1,864 research outputs found
Essential trauma management training: addressing service delivery needs in active conflict zones in eastern Myanmar
<p>Abstract</p> <p>Introduction</p> <p>Access to governmental and international nongovernmental sources of health care within eastern Myanmar's conflict regions is virtually nonexistent. Historically, under these circumstances effective care for the victims of trauma, particularly landmine injuries, has been severely deficient. Recognizing this, community-based organizations (CBOs) providing health care in these regions sought to scale up the capacity of indigenous health workers to provide trauma care.</p> <p>Case description</p> <p>The Trauma Management Program (TMP) was developed by CBOs in cooperation with a United States-based health care NGO. The goal of the TMP is to improve the capacity of local health workers to deliver effective trauma care. From 2000 to the present, international and local health care educators have conducted regular workshops to train indigenous health workers in the management of landmine injuries, penetrating and blunt trauma, shock, wound and infection care, and orthopedics. Health workers have been regularly resupplied with the surgical instruments, supplies and medications needed to provide the care learnt through TMP training workshops.</p> <p>Discussion and Evaluation</p> <p>Since 2000, approximately 300 health workers have received training through the TMP, as part of a CBO-run health system providing care for approximately 250 000 internally displaced persons (IDPs) and war-affected residents. Based on interviews with health workers, trauma registry inputs and photo/video documentation, protocols and procedures taught during training workshops have been implemented effectively in the field. Between June 2005 and June 2007, more than 200 patients were recorded in the trauma patient registry. The majority were victims of weapons-related trauma.</p> <p>Conclusion</p> <p>This report illustrates a method to increase the capacity of indigenous health workers to manage traumatic injuries. These health workers are able to provide trauma care for otherwise inaccessible populations in remote and conflicted regions. The principles learnt during the implementation of the TMP might be applied in similar settings.</p
Access To Essential Maternal Health Interventions and Human Rights Violations among Vulnerable Communities in Eastern Burma
Luke Mullany and colleagues examine access to essential maternal health interventions and human rights violations within vulnerable communities in eastern Burma
Crystallographic snapshots of sulfur insertion by lipoyl synthase
Lipoyl synthase (LipA) catalyzes the insertion of two sulfur atoms at the unactivated C6 and C8 positions of a protein-bound octanoyl chain to produce the lipoyl cofactor. To activate its substrate for sulfur insertion, LipA uses a [4Fe-4S] cluster and S-adenosylmethionine (AdoMet) radical chemistry; the remainder of the reaction mechanism, especially the source of the sulfur, has been less clear. One controversial proposal involves the removal of sulfur from a second (auxiliary) [4Fe-4S] cluster on the enzyme, resulting in destruction of the cluster during each round of catalysis. Here, we present two high-resolution crystal structures of LipA from Mycobacterium tuberculosis: one in its resting state and one at an intermediate state during turnover. In the resting state, an auxiliary [4Fe-4S] cluster has an unusual serine ligation to one of the irons. After reaction with an octanoyllysine-containing 8-mer peptide substrate and 1 eq AdoMet, conditions that allow for the first sulfur insertion but not the second insertion, the serine ligand dissociates from the cluster, the iron ion is lost, and a sulfur atom that is still part of the cluster becomes covalently attached to C6 of the octanoyl substrate. This intermediate structure provides a clear picture of iron-sulfur cluster destruction in action, supporting the role of the auxiliary cluster as the sulfur source in the LipA reaction and describing a radical strategy for sulfur incorporation into completely unactivated substrates. Keywords: iron–sulfur cluster; radical SAM enzyme; lipoic acidNational Science Foundation (U.S.) (Grant MCB-0543833
Attention Drives Synchronization of Alpha and Beta Rhythms between Right Inferior Frontal and Primary Sensory Neocortex
The right inferior frontal cortex (rIFC) is specifically associated with attentional control via the inhibition of behaviorally irrelevant stimuli and motor responses. Similarly, recent evidence has shown that alpha (7–14 Hz) and beta (15–29 Hz) oscillations in primary sensory neocortical areas are enhanced in the representation of non-attended stimuli, leading to the hypothesis that allocation of these rhythms plays an active role in optimal inattention. Here, we tested the hypothesis that selective synchronization between rIFC and primary sensory neocortex occurs in these frequency bands during inattention. We used magnetoencephalography to investigate phase synchrony between primary somatosensory (SI) and rIFC regions during a cued-attention tactile detection task that required suppression of response to uncertain distractor stimuli. Attentional modulation of synchrony between SI and rIFC was found in both the alpha and beta frequency bands. This synchrony manifested as an increase in the alpha-band early after cue between non-attended SI representations and rIFC, and as a subsequent increase in beta-band synchrony closer to stimulus processing. Differences in phase synchrony were not found in several proximal control regions. These results are the first to reveal distinct interactions between primary sensory cortex and rIFC in humans and suggest that synchrony between rIFC and primary sensory representations plays a role in the inhibition of irrelevant sensory stimuli and motor responses.National Institutes of Health (U.S.) (Grant P41RR14075)National Institutes of Health (U.S.) (Grant K25MH072941)National Institutes of Health (U.S.) (Grant K01AT003459)National Institutes of Health (U.S.) (Grant K24AT004095)National Institutes of Health (U.S.) (Grant RO1-NS045130-01)National Institutes of Health (U.S.) (Grant T32GM007484)National Science Foundation (U.S.) (Grant 0316933)National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant DGE-1147470
Concurrent whole brain radiotherapy and bortezomib for brain metastasis
Abstract
Background
Survival of patients with brain metastasis particularly from historically more radio-resistant malignancies remains dismal. A phase I study of concurrent bortezomib and whole brain radiotherapy was conducted to determine the tolerance and safety of this approach in patients with previously untreated brain metastasis.
Methods
A phase I dose escalation study evaluated the safety of bortezomib (0.9, 1.1, 1.3, 1.5, and 1.7 mg/m2) given on days 1, 4, 8 and 11 of whole brain radiotherapy. Patients with confirmed brain metastasis were recruited for participation. The primary endpoint was the dose-limiting toxicity, defined as any ≥ grade 3 non-hematologic toxicity or grade ≥ 4 hematologic toxicity from the start of treatment to one month post irradiation. Time-to-Event Continual Reassessment Method (TITE-CRM) was used to determine dose escalation. A companion study of brain diffusion tensor imaging MRI was conducted on a subset of patients to assess changes in the brain that might predict delayed cognitive effects.
Results
Twenty-four patients were recruited and completed the planned therapy. Patients with melanoma accounted for 83% of all participants. The bortezomib dose was escalated as planned to the highest dose of 1.7 mg/m2/dose. No grade 4/5 toxicities related to treatment were observed. Two patients had grade 3 dose-limiting toxicities (hyponatremia and encephalopathy). A partial or minor response was observed in 38% of patients. Bortezomib showed greater demyelination in hippocampus-associated white matter structures on MRI one month after radiotherapy compared to patients not treated with bortezomib (increase in radial diffusivity +16.8% versus 4.8%; p = 0.0023).
Conclusions
Concurrent bortezomib and whole brain irradiation for brain metastasis is well tolerated at one month follow-up, but MRI changes that have been shown to predict delayed cognitive function can be detected within one month of treatment.http://deepblue.lib.umich.edu/bitstream/2027.42/112849/1/13014_2013_Article_928.pd
A Large Sample Study of Red Giants in the Globular Cluster Omega Centauri (NGC 5139)
We present abundances of several light, alpha, Fe-peak, and neutron-capture
elements for 66 red giant branch (RGB) stars in the Galactic globular cluster
Omega Centauri. Our observations lie in the range 12.0<V<13.5 and focus on the
intermediate and metal-rich RGBs. We find that there are at least four peaks in
the metallicity distribution function at [Fe/H]=-1.75, -1.45, -1.05, and -0.75,
which correspond to about 55%, 30%, 10%, and 5% of our sample, respectively.
Additionally, the most metal-rich stars are the most centrally located. Na and
Al are correlated despite exhibiting star-to-star dispersions of more than a
factor of 10, but the distribution of those elements appears to be metallicity
dependent and are divided at [Fe/H]~-1.2. About 40-50% of stars with
[Fe/H]<-1.2 have Na and Al abundances consistent with production solely in Type
II supernovae and match observations of disk and halo stars at comparable
metallicity. The remaining metal-poor stars are enhanced in Na and Al compared
to their disk and halo counterparts and are mostly consistent with predicted
yields from >5 M_sun asymptotic giant branch (AGB) stars. At [Fe/H]>-1.2, more
than 75% of the stars are Na/Al enhanced and may have formed almost exclusively
from AGB ejecta. Most of these stars are enhanced in Na by at least 0.2 dex for
a given Al abundance than would be expected based on "normal" globular cluster
values. All stars in our sample are alpha-rich and have solar-scaled Fe-peak
abundances. Eu does not vary extensively as a function of metallicity; however,
[La/Fe] varies from about -0.4 to +2 and stars with [Fe/H]>-1.5 have [La/Eu]
values indicating domination by the s-process. A quarter of our sample have
[La/Eu]>+1 and may be the result of mass transfer in a binary system.Comment: ApJ Accepted; 90 pages, 16 Figures, 5 Table
Hormone replacement therapy and women's health: umbrella review of interventional and observational studies.
This review aims to undertake an umbrella review of systematic reviews and meta-analyses of observational and interventional studies investigating the role of hormone replacement therapy in the primary and secondary prevention of multiple health and disease outcomes in menopausal women
Apolipoprotein E is a pancreatic extracellular factor that maintains mature β-cell gene expression.
The in vivo microenvironment of tissues provides myriad unique signals to cells. Thus, following isolation, many cell types change in culture, often preserving some but not all of their in vivo characteristics in culture. At least some of the in vivo microenvironment may be mimicked by providing specific cues to cultured cells. Here, we show that after isolation and during maintenance in culture, adherent rat islets reduce expression of key β-cell transcription factors necessary for β-cell function and that soluble pancreatic decellularized matrix (DCM) can enhance β-cell gene expression. Following chromatographic fractionation of pancreatic DCM, we performed proteomics to identify soluble factors that can maintain β-cell stability and function. We identified Apolipoprotein E (ApoE) as an extracellular protein that significantly increased the expression of key β-cell genes. The ApoE effect on beta cells was mediated at least in part through the JAK/STAT signaling pathway. Together, these results reveal a role for ApoE as an extracellular factor that can maintain the mature β-cell gene expression profile
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