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3898784_7
Acute ICH stroke severity (measured by the National Institutes of Health Stroke Scale) was not significantly different across the 3 groups (median, 9 [interquartile range, 2-21] for warfarin, 8 [2-20] for NOACs, and 8 [2-19] for no OACs).
Association of Intracerebral Hemorrhage Among Patients Taking Non–Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality
3898784_8
The unadjusted in-hospital mortality rates were 32.6% for warfarin, 26.5% for NOACs, and 22.5% for no OACs.
Association of Intracerebral Hemorrhage Among Patients Taking Non–Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality
3898784_9
Compared with patients without prior use of OACs, the risk of in-hospital mortality was higher among patients with prior use of warfarin (adjusted risk difference [ARD], 9.0% [97.5% CI, 7.9% to 10.1%]; adjusted odds ratio [AOR], 1.62 [97.5% CI, 1.53 to 1.71]) and higher among patients with prior use of NOACs (ARD, 3.3%...
Association of Intracerebral Hemorrhage Among Patients Taking Non–Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality
3898784_10
Compared with patients with prior use of warfarin, patients with prior use of NOACs had a lower risk of in-hospital mortality (ARD, −5.7% [97.5% CI, −7.3% to −4.2%]; AOR, 0.75 [97.5% CI, 0.69 to 0.81]).
Association of Intracerebral Hemorrhage Among Patients Taking Non–Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality
3898784_11
The difference in mortality between NOAC-treated patients and warfarin-treated patients was numerically greater among patients with prior use of dual antiplatelet agents (32.7% vs 47.1%; ARD, −15.0% [95.5% CI, −26.3% to −3.8%]; AOR, 0.50 [97.5% CI, 0.29 to 0.86]) than among those taking these agents without prior antip...
Association of Intracerebral Hemorrhage Among Patients Taking Non–Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality
3898784_12
Conclusions and Relevance Among patients with ICH, prior use of NOACs or warfarin was associated with higher in-hospital mortality compared with no OACs.
Association of Intracerebral Hemorrhage Among Patients Taking Non–Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality
3898784_13
Prior use of NOACs, compared with prior use of warfarin, was associated with lower risk of in-hospital mortality.
Association of Intracerebral Hemorrhage Among Patients Taking Non–Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality
4347374_0
Viral replication usually requires that innate intracellular lines of defence be overcome, a task usually accomplished by specialized viral gene products.
Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
4347374_1
The virion infectivity factor (Vif) protein of human immunodeficiency virus (HIV) is required during the late stages of viral production to counter the antiviral activity of APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G; also known as CEM15), a protein expressed notably in human T lympho...
Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
4347374_2
When produced in the presence of APOBEC3G, vif-defective virus is non-infectious.
Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
4347374_3
APOBEC3G is closely related to APOBEC1, the central component of an RNA-editing complex that deaminates a cytosine residue in apoB messenger RNA.
Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
4347374_4
APOBEC family members also have potent DNA mutator activity through dC deamination; however, whether the editing potential of APOBEC3G has any relevance to HIV inhibition is unknown.
Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
4347374_5
Here, we demonstrate that it does, as APOBEC3G exerts its antiviral effect during reverse transcription to trigger G-to-A hypermutation in the nascent retroviral DNA.
Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
4347374_6
We also find that APOBEC3G can act on a broad range of retroviruses in addition to HIV, suggesting that hypermutation by editing is a general innate defence mechanism against this important group of pathogens.
Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
4381486_0
Stem cells are proposed to segregate chromosomes asymmetrically during self-renewing divisions so that older (‘immortal’) DNA strands are retained in daughter stem cells whereas newly synthesized strands segregate to differentiating cells.
Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU
4381486_1
Stem cells are also proposed to retain DNA labels, such as 5-bromo-2-deoxyuridine (BrdU), either because they segregate chromosomes asymmetrically or because they divide slowly.
Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU
4381486_2
However, the purity of stem cells among BrdU-label-retaining cells has not been documented in any tissue, and the ‘immortal strand hypothesis’ has not been tested in a system with definitive stem cell markers.
Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU
4381486_3
Here we tested these hypotheses in haematopoietic stem cells (HSCs), which can be highly purified using well characterized markers.
Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU
4381486_4
We administered BrdU to newborn mice, mice treated with cyclophosphamide and granulocyte colony-stimulating factor, and normal adult mice for 4 to 10 days, followed by 70 days without BrdU. In each case, less than 6% of HSCs retained BrdU and less than 0.5% of all BrdU-retaining haematopoietic cells were HSCs, revealin...
Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU
4381486_5
Sequential administration of 5-chloro-2-deoxyuridine and 5-iodo-2-deoxyuridine indicated that all HSCs segregate their chromosomes randomly.
Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU
4381486_6
Division of individual HSCs in culture revealed no asymmetric segregation of the label.
Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU
4381486_7
Thus, HSCs cannot be identified on the basis of BrdU-label retention and do not retain older DNA strands during division, indicating that these are not general properties of stem cells.
Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU
4388470_0
In the mammalian model of sex determination, embryos are considered to be sexually indifferent until the transient action of a sex-determining gene initiates gonadal differentiation.
Somatic sex identity is cell-autonomous in the chicken
4388470_1
Although this model is thought to apply to all vertebrates, this has yet to be established.
Somatic sex identity is cell-autonomous in the chicken
4388470_2
Here we have examined three lateral gynandromorph chickens (a rare, naturally occurring phenomenon in which one side of the animal appears male and the other female) to investigate the sex-determining mechanism in birds.
Somatic sex identity is cell-autonomous in the chicken
4388470_3
These studies demonstrated that gynandromorph birds are genuine male:female chimaeras, and indicated that male and female avian somatic cells may have an inherent sex identity.
Somatic sex identity is cell-autonomous in the chicken
4388470_4
To test this hypothesis, we transplanted presumptive mesoderm between embryos of reciprocal sexes to generate embryos containing male:female chimaeric gonads.
Somatic sex identity is cell-autonomous in the chicken
4388470_5
In contrast to the outcome for mammalian mixed-sex chimaeras, in chicken mixed-sex chimaeras the donor cells were excluded from the functional structures of the host gonad.
Somatic sex identity is cell-autonomous in the chicken
4388470_6
In an example where female tissue was transplanted into a male host, donor cells contributing to the developing testis retained a female identity and expressed a marker of female function.
Somatic sex identity is cell-autonomous in the chicken
4388470_7
Our study demonstrates that avian somatic cells possess an inherent sex identity and that, in birds, sexual differentiation is substantively cell autonomous.
Somatic sex identity is cell-autonomous in the chicken
4406819_0
The bacterial type VI secretion system (T6SS) is a large multicomponent, dynamic macromolecular machine that has an important role in the ecology of many Gram-negative bacteria.
PAAR-repeat proteins sharpen and diversify the Type VI secretion system spike
4406819_1
T6SS is responsible for translocation of a wide range of toxic effector molecules, allowing predatory cells to kill both prokaryotic as well as eukaryotic prey cells.
PAAR-repeat proteins sharpen and diversify the Type VI secretion system spike
4406819_2
The T6SS organelle is functionally analogous to contractile tails of bacteriophages and is thought to attack cells by initially penetrating them with a trimeric protein complex called the VgrG spike.
PAAR-repeat proteins sharpen and diversify the Type VI secretion system spike
4406819_3
Neither the exact protein composition of the T6SS organelle nor the mechanisms of effector selection and delivery are known.
PAAR-repeat proteins sharpen and diversify the Type VI secretion system spike
4406819_4
Here we report that proteins from the PAAR (proline-alanine-alanine-arginine) repeat superfamily form a sharp conical extension on the VgrG spike, which is further involved in attaching effector domains to the spike.
PAAR-repeat proteins sharpen and diversify the Type VI secretion system spike
4406819_5
The crystal structures of two PAAR-repeat proteins bound to VgrG-like partners show that these proteins sharpen the tip of the T6SS spike complex.
PAAR-repeat proteins sharpen and diversify the Type VI secretion system spike
4406819_6
We demonstrate that PAAR proteins are essential for T6SS-mediated secretion and target cell killing by Vibrio cholerae and Acinetobacter baylyi.
PAAR-repeat proteins sharpen and diversify the Type VI secretion system spike
4406819_7
Our results indicate a new model of the T6SS organelle in which the VgrG-PAAR spike complex is decorated with multiple effectors that are delivered simultaneously into target cells in a single contraction-driven translocation event.
PAAR-repeat proteins sharpen and diversify the Type VI secretion system spike
4414547_0
Improved sequencing technologies offer unprecedented opportunities for investigating the role of rare genetic variation in common disease.
Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer
4414547_1
However, there are considerable challenges with respect to study design, data analysis and replication.
Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer
4414547_2
Using pooled next-generation sequencing of 507 genes implicated in the repair of DNA in 1,150 samples, an analytical strategy focused on protein-truncating variants (PTVs) and a large-scale sequencing case–control replication experiment in 13,642 individuals, here we show that rare PTVs in the p53-inducible protein pho...
Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer
4414547_3
PPM1D PTV mutations were present in 25 out of 7,781 cases versus 1 out of 5,861 controls (P = 1.12 × 10−5), including 18 mutations in 6,912 individuals with breast cancer (P = 2.42 × 10−4) and 12 mutations in 1,121 individuals with ovarian cancer (P = 3.10 × 10−9).
Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer
4414547_4
Notably, all of the identified PPM1D PTVs were mosaic in lymphocyte DNA and clustered within a 370-base-pair region in the final exon of the gene, carboxy-terminal to the phosphatase catalytic domain.
Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer
4414547_5
Functional studies demonstrate that the mutations result in enhanced suppression of p53 in response to ionizing radiation exposure, suggesting that the mutant alleles encode hyperactive PPM1D isoforms.
Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer
4414547_6
Thus, although the mutations cause premature protein truncation, they do not result in the simple loss-of-function effect typically associated with this class of variant, but instead probably have a gain-of-function effect.
Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer
4414547_7
Our results have implications for the detection and management of breast and ovarian cancer risk.
Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer
4414547_8
More generally, these data provide new insights into the role of rare and of mosaic genetic variants in common conditions, and the use of sequencing in their identification.
Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer
4427392_0
The functional heart is comprised of distinct mesoderm-derived lineages including cardiomyocytes, endothelial cells and vascular smooth muscle cells.
Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population
4427392_1
Studies in the mouse embryo and the mouse embryonic stem cell differentiation model have provided evidence indicating that these three lineages develop from a common Flk-1+ (kinase insert domain protein receptor, also known as Kdr) cardiovascular progenitor that represents one of the earliest stages in mesoderm specifi...
Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population
4427392_2
To determine whether a comparable progenitor is present during human cardiogenesis, we analysed the development of the cardiovascular lineages in human embryonic stem cell differentiation cultures.
Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population
4427392_3
Here we show that after induction with combinations of activin A, bone morphogenetic protein 4 (BMP4), basic fibroblast growth factor (bFGF, also known as FGF2), vascular endothelial growth factor (VEGF, also known as VEGFA) and dickkopf homolog 1 (DKK1) in serum-free media, human embryonic-stem-cell-derived embryoid b...
Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population
4427392_4
When plated in monolayer cultures, these KDRlow/C-KITneg cells differentiate to generate populations consisting of greater than 50% contracting cardiomyocytes.
Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population
4427392_5
Populations derived from the KDRlow/C-KITneg fraction give rise to colonies that contain all three lineages when plated in methylcellulose cultures.
Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population
4427392_6
Results from limiting dilution studies and cell-mixing experiments support the interpretation that these colonies are clones, indicating that they develop from a cardiovascular colony-forming cell.
Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population
4427392_7
Together, these findings identify a human cardiovascular progenitor that defines one of the earliest stages of human cardiac development.
Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population
4456756_0
Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are crucial for many forms of neuronal plasticity, including structural long-term potentiation (sLTP), which is a correlate of an animal’s learning.
Autocrine BDNF–TrkB signalling within a single dendritic spine
4456756_1
However, it is unknown whether BDNF release and TrkB activation occur during sLTP, and if so, when and where.
Autocrine BDNF–TrkB signalling within a single dendritic spine
4456756_2
Here, using a fluorescence resonance energy transfer-based sensor for TrkB and two-photon fluorescence lifetime imaging microscopy, we monitor TrkB activity in single dendritic spines of CA1 pyramidal neurons in cultured murine hippocampal slices.
Autocrine BDNF–TrkB signalling within a single dendritic spine
4456756_3
In response to sLTP induction, we find fast (onset < 1 min) and sustained (>20 min) activation of TrkB in the stimulated spine that depends on NMDAR (N-methyl-d-aspartate receptor) and CaMKII signalling and on postsynaptically synthesized BDNF.
Autocrine BDNF–TrkB signalling within a single dendritic spine
4456756_4
We confirm the presence of postsynaptic BDNF using electron microscopy to localize endogenous BDNF to dendrites and spines of hippocampal CA1 pyramidal neurons.
Autocrine BDNF–TrkB signalling within a single dendritic spine
4456756_5
Consistent with these findings, we also show rapid, glutamate-uncaging-evoked, time-locked BDNF release from single dendritic spines using BDNF fused to superecliptic pHluorin.
Autocrine BDNF–TrkB signalling within a single dendritic spine
4456756_6
We demonstrate that this postsynaptic BDNF–TrkB signalling pathway is necessary for both structural and functional LTP.
Autocrine BDNF–TrkB signalling within a single dendritic spine
4456756_7
Together, these findings reveal a spine-autonomous, autocrine signalling mechanism involving NMDAR–CaMKII-dependent BDNF release from stimulated dendritic spines and subsequent TrkB activation on these same spines that is crucial for structural and functional plasticity.
Autocrine BDNF–TrkB signalling within a single dendritic spine
4687948_0
CONTEXT Recent animal studies have found that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lipid-lowering drugs (statins) substantially increase bone formation, but whether statin use in humans results in clinically meaningful bone formation or a reduction in the risk of osteoporotic fractures is not known.
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4687948_1
OBJECTIVE To determine whether the use of statins is associated with reduced hip fracture risk.
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4687948_2
DESIGN Case-control study.
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4687948_3
SETTING AND PATIENTS A total of 6110 New Jersey residents aged 65 years or older and enrolled in Medicare and either Medicaid or the Pharmacy Assistance for the Aged and Disabled program.
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4687948_4
Case patients (n=1222) underwent surgical repair of a hip fracture in 1994.
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4687948_5
Control patients (n=4888) were identified at a ratio of 4:1 and frequency-matched to case patients for age and sex.
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4687948_6
MAIN OUTCOME MEASURE Adjusted odds ratio (OR) of hip fracture by statin use in the 180 days and 3 years prior to the index date (the earliest date of admission for surgery), adjusted for demographic and clinical characteristics and health care utilization.
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4687948_7
RESULTS Use of statins in either the prior 180 days (adjusted OR, 0.50; 95% confidence interval [CI], 0.33-0.76) or prior 3 years (adjusted OR, 0.57; 95% CI, 0.40-0.82) was associated with a significant reduction in the risk of hip fracture, even after controlling for variables such as race, insurance status, psychoact...
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4687948_8
No significant relationship was observed between use of nonstatin lipid-lowering agents and hip fracture risk.
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4687948_9
Clear relationships were observed between the degree of reduction in hip fracture risk and the extent of statin use; there was no evidence of such relationships with nonstatin lipid-lowering agents.
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4687948_10
After adjusting for extent of statin use in the prior 3 years, current use (on the index date) was associated with a 71% reduction in risk (adjusted OR, 0.29; 95% CI, 0.10-0.81).
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4687948_11
The relationship between statin use and hip fracture risk persisted after controlling for variables such as the number of medications, the Charlson comorbidity index score, and hospitalization or nursing home stay in the last 180 days, as well as after excluding patients who were in a nursing home prior to their index ...
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4687948_12
Use of nonstatin lipid-lowering agents was not observed to be associated with reduction in hip fracture risk in any of these alternative models or analyses.
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4687948_13
CONCLUSIONS These findings support an association between statin use by elderly patients and reduction in the risk of hip fracture.
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4687948_14
Controlled trials are needed to exclude the possibility of unmeasured confounders.
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4687948_15
JAMA.
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4687948_16
2000;283:3211-3216
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.
4709641_0
Efforts to develop drugs for Alzheimer's disease (AD) have shown promise in animal studies, only to fail in human trials, suggesting a pressing need to study AD in human model systems.
Gain of toxic Apolipoprotein E4 effects in Human iPSC-Derived Neurons Is Ameliorated by a Small-Molecule Structure Corrector
4709641_1
Using human neurons derived from induced pluripotent stem cells that expressed apolipoprotein E4 (ApoE4), a variant of the APOE gene product and the major genetic risk factor for AD, we demonstrated that ApoE4-expressing neurons had higher levels of tau phosphorylation, unrelated to their increased production of amyloi...
Gain of toxic Apolipoprotein E4 effects in Human iPSC-Derived Neurons Is Ameliorated by a Small-Molecule Structure Corrector
4709641_2
ApoE4 increased Aβ production in human, but not in mouse, neurons.
Gain of toxic Apolipoprotein E4 effects in Human iPSC-Derived Neurons Is Ameliorated by a Small-Molecule Structure Corrector
4709641_3
Converting ApoE4 to ApoE3 by gene editing rescued these phenotypes, indicating the specific effects of ApoE4.
Gain of toxic Apolipoprotein E4 effects in Human iPSC-Derived Neurons Is Ameliorated by a Small-Molecule Structure Corrector
4709641_4
Neurons that lacked APOE behaved similarly to those expressing ApoE3, and the introduction of ApoE4 expression recapitulated the pathological phenotypes, suggesting a gain of toxic effects from ApoE4.
Gain of toxic Apolipoprotein E4 effects in Human iPSC-Derived Neurons Is Ameliorated by a Small-Molecule Structure Corrector
4709641_5
Treatment of ApoE4-expressing neurons with a small-molecule structure corrector ameliorated the detrimental effects, thus showing that correcting the pathogenic conformation of ApoE4 is a viable therapeutic approach for ApoE4-related AD.
Gain of toxic Apolipoprotein E4 effects in Human iPSC-Derived Neurons Is Ameliorated by a Small-Molecule Structure Corrector
4883040_0
BACKGROUND Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa.
Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis
4883040_1
In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV worldwide.
Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis
4883040_2
Antiretroviral therapy has substantial potential to prevent HIV-associated tuberculosis.
Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis
4883040_3
We conducted a systematic review of studies that analysed the impact of antiretroviral therapy on the incidence of tuberculosis in adults with HIV infection.
Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis
4883040_4
METHODS AND FINDINGS PubMed, Embase, African Index Medicus, LILACS, and clinical trial registries were systematically searched.
Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis
4883040_5
Randomised controlled trials, prospective cohort studies, and retrospective cohort studies were included if they compared tuberculosis incidence by antiretroviral therapy status in HIV-infected adults for a median of over 6 mo in developing countries.
Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis
4883040_6
For the meta-analyses there were four categories based on CD4 counts at antiretroviral therapy initiation: (1) less than 200 cells/µl, (2) 200 to 350 cells/µl, (3) greater than 350 cells/µl, and (4) any CD4 count.
Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis
4883040_7
Eleven studies met the inclusion criteria.
Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis
4883040_8
Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis in all baseline CD4 count categories: (1) less than 200 cells/µl (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.07 to 0.36), (2) 200 to 350 cells/µl (HR 0.34, 95% CI 0.19 to 0.60), (3) greater than 350 cells/µl (HR ...
Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis
4883040_9
There was no evidence of hazard ratio modification with respect to baseline CD4 count category (p = 0.20).
Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis
4883040_10
CONCLUSIONS Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis across all CD4 count strata.
Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis
4883040_11
Earlier initiation of antiretroviral therapy may be a key component of global and national strategies to control the HIV-associated tuberculosis syndemic.
Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis
4883040_12
REVIEW REGISTRATION International Prospective Register of Systematic Reviews CRD42011001209 Please see later in the article for the Editors' Summary.
Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis
4961038_0
Somatic mutations that activate phosphoinositide 3-kinase (PI3K) have been identified in the p110-alpha catalytic subunit (encoded by PIK3CA).
Effective Use of PI3K and MEK Inhibitors to Treat Mutant K-Ras G12D and PIK3CA H1047R Murine Lung Cancers