients has changed radically. This is mainly due to the recognition that many patients who are bleeding when they come in to the emergency department have an established coagulopathy before the haemodilution effects of fluid resuscitation. This has led to the use of new terminology: acute traumatic coagulopathy, acute coagulopathy of trauma shock or trauma-induced coagulopathy. The recognition of acute traumatic coagulopathy is important, because we now understand that its presence is a prognostic indicator, as it is associated with poor clinical outcome. This has driven a change in clinical management, so that the previous approach of maintaining an adequate circulating volume and oxygen carrying capacity before, as a secondary event, dealing with coagulopathy, has changed to haemostatic resuscitation as early as possible. While there is as yet no universally accepted assay or definition, many experts use prolongation of the prothrombin time to indicate that there is, indeed, a coagulopathy. Hypoxia, acidosis and hypothermia and hormonal, immunological and cytokine production, alongside consumption and blood loss, and the dilutional effects of resuscitation may occur to varying extents depending on the type of tissue damaged, the type and extent of injury, predisposing to, or amplifying, activation of coagulation, platelets, fibrinolysis. These are discussed in detail within the article.
Topics: Acute Disease; Blood Coagulation Disorders; Humans; Resuscitation; Thrombelastography; Wounds and Injuries
PubMed: 25440402
DOI: 10.1111/anae.12914 -
Biomedicines Jun 2023Sodium-glucose cotransporter 2 (SGLT2) serves as a critical glucose transporter that has been reported to be overexpressed in cancer models, followed by increased... (Review)
Review
Sodium-glucose cotransporter 2 (SGLT2) serves as a critical glucose transporter that has been reported to be overexpressed in cancer models, followed by increased glucose uptake in both mice and humans. Inhibition of its expression can robustly thwart tumor development in vitro and in vivo. SGLT2 inhibitors are a comparatively new class of antidiabetic drugs that have demonstrated anticancer effects in several malignancies, including breast, liver, pancreatic, thyroid, prostate, and lung cancers. This review aims to assess the extent of SGLT involvement in different cancer cell lines and discuss the pharmacology, mechanisms of action, and potential applications of SGLT2 inhibitors to reduce tumorigenesis and its progression. Although these agents display a common mechanism of action, they exhibit distinct affinity towards the SGLT type 2 transporter compared to the SGLT type 1 transporter and varying extents of bioavailability and half-lives. While suppression of glucose uptake has been attributed to their primary mode of antidiabetic action, SGLT2 inhibitors have demonstrated several mechanistic ways to combat cancer, including mitochondrial membrane instability, suppression of β-catenin, and PI3K-Akt pathways, increase in cell cycle arrest and apoptosis, and downregulation of oxidative phosphorylation. Growing evidence and ongoing clinical trials suggest a potential benefit of combination therapy using an SGLT2 inhibitor with the standard chemotherapeutic regimen. Nevertheless, further experimental and clinical evidence is required to characterize the expression and role of SGLTs in different cancer types, the activity of different SGLT subtypes, and their role in tumor development and progression.
PubMed: 37509506
DOI: 10.3390/biomedicines11071867 -
Annals of Gastroenterology 2018Crohn's disease (CD) is a lifelong, chronic inflammatory bowel disorder. The small bowel (SB) is involved to varying extents, and the clinical course may vary from an... (Review)
Review
Crohn's disease (CD) is a lifelong, chronic inflammatory bowel disorder. The small bowel (SB) is involved to varying extents, and the clinical course may vary from an inflammatory type to a more complicated one with stricture, fistula, and abscess formation. Esophagogastroduodenoscopy and ileocolonoscopy with biopsies are the conventional endoscopic techniques that usually establish the diagnosis. On the other hand, CD may affect SB segments that cannot be reached through these procedures. Video capsule endoscopy and enteroscopy are additional endoscopic techniques that may allow further SB evaluation in such circumstances. Computed tomographic enterography, magnetic resonance enterography, and ultrasonography are radiologic techniques that serve as a crucial adjunct to endoscopic assessment. They enable the assessment of parts of the bowel that may be difficult to reach with conventional endoscopy; this allows for the detection of active inflammation, penetrating or stricturing disease, and the appreciation of extraintestinal complications. Both endoscopic and radiologic modalities play a role in establishing the diagnosis of CD, as well as determining the disease extent, activity and response to therapy. This review is intended to evaluate these modalities in terms of specificity, sensitivity, potential side-effects, and limiting factors. This should serve as a guide to the clinician for establishing the most appropriate and reliable test within a particular clinical context.
PubMed: 29991884
DOI: 10.20524/aog.2018.0268 -
Pharmaceutics Apr 2022Drug-drug interactions (DDIs) are one of the most frequent causes of adverse drug reactions or loss of treatment efficacy. The risk of DDIs increases with polypharmacy... (Review)
Review
Drug-drug interactions (DDIs) are one of the most frequent causes of adverse drug reactions or loss of treatment efficacy. The risk of DDIs increases with polypharmacy and is therefore of particular concern in individuals likely to present comorbidities (i.e., elderly or obese individuals). These special populations, and the population of pregnant women, are characterized by physiological changes that can impact drug pharmacokinetics and consequently the magnitude of DDIs. This review compiles existing DDI studies in elderly, obese, and pregnant populations that include a control group without the condition of interest. The impact of physiological changes on the magnitude of DDIs was then analyzed by comparing the exposure of a medication in presence and absence of an interacting drug for the special population relative to the control population. Aging does not alter the magnitude of DDIs as the related physiological changes impact the victim and perpetrator drugs to a similar extent, regardless of their elimination pathway. Conversely, the magnitude of DDIs can be changed in obese individuals or pregnant women, as these conditions impact drugs to different extents depending on their metabolic pathway.
PubMed: 35456623
DOI: 10.3390/pharmaceutics14040789 -
Nature Communications Apr 2020Areas of endemism are important in biogeography because they capture facets of biodiversity not represented elsewhere. However, the scales at which they are relevant to...
Areas of endemism are important in biogeography because they capture facets of biodiversity not represented elsewhere. However, the scales at which they are relevant to research and conservation are poorly analysed. Here, we calculate weighted endemism (WE) and phylogenetic endemism (PE) separately for all birds and amphibians across the globe. We show that scale dependence is widespread for both indices and manifests across grain sizes, spatial extents and taxonomic treatments. Variations in taxonomic opinions-whether species are treated by systematic 'lumping' or 'splitting'-can profoundly affect the allocation of WE hotspots. Global patterns of PE can provide insights into complex evolutionary processes but this congruence is lost at the continental to country extents. These findings are explained by environmental heterogeneity at coarser grains, and to a far lesser extent at finer resolutions. Regardless of scale, we find widespread deficits of protection for endemism hotspots. Our study presents a framework for assessing areas for conservation that are robust to assumptions on taxonomy, spatial grain and extent.
Topics: Amphibians; Animals; Biodiversity; Biological Evolution; Birds; Classification; Conservation of Natural Resources; Geography; Linear Models; Phylogeny; Population Dynamics; Species Specificity; Temperature
PubMed: 32355257
DOI: 10.1038/s41467-020-15921-6 -
Behavioural Pharmacology Sep 2015Rat maternal behavior is a complex social behavior. Many clinically used antipsychotic drugs, including the typical drug haloperidol and the atypical drugs clozapine,... (Review)
Review
Rat maternal behavior is a complex social behavior. Many clinically used antipsychotic drugs, including the typical drug haloperidol and the atypical drugs clozapine, risperidone, olanzapine, quetiapine, aripiprazole, and amisulpride, disrupt active maternal responses (e.g. pup retrieval, pup licking, and nest building) to various extents. In this review, I present a summary of recent studies on the behavioral effects and neurobiological mechanisms of antipsychotic action on maternal behavior in rats. I argue that antipsychotic drugs at clinically relevant doses disrupt active maternal responses primarily by suppressing maternal motivation. Atypical drug-induced sedation also contributes to their disruptive effects, especially that on pup nursing. Among many potential receptor mechanisms, dopamine D2 receptors and serotonin 5-HT2A/2C receptors are shown to be critically involved in the mediation of the maternal disruptive effects of antipsychotic drugs, with D2 receptors contributing more to typical antipsychotic-induced disruptions, whereas 5-HT2A/2C receptors contributing more to atypical drug-induced disruptions. The nucleus accumbens shell-related reward circuitry is an essential neural network in the mediation of the behavioral effects of antipsychotic drugs on maternal behavior. This research not only helps understand the extent and mechanisms of impact of antipsychotic medications on human maternal care, but is also important for enhancing our understanding of the neurochemical basis of maternal behavior. It is also valuable for understanding the complete spectrum of therapeutic effects and side-effects of antipsychotic treatment. This knowledge may facilitate the development of effective intervening strategies to help patients coping with such undesirable effects.
Topics: Animals; Antipsychotic Agents; Behavior, Animal; Female; Humans; Maternal Behavior; Rats; Social Behavior
PubMed: 26221833
DOI: 10.1097/FBP.0000000000000168 -
Earth-science Reviews Dec 2022Headwater streams and inland wetlands provide essential functions that support healthy watersheds and downstream waters. However, scientists and aquatic resource...
Headwater streams and inland wetlands provide essential functions that support healthy watersheds and downstream waters. However, scientists and aquatic resource managers lack a comprehensive synthesis of national and state stream and wetland geospatial datasets and emerging technologies that can further improve these data. We conducted a review of existing United States (US) federal and state stream and wetland geospatial datasets, focusing on their spatial extent, permanence classifications, and current limitations. We also examined recent peer-reviewed literature for emerging methods that can potentially improve the estimation, representation, and integration of stream and wetland datasets. We found that federal and state datasets rely heavily on the US Geological Survey's National Hydrography Dataset for stream extent and duration information. Only eleven states (22%) had additional stream extent information and seven states (14%) provided additional duration information. Likewise, federal and state wetland datasets primarily use the US Fish and Wildlife Service's National Wetlands Inventory (NWI) Geospatial Dataset, with only two states using non-NWI datasets. Our synthesis revealed that LiDAR-based technologies hold promise for advancing stream and wetland mapping at limited spatial extents. While machine learning techniques may help to scale-up these LiDAR-derived estimates, challenges related to preprocessing and data workflows remain. High-resolution commercial imagery, supported by public imagery and cloud computing, may further aid characterization of the spatial and temporal dynamics of streams and wetlands, especially using multi-platform and multi-temporal machine learning approaches. Models integrating both stream and wetland dynamics are limited, and field-based efforts must remain a key component in developing improved headwater stream and wetland datasets. Continued financial and partnership support of existing databases is also needed to enhance mapping and inform water resources research and policy decisions.
PubMed: 36970305
DOI: 10.1016/j.earscirev.2022.104230 -
The Journal of Clinical Pediatric... Apr 2021To determine different combinations of marginal ridge shape (MRS) and contact extents in nature of the contact between primary molars and its correlation with the...
OBJECTIVES
To determine different combinations of marginal ridge shape (MRS) and contact extents in nature of the contact between primary molars and its correlation with the presence of carious lesions on radiographic examination of approximal surfaces.
STUDY DESIGN
Retrospective study of 347 clinical records, including photographs and bitewing radiographs, were assessed for intact MRS and caries extent. The carious lesions were scored (0-5, Mejàre scoring system) radiographically and correlated to the intact MRS on clinical photographs, and strength of associations quantified using logistic regression analysis and chi-square tests.
RESULTS
Primary molars, 848(contact extent), and 757(MRS) were analyzed. Combination of straight-convex(35.4%) MRS was more common (p<0.001). None of the approximal surfaces were caries-free for straight and straight MRS with 36.4% of both approximal surfaces exhibiting caries in enamel, and 38.2% of one approximal surface exhibiting caries in dentin. Approximately 90% of the primary molars with substantial contacts exhibited carious lesions in the enamel and 80% with light contacts exhibited carious lesions in the dentin (p<0.001).
CONCLUSION
Six different combinations of intact MRS were identified. Combination of concave-convex shapes exhibited caries extending into dentin. Substantial and/or light contacts between primary molars showed higher caries experience in the approximal surfaces.
Topics: Dental Caries; Dental Caries Susceptibility; Dentin; Humans; Molar; Radiography, Bitewing; Retrospective Studies
PubMed: 33951172
DOI: 10.17796/1053-4625-45.2.5 -
Ecology and Evolution Jul 2020Foundational work has examined adaptive social behavior in animals in relation to the costs and benefits of group living. Within this context, a "group" of animals... (Review)
Review
Foundational work has examined adaptive social behavior in animals in relation to the costs and benefits of group living. Within this context, a "group" of animals represents an organizational unit that is integral to the study of animal ecology and evolution.Definitions of animal group sizes are often subjective with considerable variability within and across species. However, investigations of both the extent and implications of such variability in the estimation of animal group sizes are currently lacking.Selecting ungulates as a case study, we conducted a literature review to assess prevailing practices used to determine group sizes among terrestrial Cetartiodactyla and Perissodactyla. Via this process, we examined group size definitions for 61 species across 171 peer-reviewed studies published between 1962 and 2018.These studies quantified group sizes via estimation of ungulate aggregations in space and time. Spatial estimates included a nearest neighbor distance ranging from 1.4 m to 1,000 m, and this variation was partially explained by a weak positive correlation (|| = .4, < .003) with the body size of the ungulate research subjects. The temporal extent over which group size was estimated was even broader, ranging from three minutes to 24 hr.The considerable variability in ungulate group size estimation that we observed complicates efforts to not only compare and replicate studies but also to evaluate underlying theories of group living. We recommend that researchers: (a) clearly describe the spatiotemporal extents over which they define ungulate group sizes, (b) highlight foundational empirical and ecological rationale for these extents, and (c) seek to align such extents among individual species so as to facilitate cross-system comparisons of ungulate group size dynamics. We believe an integrative approach to ungulate group size estimation would readily facilitate replication, comparability, and evaluation of competing hypotheses examining the tradeoffs of animal sociality.
PubMed: 32760498
DOI: 10.1002/ece3.6463 -
Journal of Clinical Orthopaedics and... May 2021Regeneration potential of Hamstring tendons after harvest assumes significant clinical relevance as its use has become widespread today. Methods which best assess the... (Review)
Review
BACKGROUND
Regeneration potential of Hamstring tendons after harvest assumes significant clinical relevance as its use has become widespread today. Methods which best assess the regeneration, extent and type of regeneration, plus issues related to functional loss are important for the surgeon to know. This review looks at the literature to find answers to the above questions.
PURPOSE
To summarize the evidence in support of hamstring tendon regeneration, and the most appropriate modality for evaluation of regeneration. Additionally, to evaluate the regeneration in terms of complete or partial, extent and its impact on strength deficit and functional outcomes.
METHODS
We did a systematic review of literature through specified search engines and identified 30 of 285 studies to be relevant (19 prospective and 11 retrospective).
RESULTS
Evaluation of above data suggests tissue regeneration at harvest sites does occur (78.9% of semitendinosus and 42.7% of gracilis tendons), but this regeneration is variable. No established definition of regeneration exists; MRI is an adequate tool to identify regeneration, while biopsy is confirmative. USG is a cost-effective screening method and can document distal progress of regenerate. Semitendinosus and gracilis tendons regenerate at different rates and extents, and often fuse together, but there is no evidence to state that one regenerates better than the other. Proximal retraction of the muscle-tendon junction occurs, along with some atrophy, which affects function to a variable extent. Strength deficits may persist, but they may not convert to significant functional deficits.
CONCLUSION
There is variable hamstring regeneration after harvest, with poorly defined definition of "". Some changes in the muscle itself, abnormal distal insertion and absence of regeneration in some are documented, along with strength deficits. Although overall functional deficits have been reported to be minimal, a definite change in the anatomy of the medial hamstrings is a factor to be kept in consideration. More information is needed about the long-term consequences.
PubMed: 33680834
DOI: 10.1016/j.jcot.2021.02.011