Treatment for Neonatal Abstinence Syndrome using Nonpharmacological Interventions.

OBJECTIVE: Management of neonatal abstinence syndrome includes nonpharmacological interventions, but their effectiveness may not be verified before implemented. The objective of this study is to evaluate the effectiveness of a type of bassinet in the treatment of infants with neonatal abstinence syndrome. STUDY DESIGN: This is a retrospective observational cohort study. Study setting involved a 24-bed open-bay Level III neonatal intensive care unit located in a metropolitan academic trauma facility. Participant inclusion criteria involved prenatally opioid-exposed infants ≥ 35 weeks with confirmed maternal opioid urine toxicology, required pharmacological treatment for withdrawal symptoms, and were admitted to the neonatal intensive care unit. Three subsets of study participants were analyzed over three different time periods: Group 1 were infants admitted during 2019 without nonpharmacological intervention, Group 2 who were admitted from September 2021 to February 2022 and received nonpharmacological interventions, and Group 3 included those admitted from February 2022 to March 2023 who received the same interventions as Group 2 but were managed in bassinets being used in other local facilities for neonatal abstinence syndrome. RESULTS: Group 3 had significant increases in length of stay compared with Group 1 (p = 0.006) and Group 2 (p = 0.013). Group 3 had a significantly greater length of treatment than Group 1 (p = 0.041) and a significantly higher total mg/kg morphine exposure than Group 1 (p = 0.006). CONCLUSION: Addition of the bassinet for nonpharmacological management of infants with neonatal abstinence syndrome appeared to prolong length of stay, length of treatment, and increase total mg/kg morphine exposure. As a retrospective nonrandomized study, weakness of low certainty of causality is of concern but findings strongly warrant further research before devices such as the bassinet used in this study are adopted for routine neonatal abstinence syndrome care. KEY POINTS: · Special bassinets are promoted to enhance sleep and decrease agitation.. · Such bassinets may assist infants undergoing drug withdrawal.. · Study of the bassinet failed to show benefit to this population..

Light tolerance of extended spectrum ß-lactamase producing Escherichia coli strains after repetitive exposure to far-UVC and blue LED light.

AIMS: The aim of this study was to investigate dual far-UVC (Ultraviolet-C) (222 nm) and blue LED (Light Emitting Diode) (405 nm) light on the inactivation of extended spectrum ß-lactamase-producing Escherichia coli (ESBL-Ec) and to determine if repetitive exposure to long pulses of light resulted in changes to light tolerance, and antibiotic susceptibility. METHODS AND RESULTS: Antimicrobial efficiency of dual and individual light wavelengths and development of light tolerance in E. coli was evaluated through a spread plate method after exposure to light at 25 cm. Dual light exposure for 30 min resulted in a 5-6 log10 CFU mL-1 reduction in two ESBL-Ec and two antibiotic-sensitive control E. coli strains. The overall inhibition achieved by dual light treatment was always greater than the combined reductions (log10 CFU) observed from exposure to individual light wavelengths (combined 222-405 nm), indicating a synergistic relationship between blue LED and far-UVC light when used together. Repetitive long pulses of dual and individual far-UVC light exposure resulted in light tolerance in two ESBL-Ec strains but not the antibiotic-sensitive E. coli strains. Subsequent passages of repetitive light-treated ESBL-Ec strains continued to exhibit light tolerance. Antibiotic susceptibility was determined through a standard disk diffusion method. No changes were observed in the antibiotic susceptibility profiles for any of the four strains after exposure to either dual or individual wavelengths. CONCLUSIONS: Dual light exposure was effective in the disinfection of ESBL-Ec in solution; however, antibiotic-resistant E. coli were able to develop light tolerance after repetitive exposure to light.

Comparative genomics of Clostridium species associated with vacuum-packed meat spoilage.

Bacterial species belonging to the genus Clostridium have been recognized as causative agents of blown pack spoilage (BPS) in vacuum packed meat products. Whole-genome sequencing of six New Zealand psychrotolerant clostridia isolates derived from three meat production animal types and their environments was performed to examine their roles in BPS. Comparative genome analyses have provided insight into the genomic diversity and physiology of these bacteria and divides clostridia into two separate species clusters. BPS-associated clostridia encode a large and diverse spectrum of degradative carbohydrate-active enzymes (CAZymes) that enable them to utilize the intramuscular carbohydrate stores and facilitate sporulation. In total, 516 glycoside hydrolases (GHs), 93 carbohydrate esterases (CEs), 21 polysaccharide lyases (PLs), 434 glycosyl transferases (GTs) and 211 carbohydrate-binding protein modules (CBM) with predicted activities involved in the breakdown and transport of carbohydrates were identified. Clostridia genomes have different patterns of CAZyme families and vary greatly in the number of genes within each CAZy category, suggesting some level of functional redundancy. These results suggest that BPS-associated clostridia occupy similar environmental niches but apply different carbohydrate metabolism strategies to be able to co-exist and cause meat spoilage.

Genetic Factors Affect the Survival and Behaviors of Selected Bacteria during Antimicrobial Blue Light Treatment.

Antimicrobial resistance is a global, mounting and dynamic issue that poses an immediate threat to human, animal, and environmental health. Among the alternative antimicrobial treatments proposed to reduce the external use of antibiotics is electromagnetic radiation, such as blue light. The prevailing mechanistic model is that blue light can be absorbed by endogenous porphyrins within the bacterial cell, inducing the production of reactive oxygen species, which subsequently inflict oxidative damages upon different cellular components. Nevertheless, it is unclear whether other mechanisms are involved, particularly those that can affect the efficacy of antimicrobial blue light treatments. In this review, we summarize evidence of inherent factors that may confer protection to a selected group of bacteria against blue light-induced oxidative damages or modulate the physiological characteristics of the treated bacteria, such as virulence and motility. These include descriptions of three major photoreceptors in bacteria, chemoreceptors, SOS-dependent DNA repair and non-SOS protective mechanisms. Future directions are also provided to assist with research efforts to increase the efficacy of antimicrobial blue light and to minimize the development of blue light-tolerant phenotypes.

Application of Human Factors Methods to Ensure Appropriate Infant Identification and Abduction Prevention Within the Hospital Setting.

Infant misidentification and abduction are recognized as "never" events for hospitals in the United States. As near misses are often unreported, root cause analysis of observed near misses may fail to uncover important contributors. We utilized failure mode and effects analysis to proactively identify and eliminate or reduce the risk of infant misidentification or abduction. We prioritized action plans based upon the highest risk priority failures and developed steps to eliminate the gaps in the infant identification process and the security within the Center for Women & Infants. The analysis identified 28 failure modes. Team discussion of the failure modes also yielded several collateral benefits of improvements in the unit climate. We present and discuss the action plans that were undertaken by the hospital to increase patient safety and reduce the risk of infant misidentification and abduction.

New Insights into the Reliability of Automatic Dynamic Methods for Oral Bioaccessibility Testing: A Case Study for BGS102 soil.

Dynamic flow-through extraction is attracting a great deal of attention for real-time monitoring of the bioaccessible fraction of metal species in environmental solid substrates compared to its batchwise manual counterparts. There is however a lack of studies on the harmonization and validation of in vitro dynamic methods for physiologically based extraction tests against in vivo bioavailability methods. This work is aimed at evaluating the reliability of dynamic flow-through extraction methods for estimation of oral bioaccessible fractions of Cu, Zn, Pb, Ni, Cr, and As under worst-case extraction conditions in the gastric compartment based on the BGS102 guidance soil using the in vivo validated Unified BARGE (UBM) test, commonly performed under batchwise mode. Good overall agreement between batch and dynamic UBM results was obtained for the tested elements, except for Pb, as a consequence of the slow leaching kinetics identified with the dynamic method and the contribution of readsorption phenomena in the course of the gastric digestion. Metal-soil phase associations and their relationship with gastric bioaccessible fractions were elucidated using the so-called Chemometric Identification of Substrates and Element Distributions method based on sequential extraction with a variety of chemicals of increasing acidity as applied to both static and dynamic bioaccessibility data.

Measuring the solid-phase fractionation of lead in urban and rural soils using a combination of geochemical survey data and chemical extractions.

The study used 276 urban soils and 447 rural soils collected from in and around the UK town of Northampton and focussed on the fractionation of Pb. The Pb fractionation obtained from total element data was compared to the fractionation of Pb in a subset of 10 urban soils obtained using a sequential extraction method. The fractionation of the Pb from the total element data and from the sequential extractions was estimated using a self-modelling mixture resolution statistical model. The bioaccessibility of Pb in a subset of 50 of the urban soils, as measured using the unified BARGE method, was shown to be quantitatively linked with Pb fractionation from both the total element and the sequential extraction data. Three intrinsic soil components from the regional total element data model and one physico-chemical component from the sequential extraction data model were identified as the sources of bioaccessible Pb. The source of bioaccessible Pb in both rural and urban soils was tentatively identified as a fine-grained pyromorphite mineral.

Multiple genome sequences of lactic acid bacteria, Carnobacterium divergens and Carnobacterium maltaromaticum strains, isolated from vacuum-packaged lamb meat.

Here, we report the whole-genome sequences of 11 Carnobacterium divergens and 2 Carnobacterium maltaromaticum bacteria isolated from vacuum-packed chill-stored lamb meat in New Zealand. Examination of these lactic acid bacteria (LAB) genomes will improve our knowledge of their potential antimicrobial activities and spoilage mechanisms of importance to the meat industry.

Regulated clearance of histone deacetylase 3 protects independent formation of nuclear receptor corepressor complexes.

An important step in transcriptional regulation by corepressors N-CoR and SMRT is the formation of a stable and active histone deacetylase 3 (HDAC3)-containing complex. Although N-CoR and SMRT are thought to bind HDAC3 competitively, multiple studies have shown that they do not interfere with the function of each other. How this functional independence is sustained under the competitive interaction is unclear. Here, we show that the coupling of corepressor expression with HDAC3 degradation allows cells to maintain a stable level of uncomplexed HDAC3, thereby preventing mutual interference in the assembly of N-CoR and SMRT complexes. The free uncomplexed HDAC3 is highly unstable. Unexpectedly, the rate of HDAC3 degradation is inversely correlated with the expression level of corepressors. Our results indicate that reducing one corepressor accelerates HDAC3 clearance, thus preventing an increase in complex formation between HDAC3 and the other corepressor. In addition, this study also indicates that the formation of a stable and active HDAC3-corepressor complex is a stepwise process in which the C terminus of HDAC3 plays a critical role at late steps of the assembly process.

Mechanisms of estrogen receptor antagonism toward p53 and its implications in breast cancer therapeutic response and stem cell regulation.

Estrogen receptor alpha (ERalpha) plays an important role in the onset and progression of breast cancer, whereas p53 functions as a major tumor suppressor. We previously reported that ERalpha binds to p53, resulting in inhibition of transcriptional regulation by p53. Here, we report on the molecular mechanisms by which ERalpha suppresses p53's transactivation function. Sequential ChIP assays demonstrated that ERalpha represses p53-mediated transcriptional activation in human breast cancer cells by recruiting nuclear receptor corepressors (NCoR and SMRT) and histone deacetylase 1 (HDAC1). RNAi-mediated down-regulation of NCoR resulted in increased endogenous expression of the cyclin-dependent kinase (CDK)-inhibitor p21(Waf1/Cip1) (CDKN1A) gene, a prototypic transcriptional target of p53. While 17beta-estradiol (E2) enhanced ERalpha binding to p53 and inhibited p21 transcription, antiestrogens decreased ERalpha recruitment and induced transcription. The effects of estrogen and antiestrogens on p21 transcription were diametrically opposite to their known effects on the conventional ERE-containing ERalpha target gene, pS2/TFF1. These results suggest that ERalpha uses dual strategies to promote abnormal cellular proliferation: enhancing the transcription of ERE-containing proproliferative genes and repressing the transcription of p53-responsive antiproliferative genes. Importantly, ERalpha binds to p53 and inhibits transcriptional activation by p53 in stem/progenitor cell-containing murine mammospheres, suggesting a potential role for the ER-p53 interaction in mammary tissue homeostasis and cancer formation. Furthermore, retrospective studies analyzing response to tamoxifen therapy in a subset of patients with ER-positive breast cancer expressing either wild-type or mutant p53 suggest that the presence of wild-type p53 is an important determinant of positive therapeutic response.

Genome collection of Shewanella spp. isolated from spoiled lamb.

The diversity of the genus Shewanella and their roles across a variety of ecological niches is largely unknown highlighting the phylogenetic diversity of these bacteria. From a food safety perspective, Shewanella species have been recognized as causative spoilage agents of vacuum-packed meat products. However, the genetic basis and metabolic pathways for the spoilage mechanism are yet to be explored due to the unavailability of relevant Shewanella strains and genomic resources. In this study, whole-genome sequencing of 32 Shewanella strains isolated from vacuum-packaged refrigerated spoiled lamb was performed to examine their roles in meat spoilage. Phylogenomic reconstruction revealed their genomic diversity with 28 Shewanella spp. strains belonging to the same putative novel species, two Shewanella glacialipiscicola strains (SM77 and SM91), Shewanella xiamenensis NZRM825, and Shewanella putrefaciens DSM 50426 (ATCC 8072) isolated from butter. Genome-wide clustering of orthologous gene families revealed functional groupings within the major Shewanella cluster but also considerable plasticity across the different species. Pan-genome analysis revealed conserved occurrence of spoilage genes associated with sulfur and putrescine metabolism, while the complete set of trimethylamine metabolism genes was observed in only Shewanella sp. SM74, S. glacialipiscicola SM77 and SM91 strains. Through comparative genomics, some variations were also identified pertaining to genes associated with adaptation to environmental cues such as temperature, osmotic, salt, oxidative, antimicrobial peptide, and drug resistance stresses. Here we provide a reference collection of draft Shewanella genomes for subsequent species descriptions and future investigations into the molecular spoilage mechanisms for further applications in the meat industry.

Occurrence of genes encoding spore germination in Clostridium species that cause meat spoilage.

Members of the genus Clostridium are frequently associated with meat spoilage. The ability for low numbers of spores of certain Clostridium species to germinate in cold-stored vacuum-packed meat can result in blown pack spoilage. However, little is known about the germination process of these clostridia, despite this characteristic being important for their ability to cause spoilage. This study sought to determine the genomic conditions for germination of 37 representative Clostridium strains from seven species (C. estertheticum, C. tagluense, C. frigoris, C. gasigenes, C. putrefaciens, C. aligidicarnis and C. frigdicarnis) by comparison with previously characterized germination genes from C. perfringens, C. sporogenes and C. botulinum. All the genomes analysed contained at least one gerX operon. Seven different gerX operon configuration types were identified across genomes from C. estertheticum, C. tagluense and C. gasigenes. Differences arose between the C. gasigenes genomes and those belonging to C. tagluense/C. estertheticum in the number and type of genes coding for cortex lytic enzymes, suggesting the germination pathway of C. gasigenes is different. However, the core components of the germination pathway were conserved in all the Clostridium genomes analysed, suggesting that these species undergo the same major steps as Bacillus subtilis for germination to occur.

Preclinical and randomized clinical evaluation of the p38α kinase inhibitor neflamapimod for basal forebrain cholinergic degeneration.

The endosome-associated GTPase Rab5 is a central player in the molecular mechanisms leading to degeneration of basal forebrain cholinergic neurons (BFCN), a long-standing target for drug development. As p38α is a Rab5 activator, we hypothesized that inhibition of this kinase holds potential as an approach to treat diseases associated with BFCN loss. Herein, we report that neflamapimod (oral small molecule p38α inhibitor) reduces Rab5 activity, reverses endosomal pathology, and restores the numbers and morphology of BFCNs in a mouse model that develops BFCN degeneration. We also report on the results of an exploratory (hypothesis-generating) phase 2a randomized double-blind 16-week placebo-controlled clinical trial (Clinical trial registration: NCT04001517/EudraCT #2019-001566-15) of neflamapimod in mild-to-moderate dementia with Lewy bodies (DLB), a disease in which BFCN degeneration is an important driver of disease expression. A total of 91 participants, all receiving background cholinesterase inhibitor therapy, were randomized 1:1 between neflamapimod 40 mg or matching placebo capsules (taken orally twice-daily if weight <80 kg or thrice-daily if weight >80 kg). Neflamapimod does not show an effect in the clinical study on the primary endpoint, a cognitive-test battery. On two secondary endpoints, a measure of functional mobility and a dementia rating-scale, improvements were seen that are consistent with an effect on BFCN function. Neflamapimod treatment is well-tolerated with no study drug associated treatment discontinuations. The combined preclinical and clinical observations inform on the validity of the Rab5-based pathogenic model of cholinergic degeneration and provide a foundation for confirmatory (hypothesis-testing) clinical evaluation of neflamapimod in DLB.

Virucidal Efficacy of Blue LED and Far-UVC Light Disinfection against Feline Infectious Peritonitis Virus as a Model for SARS-CoV-2.

Transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs through respiratory droplets passed directly from person to person or indirectly through fomites, such as common use surfaces or objects. The aim of this study was to determine the virucidal efficacy of blue LED (405 nm) and far-UVC (222 nm) light in comparison to standard UVC (254 nm) irradiation for the inactivation of feline infectious peritonitis virus (FIPV) on different matrices as a model for SARS-CoV-2. Wet or dried FIPV on stainless steel, plastic, or paper discs, in the presence or absence of artificial saliva, were exposed to various wavelengths of light for different time periods (1-90 min). Dual activity of blue LED and far-UVC lights were virucidal for most wet and dried FIPV within 4 to 16 min on all matrices. Individual action of blue LED and far-UVC lights were virucidal for wet FIPV but required longer irradiation times (8-90 min) to reach a 4-log reduction. In comparison, LED (265 nm) and germicidal UVC (254 nm) were virucidal on almost all matrices for both wet and dried FIPV within 1 min exposure. UVC was more effective for the disinfection of surfaces as compared to blue LED and far-UVC individually or together. However, dual action of blue LED and far-UVC was virucidal. This combination of lights could be used as a safer alternative to traditional UVC.

Development of Bacterial Spore Pouches as a Tool to Evaluate the Sterilization Efficiency-A Case Study with Microwave Sterilization Using Clostridium sporogenes and Geobacillus stearothermophilus.

In this study, novel spore pouches were developed using mashed potato as a food model inoculated with either Geobacillus stearothermophilus or Clostridium sporogenes spores. These spore pouches were used to evaluate the sterilization efficiency of Coaxially induced microwave pasteurization and sterilization (CiMPAS) as a case study. CiMPAS technology combines microwave energy (915 MHz) along with hot water immersion to sterilize food in polymeric packages. The spore pouches were placed at pre-determined specific locations, especially cold spots in each food tray before being processed using two regimes (R-121 and R-65), which consisted of 121 °C and 65 °C at 12 and 22 kW, respectively, followed by recovery and enumeration of the surviving spores. To identify cold spots or the location for inoculation, mashed potato was spiked with Maillard precursors and processed through CiMPAS, followed by measurement of lightness values (*L-values). Inactivation equivalent to of 1-2 Log CFU/g and >6 Log CFU/g for Geobacillus stearothermophilus and Clostridium sporogenes spores, respectively was obtained on the cold spots using R-121, which comprised of a total processing time of 64.2 min. Whereas, inactivation of <1 and 2-3 Log CFU/g for G. stearothermophilus and C. sporogenes spores, respectively on the cold spots was obtained using R-65 (total processing time of 68.3 min), whereas inactivation of 1-3 Log CFU/g of C. sporogenes spores was obtained on the sides of the tray. The results were reproducible across three processing replicates for each regime and inactivation at the specific locations were clearly distinguishable. The study indicated a strong potential to use spore pouches as a tool for validation studies of microwave-induced sterilization.

Do soil amendments used to improve agricultural productivity have consequences for soils contaminated with heavy metals?

This study presents an analysis of the effects of manure and lime commonly used to improve agricultural productivity and evaluates the potential for such soil amendments to mobilise/immobilise metal fractions in soils contaminated from nearby mine tailings in the Zambian Copperbelt. Lime and manure were applied at the onset of the study, and their effects were studied over two planting seasons, i.e. 2016-17 and 2017-18. Operationally defined plant-available Cd, Cu, Ni, Pb and Zn in the soil, were determined by extraction with DTPA-TEA (diethylenetriaminepentaacetic acid-triethanolamine) and 0.01 M Ca(NO3)2, before, and after, applying the amendments. In unamended soils, Cd was the most available and Ni the least. Lime application decreased extractable Cd, Cu, Ni, Pb and Zn. The response to lime was greater in soils with an initially acidic pH than in those with approximately neutral pH values. Manure increased DTPA extractable Zn, but decreased DTPA and Ca(NO3)2 extractable Cd, Cu and Pb. Combined lime and manure amendment exhibited a greater reduction in DTPA extractable Cd, Ni, Pb, Zn, as well as for Ca(NO3)2 extractable Cd compared to separate applications of lime and manure. The amendments had a significant residual effect on most of the soil fractions between season 1 and 2. The results obtained in this study showed that soil amendment with minimal lime and manure whilst benefiting agricultural productivity, may significantly reduce the mobility or plant availability of metals from contaminated agricultural soils. This is important in contaminated, typical tropical soils used for crop production by resource poor communities affected by mining or other industrial activities.

Spatial geochemistry influences the home range of elephants.

The unique geochemistry surrounding the Palabora Mining Company (PMC) land may act as a micronutrient hotspot, attracting elephants to the area. The PMC produces refined copper and extracts phosphates and other minerals. Understanding the spatial influence of geochemistry on the home range size of African elephants is important for elephant population management and conservation. The home ranges of collared elephants surrounding the PMC were significantly smaller (P = 0.001) than conspecifics in surrounding reserves, suggesting that their resource needs were met within these smaller areas. Environmental samples (soil, water and plants) were analysed from the mine area and along six transects radiating from the mine centre. Tail hair and faecal samples from elephants at the PMC, and conspecifics within the surrounding area were analysed. All samples were analysed for minerals essential to health and potentially toxic elements (PTEs; As, Ca, Cd, Cu, Fe, K, Mg, Mn, Na, P, Pb, Se, U, V and Zn). Results show that the geochemistry at the PMC is different compared to surrounding areas, with significant elevations seen in all analysed minerals and PTEs in soil closer to the mine, thereby drawing the elephants to the area. Additionally significant elevations were seen in elements analysed in water and vegetation samples. Elephant tail hair from elephants at the mine was significantly greater in Cd, whilst Mg, P, Cu, As, Cd, Pb and U concentrations were significantly greater in elephant faecal samples at the mine compared to the non-mine samples. When micronutrient hotspots overlap with human activity (such as mining), this can lead to poor human-elephant coexistence and thus conflict. When managing elephant populations, the influence of mineral provision on elephant movement must be considered. Such detailed resource information can inform conservation efforts for coordinated programmes (UN SDGs 15 and 17) and underpin sustainable economic activity (UN SDG 8, 11 and 12).

Source apportionment of micronutrients in the diets of Kilimanjaro,Tanzania and Counties of Western Kenya.

Soil, water and food supply composition data have been combined to primarily estimate micronutrient intakes and subsequent risk of deficiencies in each of the regions studied by generating new data to supplement and update existing food balance sheets. These data capture environmental influences, such as soil chemistry and the drinking water sources to provide spatially resolved crop and drinking water composition data, where combined information is currently limited, to better inform intervention strategies to target micronutrient deficiencies. Approximately 1500 crop samples were analysed, representing 86 food items across 50 sites in Tanzania in 2013 and >230 sites in Western Kenya between 2014 and 2018. Samples were analysed by ICP-MS for 58 elements, with this paper focussing on calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), selenium (Se), iodine (I), zinc (Zn) and molybdenum (Mo). In general, micronutrient supply from food groups was higher from Kilimanjaro,Tanzania than Counties in Western Kenya, albeit from a smaller sample. For both countries leafy vegetable and vegetable food groups consistently contained higher median micronutrient concentrations compared to other plant based food groups. Overall, calculated deficiency rates were <1% for Cu and Mo and close to or >90% for Ca, Zn and I in both countries. For Mg, a slightly lower risk of deficiency was calculated for Tanzania at 0 to 1% across simplified soil classifications and for female/males, compared to 3 to 20% for Kenya. A significant difference was observed for Se, where a 3 to 28% risk of deficiency was calculated for Tanzania compared to 93 to 100% in Kenya. Overall, 11 soil predictor variables, including pH and organic matter accounted for a small proportion of the variance in the elemental concentration of food. Tanzanian drinking water presented several opportunities for delivering greater than 10% of the estimated average requirement (EAR) for micronutrients. For example, 1 to 56% of the EAR for I and up to 10% for Se or 37% for Zn could be contributed via drinking water.

Industry-funded breast cancer trials show more positive results.

New research on pharmaceutical-industry sponsorship of clinical research in breast cancer shows that treatment trials funded by the industry are more likely to show positive results than studies sponsored by other sources. There are also major differences in trial design when drug companies are the funders.

Glutamate Neurotransmission in Rodent Models of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of death and disability in people younger than 45 and is a significant public health concern. In addition to primary mechanical damage to cells and tissue, TBI involves additional molecular mechanisms of injury, termed secondary injury, that continue to evolve over hours, days, weeks, and beyond. The trajectory of recovery after TBI is highly unpredictable and in many cases results in chronic cognitive and behavioral changes. Acutely after TBI, there is an unregulated release of glutamate that cannot be buffered or cleared effectively, resulting in damaging levels of glutamate in the extracellular space. This initial loss of glutamate homeostasis may initiate additional changes in glutamate regulation. The excitatory amino acid transporters (EAATs) are expressed on both neurons and glia and are the principal mechanism for maintaining extracellular glutamate levels. Diffusion of glutamate outside the synapse due to impaired uptake may lead to increased extrasynaptic glutamate signaling, secondary injury through activation of cell death pathways, and loss of fidelity and specificity of synaptic transmission. Coordination of glutamate release and uptake is critical to regulating synaptic strength, long-term potentiation and depression, and cognitive processes. In this review, we will discuss dysregulation of extracellular glutamate and glutamate uptake in the acute stage of TBI and how failure to resolve acute disruptions in glutamate homeostatic mechanisms may play a causal role in chronic cognitive symptoms after TBI.