Meropenem (Merrem, Meronem) is a broad-spectrum antibacterial agent of the carbapenem family, indicated as empirical therapy prior to the identification of causative organisms, or for disease caused ...by single or multiple susceptible bacteria in both adults and children with a broad range of serious infections. Meropenem is approved for use in complicated intra-abdominal infection (cIAI), complicated skin and skin structure infection (cSSSI) and bacterial meningitis (in paediatric patients aged > or = 3 months) in the US, and in most other countries for nosocomial pneumonia, cIAI, septicaemia, febrile neutropenia, cSSSI, bacterial meningitis, complicated urinary tract infection (UTI), obstetric and gynaecological infections, in cystic fibrosis patients with pulmonary exacerbations, and for the treatment of severe community-acquired pneumonia (CAP). Meropenem has a broad spectrum of in vitro activity against Gram-positive and Gram-negative pathogens, including extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae. It has similar efficacy to comparator antibacterial agents, including: imipenem/cilastatin in cIAI, cSSSI, febrile neutropenia, complicated UTI, obstetric or gynaecological infections and severe CAP; clindamycin plus tobramycin or gentamicin in cIAI or obstetric/gynaecological infections; cefotaxime plus metronidazole in cIAI; cefepime and ceftazidime plus amikacin in septicaemia or febrile neutropenia; and ceftazidime, clarithromycin plus ceftriaxone or amikacin in severe CAP. Meropenem has also shown similar efficacy to cefotaxime in paediatric and adult patients with bacterial meningitis, and to ceftazidime when both agents were administered with or without tobramycin in patients with cystic fibrosis experiencing acute pulmonary exacerbations. Meropenem showed greater efficacy than ceftazidime or piperacillin/tazobactam in febrile neutropenia, and greater efficacy than ceftazidime plus amikacin or tobramycin in patients with nosocomial pneumonia. Meropenem is well tolerated and has the advantage of being suitable for administration as an intravenous bolus or infusion. Its low propensity for inducing seizures means that it is suitable for treating bacterial meningitis and is the only carbapenem approved in this indication. Thus, meropenem continues to be an important option for the empirical treatment of serious bacterial infections in hospitalized patients.
It is imperative that social work programs facilitate discussions pertaining to social justice in the classroom. This gives students the space to navigate barriers to changing policy and oppressive ...systems. However, there are multiple barriers to having critical discussions of challenges in advocating for marginalized and oppressed groups. One way to engage in critical discussion is to use pop culture. The Broadway musical Hamilton provides both musical and dialog content that can be used as a foundation to discuss multiple issues related to social justice, including the roles of rioting and how to be an effective accomplice in fighting injustice. The content of Hamilton can help students explore how to start and maintain their own revolutions and facilitate social change.
The aim of this study was to assess the potential effectiveness of secure attachment priming in outpatients with depressive disorders.
Forty-eight participants engaged in secure attachment priming or ...neutral priming in the laboratory (Time 1), after which they received three daily consecutive primes via text message (Times 2–4), aimed at maintaining the effects from Time 1. A follow-up one day later (Time 5) was also included. Dependent measures were assessed at Times 1, 4 and 5.
Participants in the secure attachment priming condition experienced higher felt-security than the control group at all time-points, indicating that the felt-security benefit was maintained through repeated priming. Secure priming had a greater impact on reducing symptoms of anxiety and depression in comparison to the control prime, though the differences were only significant at Time 4.
The moderate sample size limited our statistical power.
This study was the first experiment using repeated secure attachment priming within a clinical sample. Our findings have potential clinical implications; security priming could be used alongside other treatments to improve outcome. Recommendations for further research are discussed.
•We repeatedly primed attachment security in outpatients with depressive disorders.•We induced felt-security after lab, text-message primes and at 1 day follow-up.•Security-primed patients reported lower depressed and anxious mood after last prime.
Optimization of lead compound 1, through extensive use of structure-based design and a focus on PI3Kδ potency, isoform selectivity, and inhaled PK properties, led to the discovery of clinical ...candidates 2 (GSK2269557) and 3 (GSK2292767) for the treatment of respiratory indications via inhalation. Compounds 2 and 3 are both highly selective for PI3Kδ over the closely related isoforms and are active in a disease relevant brown Norway rat acute OVA model of Th2-driven lung inflammation.
•MSI allows the in situ mapping of molecules directly from tissues.•Brain images showed changes in most lipids classes 3 days after TBI.•Signaling lipids such as increase in ceramides increased as ...early as 1 day after the injury.•More diffuse lipid changes are observed outside of the injured area.•Ceramides, diacylglycerols and cholesteryl esters are good biomarkers for TBI.
Mild traumatic brain injury (TBI) is a common public health issue that may contribute to chronic degenerative disorders. Membrane lipids play a key role in tissue responses to injury, both as cell signals and as components of membrane structure and cell signaling. This study demonstrates the ability of high resolution mass spectrometry imaging (MSI) to assess sequences of responses of lipid species in a rat controlled cortical impact model for concussion.
A matrix of implanted silver nanoparticles was implanted superficially in brain sections for matrix-assisted laser desorption (MALDI) imaging of 50μm diameter microdomains across unfixed cryostat sections of rat brain. Ion-mobility time-of-flight MS was used to analyze and map changes over time in brain lipid composition in a rats after Controlled Cortical Impact (CCI) TBI.
Brain MS images showed changes in sphingolipids near the CCI site, including increased ceramides and decreased sphingomyelins, accompanied by changes in glycerophospholipids and cholesterol derivatives. The kinetics differed for each lipid class; for example ceramides increased as early as 1 day after the injury whereas other lipids changes occurred between 3 and 7 days post injury.
Silver nanoparticles MALDI matrix is a sensitive new tool for revealing previously undetectable cellular injury response and remodeling in neural, glial and vascular structure of the brain.
Lipid biochemical and structural changes after TBI could help highlighting molecules that can be used to determine the severity of such injuries as well as to evaluate the efficacy of potential treatments.
Neural circuit wiring relies on selective synapse formation whereby a presynaptic release apparatus is matched with its cognate postsynaptic machinery. At metabotropic synapses, the molecular ...mechanisms underlying this process are poorly understood. In the mammalian retina, rod photoreceptors form selective contacts with rod ON-bipolar cells by aligning the presynaptic voltage-gated Ca2+ channel directing glutamate release (CaV1.4) with postsynaptic mGluR6 receptors. We show this coordination requires an extracellular protein, α2δ4, which complexes with CaV1.4 and the rod synaptogenic mediator, ELFN1, for trans-synaptic alignment with mGluR6. Eliminating α2δ4 in mice abolishes rod synaptogenesis and synaptic transmission to rod ON-bipolar cells, and disrupts postsynaptic mGluR6 clustering. We further find that in rods, α2δ4 is crucial for organizing synaptic ribbons and setting CaV1.4 voltage sensitivity. In cones, α2δ4 is essential for CaV1.4 function, but is not required for ribbon organization, synaptogenesis, or synaptic transmission. These findings offer insights into retinal pathologies associated with α2δ4 dysfunction.
•α2δ4 is essential for organizing the presynaptic compartment of rod photoreceptors•Elimination of α2δ4 in mice abolishes synaptic contacts of rods, but not cones•α2δ4 forms a macromolecular complex with the rod synaptogenic mediator, ELFN1•α2δ4 sets the abundance and biophysical properties of CaV1.4 channels
The authors identify a critical molecule that plays an essential role for wiring rod photoreceptors into the retinal circuitry. They show that the development of rod presynaptic compartments requires the α2δ4 protein, which recruits the synaptogenic mediator ELFN1 to enable synapse formation.
To examine the perceptions of health professionals regarding the gaps in mental health service provision in Australia and their need for assistance in managing patients with mental illness.
A total ...of 570 health professionals participated in an anonymous online survey in January 2018 that assessed: i) health professionals’ current levels of need for assistance in the management of patients with mental health conditions; and ii) perceived gaps in the mental health care system, and how these can be addressed. Data were analysed using a mixed‐methods approach.
Of those surveyed, 71.2% of health professionals and 77.3% of general practitioners reported that they required assistance in managing their patients with at least one stage of care for at least one type of mental disorder. Qualitative analyses revealed eight major themes in health professionals’ perceptions of gaps in mental health service provision, including affordability and accessibility, the problems with crisis‐driven care and the ‘missing middle’.
Overall, the results of this study provide a concerning insight into the substantial gaps in mental health care within the Australian system.
The results of this study add weight to ongoing calls for reform of and increased investment in the Australian mental health care system.
Rationale
In utero opioid exposure is associated with lower weight and a neonatal opioid withdrawal syndrome (NOWS) at birth, along with longer-term adverse neurodevelopmental outcomes and mood ...disorders. While NOWS is sometimes treated with continued opioids, clinical studies have not addressed if long-term neurobehavioral outcomes are worsened with continued postnatal exposure to opioids. In addition, pre-clinical studies comparing in utero only opioid exposure to continued post-natal opioid administration for withdrawal mitigation are lacking.
Objectives
Here, we sought to understand the impact of continued postnatal opioid exposure on long term behavioral consequences.
Methods
We implemented a rodent perinatal opioid exposure model of oxycodone (Oxy) exposure that included Oxy exposure until birth (short Oxy) and continued postnatal opioid exposure (long Oxy) spanning gestation through birth and lactation.
Results
Short Oxy exposure was associated with a sex-specific increase in weight gain trajectory in adult male mice. Long Oxy exposure caused an increased weight gain trajectory in adult males and alterations in nociceptive processing in females. Importantly, there was no evidence of long-term social behavioral deficits, anxiety, hyperactivity, or memory deficits following short or long Oxy exposure.
Conclusions
Our findings suggest that offspring with prolonged opioid exposure experienced some long-term sequelae compared to pups with opioid cessation at birth. These results highlight the potential long-term consequences of opioid administration as a mitigation strategy for clinical NOWS symptomology and suggest alternatives should be explored.
Electronic mental health (e-mental health) programs for people with an intellectual disability are currently underexplored but may provide a way of mitigating some of the barriers that this ...population faces in accessing appropriate mental health services.
The aim of this study was to examine the feasibility and acceptability of Healthy Mind, an e-mental health program for adults with an intellectual disability developed by the Black Dog Institute, focusing on the design and implementation of the website.
A qualitative research design was used, which involved semistructured interviews and focus groups with people with an intellectual disability, support workers, and allied health professionals. People with an intellectual disability were also observed while using the website. A thematic analysis was used to interrogate the interview transcripts and observational field notes.
Participants found the content of the website informative and appreciated the many ways that the website had been made accessible to users. Participants voiced some differing requirements regarding the way information should be presented and accessed on the website. Acknowledging different types of support needs was identified as an important issue for website dissemination.
The Healthy Mind website promises to provide an excellent tool for people with ID and their supporters. This research has pragmatic implications for the future development and implementation of the program, while contributing to knowledge in the broader fields of e-mental health and inclusive design for people with an intellectual disability.
Brain metastases (BM) are among the most devastating and debilitating complications of melanoma. This retrospective study was conducted to gain a better understanding of patient and disease ...characteristics that have the greatest impact on overall survival in melanoma patients with BM; therapeutic interventions were also assessed. The records of all patients diagnosed with cutaneous melanoma and BM who were seen at Memorial Sloan-Kettering Cancer Center between 1991 and 2001 were retrospectively reviewed. A variety of factors, including age at diagnosis of stage IV disease, gender, race, disease stage at diagnosis, presence of BM at diagnosis of stage IV disease, neurologic symptoms, radiographic findings, number of BM, status and site(s) of extracranial metastasis, and treatment modalities, were analyzed for correlation with overall survival using univariate and multivariate Cox regression models. The records of 355 patients with BM were included in the analysis. On univariate analysis, seven patient and disease characteristics were significantly associated with poorer survival: age > 65 years, extracranial metastases, BM at stage IV diagnosis, neurologic symptoms, four or more BM, hydrocephalus, and leptomeningeal metastases. Of these, age, extracranial metastasis, neurologic symptoms, and number of BM were significantly associated with poorer survival in a multivariate analysis. Multivariate analysis of treatment modalities suggested that patients who had surgery, radiosurgery, or chemotherapy with temozolomide had improved survival outcomes, although this analysis has limitations. The prognostic factors identified in this retrospective study should be considered when making treatment decisions for patients with BM and used as stratification factors in future clinical trials.
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