Miracle-dz/UniFAR-FTUs huggingface dataset:
Lactate supplementation in severe traumatic brain injured adults by primed constant infusion of sodium L‐lactate

Carbohydrate fuel augmentation following traumatic brain injury may be a viable treatment to improve recovery when cerebral oxidative metabolism of glucose is depressed. We performed a primed constant sodium L‐lactate infusion in 11 moderate to severely brain injured adults. Blood was collected before and periodically during the infusion study. We quantified global cerebral uptake of glucose and lactate and other systemic metabolites associated with energy metabolism. Our hypothesis was that cerebral lactate uptake, as measured by the arteriovenous difference of lactate (AVDlac), would increase in severely injured TBI patients in the neurocritical care unit. Infusion of sodium L‐lactate changed net cerebral lactate release, where the arteriovenous difference of lactate is negative, to net cerebral lactate uptake. Results from a mixed effects model of AVDlac with the fixed effects of infusion time, arterial lactate concentration, arterial glucose concentration and arteriovenous difference of glucose shows that doubling arterial lactate concentration (from .92 to 1.84 mM) results in an increase in AVDlac from −. 078 mM to . 090 mM. We did not detect changes in systemic glucose during the course of the infusion study and observed significant changes in alanine (30% [20 39]), glutamine (34% [24 43]), acetate (87% [60 113]), valine (40% [28 51]), and leucine (24% [16 32]) from baseline levels. Further studies are required to establish the impact of lactate supplementation on cerebral and systemic flux of lactate, on gluconeogenesis, and on the impact on cerebral energetics following injury. © 2017 Wiley Periodicals, Inc.
When is the Phalen's Test of Diagnostic Value: An Electrophysiologic Analysis?

The authors performed nerve conduction studies on 54 hands in patients referred with the clinical diagnosis of carpal tunnel syndrome. The authors studied the motor and sensory latencies of the median and ulnar nerves and compared them with each other. The authors divided the results into hands with no, mild, moderate, or severe carpal tunnel syndrome. The authors correlated these results with the presences or absence of the Phalen's sign. The authors concluded that the Phalen's sign is present mostly in the moderate to severe median nerve entrapment, but still can sometimes be present as a false positivity in normal hands.
Mitochondrial redox signaling: Interaction of mitochondrial reactive oxygen species with other sources of oxidative stress.

SIGNIFICANCE Oxidative stress is a well established hallmark of cardiovascular disease and there is strong evidence for a causal role of reactive oxygen and nitrogen species (RONS) therein. RECENT ADVANCES Improvement of cardiovascular complications by genetic deletion of RONS producing enzymes and overexpression of RONS degrading enzymes proved the involvement of these species in cardiovascular disease at a molecular level. Vice versa, overexpression of RONS producing enzymes as well as deletion of antioxidant enzymes was demonstrated to aggravate cardiovascular complications. CRITICAL ISSUES With the present overview we present and discuss different pathways how mitochondrial RONS interact (crosstalk) with other sources of oxidative stress, namely NADPH oxidases, xanthine oxidase and an uncoupled nitric oxide synthase. The potential mechanisms of how this crosstalk proceeds are discussed in detail. Several examples from the literature are summarized (including hypoxia, angiotensin II mediated vascular dysfunction, cellular starvation, nitrate tolerance, aging, hyperglycemia, β-amyloid stress and others) and the underlying mechanisms are put together to a more general concept of redox-based activation of different sources of RONS via enzyme-specific "redox switches". Mitochondria play a key role in this concept providing redox triggers for oxidative damage in the cardiovascular system but also act as amplifiers to increase the burden of oxidative stress. FUTURE DIRECTIONS Based on these considerations, the characterization of the role of mitochondrial RONS formation in cardiac disease as well as inflammatory processes but also the role of mitochondria as potential therapeutic targets in these pathophysiological states should be addressed in more detail in the future.
Myelin as an inflammatory mediator: Myelin interactions with complement, macrophages, and microglia in spinal cord injury

Spinal cord injury (SCI) triggers chronic intraspinal inflammation consisting of activated resident and infiltrating immune cells (especially microglia/macrophages). The environmental factors contributing to this protracted inflammation are not well understood; however, myelin lipid debris is a hallmark of SCI. Myelin is also a potent macrophage stimulus and target of complement‐mediated clearance and inflammation. The downstream effects of these neuroimmune interactions have the potential to contribute to ongoing pathology or facilitate repair. This depends in large part on whether myelin drives pathological or reparative macrophage activation states, commonly referred to as M1 (proinflammatory) or M2 (alternatively) macrophages, respectively. Here we review the processes by which myelin debris may be cleared through macrophage surface receptors and the complement system, how this differentially influences macrophage and microglial activation states, and how the cellular functions of these myelin macrophages and complement proteins contribute to chronic inflammation and secondary injury after SCI.
Effects of Seizures on Cardiac Function

Various chronic and acute autonomic effects on the heart are seen during epileptic seizures, and some have been implicated in cases of sudden unexpected death in epilepsy (SUDEP). Chronic autonomic dysfunction, either congenital or acquired through seizures or medications, and structural changes of the heart may all predispose patients to SUDEP. Acute autonomic changes during seizures, in particular ictal bradycardia or transient ischemia, may indicate an increased and preventable risk of mortality in patients with epilepsy. However, there is no definite epidemiologic evidence associating any of the chronic or acute cardiac effects of seizures with SUDEP. Cases of SUDEP and near-SUDEP recorded during long-term electroencephalography monitoring offer some insight into the potential mechanisms leading to SUDEP. These cases suggest that autonomic instability ending in cardiorespiratory arrest may be provoked by postictal suppression rather than by ictal activation of the autonomic nervous system. Additional epidemiologic studies on high-risk populations and access to recorded cases of SUDEP may provide more details about the exact sequence of events leading to death and thus guide the development of possible preventive strategies.
Eat-me: autophagy, phagocytosis, and reactive oxygen species signaling.

SIGNIFICANCE Phagocytosis is required for the clearance of dying cells. The subsequent regulation of inflammatory responses by phagocytic cells is mediated by both innate and adaptive immune responses. Autophagy, an evolutionarily ancient process of lysosomal self-digestion of organelles, protein aggregates, apoptotic corpses, and cytosolic pathogens, has only recently become appreciated for its dynamic relationship with phagocytosis, including newly discovered autophagic-phagocytosis "hybrid" processes such as microtubule-associated protein 1 light chain 3-associated phagocytosis (LAP). RECENT ADVANCES Signal transduction by reactive oxygen species (ROS) plays a critical role in the modulation of autophagy, phagocytosis, and LAP, and serves as both a link and an additional layer of regulation between these processes. Furthermore, specific targets for oxidation by ROS molecules have recently begun to become identified in each of these processes, as have "shared" proteins that facilitate the successful completion of both autophagy and phagocytosis. High mobility group box 1 is at the crossroads of autophagy, phagocytosis, and oxidative stress. CRITICAL ISSUES In this review, we discuss the most recent findings that link elements of autophagy and phagocytosis, specifically through redox-dependent signal transduction. These interconnected cellular processes are placed in the context of cell death and immunity in both health and disease. FUTURE DIRECTIONS Given the broad roles that autophagy, phagocytosis, and ROS signaling play in human health, disease, and the maintenance of cellular and organismal homeostatic balance, it is important to delineate intersections between these pathways and uncover targets for potential therapeutic intervention in the setting of autoimmune and inflammatory diseases.
Angiogenesis in the infarcted myocardium.

SIGNIFICANCE Proangiogenic therapy appeared a promising strategy for the treatment of patients with acute myocardial infarction (MI), as de novo formation of microvessels, has the potential to salvage ischemic myocardium at early stages after MI, and is also essential to prevent the transition to heart failure through the control of cardiomyocyte hypertrophy and contractility. RECENT ADVANCES Exciting preclinical studies evaluating proangiogenic therapies for MI have prompted the initiation of numerous clinical trials based on protein or gene transfer delivery of growth factors and administration of stem/progenitor cells, mainly from bone marrow origin. Nonetheless, these clinical trials showed mixed results in patients with acute MI. CRITICAL ISSUES Even though methodological caveats, such as way of delivery for angiogenic growth factors (e.g., protein vs. gene transfer) and stem/progenitor cells or isolation/culture procedure for regenerative cells might partially explain the failure of such trials, it appears that delivery of a single growth factor or cell type does not support angiogenesis sufficiently to promote cardiac repair. FUTURE DIRECTIONS Optimization of proangiogenic therapies might include stimulation of both angiogenesis and vessel maturation and/or the use of additional sources of stem/progenitor cells, such as cardiac progenitor cells. Experimental unraveling of the mechanisms of angiogenesis, vessel maturation, and endothelial cell/cardiomyocyte cross talk in the ischemic heart, analysis of emerging pathways, as well as a better understanding of how cardiovascular risk factors impact endogenous and therapeutically stimulated angiogenesis, would undoubtedly pave the way for the development of novel and hopefully efficient angiogenesis targeting therapeutics for the treatment of acute MI.
Comparison of the efficacy and safety of 1.5 compared with 3.0 g oral slow-release mesalazine (Pentasa) in the maintenance treatment of ulcerative colitis

Objective: To investigate a possible dose–effect relationship with two dosages of oral slow-release mesalazine in patients with quiescent ulcerative colitis. Method: One hundred and sixty-nine patients with ulcerative colitis in remission were treated with either 1.5 or 3.0 g/day mesalazine for 1 year or until relapse into active colitis. Results: Fewer of the 3.0 g dose group relapsed than of the 1.5 g dose group (33 compared with 46%). This difference failed to reach statistical significance (P=0.057). A significant relationship between age and relapse rate was established. No dose-related adverse events were found. Three serious drug-related adverse events were, however, reported. All of the serious adverse reactions resolved after the medication was discontinued. Conclusion: There is a trend for high doses of oral mesalazine to be more effective in prevention of relapse of ulcerative colitis. These higher doses are not associated with a higher incidence of adverse reactions.
Primary health care, partnership and polemic : child and family health nursing support in early parenting

This qualitative research utilised a health services research framework and ethnographic methods to explore, describe and analyse contemporary child and family health (C&FH) nursing practice in an area of New South Wales, and identify the major factors that impact on their ability to effectively support families. The research identified the complexity of current C&FH nursing practice and changes in the philosophy that underpinned this at the policy level that were difficult to adopt. Despite a change in policy direction that advocated a partnership approach, nurses predominantly continue to frame their practice within an "expert" model. The nurses also struggled to deliver new service models while maintaining access for all families. Some explanations for the tensions experienced by the nurses relate to their age and educational preparation within the workforce. Other factors relate to the structures and management systems evident within the health service that employs them. To effectively support new families within the community, health systems must adequately resource services and support C&FH nurses in changing from a paradigm of expert to partner, consistent with primary health care practice.
Epidemiological aspects of appendicitis in a rural setup

Aim: The aim was to study the 3-year epidemiological trend of acute appendicitis in a rural setup. Materials and Methods: This is a retrospective study of patients who were admitted with a diagnosis of appendicitis over a period of 3 years excluding negative appendectomy cases. Totally, 130 cases were diagnosed as an acute appendicitis, on clinical suspicion and investigations during this period. We reviewed and studied these cases regarding incidence of appendicitis in different age groups, sex, according to dietary pattern and seasonal trend. Results: Occurrence of appendicitis was the highest in the 11-20 years age group which constituted 44.6%. Followed by 21-30 years age group, which constituted 36.1%. The incidence of appendicitis between the age group 31 and 40 years constituted 11.5% while between 0 and 10 years age group was 3%. Between 41-50 years and 51-75 years of age group 2.3% each. The youngest case recorded was 8 years of age and the oldest 65 years of age. In this study occurrence of appendicitis in both male and female was almost equal. Nonvegetarians were affected more than vegetarians. The occurrence of appendicitis was peak in the spring and low in the summer. Conclusion: Acute appendicitis should be suspected irrespective of age, sex and socioeconomic status of individual. Age-specific occurrence, sex ratio of appendicitis give the impression that epidemiologic features of acute appendicitis are different with worldwide data. It is difficult to diagnose appendicitis in young children, young women and elderly people. Total leukocyte count, urine microscopy, ultrasonography and computed tomography abdomen should be used as a diagnostic aid in doubtful cases in association with physical findings, but it does not replace the clinical skills of a general surgeon.
A Commentary on Phytoestrogens and Disease

On the most basic level, phytoestrogens can be defined as compounds found in plants that exhibit estrogen-like activity in the human body. Phytoestrogens are considered functional foods because of their diverse physiological effects beyond basic nutritional functions. The 2 primary categories of phytoestrogens found in food are lignans and isoflavones. Lignans are one major class of phytoestrogens and act as antioxidants in the body and are sources of dietary fiber, found in flaxseed, sesame seed, and some cereal grains. Isoflavones may act as phytoestrogens in the body and are found in legumes. There has been a significant amount of scientific research conducted on the health effects of dietary phytoestrogen, resulting in persuasive evidence of both the benefits and dangers of their consumption. Clinical recommendations have shifted significantly over time in response to emerging research findings, which has led to confusion in the general public and inconsistent medical advice from health care providers and health educators. The purpose of this commentary is to clarify the link between dietary consumption of foods with phytoestrogen content and disease to health educators, such that they will be able to advise others with current information.
Wild boars as reservoirs of extended‐spectrum beta‐lactamase (ESBL) producing Escherichia coli of different phylogenetic groups

ESBL‐producing E. coli isolates have been isolated from eight of seventy seven faecal samples (10.4%) of wild boars in Portugal. The ESBL types identified by PCR and sequencing were blaCTX‐M‐1 (6 isolates) and blaCTX‐M‐1 + blaTEM1‐b (2 isolates). Further resistance genes detected included tet (A) or tet (B) (in three tetracycline‐resistant isolates), aad A (in three streptomycin‐resistant isolates), cml A (in one chloramphenicol‐resistant isolate), sul 1 and/or sul 2 and/or sul 3 (in all sulfonamide‐resistant isolates). The intI 1 gene encoding class 1 integrase was detected in all ESBL‐producing E. coli isolates. One isolate also carried the intI 2 gene, encoding class 2 integrase. The ESBL‐producing E. coli isolates could be assigned to phylogenetic groups B1 (3 isolates), B2 (3 isolates) or A (2 isolates). Amino acid change in GyrA protein (Ser83Leu or Asp87Tyr) was detected in three nalidixic acid‐resistant and ciprofloxacin‐susceptible isolates. Two amino acid changes in GyrA (Ser83Leu + Asp87Asn) and one in ParC (Ser80Ile) were identified in two nalidixic acid‐ and ciprofloxacin‐resistant isolates. As evidenced by this study wild boars could be a reservoir of antimicrobial resistance genes. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Interplay between heme oxygenase-1 and miR-378 affects non-small cell lung carcinoma growth, vascularization, and metastasis.

AIMS Heme oxygenase-1 (HO-1, HMOX1) can prevent tumor initiation; while in various tumors, it has been demonstrated to promote growth, angiogenesis, and metastasis. Here, we investigated whether HMOX1 can modulate microRNAs (miRNAs) and regulate human non-small cell lung carcinoma (NSCLC) development. RESULTS Stable HMOX1 overexpression in NSCLC NCI-H292 cells up-regulated tumor-suppressive miRNAs, whereas it significantly diminished the expression of oncomirs and angiomirs. The most potently down-regulated was miR-378. HMOX1 also up-regulated p53, down-regulated angiopoietin-1 (Ang-1) and mucin-5AC (MUC5AC), reduced proliferation, migration, and diminished angiogenic potential. Carbon monoxide was a mediator of HMOX1 effects on proliferation, migration, and miR-378 expression. In contrast, stable miR-378 overexpression decreased HMOX1 and p53; while enhanced expression of MUC5AC, vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), and Ang-1, and consequently increased proliferation, migration, and stimulation of endothelial cells. Adenoviral delivery of HMOX1 reversed miR-378 effect on the proliferation and migration of cancer cells. In vivo, HMOX1 overexpressing tumors were smaller, less vascularized and oxygenated, and less metastatic. Overexpression of miR-378 exerted opposite effects. Accordingly, in patients with NSCLC, HMOX1 expression was lower in metastases to lymph nodes than in primary tumors. INNOVATION AND CONCLUSION In vitro and in vivo data indicate that the interplay between HMOX1 and miR-378 significantly modulates NSCLC progression and angiogenesis, suggesting miR-378 as a new therapeutic target. REBOUND TRACK: This work was rejected during standard peer review and rescued by Rebound Peer Review (Antioxid Redox Signal 16, 293-296, 2012) with the following serving as open reviewers: James F. George, Mahin D. Maines, Justin C. Mason, and Yasufumi Sato.
Cancer phototherapy via selective photoinactivation of respiratory chain oxidase to trigger a fatal superoxide anion burst.

AIMS Here, we develop a novel cancer treatment modality using mitochondria-targeting, high-fluence, low-power laser irradiation (HF-LPLI) in mouse tumor models and explore the mechanism of mitochondrial injury by HF-LPLI. RESULTS We demonstrated that the initial reaction after photon absorption was photosensitization of cytochrome c oxidase (COX), to inhibit enzymatic activity of COX in situ and cause respiratory chain superoxide anion (O2(-•)) burst. We also found that HF-LPLI exerted its main tumor killing effect through mitochondrial O2(-•) burst via electron transport chain (ETC). These phenomena were completely absent in the respiration-deficient cells and COX knockdown cells. With a carefully selected irradiation protocol, HF-LPLI could efficaciously destroy tumors. The inhibition of enzymatic activity of COX and generation of O2(-•) by HF-LPLI in vivo were also detected. INNOVATION It is the first time that the mechanism involved in the interaction between light and its photoacceptor under HF-LPLI treatment is clarified. Our results clearly indicate that HF-LPLI initiates its effects via targeted COX photoinactivation and that the tumor-killing efficacy is dependent of the subsequent mitochondrial O2(-•) burst via ETC. CONCLUSION Based on both in vitro and in vivo results, we conclude that HF-LPLI can selectively photoinactivate respiratory chain oxidase to trigger a fatal mitochondrial O2(-•) burst, producing oxidative damage on cancer cells. This study opens up the possibilities of applications of HF-LPLI as a mitochondria-targeting cancer phototherapy.
The polymorphism of platelet membrane integrin α2β1 (α2807TT) is associated with premature onset of fetal loss

Summary Inherited thrombophilia could increase susceptibility to adverse pregnancy outcomes such as fetal loss. We determined the G1691A mutation of the factorV gene (FVL), the G20210A mutation of the prothrombin gene, the C677T polymorphism of the methylenetetrahydrofolate-reductase (MTHFR) gene, the HPA-1 polymorphism of the β3 subunit of the platelet integrin αIIbβ3 and the C807T polymorphism of the α2 subunit of integrin α2 β1 in 104 women with fetal loss and 277 normal women. In a subgroup analysis of women with recurrent early fetal loss (n=34), the prevalence of the genetic markers did not differ significantly between the women with early fetal loss and the normal women. However, in this subgroup of patients the onset of fetal loss was significantly earlier in women with the α2807TT genotype (7.1 ± 1.9 vs. 8.8 ± 1.5 weeks, p=0.001). No such significant difference was observed in carriers of the other genetic markers. In the subgroup analysis of women with late fetal loss (n=70), only the prevalence of heterozygous FVL was significantly associated with late fetal loss (odds ratio 3.2, p=0.002). There was no significant association of any genetic risk factor with premature fetal loss in the subgroup analysis of women with at least one late miscarriage.This study demonstrates a significant association of the α2 807TT genotype of the platelet membrane integrin α2β1 with premature onset of early fetal loss. It appears that this risk factor does not induce the pathomechanism, but modulates the course of fetal loss. Furthermore, our study confirms the association of FVL with late fetal loss.