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Mirror therapy: An adjunct to conventional pharmacotherapy in phantom limb pain

Datta, Rashmi; Dhar, Mridul
Fonte: Medknow Publications & Media Pvt Ltd Publicador: Medknow Publications & Media Pvt Ltd
Tipo: Text
Publicado em //2015 Português

Quantity and Size Distribution of Cough-Generated Aerosol Particles Produced by Influenza Patients During and After Illness

Lindsley, William G.; Pearce, Terri A.; Hudnall, Judith B.; Davis, Kristina A.; Davis, Stephen M.; Fisher, Melanie A.; Khakoo, Rashida; Palmer, Jan E.; Clark, Karen E.; Celik, Ismail; Coffey, Christopher C.; Blachere, Francoise M.; Beezhold, Donald H.
Fonte: PubMed Publicador: PubMed
Tipo: Text
Publicado em //2012 Português
The question of whether influenza is transmitted to a significant degree by aerosols remains controversial, in part, because little is known about the quantity and size of potentially infectious airborne particles produced by people with influenza. In this study, the size and amount of aerosol particles produced by nine subjects during coughing were measured while they had influenza and after they had recovered, using a laser aerosol particle spectrometer with a size range of 0.35 to 10 μm. Individuals with influenza produce a significantly greater volume of aerosol when ill compared with afterward (p = 0.0143). When the patients had influenza, their average cough aerosol volume was 38.3 picoliters (pL) of particles per cough (SD 43.7); after patients recovered, the average volume was 26.4 pL per cough (SD 45.6). The number of particles produced per cough was also higher when subjects had influenza (average 75,400 particles/cough, SD 97,300) compared with afterward (average 52,200, SD 98,600), although the difference did not reach statistical significance (p = 0.1042). The average number of particles expelled per cough varied widely from patient to patient, ranging from 900 to 302,200 particles/cough while subjects had influenza and 1100 to 308...

Serosurvey for Zoonotic Viral and Bacterial Pathogens Among Slaughtered Livestock in Egypt

Horton, Katherine C.; Wasfy, Momtaz; Samaha, Hamed; Abdel-Rahman, Bassem; Safwat, Sameh; Abdel Fadeel, Moustafa; Mohareb, Emad; Dueger, Erica
Fonte: PubMed Publicador: PubMed
Tipo: Text
Português

Positive Psychological Factors are Associated with Lower PTSD Symptoms among Police Officers: Post Hurricane Katrina

McCanlies, Erin C.; Mnatsakanova, Anna; Andrew, Michael E.; Burchfiel, Cecil M.; Violanti, John M.
Fonte: PubMed Publicador: PubMed
Tipo: Text
Publicado em /12/2014 Português
Following Hurricane Katrina, police officers in the New Orleans geographic area faced a number of challenges. This cross-sectional study examined the association between resilience, satisfaction with life, gratitude, posttraumatic growth, and symptoms of posttraumatic stress disorder in 84 male and 30 female police officers from Louisiana. Protective factors were measured using the Connor–Davidson Resilience scale, Satisfaction with Life Scale, the Gratitude Questionnaire, and the Posttraumatic Growth inventory. Symptoms of posttraumatic stress disorder were measured using the Posttraumatic Stress Disorder Checklist—Civilian (PCL-C). Potential associations were measured using linear regression and analysis of variance. Models were adjusted for age, sex, race, education, and alcohol. Mean PCL-C symptoms were 29.5 ± 14.5 for females and 27.8 ± 12.1 for males. Adjusted mean levels of PCL-C symptoms significantly decreased as quartiles of resilience (p <.001), satisfaction with life (p <.001), and gratitude (p <.001) increased. In contrast, PCL-C symptoms were not associated with posttraumatic growth in this sample. These results indicate that positive factors such as resilience, satisfaction with life, and gratitude may help mitigate symptoms of posttraumatic stress disorder. To further explore these relationships...

Myths and Mysteries Surrounding Bacillus Calmette-Guérin Therapy for Bladder Cancer

Kamat, Ashish M.; Orten, Sima
Fonte: PubMed Publicador: PubMed
Tipo: Text
Português
Intravesical immunotherapy with bacillus Calmette-Guérin (BCG) has been used by urologists worldwide since its approval in 1990 by the US Food and Drug Administration. After 23 yr, it is fair to say that BCG remains the only truly effective intravesical therapy for non–muscle-invasive bladder cancer (NMIBC), with proven effects reducing recurrence and prolonging survival. It would also be fair to say that, as with any longstanding, “old” remedy, many misconceptions and myths have emerged over the years regarding its use, efficacy, and tolerability. These misconceptions regarding BCG often stand in the way of its delivery and optimal care of our patients. In this paper, we aim to dispel some of these myths, following the text of the primary authors' “Critical Discussion Session” at the 2013 annual meeting of the American Urological Association in San Diego, California.

Electrophysiological Motor Unit Number Estimation (MUNE) Measuring Compound Muscle Action Potential (CMAP) in Mouse Hindlimb Muscles

Arnold, W. David; Sheth, Kajri A.; Wier, Christopher G.; Kissel, John T.; Burghes, Arthur H.; Kolb, Stephen J.
Fonte: PubMed Publicador: PubMed
Tipo: Text
Publicado em 25/09/2015 Português
Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the functional status of a motor unit pool in vivo. These measures can provide insight into the normal development and degeneration of the neuromuscular system. These measures have clear translational potential because they are routinely applied in diagnostic and clinical human studies. We present electrophysiological techniques similar to those employed in humans to allow recordings of mouse sciatic nerve function. The CMAP response represents the electrophysiological output from a muscle or group of muscles following supramaximal stimulation of a peripheral nerve. MUNE is an electrophysiological technique that is based on modifications of the CMAP response. MUNE is a calculated value that represents the estimated number of motor neurons or axons (motor control input) supplying the muscle or group of muscles being tested. We present methods for recording CMAP responses from the proximal leg muscles using surface recording electrodes following the stimulation of the sciatic nerve in mice. An incremental MUNE technique is described using submaximal stimuli to determine the average single motor unit potential (SMUP) size. MUNE is calculated by dividing the CMAP amplitude (peak-to-peak) by the SMUP amplitude (peak-to-peak). These electrophysiological techniques allow repeated measures in both neonatal and adult mice in such a manner that facilitates rapid analysis and data collection while reducing the number of animals required for experimental testing. Furthermore...

The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development

Ortega-Molina, Ana; Boss, Isaac W.; Canela, Andres; Pan, Heng; Jiang, Yanwen; Zhao, Chunying; Jiang, Man; Hu, Deqing; Agirre, Xabier; Niesvizky, Itamar; Lee, Ji-Eun; Chen, Hua-Tang; Ennishi, Daisuke; Scott, David W.; Mottok, Anja; Hother, Christoffer; Liu
Fonte: PubMed Publicador: PubMed
Tipo: Text
Português
The lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL). However, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center (GC) involution, impedes B cell differentiation and class switch recombination (CSR). Integrative genomic analyses indicate that KMT2D affects H3K4 methylation and expression of a specific set of genes including those in the CD40, JAK-STAT, Toll-like receptor, and B cell receptor pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3, and TNFRSF14. Therefore, KMT2D mutations may promote malignant outgrowth by perturbing the expression of tumor suppressor genes that control B cell activating pathways.

Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review

Canestaro, William J.; Austin, Melissa A.; Thummel, Kenneth E.
Fonte: PubMed Publicador: PubMed
Tipo: Text
Português
Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors, have proven efficacy in both lowering low-density-lipoprotein levels and preventing major coronary events, making them one of the most commonly prescribed drugs in the United States. Statins exhibit a class-wide side effect of muscle toxicity and weakness, which has led regulators to impose both dosage limitations and a recall. This review focuses on the best-characterized genetic factors associated with increased statin muscle concentrations, including the genes encoding cytochrome P450 enzymes (CYP2D6, CYP3A4, and CYP3A5), a mitochondrial enzyme (GATM), an influx transporter (SLCO1B1), and efflux transporters (ABCB1 and ABCG2). A systematic literature review was conducted to identify relevant research evaluating the significance of genetic variants predictive of altered statin concentrations and subsequent statin-related myopathy. Studies eligible for inclusion must have incorporated genotype information and must have associated it with some measure of myopathy, either creatine kinase levels or self-reported muscle aches and pains. After an initial review, focus was placed on seven genes that were adequately characterized to provide a substantive review: CYP2D6...

The influence of social determinants on sexual risk among out-of-school African American female adolescents

Browne, Felicia A.; Wechsberg, Wendee M.; White, Vanessa M.; Ellerson, Rachel Middlesteadt; Raiford, Jerris L.; Carry, Monique G.; Herbst, Jeffrey H.
Fonte: PubMed Publicador: PubMed
Tipo: Text
Português
Formative research was conducted to understand the social determinants of HIV risk among African American female adolescents as part of a systematic adaptation of an evidence-based behavioral HIV prevention intervention, the Women’s CoOp. Semi-structured in-depth interviews were conducted between November 2008 and April 2009 with 20 African American female adolescents aged 16–18 who reported engaging in sex, using alcohol or other drugs, and dropping out of school. All interviews were audio recorded, transcribed, and coded for key themes and emergent content patterns. The findings indicate that while female adolescents are knowledgeable about HIV and other sexually transmitted infections (STIs), myriad social factors relate to their level of risk. Interpersonal relationships, primarily with older boyfriends and friends, played a pivotal role in their decision-making regarding sex risk behavior, substance use, and educational attainment. A lack of viable employment opportunities, exacerbated by the lack of a high school education, resulted in some young women trading sex to make money. In addition, violence, victimization, and gang involvement are pervasive in their communities. Out-of-school African American female adolescents face a plethora of issues that are directly and indirectly related to their sex risk behaviors and consequently their HIV/STI risk. To reach a vulnerable population disproportionately affected by HIV and other STIs...

New Approach for Near-Real-Time Measurement of Elemental Composition of Aerosol Using Laser-Induced Breakdown Spectroscopy

Diwakar, Prasoon; Kulkarni, Pramod; Birch, M. Eileen
Fonte: PubMed Publicador: PubMed
Tipo: Text
Português
A new approach has been developed for making near-real-time measurement of elemental composition of aerosols using plasma spectroscopy. The method allows preconcentration of miniscule particle mass (pg to ng) directly from the sampled aerosol stream through electrostatic deposition of charged particles (30–900 nm) onto a flat-tip microneedle electrode. The collected material is subsequently ablated from the electrode and monitored by laser-induced breakdown spectroscopy. Atomic emission spectra were collected using a broadband spectrometer with a wavelength range of 200–980 nm. A single-sensor delay time of 1.3 μs was used in the spectrometer for all elements to allow simultaneous measurement of multiple elements. The system was calibrated for various elements including Cd, Cr, Cu, Mn, Na, and Ti. The absolute mass detection limits for these elements were experimentally determined and found to be in the range of 0.018–5 ng. The electrostatic collection technique has many advantages over other substrate-based methods involving aerosol collection on a filter or its focused deposition using an aerodynamic lens. Because the particle mass is collected over a very small area that is smaller than the spatial extent of the laser-induced plasma...

The Endospore-Forming Pathogen Bacillus cereus Exploits a Small Colony Variant-Based Diversification Strategy in Response to Aminoglycoside Exposure

Frenzel, Elrike; Kranzler, Markus; Stark, Timo D.; Hofmann, Thomas; Ehling-Schulz, Monika
Fonte: American Society of Microbiology Publicador: American Society of Microbiology
Tipo: Text
Publicado em 08/12/2015 Português
Bacillus cereus is among the microorganisms most often isolated from cases of food spoilage and causes gastrointestinal diseases as well as nongastrointestinal infections elicited by the emetic toxin cereulide, enterotoxins, and a panel of tissue-destructive virulence factors. This opportunistic pathogen is increasingly associated with rapidly fatal clinical infections especially linked to neonates and immunocompromised individuals. Fatality results from either the misdiagnosis of B. cereus as a contaminant of the clinical specimen or from failure of antibiotic therapy. Here we report for the first time that exposure to aminoglycoside antibiotics induces a phenotype switching of emetic B. cereus subpopulations to a slow-growing small colony variant (SCV) state. Along with altered antibiotic resistance, SCVs showed distinct phenotypic and metabolic properties, bearing the risk of antibiotic treatment failure and of clinical misdiagnosis by standard identification tests used in routine diagnostic. The SCV subpopulation is characterized by enhanced production of the toxin cereulide, but it does not secrete tissue-destructive and immune system-affecting enzymes such as sphingomyelinase and phospholipase. SCVs showed significantly prolonged persistence and decreased virulence in the Galleria mellonella model for bacterial infections...

Kaposi’s Sarcoma-Associated Herpesvirus Interleukin-6 Modulates Endothelial Cell Movement by Upregulating Cellular Genes Involved in Migration

Giffin, Louise; West, John A.; Damania, Blossom
Fonte: American Society of Microbiology Publicador: American Society of Microbiology
Tipo: Text
Publicado em 08/12/2015 Português
Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of human Kaposi’s sarcoma, a tumor that arises from endothelial cells, as well as two B cell lymphoproliferative diseases, primary effusion lymphoma and multicentric Castleman’s disease. KSHV utilizes a variety of mechanisms to evade host immune responses and promote cellular transformation and growth in order to persist for the life of the host. A viral homolog of human interleukin-6 (hIL-6) named viral interleukin-6 (vIL-6) is encoded by KSHV and expressed in KSHV-associated cancers. Similar to hIL-6, vIL-6 is secreted, but the majority of vIL-6 is retained within the endoplasmic reticulum, where it can initiate functional signaling through part of the interleukin-6 receptor complex. We sought to determine how intracellular vIL-6 modulates the host endothelial cell environment by analyzing vIL-6’s impact on the endothelial cell transcriptome. vIL-6 significantly altered the expression of many cellular genes associated with cell migration. In particular, vIL-6 upregulated the host factor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) at the protein and message levels. CEACAM1 has been implicated in tumor invasion and metastasis and promotes migration and vascular remodeling in endothelial cells. We report that vIL-6 upregulates CEACAM1 by a STAT3-dependent mechanism and that CEACAM1 promotes vIL-6-mediated migration. Furthermore...

Transcriptomic Analysis of Chronic Hepatitis B and C and Liver Cancer Reveals MicroRNA-Mediated Control of Cholesterol Synthesis Programs

Selitsky, Sara R.; Dinh, Timothy A.; Toth, Cynthia L.; Kurtz, C. Lisa; Honda, Masao; Struck, Benjamin R.; Kaneko, Shuichi; Vickers, Kasey C.; Lemon, Stanley M.; Sethupathy, Praveen
Fonte: American Society of Microbiology Publicador: American Society of Microbiology
Tipo: Text
Publicado em 08/12/2015 Português
Chronic hepatitis B (CHB), chronic hepatitis C (CHC), and associated hepatocellular carcinoma (HCC) are characterized by cholesterol imbalance and dyslipidemia; however, the key regulatory drivers of these phenotypes are incompletely understood. Using gene expression microarrays and high-throughput sequencing of small RNAs, we performed integrative analysis of microRNA (miRNA) and gene expression in nonmalignant and matched cancer tissue samples from human subjects with CHB or CHC and HCC. We also carried out follow-up functional studies of specific miRNAs in a cell-based system. These studies led to four major findings. First, pathways affecting cholesterol homeostasis were among the most significantly overrepresented among genes dysregulated in chronic viral hepatitis and especially in tumor tissue. Second, for each disease state, specific miRNA signatures that included miRNAs not previously associated with chronic viral hepatitis, such as miR-1307 in CHC, were identified. Notably, a few miRNAs, including miR-27 and miR-224, were components of the miRNA signatures of all four disease states: CHB, CHC, CHB-associated HCC, and CHC-associated HCC. Third, using a statistical simulation method (miRHub) applied to the gene expression data...

IS26-Mediated Precise Excision of the IS26-aphA1a Translocatable Unit

Harmer, Christopher J.; Hall, Ruth M.
Fonte: American Society of Microbiology Publicador: American Society of Microbiology
Tipo: Text
Publicado em 08/12/2015 Português
We recently showed that, in the absence of RecA-dependent homologous recombination, the Tnp26 transposase catalyzes cointegrate formation via a conservative reaction between two preexisting IS26, and this is strongly preferred over replicative transposition to a new site. Here, the reverse reaction was investigated by assaying for precise excision of the central region together with a single IS26 from a compound transposon bounded by IS26. In a recA mutant strain, Tn4352, a kanamycin resistance transposon carrying the aphA1a gene, was stable. However, loss of kanamycin resistance due to precise excision of the translocatable unit (TU) from the closely related Tn4352B, leaving behind the second IS26, occurred at high frequency. Excision occurred when Tn4352B was in either a high- or low-copy-number plasmid. The excised circular segment, known as a TU, was detected by PCR. Excision required the IS26 transposase Tnp26. However, the Tnp26 of only one IS26 in Tn4352B was required, specifically the IS26 downstream of the aphA1a gene, and the excised TU included the active IS26. The frequency of Tn4352B TU loss was influenced by the context of the transposon, but the critical determinant of high-frequency excision was the presence of three G residues in Tn4352B replacing a single G in Tn4352. These G residues are located immediately adjacent to the two G residues at the left end of the IS26 that is upstream of the aphA1a gene. Transcription of tnp26 was not affected by the additional G residues...

Structural Insight into How Bacteria Prevent Interference between Multiple Divergent Type IV Secretion Systems

Gillespie, Joseph J.; Phan, Isabelle Q. H.; Scheib, Holger; Subramanian, Sandhya; Edwards, Thomas E.; Lehman, Stephanie S.; Piitulainen, Hanna; Sayeedur Rahman, M.; Rennoll-Bankert, Kristen E.; Staker, Bart L.; Taira, Suvi; Stacy, Robin; Myler, Peter J.;
Fonte: American Society of Microbiology Publicador: American Society of Microbiology
Tipo: Text
Publicado em 08/12/2015 Português
Prokaryotes use type IV secretion systems (T4SSs) to translocate substrates (e.g., nucleoprotein, DNA, and protein) and/or elaborate surface structures (i.e., pili or adhesins). Bacterial genomes may encode multiple T4SSs, e.g., there are three functionally divergent T4SSs in some Bartonella species (vir, vbh, and trw). In a unique case, most rickettsial species encode a T4SS (rvh) enriched with gene duplication. Within single genomes, the evolutionary and functional implications of cross-system interchangeability of analogous T4SS protein components remains poorly understood. To lend insight into cross-system interchangeability, we analyzed the VirB8 family of T4SS channel proteins. Crystal structures of three VirB8 and two TrwG Bartonella proteins revealed highly conserved C-terminal periplasmic domain folds and dimerization interfaces, despite tremendous sequence divergence. This implies remarkable structural constraints for VirB8 components in the assembly of a functional T4SS. VirB8/TrwG heterodimers, determined via bacterial two-hybrid assays and molecular modeling, indicate that differential expression of trw and vir systems is the likely barrier to VirB8-TrwG interchangeability. We also determined the crystal structure of Rickettsia typhi RvhB8-II and modeled its coexpressed divergent paralog RvhB8-I. Remarkably...

Impact of Anaerobiosis on Expression of the Iron-Responsive Fur and RyhB Regulons

Beauchene, Nicole A.; Myers, Kevin S.; Chung, Dongjun; Park, Dan M.; Weisnicht, Allison M.; Keleş, Sündüz; Kiley, Patricia J.
Fonte: American Society of Microbiology Publicador: American Society of Microbiology
Tipo: Text
Publicado em 15/12/2015 Português
Iron, a major protein cofactor, is essential for most organisms. Despite the well-known effects of O2 on the oxidation state and solubility of iron, the impact of O2 on cellular iron homeostasis is not well understood. Here we report that in Escherichia coli K-12, the lack of O2 dramatically changes expression of genes controlled by the global regulators of iron homeostasis, the transcription factor Fur and the small RNA RyhB. Using chromatin immunoprecipitation sequencing (ChIP-seq), we found anaerobic conditions promote Fur binding to more locations across the genome. However, by expression profiling, we discovered that the major effect of anaerobiosis was to increase the magnitude of Fur regulation, leading to increased expression of iron storage proteins and decreased expression of most iron uptake pathways and several Mn-binding proteins. This change in the pattern of gene expression also correlated with an unanticipated decrease in Mn in anaerobic cells. Changes in the genes posttranscriptionally regulated by RyhB under aerobic and anaerobic conditions could be attributed to O2-dependent changes in transcription of the target genes: aerobic RyhB targets were enriched in iron-containing proteins associated with aerobic energy metabolism...

Comparison of diffusion charging and mobility-based methods for measurement of aerosol agglomerate surface area

Ku, Bon Ki; Kulkarni, Pramod
Fonte: PubMed Publicador: PubMed
Tipo: Text
Publicado em /05/2012 Português
We compare different approaches to measure surface area of aerosol agglomerates. The objective was to compare field methods, such as mobility and diffusion charging based approaches, with laboratory approach, such as Brunauer, Emmett, Teller (BET) method used for bulk powder samples. To allow intercomparison of various surface area measurements, we defined ‘geometric surface area’ of agglomerates (assuming agglomerates are made up of ideal spheres), and compared various surface area measurements to the geometric surface area. Four different approaches for measuring surface area of agglomerate particles in the size range of 60–350 nm were compared using (i) diffusion charging-based sensors from three different manufacturers, (ii) mobility diameter of an agglomerate, (iii) mobility diameter of an agglomerate assuming a linear chain morphology with uniform primary particle size, and (iv) surface area estimation based on tandem mobility–mass measurement and microscopy. Our results indicate that the tandem mobility–mass measurement, which can be applied directly to airborne particles unlike the BET method, agrees well with the BET method. It was also shown that the three diffusion charging-based surface area measurements of silver agglomerates were similar within a factor of 2 and were lower than those obtained from the tandem mobility–mass and microscopy method by a factor of 3–10 in the size range studied. Surface area estimated using the mobility diameter depended on the structure or morphology of the agglomerate with significant underestimation at high fractal dimensions approaching 3.

Effects of sub-Tenon’s capsule triamcinolone acetonide injection combined with microaneurysm photocoagulation on diabetic macular edema

Oshitari, Toshiyuki; Nonomura, Sakiko; Arai, Miyuki; Takatsuna, Yoko; Sato, Eiju; Baba, Takayuki; Yamamoto, Shuichi
Fonte: Dove Medical Press Publicador: Dove Medical Press
Tipo: Text
Publicado em 07/12/2015 Português

Clinical features of infectious keratitis at a tertiary referral center in a rural area of Korea

Lee, Seung-Jun; Lee, Jang Hun; Kim, Moosang; Han, Sang Beom; Hyon, Joon Young
Fonte: Dove Medical Press Publicador: Dove Medical Press
Tipo: Text
Publicado em 07/12/2015 Português

Potential role for mammalian target of rapamycin inhibitors as first-line therapy in hormone receptor–positive advanced breast cancer

Beck, J Thaddeus
Fonte: Dove Medical Press Publicador: Dove Medical Press
Tipo: Text
Publicado em 07/12/2015 Português
Despite advances in cytotoxic chemotherapy and targeted therapies, 5-year survival rates remain low for patients with advanced breast cancer at diagnosis. This highlights the limited effectiveness of current treatment options. An improved understanding of cellular functions associated with the development and progression of breast cancer has resulted in the creation of a number of novel targeted molecular therapies. However, more work is needed to improve outcomes, particularly in the first-line recurrent or metastatic hormone receptor–positive breast cancer setting. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) pathway is a major intracellular signaling pathway that is often upregulated in breast cancer, and overactivation of this pathway has been associated with primary or developed resistance to endocrine treatment. Clinical data from the Phase III Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study of the mTOR inhibitor everolimus combined with exemestane in hormone receptor–positive advanced breast cancer were very promising, highlighting the potential role of mTOR inhibitors in combination with endocrine therapies as a first-line treatment option for these patients. It is hoped that the use of mTOR inhibitors combined with current standard-of-care endocrine therapies...