Relationship Education Research: Current Status and Future Directions

PubMed Central

Markman, Howard J.; Rhoades, Galena K.

2011-01-01

The overarching aim of this paper is to review research on relationship education programs and approaches that have been published or accepted for publication since the last review article in 2002. This paper provides a critical overview of the relationship education field and sets an agenda for research and practice for the next decade. A theme weaved throughout the paper are the ways in which relationship education is similar and different from couples therapy and we conclude that there can be a synergistic, healthy marriage between the two. We then provide recommendations for future directions for research in the relationship education field. Finally, the co-authors comment on our experiences in both the relationship education field and couples therapy field as both researchers and interventionists. PMID:22283386

Current status and future perspectives of sonodynamic therapy in glioma treatment.

PubMed

Wang, Xiaobing; Jia, Yali; Wang, Pan; Liu, Quanhon; Zheng, Hairong

2017-07-01

Malignant glioma is one of the most challenging central nervous system diseases to treat, and has high rates of recurrence and mortality. The current therapies include surgery, radiation therapy, and chemotherapy, although these approaches often failed to control tumor progression or improve patient survival. Sonodynamic therapy is a developing cancer treatment that uses ultrasound combined with a sonosensitizer to synergistically kill tumor cells, and has provided impressive results in both in vitro and in vivo studies. The ultrasound waves can penetrate deep tissues and reversibly open the blood-brain barrier to enhance drug delivery to the brain. Thus, sonodynamic therapy has a promising potential in glioma treatment. In this review, we summarize the studies that have confirmed the pre-clinical efficacy of sonodynamic therapy for glioma treatment, and discuss the future directions for this emerging treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Sarcoidosis: an update on current pharmacotherapy options and future directions.

PubMed

Brito-Zerón, Pilar; Pérez-Alvarez, Roberto; Pallarés, Lucio; Retamozo, Soledad; Baughman, Robert P; Ramos-Casals, Manuel

2016-12-01

Sarcoidosis is a systemic disease of unknown etiology characterized by the development of non-caseating epitheloid granulomas. The lungs are the most commonly involved organ (>90% of cases), followed by the lymph nodes, the skin, and the eyes. Areas covered: This review summarizes current pharmacotherapy options and future directions for the development of new therapies. Glucocorticoids are the first-line therapy for sarcoidosis. For patients with the most severe forms of sarcoidosis (who will need glucocorticoids for long periods) and for those intolerant or refractory, immunosuppressive drugs are used as sparing agents. The management of extrathoracic sarcoidosis must be tailored to the specific organ or organs involved; however, there is limited data from controlled trials to guide the treatment of these patients. The emergence of biological therapies has increased the therapeutic armamentarium available to treat sarcoidosis, with monoclonal anti-TNF agents being the most promising, but their use is still limited by a lack of licensing and costs. Expert commentary: The treatment of sarcoidosis is still not totally standardized. New effective therapies are urgently needed to enable the reduction or replacement of long-term therapy with glucocorticoids in patients with sarcoidosis.

Dialectical Behaviour Therapy: Description, Research and Future Directions

ERIC Educational Resources Information Center

Swales, Michaela A.

2009-01-01

Dialectical Behaviour Therapy (DBT) is a cognitive behavioural treatment initially developed for adult women with a diagnosis of borderline personality disorder (BPD) and a history of chronic suicidal behaviour (Linehan, 1993a; 1993b). DBT was the first treatment for BPD to demonstrate its efficacy in a randomised controlled trial (Linehan ,…

Taking Stock of Retinal Gene Therapy: Looking Back and Moving Forward.

PubMed

Bennett, Jean

2017-05-03

Over the past 20 years, there has been tremendous progress in retinal gene therapy. The safety and efficacy results in one early-onset severe blinding disease may lead to the first gene therapy drug approval in the United States. Here, we review how far the field has come over the past two decades and speculate on the directions that the field will take in the future. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Host-directed therapies for infectious diseases: current status, recent progress, and future prospects.

PubMed

Zumla, Alimuddin; Rao, Martin; Wallis, Robert S; Kaufmann, Stefan H E; Rustomjee, Roxana; Mwaba, Peter; Vilaplana, Cris; Yeboah-Manu, Dorothy; Chakaya, Jeremiah; Ippolito, Giuseppe; Azhar, Esam; Hoelscher, Michael; Maeurer, Markus

2016-04-01

Despite extensive global efforts in the fight against killer infectious diseases, they still cause one in four deaths worldwide and are important causes of long-term functional disability arising from tissue damage. The continuing epidemics of tuberculosis, HIV, malaria, and influenza, and the emergence of novel zoonotic pathogens represent major clinical management challenges worldwide. Newer approaches to improving treatment outcomes are needed to reduce the high morbidity and mortality caused by infectious diseases. Recent insights into pathogen-host interactions, pathogenesis, inflammatory pathways, and the host's innate and acquired immune responses are leading to identification and development of a wide range of host-directed therapies with different mechanisms of action. Host-directed therapeutic strategies are now becoming viable adjuncts to standard antimicrobial treatment. Host-directed therapies include commonly used drugs for non-communicable diseases with good safety profiles, immunomodulatory agents, biologics (eg monoclonal antibodies), nutritional products, and cellular therapy using the patient's own immune or bone marrow mesenchymal stromal cells. We discuss clinically relevant examples of progress in identifying host-directed therapies as adjunct treatment options for bacterial, viral, and parasitic infectious diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

T Cells

MedlinePlus

... cells — have proven successful in treating animals with experimental allergic encephalomyelitis (EAE), an animal model of MS. Pilot clinical trials are in progress. Future experimental therapies may involve antibodies directed against the cytokines ...

The Mechanisms of Manual Therapy in the Treatment of Musculoskeletal Pain: A Comprehensive Model

PubMed Central

Bialosky, Joel E; Bishop, Mark D; Price, Don D; Robinson, Michael E; George, Steven Z

2009-01-01

Prior studies suggest manual therapy (MT) as effective in the treatment of musculoskeletal pain; however, the mechanisms through which MT exerts its effects are not established. In this paper we present a comprehensive model to direct future studies in MT. This model provides visualization of potential individual mechanisms of MT that the current literature suggests as pertinent and provides a framework for the consideration of the potential interaction between these individual mechanisms. Specifically, this model suggests that a mechanical force from MT initiates a cascade of neurophysiological responses from the peripheral and central nervous system which are then responsible for the clinical outcomes. This model provides clear direction so that future studies may provide appropriate methodology to account for multiple potential pertinent mechanisms. PMID:19027342

Insomnia in the Military: Application and Effectiveness of Cognitive and Pharmacologic Therapies.

PubMed

Capaldi, Vincent F; Kim, Jessica R; Grillakis, Antigone A; Taylor, Maura R; York, Carla M

2015-10-01

Insomnia is one of the most common complaints of US armed service members. Diagnosis and treatment of insomnia in active duty and veteran populations are often complicated by comorbid disorders experienced by military personnel, such as post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI). Cognitive behavioral therapy for insomnia (CBTi), pharmacologic interventions, and alternative therapies are discussed as relevant to their applications within military populations. Future directions in research are suggested.

Accomplishments in 2007 in the treatment of advanced colorectal cancer.

PubMed

Goldberg, Richard M; Carrato, Alfredo

2008-05-01

Overview of the Disease IncidencePrognosis Prognostic or Predictive FactorsCurrent General Therapy Standards and Regional Variations STANDARDS IN THE US AND EUROPE: Combination Therapy Plus a Biologic FOCUS and CAIRO 1: Serial Single Agents vs. Combination TherapyStop-and-Go StrategyLimited Availability of Biologics in Some RegionsAccomplishments During the Year TherapyWhat Needs To Be Done Controversies and Disagreements BOND-2 and PACCE: Chemotherapy + Bevacizumab + Cetuximab or PanitumumabSpecial Populations (Elderly and Poor Performance Status)Future Directions Comments on ResearchObstacles to Progress.

Accomplishments in 2007 in the Treatment of Advanced Colorectal Cancer

PubMed Central

Carrato, Alfredo

2008-01-01

Overview of the Disease IncidencePrognosis Prognostic or Predictive FactorsCurrent General Therapy Standards and Regional Variations Standards in the US and Europe: Combination Therapy Plus a Biologic FOCUS and CAIRO 1: Serial Single Agents vs. Combination TherapyStop-and-Go StrategyLimited Availability of Biologics in Some RegionsAccomplishments During the Year TherapyWhat Needs To Be Done Controversies and Disagreements BOND-2 and PACCE: Chemotherapy + Bevacizumab + Cetuximab or PanitumumabSpecial Populations (Elderly and Poor Performance Status)Future Directions Comments on ResearchObstacles to Progress PMID:19352463

Future Directions in Idiopathic Pulmonary Fibrosis Research. An NHLBI Workshop Report

PubMed Central

Blackwell, Timothy S.; Tager, Andrew M.; Borok, Zea; Moore, Bethany B.; Schwartz, David A.; Anstrom, Kevin J.; Bar-Joseph, Ziv; Bitterman, Peter; Blackburn, Michael R.; Bradford, William; Brown, Kevin K.; Chapman, Harold A.; Collard, Harold R.; Cosgrove, Gregory P.; Deterding, Robin; Doyle, Ramona; Flaherty, Kevin R.; Garcia, Christine Kim; Hagood, James S.; Henke, Craig A.; Herzog, Erica; Hogaboam, Cory M.; Horowitz, Jeffrey C.; King, Talmadge E.; Loyd, James E.; Lawson, William E.; Marsh, Clay B.; Noble, Paul W.; Noth, Imre; Sheppard, Dean; Olsson, Julie; Ortiz, Luis A.; O’Riordan, Thomas G.; Oury, Tim D.; Raghu, Ganesh; Roman, Jesse; Sime, Patricia J.; Sisson, Thomas H.; Tschumperlin, Daniel; Violette, Shelia M.; Weaver, Timothy E.; Wells, Rebecca G.; White, Eric S.; Kaminski, Naftali; Martinez, Fernando J.; Wynn, Thomas A.; Thannickal, Victor J.

2014-01-01

The median survival of patients with idiopathic pulmonary fibrosis (IPF) continues to be approximately 3 years from the time of diagnosis, underscoring the lack of effective medical therapies for this disease. In the United States alone, approximately 40,000 patients die of this disease annually. In November 2012, the NHLBI held a workshop aimed at coordinating research efforts and accelerating the development of IPF therapies. Basic, translational, and clinical researchers gathered with representatives from the NHLBI, patient advocacy groups, pharmaceutical companies, and the U.S. Food and Drug Administration to review the current state of IPF research and identify priority areas, opportunities for collaborations, and directions for future research. The workshop was organized into groups that were tasked with assessing and making recommendations to promote progress in one of the following six critical areas of research: (1) biology of alveolar epithelial injury and aberrant repair; (2) role of extracellular matrix; (3) preclinical modeling; (4) role of inflammation and immunity; (5) genetic, epigenetic, and environmental determinants; (6) translation of discoveries into diagnostics and therapeutics. The workshop recommendations provide a basis for directing future research and strategic planning by scientific, professional, and patient communities and the NHLBI. PMID:24160862

Future directions in idiopathic pulmonary fibrosis research. An NHLBI workshop report.

PubMed

Blackwell, Timothy S; Tager, Andrew M; Borok, Zea; Moore, Bethany B; Schwartz, David A; Anstrom, Kevin J; Bar-Joseph, Ziv; Bitterman, Peter; Blackburn, Michael R; Bradford, William; Brown, Kevin K; Chapman, Harold A; Collard, Harold R; Cosgrove, Gregory P; Deterding, Robin; Doyle, Ramona; Flaherty, Kevin R; Garcia, Christine Kim; Hagood, James S; Henke, Craig A; Herzog, Erica; Hogaboam, Cory M; Horowitz, Jeffrey C; King, Talmadge E; Loyd, James E; Lawson, William E; Marsh, Clay B; Noble, Paul W; Noth, Imre; Sheppard, Dean; Olsson, Julie; Ortiz, Luis A; O'Riordan, Thomas G; Oury, Tim D; Raghu, Ganesh; Roman, Jesse; Sime, Patricia J; Sisson, Thomas H; Tschumperlin, Daniel; Violette, Shelia M; Weaver, Timothy E; Wells, Rebecca G; White, Eric S; Kaminski, Naftali; Martinez, Fernando J; Wynn, Thomas A; Thannickal, Victor J; Eu, Jerry P

2014-01-15

The median survival of patients with idiopathic pulmonary fibrosis (IPF) continues to be approximately 3 years from the time of diagnosis, underscoring the lack of effective medical therapies for this disease. In the United States alone, approximately 40,000 patients die of this disease annually. In November 2012, the NHLBI held a workshop aimed at coordinating research efforts and accelerating the development of IPF therapies. Basic, translational, and clinical researchers gathered with representatives from the NHLBI, patient advocacy groups, pharmaceutical companies, and the U.S. Food and Drug Administration to review the current state of IPF research and identify priority areas, opportunities for collaborations, and directions for future research. The workshop was organized into groups that were tasked with assessing and making recommendations to promote progress in one of the following six critical areas of research: (1) biology of alveolar epithelial injury and aberrant repair; (2) role of extracellular matrix; (3) preclinical modeling; (4) role of inflammation and immunity; (5) genetic, epigenetic, and environmental determinants; (6) translation of discoveries into diagnostics and therapeutics. The workshop recommendations provide a basis for directing future research and strategic planning by scientific, professional, and patient communities and the NHLBI.

Developing Therapies for Heart Failure with Preserved Ejection Fraction: Current State and Future Directions

PubMed Central

Butler, Javed; Fonarow, Gregg C.; Zile, Michael R.; Lam, Carolyn S.; Roessig, Lothar; Schelbert, Erik B.; Shah, Sanjiv J.; Ahmed, Ali; Bonow, Robert O.; Cleland, John GF; Cody, Robert J.; Chioncel, Ovidiu; Collins, Sean P.; Dunnmon, Preston; Filippatos, Gerasimos; Lefkowitz, Martin P.; Marti, Catherine N.; McMurray, John J.; Misselwitz, Frank; Nodari, Savina; O’Connor, Christopher; Pfeffer, Marc A.; Pieske, Burkert; Pitt, Bertram; Rosano, Guiseppe; Sabbah, Hani N.; Senni, Michele; Solomon, Scott D.; Stockbridge, Norman; Teerlink, John R.; Georgiopoulou, Vasiliki V.; Gheorghiade, Mihai

2014-01-01

The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the FDA and included representatives from academia, industry and regulatory agencies. This document summarizes the proceedings from this meeting. PMID:24720916

Current available therapies and future directions in the treatment of malignant gliomas

PubMed Central

Desjardins, Annick; Reardon, David A; Vredenburgh, James J

2009-01-01

The prognosis of patients diagnosed with malignant glioma (MG) remains poor. However, recent advances in neuro-oncology allowing a better understanding of this particular disease have allowed the development of new therapeutics. Many molecular genetic and signal transduction pathway targets have been identified that are now being investigated. Novel locoregional treatments, as well as strategies to improve regional delivery, are being evaluated. Studies of combinations of these approaches are also underway. In this review, we will discuss the current and future therapies under evaluation for the treatment of malignant gliomas. PMID:19707392

Internet-based Cognitive Behavioral Therapy for Depression: Current Progress & Future Directions

PubMed Central

Webb, Christian A.; Rosso, Isabelle M.; Rauch, Scott L.

2016-01-01

The World Health Organization (WHO) estimates that during a given 12-month period approximately 34 million people suffering from major depressive disorder go untreated in Europe and the Americas alone.1 Barriers to treatment include geographic distance, lack of mental health insurance, prohibitive cost of treatment, long wait-lists, and perceived stigma. Over the past two decades internet-based cognitive behavioral therapy (iCBT) programs have proliferated. A growing body of research supports the efficacy of iCBT for depression and other psychiatric conditions, and these programs may help address barriers that hinder access to effective treatment. The present review describes common iCBT programs along with the evidence base supporting their efficacy in reducing symptoms of depression, reviews research on moderators of treatment response, and provides suggestions for future directions in research and care. PMID:28475503

Restorative retinal laser therapy: Present state and future directions.

PubMed

Chhablani, Jay; Roh, Young Jung; Jobling, Andrew I; Fletcher, Erica L; Lek, Jia Jia; Bansal, Pooja; Guymer, Robyn; Luttrull, Jeffrey K

Because of complications and side effects, conventional laser therapy has taken a back seat to drugs in the treatment of macular diseases. Despite this, research on new laser modalities remains active. In particular, various approaches are being pursued to preserve and improve retinal structure and function. These include micropulsing, various exposure titration algorithms, and real-time temperature feedback control of short-pulse continuous wave lasers, and ultra-short-pulse nanosecond lasers. Some of these approaches are at the preclinical stage of development, whereas others are available for clinical use. Cell biology is providing important insights into the mechanisms of action of retinal laser treatment. We outline the technological bases of current laser platforms, their basic science, therapeutic concepts, clinical experience, and future directions for retinal laser treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Management of fibromyalgia syndrome in 2016

PubMed Central

Okifuji, Akiko; Gao, Jeff; Bokat, Christina; Hare, Bradford D

2016-01-01

Fibromyalgia syndrome is a chronic pain disorder and defies definitively efficacious therapy. In this review, we summarize the results from the early treatment research as well as recent research evaluating the pharmacological, interventional and nonpharmacological therapies. We further discuss future directions of fibromyalgia syndrome management; we specifically focus on the issues that are associated with currently available treatments, such as the need for personalized approach, new technologically oriented and interventional treatments, the importance of understanding and harnessing placebo effects and enhancement of patient engagement in therapy. PMID:27306300

State-of-the-art implantable cardiac assist device therapy for heart failure: bridge to transplant and destination therapy.

PubMed

Park, S J; Kushwaha, S S; McGregor, C G A

2012-01-01

Congestive heart failure is associated with poor quality of life (QoL) and low survival rates. The development of state-of-the-art cardiac devices holds promise for improved therapy in patients with heart failure. The field of implantable cardiac assist devices is changing rapidly with the emergence of continuous-flow pumps (CFPs). The important developments in this field, including pertinent clinical trials, registry reports, innovative research, and potential future directions are discussed in this paper.

Management of fibromyalgia syndrome in 2016.

PubMed

Okifuji, Akiko; Gao, Jeff; Bokat, Christina; Hare, Bradford D

2016-05-01

Fibromyalgia syndrome is a chronic pain disorder and defies definitively efficacious therapy. In this review, we summarize the results from the early treatment research as well as recent research evaluating the pharmacological, interventional and nonpharmacological therapies. We further discuss future directions of fibromyalgia syndrome management; we specifically focus on the issues that are associated with currently available treatments, such as the need for personalized approach, new technologically oriented and interventional treatments, the importance of understanding and harnessing placebo effects and enhancement of patient engagement in therapy.

Immunotherapy for advanced melanoma: future directions.

PubMed

Valpione, Sara; Campana, Luca G

2016-02-01

As calculated by the meta-analysis of Korn et al., the prognosis of metastatic melanoma in the pretarget and immunological therapy era was poor, with a median survival of 6.2 and a 1-year life expectancy of 25.5%. Nowadays, significant advances in melanoma treatment have been gained, and immunotherapy is one of the promising approaches to get to durable responses and survival improvement. The aim of the present review is to highlight the recent innovations in melanoma immunotherapy and to propose a critical perspective of the future directions of this enthralling oncology subspecialty.

Inorganic chemistry in nuclear imaging and radiotherapy: current and future directions

PubMed Central

Carroll, Valerie; Demoin, Dustin W.; Hoffman, Timothy J; Jurisson, Silvia S

2013-01-01

Summary Radiometals play an important role in diagnostic and therapeutic radiopharmaceuticals. This field of radiochemistry is multidisciplinary, involving radiometal production, separation of the radiometal from its target, chelate design for complexing the radiometal in a biologically stable environment, specific targeting of the radiometal to its in vivo site, and nuclear imaging and/or radiotherapy applications of the resultant radiopharmaceutical. The critical importance of inorganic chemistry in the design and application of radiometal-containing imaging and therapy agents is described from a historical perspective to future directions. PMID:25382874

Bioengineering Strategies for Designing Targeted Cancer Therapies

PubMed Central

Wen, Xuejun

2014-01-01

The goals of bioengineering strategies for targeted cancer therapies are (1) to deliver a high dose of an anticancer drug directly to a cancer tumor, (2) to enhance drug uptake by malignant cells, and (3) to minimize drug uptake by nonmalignant cells. Effective cancer-targeting therapies will require both passive- and active targeting strategies and a thorough understanding of physiologic barriers to targeted drug delivery. Designing a targeted therapy includes the selection and optimization of a nanoparticle delivery vehicle for passive accumulation in tumors, a targeting moiety for active receptor-mediated uptake, and stimuli-responsive polymers for control of drug release. The future direction of cancer targeting is a combinatorial approach, in which targeting therapies are designed to use multiple targeting strategies. The combinatorial approach will enable combination therapy for delivery of multiple drugs and dual ligand targeting to improve targeting specificity. Targeted cancer treatments in development and the new combinatorial approaches show promise for improving targeted anticancer drug delivery and improving treatment outcomes. PMID:23768509

Advances in Monitoring Cell-Based Therapies with Magnetic Resonance Imaging: Future Perspectives

PubMed Central

Ngen, Ethel J.; Artemov, Dmitri

2017-01-01

Cell-based therapies are currently being developed for applications in both regenerative medicine and in oncology. Preclinical, translational, and clinical research on cell-based therapies will benefit tremendously from novel imaging approaches that enable the effective monitoring of the delivery, survival, migration, biodistribution, and integration of transplanted cells. Magnetic resonance imaging (MRI) offers several advantages over other imaging modalities for elucidating the fate of transplanted cells both preclinically and clinically. These advantages include the ability to image transplanted cells longitudinally at high spatial resolution without exposure to ionizing radiation, and the possibility to co-register anatomical structures with molecular processes and functional changes. However, since cellular MRI is still in its infancy, it currently faces a number of challenges, which provide avenues for future research and development. In this review, we describe the basic principle of cell-tracking with MRI; explain the different approaches currently used to monitor cell-based therapies; describe currently available MRI contrast generation mechanisms and strategies for monitoring transplanted cells; discuss some of the challenges in tracking transplanted cells; and suggest future research directions. PMID:28106829

Indirect vs Direct Voice Therapy for Children With Vocal Nodules: A Randomized Clinical Trial.

PubMed

Hartnick, Christopher; Ballif, Catherine; De Guzman, Vanessa; Sataloff, Robert; Campisi, Paolo; Kerschner, Joseph; Shembel, Adrianna; Reda, Domenic; Shi, Helen; Sheryka Zacny, Elinore; Bunting, Glenn

2018-02-01

Benign vocal fold nodules affect 12% to 22% of the pediatric population, and 95% of otolaryngologists recommend voice therapy as treatment. However, no randomized clinical trials that we are aware of have shown its benefits. To determine the impact of voice therapy in children with vocal fold nodules according to pretherapy and posttherapy scores on the Pediatric Voice-Related Quality of Life (PVRQOL) survey; secondary objectives included changes in phonatory parameters. For this multicenter randomized clinical trial, 114 children ages 6 to 10 years with vocal fold nodules, PVRQOL scores less than 87.5, and dysphonia for longer than 12 weeks were recruited from outpatient voice and speech clinics. This age range was identified because these patients have not experienced pubertal changes of the larynx, tolerate stroboscopy, and cooperate with voice therapy. Participants were blinded to treatment arm. Participants received either indirect or direct therapy for 8 to 12 weeks. Indirect therapy focused on education and discussion of voice principles, while direct treatment used the stimulus, response, antecedent paradigm. The primary outcome measure was PVRQOL score change before and after treatment. Secondary phonatory measures were also compared. Overall, 114 children were recruited for study (mean [SD] age, 8 [1.4] years; 83 males [73%]); with 57 randomized to receive either indirect or direct therapy. Both direct and indirect therapy approaches showed significant differences in PVRQOL scores pretherapy to posttherapy. The mean increase in PVRQOL score for direct therapy was 19.2, and 14.7 for indirect therapy (difference, 4.5; 95.3% CI, -10.8 to 19.8). Of 44 participants in the direct therapy group, 27 (61%) achieved a clinically meaningful PVRQOL improvement, compared with 26 of 49 (53%) for indirect therapy (difference, 8%; 95% CI, -12 to 28). Post hoc stratification showed robust effects in the direct therapy group for older children (Cohen d = 0.50) and the latter two-thirds of participants (Cohen d = 0.46). Vocal fold nodules reduced in size in 31% (22 of 70) and completely resolved in 11% (8 of 70) of participants who consented to a second set of images after going through the recruitment process. Both direct and indirect voice therapy improved voice-related quality of life in children with vocal fold nodules, although there was no significant difference between approaches. Future studies may focus upon which voice therapy approaches are effective in treating age-defined populations. clinicaltrials.gov Identifier: NCT01255735.

Uveal Melanoma: From Diagnosis to Treatment and the Science in Between

PubMed Central

Chattopahdyay, Chandrani; Kim, Dae Won; Gombos, Dan; Oba, Junna; Qin, Yong; Williams, Michelle; Esmaeli, Bita; Grimm, Elizabeth; Wargo, Jennifer; Woodman, Scott; Patel, Sapna

2017-01-01

Melanomas of the choroid, ciliary body, and iris of the eye are collectively known as uveal melanomas. These cancers represent 5% of all melanoma diagnoses in the U.S., an age-adjusted risk of 5 per million. These less frequent melanomas are dissimilar to their more common cutaneous melanoma relative, with differing risk factors, primary treatment, anatomical spread, molecular changes, and responses to systemic therapy. Once metastatic, therapy options are limited, and often extrapolated from cutaneous melanoma therapies despite routine exclusion of uveal melanoma from clinical trials. Clinical trials directed at uveal melanoma have been completed or are in progress and data from these well-designed investigations will help guide future directions in this orphan disease. PMID:26991400

Newer influenza antivirals, biotherapeutics and combinations.

PubMed

Hayden, Frederick G

2013-01-01

This summary provides an overview of investigational antiviral agents for influenza and of future directions for development of influenza therapeutics. While progress in developing clinically useful antiviral agents for influenza has been generally slow, especially with respect to seriously ill and high-risk patients, important clinical studies of intravenous neuraminidase inhibitors, antibodies and drug combinations are currently in progress. The current decade offers the promise of developing small molecular weight inhibitors with novel mechanisms of action, including host-directed therapies, new biotherapeutics and drug combinations, that should provide more effective antiviral therapies and help mitigate the problem of antiviral resistance. Immunomodulatory interventions also offer promise but need to be based on better understanding of influenza pathogenesis, particularly in seriously ill patients. The development of combination interventions, immunomodulators and host-directed therapies presents unique clinical trial design and regulatory hurdles that remain to be addressed. © 2012 Blackwell Publishing Ltd.

Special report: workshop on 4D-treatment planning in actively scanned particle therapy--recommendations, technical challenges, and future research directions.

PubMed

Knopf, Antje; Bert, Christoph; Heath, Emily; Nill, Simeon; Kraus, Kim; Richter, Daniel; Hug, Eugen; Pedroni, Eros; Safai, Sairos; Albertini, Francesca; Zenklusen, Silvan; Boye, Dirk; Söhn, Matthias; Soukup, Martin; Sobotta, Benjamin; Lomax, Antony

2010-09-01

This article reports on a 4D-treatment planning workshop (4DTPW), held on 7-8 December 2009 at the Paul Scherrer Institut (PSI) in Villigen, Switzerland. The participants were all members of institutions actively involved in particle therapy delivery and research. The purpose of the 4DTPW was to discuss current approaches, challenges, and future research directions in 4D-treatment planning in the context of actively scanned particle radiotherapy. Key aspects were addressed in plenary sessions, in which leaders of the field summarized the state-of-the-art. Each plenary session was followed by an extensive discussion. As a result, this article presents a summary of recommendations for the treatment of mobile targets (intrafractional changes) with actively scanned particles and a list of requirements to elaborate and apply these guidelines clinically.

Precision Oncology and Genomically Guided Radiation Therapy: A Report From the American Society for Radiation Oncology/American Association of Physicists in Medicine/National Cancer Institute Precision Medicine Conference.

PubMed

Hall, William A; Bergom, Carmen; Thompson, Reid F; Baschnagel, Andrew M; Vijayakumar, Srinivasan; Willers, Henning; Li, X Allen; Schultz, Christopher J; Wilson, George D; West, Catharine M L; Capala, Jacek; Coleman, C Norman; Torres-Roca, Javier F; Weidhaas, Joanne; Feng, Felix Y

2018-06-01

To summarize important talking points from a 2016 symposium focusing on real-world challenges to advancing precision medicine in radiation oncology, and to help radiation oncologists navigate the practical challenges of precision, radiation oncology. The American Society for Radiation Oncology, American Association of Physicists in Medicine, and National Cancer Institute cosponsored a meeting on precision medicine in radiation oncology. In June 2016 numerous scientists, clinicians, and physicists convened at the National Institutes of Health to discuss challenges and future directions toward personalized radiation therapy. Various breakout sessions were held to discuss particular components and approaches to the implementation of personalized radiation oncology. This article summarizes the genomically guided radiation therapy breakout session. A summary of existing genomic data enabling personalized radiation therapy, ongoing clinical trials, current challenges, and future directions was collected. The group attempted to provide both a current overview of data that radiation oncologists could use to personalize therapy, along with data that are anticipated in the coming years. It seems apparent from the provided review that a considerable opportunity exists to truly bring genomically guided radiation therapy into clinical reality. Genomically guided radiation therapy is a necessity that must be embraced in the coming years. Incorporating these data into treatment recommendations will provide radiation oncologists with a substantial opportunity to improve outcomes for numerous cancer patients. More research focused on this topic is needed to bring genomic signatures into routine standard of care. Published by Elsevier Inc.

The Current Status and Future Directions of Heavy Charged Particle Therapy in Medicine

NASA Astrophysics Data System (ADS)

Levy, Richard P.; Blakely, Eleanor A.; Chu, William T.; Coutrakon, George B.; Hug, Eugen B.; Kraft, Gerhard; Tsujii, Hirohiko

2009-03-01

As aggressive, 3D-conformal treatment has become the clearly accepted goal of radiation oncology, heavy charged-particle treatment with protons and heavier ions has concurrently and relentlessly ascended to the forefront. Protons and helium nuclei, with relatively low linear-energy-transfer (LET) properties, have consistently been demonstrated to be beneficial for aggressive (high-dose) local treatment of many types of tumors. Protons have been applied to the majority of solid tumors, and have reached a high degree of general acceptance in radiation oncology after three decades and 55,000 patients treated. However, some 15% to 20% of tumor types have proven resistant to even the most aggressive low-LET irradiation. For these radio-resistant tumors, treatment with heavier ions (e.g., carbon) offers great potential benefit. These high-LET particles have increased relative biological effectiveness (RBE) that reaches its maximum in the Bragg peak. Irradiation with these heavier ions offers the unique combination of excellent 3D-dose distribution and increased RBE. We are presently witnessing several, important parallel developments in particle therapy. Protons will likely continue their exponential growth phase, and more compact design systems will make protons available to a larger patient population—thus becoming the "heavy charged particle of choice" for Cancer Centers with limited financial resources. In parallel, major academic efforts will further advance the field of heavier ion therapy, exploring all opportunities for particle treatment and continuing the search for the ideal particle(s) for specific tumors. The future of ion therapy will be best realized by clinical trials that have ready access to top-quality delivery of both protons and heavier ions that can be accurately shaped for treatment of a specific pathology, and which will permit direct randomized-trial comparison of the effectiveness of the various ions for different diseases. Optimal results will require: (1) sophisticated target delineation that integrates CT, MRI and PET imaging; (2) reliable RBE modeling algorithms; (3) efficient beam-scanning technology that compensates for organ movements; (4) online beam control proximal to and within the patient; and (5) better understanding of dose-fractionation parameters. The current status and the anticipated future directions of the role of particle therapy in medicine is a complex subject that involves a very intimate interplay of radiobiology, accelerator physics and radiation oncology. The intention of this relatively brief manuscript is to describe the underlying principles, present the historical developments, highlight the clinical results, focus on the technical advances, and suggest likely future directions. We have also attempted to present a balanced, consensus view of the past achievements and current strategies in particle therapy, in a manner of interest both to long-term experts and to educated newcomers to this field.

Immunotherapy for pancreatic cancer: present and future.

PubMed

Aroldi, Francesca; Zaniboni, Alberto

2017-06-01

Despite the identification of some efficient drugs for the treatment of metastatic pancreatic cancer, this tumor remains one of the most lethal cancers and is characterized by a strong resistance to therapies. Pancreatic cancer has some unique features including the presence of a microenvironment filled with immunosuppressive mediators and a dense stroma, which is both a physical barrier to drug penetration and a dynamic entity involved in immune system control. Therefore, the immune system has been hypothesized to play an important role in pancreatic cancer. Thus, therapies acting on innate or adaptive immunity are being investigated. Here, we review the literature, report the most interesting results and hypothesize future treatment directions.

Health psychology as a context for massage therapy: a conceptual model with CAM as mediator.

PubMed

Hymel, Glenn M; Rich, Grant J

2014-04-01

Health psychology represents a context within which massage therapy research, education, and practice can be positioned for the mutual benefit of both. Furthermore, complementary and alternative medicine (CAM) more often than not plays a mediating role in relating massage therapy to health psychology. On occasion, though, the linkage between health psychology and massage therapy can be quite direct without the mediating influence of CAM. This paper, accordingly, advances a conceptual model via both flowchart and Venn diagram displays for viewing the health psychology context for massage therapy with the possibility of CAM as a mediating factor. Attention is also given to the broad range of issues constituting contemporary health psychology as well as its correspondence to an equally diverse array of client populations and health conditions addressed in massage therapy research. Future directions in the areas of health psychology, CAM, and massage therapy are proposed with a view toward a mutual and reciprocal benefit accruing to these behavioral and health science arenas. Copyright © 2013 Elsevier Ltd. All rights reserved.

Taking Sides: An Integrative Review of the Impact of Laterality and Polarity on Efficacy of Therapeutic Transcranial Direct Current Stimulation for Anomia in Chronic Poststroke Aphasia

PubMed Central

Sandars, Margaret; Cloutman, Lauren; Woollams, Anna M.

2016-01-01

Anomia is a frequent and persistent symptom of poststroke aphasia, resulting from damage to areas of the brain involved in language production. Cortical neuroplasticity plays a significant role in language recovery following stroke and can be facilitated by behavioral speech and language therapy. Recent research suggests that complementing therapy with neurostimulation techniques may enhance functional gains, even amongst those with chronic aphasia. The current review focuses on the use of transcranial Direct Current Stimulation (tDCS) as an adjunct to naming therapy for individuals with chronic poststroke aphasia. Our survey of the literature indicates that combining therapy with anodal (excitatory) stimulation to the left hemisphere and/or cathodal (inhibitory) stimulation to the right hemisphere can increase both naming accuracy and speed when compared to the effects of therapy alone. However, the benefits of tDCS as a complement to therapy have not been yet systematically investigated with respect to site and polarity of stimulation. Recommendations for future research to help determine optimal protocols for combined therapy and tDCS are outlined. PMID:26819777

Phospholipid micelle-based magneto-plasmonic nanoformulation for magnetic field-directed, imaging-guided photo-induced cancer therapy.

PubMed

Ohulchanskyy, Tymish Y; Kopwitthaya, Atcha; Jeon, Mansik; Guo, Moran; Law, Wing-Cheung; Furlani, Edward P; Kim, Chulhong; Prasad, Paras N

2013-11-01

We present a magnetoplasmonic nanoplatform combining gold nanorods (GNR) and iron-oxide nanoparticles within phospholipid-based polymeric nanomicelles (PGRFe). The gold nanorods exhibit plasmon resonance absorbance at near infrared wavelengths to enable photoacoustic imaging and photothermal therapy, while the Fe3O4 nanoparticles enable magnetophoretic control of the nanoformulation. The fabricated nanoformulation can be directed and concentrated by an external magnetic field, which provides enhancement of a photoacoustic signal. Application of an external field also leads to enhanced uptake of the magnetoplasmonic formulation by cancer cells in vitro. Under laser irradiation at the wavelength of the GNR absorption peak, the PGRFe formulation efficiently generates plasmonic nanobubbles within cancer cells, as visualized by confocal microscopy, causing cell destruction. The combined magnetic and plasmonic functionalities of the nanoplatform enable magnetic field-directed, imaging-guided, enhanced photo-induced cancer therapy. In this study, a nano-formulation of gold nanorods and iron oxide nanoparticles is presented using a phospholipid micelle-based delivery system for magnetic field-directed and imaging-guided photo-induced cancer therapy. The gold nanorods enable photoacoustic imaging and photothermal therapy, while the Fe3O4 nanoparticles enable magnetophoretic control of the formulation. This and similar systems could enable more precise and efficient cancer therapy, hopefully in the near future, after additional testing. Copyright © 2013 Elsevier Inc. All rights reserved.

Vitamin K antagonists and direct thrombin inhibitors: present and future.

PubMed

Pineo, Graham F; Hull, Russell D

2005-02-01

Warfarin and related compounds are efficacious and safe in a variety of clinical thrombotic disorders; however, these drugs have a narrow therapeutic window, whereby inadequate therapy is associated with an increased thrombotic risk and overanticoagulation is associated with bleeding. Therefore, attempts have been made to develop alternatives to warfarin. Ximelagatran, an oral direct thrombin inhibitor, has been shown to be as efficacious and safe as warfarin for the prevention and treatment of different thrombotic disorders. This article reviews the pharmacology of the coumarins, the most commonly used vitamin K antagonists, and the practical aspects regarding their use in the management of thrombotic disorders. The future role of the oral direct thrombin inhibitor ximelagatran also is reviewed.

PSMA Theranostics: Current Status and Future Directions

PubMed Central

Afshar-Oromieh, Ali; Jadvar, Hossein; Ahmadzadehfar, Hojjat

2018-01-01

Prostate-specific membrane antigen (PSMA) is a promising target for imaging diagnostics and targeted radionuclide therapy (theranostics) of prostate cancer and its metastases. There is increasing evidence of encouraging response rates and a low toxicity profile of radioligand therapy (RLT) of metastatic castration-resistant prostate cancer using 177Lu-labeled PSMA ligands. In this article, we review the current status of diagnostics and therapy using radiolabeled PSMA ligands. We also suggest protocols for patient selection criteria and conduct of PSMA-based RLT. Challenges and opportunities of PSMA theranostics are discussed. PMID:29873291

[Biological therapies in systemic lupus erythematosus].

PubMed

Cairoli, Ernesto; Espinosa, Gerard; Cervera, Ricard

2010-07-01

The immunosuppressive agents used in patients with systemic lupus erythematosus (SLE) have significantly improved prognosis. However, it is necessary to develop more specific immunosuppressive treatments with less toxicity. Better understanding of the mechanisms involved in the loss of tolerance in autoimmune diseases has contributed to the development of potential new treatments called biologic therapies. The targets of these biological therapies are directed toward the B cell depletion, interference in the co-stimulation signals and the blockade of cytokines. Therapies using anti-CD20 monoclonal antibodies have shown satisfactory results especially in patients with SLE refractory to conventional treatment. The biological therapies provide encouraging results that represent a possible option in the treatment of refractory patients as well as a potential therapy in the future management of SLE.

ROLE OF YOGA IN THE TREATMENT OF NEUROTIC DISORDERS: CURRENT STATUS AND FUTURE DIRECTIONS

PubMed Central

Grover, Poonam; Varma, V.K.; Pershad, D.; Verma, S.K.

1994-01-01

A large number of studies have consistently demonstrated the potential of yoga, not only in the treatment of psychiatric and psychosomatic disorder but also in promoting positive physical and mental health. This paper reviews various studies on the treatment of neurosis with techniques derived from yoga. A few lacunae have been identified and possible directions for future research are outlined. It is hoped that research along these lines will develop a standardized method of yoga therapy which can be utilized and integrated within the existing methods of treatment of neurotic disorders. PMID:21743694

Not Missing the Future: A Call to Action for Investigating the Role of Regenerative Medicine Therapies in Pediatric/Adolescent Sports Injuries.

PubMed

Best, Thomas M; Caplan, Arnold; Coleman, Michael; Goodrich, Laurie; Hurd, Jason; Kaplan, Lee D; Noonan, Ben; Schoettle, Philip; Scott, Christopher; Stiene, Henry; Huard, Johnny

In August 2016, a group including sport medicine clinicians, researchers, and a bioethicist met in Vail, Colorado to discuss regenerative medicine and its potential role in youth sports injuries. There was consensus that a call to action is urgently needed to understand the current evidence base, the risks and rewards, and future directions of research and clinical practice for regenerative medicine therapies in youth sports. We present here a summary of our meeting, which was supported by the National Youth Sports Health and Safety Institute (NYSHSI), a partnership between the American College of Sports Medicine (ACSM) and Sanford Health. The group's goal is to educate practitioners and the public, and to pioneer a means of accumulating meaningful clinical data on regenerative medicine therapies in pediatric and adolescent athletes.

Art Therapy for Chronic Pain: Applications and Future Directions

ERIC Educational Resources Information Center

Angheluta, Anne-Marie; Lee, Bonnie K.

2011-01-01

Chronic pain is acknowledged as a phenomenological experience resulting from biological, psychological, and social interactions. Consequently, treatment for this complex and debilitating health phenomenon is often approached from multidisciplinary and biopsychosocial perspectives. One approach to treating chronic pain involves implementing…

Transcatheter mitral direct annuloplasty: state of the art.

PubMed

Maisano, F; Kuck, K H

2014-06-01

Transcatheter mitral interventions are emerging as a novel therapy for patients with severe symptomatic mitral regurgitation who are deemed to be high risk or inoperable. Surgical treatment of mitral regurgitation includes a wide spectrum of therapies, ranging from leaflet and annular repair, to mitral valve replacement. Annuloplasty plays a fundamental role in open heart mitral valve repair, since it is associated with longer durability and higher degree of mitral regurgitation reduction. Direct annuloplasty is the interventional methodology most closely reproducing open heart annular repair. We describe the challenges and opportunities of the most promising technologies currently under development which will become available in clinical practice in the next future.

Biomechanics in dermatology: Recent advances and future directions.

PubMed

Lewinson, Ryan T; Haber, Richard M

2017-02-01

Biomechanics is increasingly being recognized as an important research area in dermatology. To highlight only a few examples, biomechanics has contributed to the development of novel topical therapies for aesthetic and medical purposes, enhanced our understanding of the pathogenesis of plantar melanoma, and provided insight into the epidemiology of psoriatic disease. This article summarizes the findings from recent studies to demonstrate the important role that biomechanics may have in dermatologic disease and therapy and places these biomechanical findings in a clinical context for the practicing physician. In addition, areas for future biomechanics research and development in dermatology are discussed. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Update on B-cell targeted therapies for systemic lupus erythematosus.

PubMed

Mok, Chi Chiu

2014-06-01

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by flares and remission, leading to accrual of organ damage over time as a result of persistent tissue inflammation and treatment-related complications. Novel therapies aiming at better treatment response and fewer adverse effects are being tested in the pipeline. This review summarizes the B-cell abnormalities observed in patients with SLE, and updates recent data on the efficacy and safety of B-cell targeted therapies in the treatment of SLE. The pitfalls of clinical trial design and future directions of the development of SLE therapeutics are discussed. The variability of clinical response to treatment in SLE reflects the clinical and immunological heterogeneity of the disease. The treatment plan for patients with SLE should be individualized with the aim of eradicating disease activity, preventing flares and minimizing treatment-related complications. Despite the disappointment of recent clinical trials, B-cell remains the promising target of future SLE therapies. Results from ongoing clinical trials on B-cell targeted biological agents are eagerly awaited.

Two-step polymer- and liposome-enzyme prodrug therapies for cancer: PDEPT and PELT concepts and future perspectives.

PubMed

Scomparin, Anna; Florindo, Helena F; Tiram, Galia; Ferguson, Elaine L; Satchi-Fainaro, Ronit

2017-09-01

Polymer-directed enzyme prodrug therapy (PDEPT) and polymer enzyme liposome therapy (PELT) are two-step therapies developed to provide anticancer drugs site-selective intratumoral accumulation and release. Nanomedicines, such as polymer-drug conjugates and liposomal drugs, accumulate in the tumor site due to extravasation-dependent mechanism (enhanced permeability and retention - EPR - effect), and further need to cross the cellular membrane and release their payload in the intracellular compartment. The subsequent administration of a polymer-enzyme conjugate able to accumulate in the tumor tissue and to trigger the extracellular release of the active drug showed promising preclinical results. The development of polymer-enzyme, polymer-drug conjugates and liposomal drugs had undergone a vast advancement over the past decades. Several examples of enzyme mimics for in vivo therapy can be found in the literature. Moreover, polymer therapeutics often present an enzyme-sensitive mechanism of drug release. These nanomedicines can thus be optimal substrates for PDEPT and this review aims to provide new insights and stimuli toward the future perspectives of this promising combination. Copyright © 2017 Elsevier B.V. All rights reserved.

Juliette Alvin: her legacy for music therapy in Japan.

PubMed

Haneishi, Eri

2005-01-01

This historical study explored the contributions of Juliette Alvin to the early development of Japanese music therapy. Alvin visited Japan twice, once in 1967 and once in 1969. Despite the brevity of her stays, Alvin presented Japanese music therapy pioneers with a vivid picture of music therapy profession and clinical practice. Professional associations were launched, catalyzed by her visit. Alvin's clinical demonstrations inspired one of the music therapy pioneers to explore not only his own philosophy but a comprehensive view of the future direction of Japanese music therapy. A young musician, who worked as an assistant in Alvin's sessions, adopted her approach and became a leader in Japanese music therapy. Information about Alvin were obtained from letters, books, newspapers, journal articles, interviews with Japanese music therapy pioneers, and Alvin's own reports on her practice in Japan. Implications of Alvin's approach are also discussed for the role that music therapy today can play in addressing the needs of clients.

Newer influenza antivirals, biotherapeutics and combinations

PubMed Central

Hayden, Frederick G.

2012-01-01

Please cite this paper as: Hayden FG. (2012) Newer Influenza Antivirals, Biotherapeutics and Combinations. Influenza and Other Respiratory Viruses 7(Suppl. 1), 63–75. This summary provides an overview of investigational antiviral agents for influenza and of future directions for development of influenza therapeutics. While progress in developing clinically useful antiviral agents for influenza has been generally slow, especially with respect to seriously ill and high‐risk patients, important clinical studies of intravenous neuraminidase inhibitors, antibodies and drug combinations are currently in progress. The current decade offers the promise of developing small molecular weight inhibitors with novel mechanisms of action, including host‐directed therapies, new biotherapeutics and drug combinations, that should provide more effective antiviral therapies and help mitigate the problem of antiviral resistance. Immunomodulatory interventions also offer promise but need to be based on better understanding of influenza pathogenesis, particularly in seriously ill patients. The development of combination interventions, immunomodulators and host‐directed therapies presents unique clinical trial design and regulatory hurdles that remain to be addressed. PMID:23279899

Contemporary Cognitive Behavior Therapy: A Review of Theory, History, and Evidence.

PubMed

Thoma, Nathan; Pilecki, Brian; McKay, Dean

2015-09-01

Cognitive behavior therapy (CBT) has come to be a widely practiced psychotherapy throughout the world. The present article reviews theory, history, and evidence for CBT. It is meant as an effort to summarize the forms and scope of CBT to date for the uninitiated. Elements of CBT such as cognitive therapy, behavior therapy, and so-called "third wave" CBT, such as dialectical behavior therapy (DBT) and acceptance and commitment therapy (ACT) are covered. The evidence for the efficacy of CBT for various disorders is reviewed, including depression, anxiety disorders, personality disorders, eating disorders, substance abuse, schizophrenia, chronic pain, insomnia, and child/adolescent disorders. The relative efficacy of medication and CBT, or their combination, is also briefly considered. Future directions for research and treatment development are proposed.

Mistletoe in conventional oncological practice: exemplary cases.

PubMed

Legnani, Walter

2008-09-01

Mistletoe therapy, a cancer treatment suggested by Rudolf Steiner in 1920, is a typical and specific anthroposophic therapy, but could become more important today in the field of mainstream medicine. This article analyzes some of the most typical effects of mistletoe therapy based on the experience of more than 100 cases. A few patients were chosen who appear exemplary of the opportunities offered by mistletoe therapy. Their clinical history demonstrates an improvement in clinical condition and performance status, better quality of life, improved psychological status, reduction of infective events, better tolerance of concomitant chemoradiotherapy, and even a direct reduction of tumor size. The conclusion is that the patients may be indicative for future prospective clinical studies designed to confirm a real efficacy of mistletoe in cancer therapy.

Fighting fire with fire: attacking the complexity of human tumors with armed therapeutic viruses.

PubMed

Hermiston, Terry

2002-08-01

Cancer gene therapies have centered on the use of a single gene, directed against a particular property or single aspect of tumor biology, to treat neoplastic disease. These therapies have met with limited clinical success. This is, perhaps, not surprising given the complex and heterogeneous nature of solid tumors. Treatments targeted at confronting multiple dimensions of human tumors are needed. Armed therapeutic viruses (oncolytic viruses carrying therapeutic genes) represent a system where the concerted action of multiple therapeutics can be joined into a single agent, and represent a promising avenue for developing future cancer therapies.

Psychotherapy for Borderline Personality Disorder: Progress and Remaining Challenges.

PubMed

Links, Paul S; Shah, Ravi; Eynan, Rahel

2017-03-01

The main purpose of this review was to critically evaluate the literature on psychotherapies for borderline personality disorder (BPD) published over the past 5 years to identify the progress with remaining challenges and to determine priority areas for future research. A systematic review of the literature over the last 5 years was undertaken. The review yielded 184 relevant abstracts, and after applying inclusion criteria, 16 articles were fully reviewed based on the articles' implications for future research and/or clinical practice. Our review indicated that patients with various severities benefited from psychotherapy; more intensive therapies were not significantly superior to less intensive therapies; enhancing emotion regulation processes and fostering more coherent self-identity were important mechanisms of change; therapies had been extended to patients with BPD and posttraumatic stress disorder; and more research was needed to be directed at functional outcomes.

Surface engineering of graphene-based nanomaterials for biomedical applications.

PubMed

Shi, Sixiang; Chen, Feng; Ehlerding, Emily B; Cai, Weibo

2014-09-17

Graphene-based nanomaterials have attracted tremendous interest over the past decade due to their unique electronic, optical, mechanical, and chemical properties. However, the biomedical applications of these intriguing nanomaterials are still limited due to their suboptimal solubility/biocompatibility, potential toxicity, and difficulties in achieving active tumor targeting, just to name a few. In this Topical Review, we will discuss in detail the important role of surface engineering (i.e., bioconjugation) in improving the in vitro/in vivo stability and enriching the functionality of graphene-based nanomaterials, which can enable single/multimodality imaging (e.g., optical imaging, positron emission tomography, magnetic resonance imaging) and therapy (e.g., photothermal therapy, photodynamic therapy, and drug/gene delivery) of cancer. Current challenges and future research directions are also discussed and we believe that graphene-based nanomaterials are attractive nanoplatforms for a broad array of future biomedical applications.

Vaccines: an ongoing promise?

PubMed

Alsahli, M; Farrell, R J; Michetti, P

2001-01-01

Over the past decade, intensive research has focused on developing a vaccine therapy for Helicobacter pylori. Substantial unresolved questions cloud the current approach, and the development of a vaccine against this unique organism has proved very challenging. Many candidate vaccines have been tested in animal models. The immunogenicity and the safety of some vaccine formulations have been recently evaluated through clinical trials, and the efficacy of these vaccine therapies in humans will be determined in the near future. This article will provide an overview of the current knowledge of natural and vaccine-induced immune responses to H. pylori infection. It will also review past vaccine successes and failures in animal models and the limited experience to date in using vaccine therapy in humans. Several obstacles to H. pylori vaccine development efforts along with the future direction of these efforts will be discussed. Copyright 2001 S. Karger AG, Basel

Surface Engineering of Graphene-Based Nanomaterials for Biomedical Applications

PubMed Central

2015-01-01

Graphene-based nanomaterials have attracted tremendous interest over the past decade due to their unique electronic, optical, mechanical, and chemical properties. However, the biomedical applications of these intriguing nanomaterials are still limited due to their suboptimal solubility/biocompatibility, potential toxicity, and difficulties in achieving active tumor targeting, just to name a few. In this Topical Review, we will discuss in detail the important role of surface engineering (i.e., bioconjugation) in improving the in vitro/in vivo stability and enriching the functionality of graphene-based nanomaterials, which can enable single/multimodality imaging (e.g., optical imaging, positron emission tomography, magnetic resonance imaging) and therapy (e.g., photothermal therapy, photodynamic therapy, and drug/gene delivery) of cancer. Current challenges and future research directions are also discussed and we believe that graphene-based nanomaterials are attractive nanoplatforms for a broad array of future biomedical applications. PMID:25117569

Clinical proteomics-driven precision medicine for targeted cancer therapy: current overview and future perspectives.

PubMed

Zhou, Li; Wang, Kui; Li, Qifu; Nice, Edouard C; Zhang, Haiyuan; Huang, Canhua

2016-01-01

Cancer is a common disease that is a leading cause of death worldwide. Currently, early detection and novel therapeutic strategies are urgently needed for more effective management of cancer. Importantly, protein profiling using clinical proteomic strategies, with spectacular sensitivity and precision, offer excellent promise for the identification of potential biomarkers that would direct the development of targeted therapeutic anticancer drugs for precision medicine. In particular, clinical sample sources, including tumor tissues and body fluids (blood, feces, urine and saliva), have been widely investigated using modern high-throughput mass spectrometry-based proteomic approaches combined with bioinformatic analysis, to pursue the possibilities of precision medicine for targeted cancer therapy. Discussed in this review are the current advantages and limitations of clinical proteomics, the available strategies of clinical proteomics for the management of precision medicine, as well as the challenges and future perspectives of clinical proteomics-driven precision medicine for targeted cancer therapy.

Stem cell technology for tendon regeneration: current status, challenges, and future research directions

PubMed Central

Lui, Pauline Po Yee

2015-01-01

Tendon injuries are a common cause of physical disability. They present a clinical challenge to orthopedic surgeons because injured tendons respond poorly to current treatments without tissue regeneration and the time required for rehabilitation is long. New treatment options are required. Stem cell-based therapies offer great potential to promote tendon regeneration due to their high proliferative, synthetic, and immunomodulatory activities as well as their potential to differentiate to the target cell types and undergo genetic modification. In this review, I first recapped the challenges of tendon repair by reviewing the anatomy of tendon. Next, I discussed the advantages and limitations of using different types of stem cells compared to terminally differentiated cells for tendon tissue engineering. The safety and efficacy of application of stem cells and their modified counterparts for tendon tissue engineering were then summarized after a systematic literature search in PubMed. The challenges and future research directions to enhance, optimize, and standardize stem cell-based therapies for augmenting tendon repair were then discussed. PMID:26715856

Anaplastic lymphoma kinase inhibitors in brain metastases from ALK+ non-small cell lung cancer: hitting the target even in the CNS.

PubMed

Klempner, Samuel J; Ou, Sai-Hong Ignatius

2015-06-01

The paradigm shift occurring in non-small cell lung cancer (NSCLC) is encapsulated by the management of patients harboring oncogenic anaplastic lymphoma kinase (ALK) rearrangements. The unprecedented improvements in patient outcomes resulting from ALK-directed therapy have led to the appreciation of patterns of disease progression. Early studies have suggested that some tyrosine kinase inhibitors (TKIs), including ALK TKIs, inefficiently penetrated the blood brain barrier. With the increasing appreciation of the CNS as a sanctuary site in ALK TKI-treated patients, there is increasing focus and importance on the prevention and control of CNS metastases in ALK-rearranged NSCLC. The spectrum of CNS activity is variable among the currently available ALK TKI therapies and further studies are ongoing. In the following review we discuss the ability of current and future ALK inhibitors (ALK-i) to control and prevent CNS progression in patients with ALK-rearranged NSCLC. The potential implications for TKI sequencing and important future research directions are discussed.

Molecular and cellular biology of cerebral arteriovenous malformations: a review of current concepts and future trends in treatment.

PubMed

Rangel-Castilla, Leonardo; Russin, Jonathan J; Martinez-Del-Campo, Eduardo; Soriano-Baron, Hector; Spetzler, Robert F; Nakaji, Peter

2014-09-01

Arteriovenous malformations (AVMs) are classically described as congenital static lesions. However, in addition to rupturing, AVMs can undergo growth, remodeling, and regression. These phenomena are directly related to cellular, molecular, and physiological processes. Understanding these relationships is essential to direct future diagnostic and therapeutic strategies. The authors performed a search of the contemporary literature to review current information regarding the molecular and cellular biology of AVMs and how this biology will impact their potential future management. A PubMed search was performed using the key words "genetic," "molecular," "brain," "cerebral," "arteriovenous," "malformation," "rupture," "management," "embolization," and "radiosurgery." Only English-language papers were considered. The reference lists of all papers selected for full-text assessment were reviewed. Current concepts in genetic polymorphisms, growth factors, angiopoietins, apoptosis, endothelial cells, pathophysiology, clinical syndromes, medical treatment (including tetracycline and microRNA-18a), radiation therapy, endovascular embolization, and surgical treatment as they apply to AVMs are discussed. Understanding the complex cellular biology, physiology, hemodynamics, and flow-related phenomena of AVMs is critical for defining and predicting their behavior, developing novel drug treatments, and improving endovascular and surgical therapies.

Monitoring needs and goal-directed fluid therapy within an enhanced recovery program.

PubMed

Minto, Gary; Scott, Michael J; Miller, Timothy E

2015-03-01

Patients having major abdominal surgery need perioperative fluid supplementation; however, enhanced recovery principles mitigate against many of the factors that traditionally led to relative hypovolemia in the perioperative period. An estimate of fluid requirements for abdominal surgery can be made but individualization of fluid prescription requires consideration of clinical signs and hemodynamic variables. The literature supports goal-directed fluid therapy. Application of this evidence to justify stroke volume optimization in the setting of major surgery within an enhanced recovery program is controversial. This article places the evidence in context, reviews controversies, and suggests implications for current practice and future research. Copyright © 2015 Elsevier Inc. All rights reserved.

A Novel Therapy for People Who Attempt Suicide and Why We Need New Models of Suicide

PubMed Central

Michel, Konrad; Valach, Ladislav; Gysin-Maillart, Anja

2017-01-01

This paper presents a model of suicidal behaviour based on suicide as a goal-directed action, and its implications. An action theoretical model has guided the authors in the development of a brief therapy for individuals who attempt suicide (ASSIP—Attempted Suicide Short Intervention Program). Key elements are an early therapeutic alliance, narrative interviewing, psychoeducation, a joint case conceptualization, safety planning, and regular letters over 24 months. In a randomized controlled trial, ASSIP was highly effective in reducing the risk of suicide reattempts. The therapeutic elements in this treatment are described and possible implications for future directions in clinical suicide prevention discussed. PMID:28257071

Cancer Treatment Using Peptides: Current Therapies and Future Prospects

PubMed Central

Thundimadathil, Jyothi

2012-01-01

This paper discusses the role of peptides in cancer therapy with special emphasis on peptide drugs which are already approved and those in clinical trials. The potential of peptides in cancer treatment is evident from a variety of different strategies that are available to address the progression of tumor growth and propagation of the disease. Use of peptides that can directly target cancer cells without affecting normal cells (targeted therapy) is evolving as an alternate strategy to conventional chemotherapy. Peptide can be utilized directly as a cytotoxic agent through various mechanisms or can act as a carrier of cytotoxic agents and radioisotopes by specifically targeting cancer cells. Peptide-based hormonal therapy has been extensively studied and utilized for the treatment of breast and prostate cancers. Tremendous amount of clinical data is currently available attesting to the efficiency of peptide-based cancer vaccines. Combination therapy is emerging as an important strategy to achieve synergistic effects in fighting cancer as a single method alone may not be efficient enough to yield positive results. Combining immunotherapy with conventional therapies such as radiation and chemotherapy or combining an anticancer peptide with a nonpeptidic cytotoxic drug is an example of this emerging field. PMID:23316341

A narrative review of schemas and schema therapy outcomes in the eating disorders.

PubMed

Pugh, Matthew

2015-07-01

Whilst cognitive-behavioural therapy has demonstrated efficacy in the treatment of eating disorders, therapy outcomes and current conceptualizations still remain inadequate. In light of these shortcomings there has been growing interest in the utility of schema therapy applied to eating pathology. The present article first provides a narrative review of empirical literature exploring schemas and schema processes in eating disorders. Secondly, it critically evaluates outcome studies assessing schema therapy applied to eating disorders. Current evidence lends support to schema-focused conceptualizations of eating pathology and confirms that eating disorders are characterised by pronounced maladaptive schemas. Treatment outcomes also indicate that schema therapy, the schema-mode approach, and associated techniques are promising interventions for complex eating disorders. Implications for clinical practice and future directions for research are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cell therapy for heart failure: a comprehensive overview of experimental and clinical studies, current challenges, and future directions.

PubMed

Sanganalmath, Santosh K; Bolli, Roberto

2013-08-30

Despite significant therapeutic advances, the prognosis of patients with heart failure (HF) remains poor, and current therapeutic approaches are palliative in the sense that they do not address the underlying problem of the loss of cardiac tissue. Stem cell-based therapies have the potential to fundamentally transform the treatment of HF by achieving what would have been unthinkable only a few years ago-myocardial regeneration. For the first time since cardiac transplantation, a therapy is being developed to eliminate the underlying cause of HF, not just to achieve damage control. Since the initial report of cell therapy (skeletal myoblasts) in HF in 1998, research has proceeded at lightning speed, and numerous preclinical and clinical studies have been performed that support the ability of various stem cell populations to improve cardiac function and reduce infarct size in both ischemic and nonischemic cardiomyopathy. Nevertheless, we are still at the dawn of this therapeutic revolution. Many important issues (eg, mechanism(s) of action of stem cells, long-term engraftment, optimal cell type(s), and dose, route, and frequency of cell administration) remain to be resolved, and no cell therapy has been conclusively shown to be effective. The purpose of this article is to critically review the large body of work performed with respect to the use of stem/progenitor cells in HF, both at the experimental and clinical levels, and to discuss current controversies, unresolved issues, challenges, and future directions. The review focuses specifically on chronic HF; other settings (eg, acute myocardial infarction, refractory angina) are not discussed.

Chimaeric antigen receptor T-cell therapy for tumour immunotherapy

PubMed Central

Sha, Huan-huan; Wang, Dan-dan; Yan, Da-li; Hu, Yong; Yang, Su-jin; Liu, Si-wen

2017-01-01

Chimaeric antigen receptor (CAR) T-cell therapies, as one of the cancer immunotherapies, have heralded a new era of treating cancer. The accumulating data, especially about CAR-modified T cells against CD19 support that CAR T-cell therapy is a highly effective immune therapy for B-cell malignancies. Apart from CD19, there have been many trials of CAR T cells directed other tumour specific or associated antigens (TSAs/TAAs) in haematologic malignancies and solid tumours. This review will briefly summarize basic CAR structure, parts of reported TSAs/TAAs, results of the clinical trials of CAR T-cell therapies as well as two life-threatening side effects. Experiments in vivo or in vitro, ongoing clinical trials and the outlook for CAR T-cell therapies also be included. Our future efforts will focus on identification of more viable cancer targets and more strategies to make CAR T-cell therapy safer. PMID:28053197

Medical treatment of Cushing's Disease.

PubMed

Cuevas-Ramos, Daniel; Fleseriu, Maria

2016-09-01

Cushing's Syndrome (CS) is a serious endocrine disease that results from the adverse clinical consequences of chronic exposure to high levels of glucocorticoids. Most patients with endogenous CS have an adrenocorticotropin (ACTH)-secreting pituitary corticotroph adenoma, i.e. Cushing's Disease (CD). The first-line therapy for CD is transsphenoidal pituitary surgery. If tumor removal is incomplete or unsuccessful, persistent hypercortisolism will require further treatment. Repeat surgery, medical therapy, radiation and bilateral adrenalectomy are all second line therapy options; however, medical therapy can be also used as first line therapy in patients who cannot undergo surgery, or to decrease cortisol values and/or improve co-morbidities. Medications used in the treatment of CD, classified into three groups: pituitary directed drugs, adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers, are reviewed. Future 'on the horizon' treatment options are also discussed.

Adoptive Cell Therapy for Metastatic Melanoma.

PubMed

Merhavi-Shoham, Efrat; Itzhaki, Orit; Markel, Gal; Schachter, Jacob; Besser, Michal J

Adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TILs) is a powerful form of immunotherapy by inducing durable complete responses that significantly extend the survival of melanoma patients. Mutation-derived neoantigens were recently identified as key factors for tumor recognition and rejection by TILs. The isolation of T-cell receptor (TCR) genes directed against neoantigens and their retransduction into peripheral T cells may provide a new form of ACT.Genetic modifications of T cells with chimeric antigen receptors (CARs) have demonstrated remarkable clinical results in hematologic malignancies, but are so far less effective in solid tumors. Only very limited reports exist in melanoma. Progress in CAR T-cell engineering, including neutralization of inhibitory signals or additional safety switches, may open opportunities also in melanoma.We review clinical results and latest developments of adoptive therapies with TILs, T-cell receptor, and CAR-modified T cells and discuss future directions for the treatment of melanoma.

Adjuvant therapy in renal cell carcinoma: does higher risk for recurrence improve the chance for success?

PubMed

Figlin, R A; Leibovich, B C; Stewart, G D; Negrier, S

2018-02-01

The success of targeted therapies, including inhibitors of the vascular endothelial growth factor pathway or the mammalian target of rapamycin, in the treatment of metastatic renal cell carcinoma led to interest in testing their efficacy in the adjuvant setting. Results from the first trials are now available, with other studies due to report imminently. This review provides an overview of adjuvant targeted therapy in renal cell carcinoma, including interpretation of currently available conflicting data and future direction of research. We discuss the key differences between the completed targeted therapy adjuvant trials, and highlight the importance of accurately identifying patients who are likely to benefit from adjuvant treatment. We also consider reasons why blinded independent radiology review and treatment dose may prove critical for adjuvant treatment success. The implications of using disease-free survival as a surrogate end point for overall survival from the patient perspective and measurement of health benefit have recently been brought into focus and are discussed. Finally, we discuss how the ongoing adjuvant trials with targeted therapies and checkpoint inhibitors may improve our understanding and ability to prevent tumor recurrence after nephrectomy in the future.

Mindfulness-based cognitive therapy for depression: trends and developments.

PubMed

MacKenzie, Meagan B; Kocovski, Nancy L

2016-01-01

Mindfulness-based cognitive therapy (MBCT) was developed as a psychological intervention for individuals at risk of depressive relapse. Possible mechanisms of change for this intervention are in line with its theoretical underpinnings, and include increases in mindfulness and/or decreases in negative repetitive thoughts. This review provides an overview of current trends in MBCT research, including efficacy and questions regarding the specific effects of MBCT in light of recent comparisons with structurally equivalent control conditions, mechanisms of change, and moderators of treatment outcome. In addition, future directions are discussed, such as challenges with training an adequate number of therapists and disseminating this therapy.

Breakthrough Therapies: Cystic Fibrosis (CF) Potentiators and Correctors

PubMed Central

Solomon, George M.; Marshall, Susan G.; Ramsey, Bonnie W.; Rowe, Steven M.

2015-01-01

Cystic Fibrosis is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene resulting in abnormal protein function. Recent advances of targeted molecular therapies and high throughput screening have resulted in multiple drug therapies that target many important mutations in the CFTR protein. In this review, we provide the latest results and current progress of CFTR modulators for the treatment of cystic fibrosis, focusing on potentiators of CFTR channel gating and Phe508del processing correctors for the Phe508del CFTR mutation. Special emphasis is placed on the molecular basis underlying these new therapies and emerging results from the latest clinical trials. The future directions for augmenting the rescue of Phe508del with CFTR modulators is also emphasized. PMID:26097168

Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

NASA Astrophysics Data System (ADS)

Liu, Yang; Yuan, Hsiangkuo; Fales, Andrew; Register, Janna; Vo-Dinh, Tuan

2015-08-01

Plasmonics-active gold nanoparticles offer excellent potential in molecular imaging and cancer therapy. Among them, gold nanostars (AuNS) exhibit cross-platform flexibility as multimodal contrast agents for macroscopic X-ray computer tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), as well as nanoprobes for photoacoustic tomography (PAT), two-photon photoluminescence (TPL) and surface-enhanced Raman spectroscopy (SERS). Their surfactant-free surface enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy. This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed.

Future Directions for Monitoring Treatment Response in Colorectal Cancer

PubMed Central

Walker, Avery S.; Zwintscher, Nathan P.; Johnson, Eric K.; Maykel, Justin A.; Stojadinovic, Alexander; Nissan, Aviram; Avital, Itzhak; Brücher, Björn LDM; Steele, Scott R.

2014-01-01

Treatment of advanced colon and rectal cancer has significantly evolved with the introduction of neoadjuvant chemoradiation therapy so much that, along with more effective chemotherapy regimens, surgery has been considered unnecessary among some institutions for select patients. The tumor response to these treatments has also improved and ultimately has been shown to have a direct effect on prognosis. Yet, the best way to monitor that response, whether clinically, radiologically, or with laboratory findings, remains controversial. The authors' aim is to briefly review the options available and, more importantly, examine emerging and future options to assist in monitoring treatment response in cases of locally advanced rectal cancer and metastatic colon cancer. PMID:24396497

Combination therapies for the treatment of HER2-positive breast cancer: current and future prospects.

PubMed

Brandão, Mariana; Pondé, Noam F; Poggio, Francesca; Kotecki, Nuria; Salis, Mauren; Lambertini, Matteo; de Azambuja, Evandro

2018-05-24

HER2-positive disease is an aggressive subtype of breast cancer that has been revolutionized by anti-HER2 directed therapies. Multiple drugs have been developed and are currently in clinical use, including trastuzumab, lapatinib, pertuzumab, T-DM1, and neratinib, alone or combined in 'dual HER2-blockade' regimens. Areas covered: A comprehensive literature review was performed regarding the current state and the future of combination regimens containing anti-HER2 agents, focusing on their efficacy, toxicity, and cost-effectiveness. Expert commentary: The combination of trastuzumab/pertuzumab is approved in all disease settings, while trastuzumab/neratinib is approved in the adjuvant setting and trastuzumab/lapatinib in metastatic disease. Meanwhile, as breast cancer biology and resistance mechanisms become clearer, combinations with drugs like PI3K/Akt/mTOR inhibitors, CDK4/6 inhibitors, anti-PD(L)1 antibodies, endocrine therapy, and new anti-HER2 agents (panHER and HER2 tyrosine kinase inhibitors, bispecific antibodies, anti-HER3 antibodies, and antibody-drug conjugates) are being extensively tested in clinical trials. More specific strategies for the 'triple-positive' (estrogen receptor-positive/HER2-positive) disease are also being explored. However, there is an urgent need for the development of predictive biomarkers for a better tailoring of anti-HER2 directed therapy. This is the only way to further improve clinical outcomes and quality of life and to decrease costs and toxicities of unnecessary treatments.

Non-invasive brain stimulation approaches to fibromyalgia pain

PubMed Central

Short, Baron; Borckardt, Jeffrey J; George, Mark; Beam, Will; Reeves, Scott T

2010-01-01

Fibromyalgia is a poorly understood disorder that likely involves central nervous system sensory hypersensitivity. There are a host of genetic, neuroendocrine and environmental abnormalities associated with the disease, and recent research findings suggest enhanced sensory processing, and abnormalities in central monoamines and cytokines expression in patients with fibromyalgia. The morbidity and financial costs associated with fibromyalgia are quite high despite conventional treatments with antidepressants, anticonvulsants, low-impact aerobic exercise and psychotherapy. Noninvasive brain stimulation techniques, such as transcranial direct current stimulation, transcranial magnetic stimulation, and electroconvulsive therapy are beginning to be studied as possible treatments for fibromyalgia pain. Early studies appear promising but more work is needed. Future directions in clinical care may include innovative combinations of noninvasive brain stimulation, pharmacological augmentation, and behavior therapies. PMID:21841959

Historical perspectives and future directions in the surgical management of retroperitoneal sarcoma.

PubMed

Tseng, William W; Seo, Hyun Jae; Pollock, Raphael E; Gronchi, Alessandro

2018-01-01

Retroperitoneal sarcomas (RPS) have fascinated and intrigued physicians both past and present. Operative mortality rates were historically very high and complete resection was not possible for the majority of patients until only the last 2 decades. More recently, changes to the surgical approach and clinical decision-making in RPS have improved patient outcomes. With select integration of nonsurgical therapies, continued RPS-specific research, and ongoing collaborative efforts among major referral centers, the future appears promising. © 2017 Wiley Periodicals, Inc.

Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises.

PubMed

Aragon-Ching, Jeanny B; Trump, Donald L

2016-09-01

Bladder urothelial cancers remain an important urologic cancer with limited treatment options in the locally advanced and metastatic setting. While neoadjuvant chemotherapy for locally advanced muscle-invasive cancers has shown overall survival benefit, clinical uptake in practice have lagged behind. Controversies surrounding adjuvant chemotherapy use are also ongoing. Systemic therapies for metastatic bladder cancer have largely used platinum-based therapies without effective standard second-line therapy options for those who fail, although vinflunine is approved in Europe as a second-line therapy based on a Phase III trial, and most recently, atezolizumab, a checkpoint inhibitor, was approved by the US FDA. Given increasing recognition of mutational signatures expressed in urothelial carcinomas, several promising agents with use of VEGF-targeted therapies, HER2-directed agents and immunotherapies with PD-1/PD-L1 antibodies in various settings are discussed herein.

Cardiac gene therapy: Recent advances and future directions.

PubMed

Mason, Daniel; Chen, Yu-Zhe; Krishnan, Harini Venkata; Sant, Shilpa

2015-10-10

Gene therapy has the potential to serve as an adaptable platform technology for treating various diseases. Cardiovascular disease is a major cause of mortality in the developed world and genetic modification is steadily becoming a more plausible method to repair and regenerate heart tissue. Recently, new gene targets to treat cardiovascular disease have been identified and developed into therapies that have shown promise in animal models. Some of these therapies have advanced to clinical testing. Despite these recent successes, several barriers must be overcome for gene therapy to become a widely used treatment of cardiovascular diseases. In this review, we evaluate specific genetic targets that can be exploited to treat cardiovascular diseases, list the important delivery barriers for the gene carriers, assess the most promising methods of delivering the genetic information, and discuss the current status of clinical trials involving gene therapies targeted to the heart. Copyright © 2015 Elsevier B.V. All rights reserved.

HIV Treatment and Prevention: An Overview of Recommendations From the 2016 IAS–USA Antiretroviral Guidelines Panel

PubMed Central

Volberding, Paul A.

2017-01-01

Updated recommendations from the IAS–USA Antiretroviral Guidelines Panel on antiretroviral therapy for the treatment and prevention of HIV infection in adults were published in the Journal of the American Medical Association in 2016. The updated, evidence-based recommendations address when to initiate antiretroviral therapy, recommended initial antiretroviral regimens, including integrase strand transfer inhibitor (InSTI)-based regimens, recommended regimens for persons in whom an InSTI is not an option, and special treatment considerations. The interface between antiretroviral therapy and opportunistic infections, when and how to switch antiretroviral therapy, laboratory monitoring, engagement in care, adherence to antiretroviral therapy, and use of antiretroviral therapy as HIV prevention are also discussed, as well as future directions in HIV treatment. This article summarizes an IAS–USA continuing education webinar presented by Paul A. Volberding, MD, in August 2016. PMID:28402930

Chemical compound-based direct reprogramming for future clinical applications

PubMed Central

Takeda, Yukimasa; Harada, Yoshinori; Yoshikawa, Toshikazu; Dai, Ping

2018-01-01

Recent studies have revealed that a combination of chemical compounds enables direct reprogramming from one somatic cell type into another without the use of transgenes by regulating cellular signaling pathways and epigenetic modifications. The generation of induced pluripotent stem (iPS) cells generally requires virus vector-mediated expression of multiple transcription factors, which might disrupt genomic integrity and proper cell functions. The direct reprogramming is a promising alternative to rapidly prepare different cell types by bypassing the pluripotent state. Because the strategy also depends on forced expression of exogenous lineage-specific transcription factors, the direct reprogramming in a chemical compound-based manner is an ideal approach to further reduce the risk for tumorigenesis. So far, a number of reported research efforts have revealed that combinations of chemical compounds and cell-type specific medium transdifferentiate somatic cells into desired cell types including neuronal cells, glial cells, neural stem cells, brown adipocytes, cardiomyocytes, somatic progenitor cells, and pluripotent stem cells. These desired cells rapidly converted from patient-derived autologous fibroblasts can be applied for their own transplantation therapy to avoid immune rejection. However, complete chemical compound-induced conversions remain challenging particularly in adult human-derived fibroblasts compared with mouse embryonic fibroblasts (MEFs). This review summarizes up-to-date progress in each specific cell type and discusses prospects for future clinical application toward cell transplantation therapy. PMID:29739872

Neural stimulation for Parkinson's disease: current therapies and future directions.

PubMed

Neimat, Joseph S; Hamani, Clement; Lozano, Andres M

2006-01-01

Neural stimulation has rapidly become an integral tool in the treatment of Parkinson's disease and other movement disorders. Today it serves as an important adjunct to medical therapy that continues to gain applicability to patients in whom the disease has progressed significantly. Studies have demonstrated efficacy in several deep-brain targets, with prolonged benefit exceeding 5-year follow-up times. Continuing study is teaching us more about the mechanism of deep-brain stimulation effect. New targets, which may treat the disease more successfully, are being examined. In this review, the history of deep-brain stimulation, the rationale for the known targets of stimulation; the clinical evidence demonstrating their benefit and, finally, future perspectives on new treatments that are being investigated and may have an impact on the field are discussed.

Cirrhotic portal hypertension: current and future medical therapy for primary and secondary prevention of variceal bleeding.

PubMed

Laleman, W; Nevens, F

2006-08-01

Portal hypertension (PHT) is the most common complication of chronic liver disease and develops in the vast majority of patients with cirrhosis. It is characterized by an increase of the portal vein pressure, and leads to the development of gastroesophageal varices, ascites, renal dysfunction and hepatic encephalopathy. Over the years, it has become clear that a decrease in portal pressure is not only protective against the risk of variceal (re)bleeding but is also associated with a lower long-term risk of developing other complications and with an improved long-term survival. At present, non-selective b-blockers remain the medical treatment of choice for both primary and secondary prophylaxis. However, recent advances in the knowledge of the pathophysiology of cirrhotic PHT have directed future therapy towards the increased intrahepatic vascular resistance, which in part is determined by an increased hepatic vascular tone. This increased vasculogenic component provides the motivation to the use of therapies aimed at increasing intrahepatic vasorelaxing capacity on the one hand and at antagonizing excessive intrahepatic vasoconstrictor force on the other hand. This review covers current and future developments in the treatment of PHT with regard to primary and secondary prophylaxis.

Gene therapy comes of age.

PubMed

Dunbar, Cynthia E; High, Katherine A; Joung, J Keith; Kohn, Donald B; Ozawa, Keiya; Sadelain, Michel

2018-01-12

After almost 30 years of promise tempered by setbacks, gene therapies are rapidly becoming a critical component of the therapeutic armamentarium for a variety of inherited and acquired human diseases. Gene therapies for inherited immune disorders, hemophilia, eye and neurodegenerative disorders, and lymphoid cancers recently progressed to approved drug status in the United States and Europe, or are anticipated to receive approval in the near future. In this Review, we discuss milestones in the development of gene therapies, focusing on direct in vivo administration of viral vectors and adoptive transfer of genetically engineered T cells or hematopoietic stem cells. We also discuss emerging genome editing technologies that should further advance the scope and efficacy of gene therapy approaches. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Current and Emerging Directions in the Treatment of Eating Disorders

PubMed Central

Brown, Tiffany A.; Keel, Pamela K.

2012-01-01

Eating disorders are a significant source of psychiatric morbidity in young women and demonstrate high comorbidity with mood, anxiety, and substance use disorders. Thus, clinicians may encounter eating disorders in the context of treating other conditions. This review summarizes the efficacy of current and emerging treatments for anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Treatment trials were identified using electronic and manual searches and by reviewing abstracts from conference proceedings. Family based therapy has demonstrated superiority for adolescents with AN but no treatment has established superiority for adults. For BN, both 60 mg fluoxetine and cognitive behavioral therapy (CBT) have well-established efficacy. For BED, selective serotonin reuptake inhibitors, CBT, and interpersonal psychotherapy have demonstrated efficacy. Emerging directions for AN include investigation of the antipsychotic olanzapine and several novel psychosocial treatments. Future directions for BN and BED include increasing CBT disseminability, targeting affect regulation, and individualized stepped-care approaches. PMID:22879753

Cognitive rehabilitation for patients with schizophrenia in Korea.

PubMed

Lee, Won Hye; Lee, Woo Kyeong

2017-02-01

Psychosocial rehabilitation programs received mental health professional support in addition to traditional medication therapy. Many psychosocial programs were developed since the 1990s, including cognitive remediation therapy. In this review, we focus on cognitive remediation therapy in Korea since the 1990s. We review several cognitive rehabilitation programs developed in Korea and their outcome studies and suggest future research directions and prospects. We reviewed cognitive rehabilitation programs including social cognitive training as well as more recent forms of computerized cognitive rehabilitation. Although there are differences in cognitive domains by training targets, almost all neurocognitive remediation trainings in Korea have beneficial effects on early visual processing, various attention types, and executive function. Future studies need to investigate the mechanisms and various mediators underlying the relationships between cognitive functions and functional outcomes. With more comprehensive cognitive and social cognitive programs, we can enhance both cognition and functional outcomes of the patients with schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Charged-particle therapy in cancer: clinical uses and future perspectives.

PubMed

Durante, Marco; Orecchia, Roberto; Loeffler, Jay S

2017-08-01

Radiotherapy with high-energy charged particles has become an attractive therapeutic option for patients with several tumour types because this approach better spares healthy tissue from radiation than conventional photon therapy. The cost associated with the delivery of charged particles, however, is higher than that of even the most elaborate photon-delivery technologies. Reliable evidence of the relative cost-effectiveness of both modalities can only come from the results of randomized clinical trials. Thus, the hurdles that currently limit direct comparisons of these two approaches in clinical trials, especially those related to insurance coverage, should be removed. Herein, we review several randomized trials of charged-particle therapies that are ongoing, with results that will enable selective delivery to patients who are most likely to benefit from them. We also discuss aspects related to radiobiology, including the immune response and hypoxia, which will need to be taken into consideration in future randomized trials to fully exploit the potential of charged particles.

Cell Therapy for Lung Diseases. Report from an NIH–NHLBI Workshop, November 13–14, 2012

PubMed Central

Matthay, Michael A.; Anversa, Piero; Bhattacharya, Jahar; Burnett, Bruce K.; Chapman, Harold A.; Hare, Joshua M.; Hei, Derek J.; Hoffman, Andrew M.; Kourembanas, Stella; McKenna, David H.; Ortiz, Luis A.; Ott, Harald C.; Tente, William; Thébaud, Bernard; Trapnell, Bruce C.; Weiss, Daniel J.; Yuan, Jason X.-J.

2013-01-01

The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health convened the Cell Therapy for Lung Disease Working Group on November 13–14, 2012, to review and formulate recommendations for future research directions. The workshop brought together investigators studying basic mechanisms and the roles of cell therapy in preclinical models of lung injury and pulmonary vascular disease, with clinical trial experts in cell therapy for cardiovascular diseases and experts from the NHLBI Production Assistance for Cell Therapy program. The purpose of the workshop was to discuss the current status of basic investigations in lung cell therapy, to identify some of the scientific gaps in current knowledge regarding the potential roles and mechanisms of cell therapy in the treatment of lung diseases, and to develop recommendations to the NHLBI and the research community on scientific priorities and practical steps that would lead to first-in-human trials of lung cell therapy. PMID:23713908

Gene delivery for cancer therapy.

PubMed

Zhang, Teng

2014-01-01

Gene therapy has potential in the treatment of human cancers. However, its clinical implication has only achieved little success due to the lack of an efficient gene delivery system. A major hurdle in the current available approaches is in the ability to transduce target tissues at very high efficiencies that ultimately lead to therapeutic levels of transgene expression. This review outlines the characteristics and utilities of several available gene delivery systems, including their advantages and drawbacks in the context of cancer treatment. A perspective of existing challenges and future directions is also included.

Targeted genetic and viral therapy for advanced head and neck cancers.

PubMed

Huang, Pin-I; Chang, Ju-Fang; Kirn, David H; Liu, Ta-Chiang

2009-06-01

Head and neck cancers usually present with advanced disease and novel therapies are urgently needed. Genetic therapy aims at restoring malfunctioned tumor suppressor gene(s) or introducing proapoptotic genes. Oncolytic virotherapeutics induce multiple cycles of cancer-specific virus replication, followed by oncolysis, virus spreading and infection of adjacent cancer cells. Oncolytic viruses can also be armed to express therapeutic transgene(s). Recent advances in preclinical and clinical studies are revealing the potential of both therapeutic classes for advanced head and neck cancers, including the approval of two products (Gendicine and H101) by a governmental agency. This review summarizes the available clinical data to date and discusses the challenges and future directions.

Technologies and combination therapies for enhancing movement training for people with a disability

PubMed Central

2012-01-01

There has been a dramatic increase over the last decade in research on technologies for enhancing movement training and exercise for people with a disability. This paper reviews some of the recent developments in this area, using examples from a National Science Foundation initiated study of mobility research projects in Europe to illustrate important themes and key directions for future research. This paper also reviews several recent studies aimed at combining movement training with plasticity or regeneration therapies, again drawing in part from European research examples. Such combination therapies will likely involve complex interactions with motor training that must be understood in order to achieve the goal of eliminating severe motor impairment. PMID:22463132

Evidence-based review of interventions for autism used in or of relevance to occupational therapy.

PubMed

Case-Smith, Jane; Arbesman, Marian

2008-01-01

Occupational therapy practitioners are among the professionals who provide services to children and adults with autism spectrum disorder (ASD), embracing both leadership and supportive roles in service delivery. The study's primary aims were as follows: (1) to identify, evaluate, and synthesize the research literature on interventions for ASD of relevance to occupational therapy and (2) to interpret and apply the research literature to occupational therapy. A total of 49 articles met the authors' criteria and were included in the review. Six categories of research topics were identified, the first 3 of which are most closely related to occupational therapy: (1) sensory integration and sensory-based interventions; (2) relationship-based, interactive interventions; (3) developmental skill-based programs; (4) social cognitive skill training; (5) parent-directed or parent-mediated approaches; and (6) intensive behavioral intervention. Under each category, themes supported by research evidence and applicable to occupational therapy were defined. The findings have implications for intervention methods, communication regarding efficacious practices to professionals and consumers, and future occupational therapy research.

Emerging Therapies for Scar Prevention

PubMed Central

Block, Lisa; Gosain, Ankush; King, Timothy W.

2015-01-01

Significance: There are ∼12 million traumatic lacerations treated in the United States emergency rooms each year, 250 million surgical incisions created worldwide every year, and 11 million burns severe enough to warrant medical treatment worldwide. In the United States, over $20 billion dollars per year are spent on the treatment and management of scars. Recent Advances: Investigations into the management of scar therapies over the last decade have advanced our understanding related to the care of cutaneous scars. Scar treatment methods are presented including topical, intralesional, and mechanical therapies in addition to cryotherapy, radiotherapy, and laser therapy. Critical Issues: Current treatment options for scars have significant limitations. This review presents the current and emerging therapies available for scar management and the scientific evidence for scar management is discussed. Future Directions: Based upon our new understanding of scar formation, innovative scar therapies are being developed. Additional research on the basic science of scar formation will lead to additional advances and novel therapies for the treatment of cutaneous scars. PMID:26487979

Genomics, microRNA, epigenetics, and proteomics for future diagnosis, treatment and monitoring response in upper GI cancers.

PubMed

Brücher, Björn L D M; Li, Yan; Schnabel, Philipp; Daumer, Martin; Wallace, Timothy J; Kube, Rainer; Zilberstein, Bruno; Steele, Scott; Voskuil, Jan L A; Jamall, Ijaz S

2016-03-01

One major objective for our evolving understanding in the treatment of cancers will be to address how a combination of diagnosis and treatment strategies can be used to integrate patient and tumor variables with an outcome-oriented approach. Such an approach, in a multimodal therapy setting, could identify those patients (1) who should undergo a defined treatment (personalized therapy) (2) in whom modifications of the multimodal therapy due to observed responses might lead to an improvement of the response and/or prognosis (individualized therapy), (3) who might not benefit from a particular toxic treatment regimen, and (4) who could be identified early on and thereby be spared the morbidity associated with such treatments. These strategies could lead in the direction of precision medicine and there is hope of integrating translational molecular data to improve cancer classifications. In order to achieve these goals, it is necessary to understand the key issues in different aspects of biotechnology to anticipate future directions of personalized and individualized diagnosis and multimodal treatment strategies. Providing an overview of translational data in cancers proved to be a challenge as different methods and techniques used to obtain molecular data are used and studies are based on different tumor entities with different tumor biology and prognoses as well as vastly different therapeutic approaches. The pros and cons of the available methodologies and the potential response data in genomics, microRNA, epigenetics and proteomics with a focus on upper gastrointestinal cancers are considered herein to allow for an understanding of where these technologies stand with respect to cancer diagnosis, prognosis and treatment.

Translational Research on the Way to Effective Therapy for Alzheimer Disease

PubMed Central

Rosenberg, Roger N.

2006-01-01

Context Alzheimer disease (AD) is a major public health issue with a prediction of 12 million Americans being affected by 2025 from the present 4 million. Molecular and genetic findings have provided significant insights into the roles that amyloid, tau, and apolipoprotein E isoforms have in the causation of AD. A central issue in AD pathogenesis is the amyloid cascade hypothesis. It states that abnormal amyloid processing and accumulation is the primary causative factor of AD and other associated neuropathologic abnormalities are of secondary consequence. It is presented to provide the rationale for novel drug and vaccination therapeutic strategies. Future research directed at prediction and prevention of AD through a genomic and proteomic analysis with identification of multiple polymorphic genes that interact, resulting in increased risk for late-onset AD, are the realistic and ultimate goals. A new approach for drug development is required, one that will emphasize a genomic and proteomic analysis to identify at-risk gene sets whose genetic expression is sufficient to cause late onset, sporadic AD. Prediction and prevention of disease prior to clinical signs and symptoms are the goals. Objective A review and analysis from electronic literature databases and subsequent reference searches of the molecular genetic data including pertinent genetic mutations and abnormal biochemical findings causal of AD, are cited. The amyloid cascade hypothesis, the contributions of apolipoprotein E, and hyperphosphorylated tau are discussed as to their roles in pathogenesis. Molecular targets for potential drug and vaccination therapies are cited from a critical assessment of the molecular and biomedical data. These data form the basis for rational, target-specific drug and vaccination therapies currently employed and planned for the near future. Phase 2 and 3 clinical trial results of drug and vaccination therapies are cited. Conclusions A new approach is needed as current pharmacologic therapy directed at symptomatic relief has proved to be marginally effective. The genomic and proteomic basis of AD will be defined in the near future, and corresponding molecular therapeutic targets will be identified. Genomic neurology has arrived and its application to resolving AD is our best hope. PMID:16275806

Translational research on the way to effective therapy for Alzheimer disease.

PubMed

Rosenberg, Roger N

2005-11-01

Alzheimer disease (AD) is a major public health issue with a prediction of 12 million Americans being affected by 2025 from the present 4 million. Molecular and genetic findings have provided significant insights into the roles that amyloid, tau, and apolipoprotein E isoforms have in the causation of AD. A central issue in AD pathogenesis is the amyloid cascade hypothesis. It states that abnormal amyloid processing and accumulation is the primary causative factor of AD and other associated neuropathologic abnormalities are of secondary consequence. It is presented to provide the rationale for novel drug and vaccination therapeutic strategies. Future research directed at prediction and prevention of AD through a genomic and proteomic analysis with identification of multiple polymorphic genes that interact, resulting in increased risk for late-onset AD, are the realistic and ultimate goals. A new approach for drug development is required, one that will emphasize a genomic and proteomic analysis to identify at-risk gene sets whose genetic expression is sufficient to cause late onset, sporadic AD. Prediction and prevention of disease prior to clinical signs and symptoms are the goals. A review and analysis from electronic literature databases and subsequent reference searches of the molecular genetic data. including pertinent genetic mutations and abnormal biochemical findings causal of AD, are cited. The amyloid cascade hypothesis, the contributions of apolipoprotein E, and hyperphosphorylated tau are discussed as to their roles in pathogenesis. Molecular targets for potential drug and vaccination therapies are cited from a critical assessment of the molecular and biomedical data. These data form the basis for rational, target-specific drug and vaccination therapies currently employed and planned for the near future. Phase 2 and 3 clinical trial results of drug and vaccination therapies are cited. A new approach is needed as current pharmacologic therapy directed at symptomatic relief has proved to be marginally effective. The genomic and proteomic basis of AD will be defined in the near future, and corresponding molecular therapeutic targets will be identified. Genomic neurology has arrived and its application to resolving AD is our best hope.

Cultivating stem cells for treating amyotrophic lateral sclerosis

PubMed Central

Li, Shengwen Calvin; Yin, Hong Zhen; Loudon, William G; Weiss, John H

2012-01-01

This editorial addresses the current challenges and future directions in the use of stem cells as an approach for treating amyotrophic lateral sclerosis. A wide variety of literature has been reviewed to enlighten the reader on the many facets of stem cell research that are important to consider before using them for a cell based therapy. PMID:23516096

The Potential of Gait Analysis to Contribute to Differential Diagnosis of Early Stage Dementia: Current Research and Future Directions

ERIC Educational Resources Information Center

Morgan, Debra; Funk, Melanie; Crossley, Margaret; Basran, Jenny; Kirk, Andrew; Bello-Haas, Vanina Dal

2007-01-01

Early differential diagnosis of dementia is becoming increasingly important as new pharmacologic therapies are developed, as these treatments are not equally effective for all types of dementia. Early detection and differential diagnosis also facilitates informed family decision making and timely access to appropriate services. Information about…

Management of Child and Adolescent Eating Disorders: The Current Evidence Base and Future Directions

ERIC Educational Resources Information Center

Gowers, Simon; Bryant-Waugh, Rachel

2004-01-01

Although eating disorders in children and adolescents remain a serious cause of morbidity and mortality, the evidence base for effective interventions is surprisingly weak. The adult literature is growing steadily, but this is mainly with regard to psychological therapies for bulimia nervosa and to some extent in the field of pharmacotherapy. This…

[Pneumonia -- historical development, current status, future prospects].

PubMed

Welte, T

2010-09-01

Pneumonia is one of the oldest and best known diseases in mankind. Morbidity and mortality of this disease are remarkable. This has not been changed with the development of modern antibiotic therapy. On the contrary new challenges have arisen, more elderly and comorbid patients are involved and an increase in antibiotic resistance has appeared. An improvement in diagnosis and the introduction of risk stratification approaches has led to a standardisation in therapy. Vaccination strategies for special pathogens like S. PNEUMONIAE have reduced the burden of disease. For decades research was focused on the development of new antibiotics. The failure of this strategy has directed more attention to the host-pathogen interaction. Modulation of innate immunity is one of the key issues to overcome the future challenges in this field. Copyright Georg Thieme Verlag KG Stuttgart . New York.

Tele-yoga for Chronic Pain: Current Status and Future Directions.

PubMed

Mathersul, Danielle C; Mahoney, Louise A; Bayley, Peter J

2018-01-01

Pain is a pervasive, debilitating disorder that is resistant to long-term pharmacological interventions. Although psychological therapies such as cognitive behavior therapy demonstrate moderate efficacy, many individuals continue to have ongoing difficulties following treatment. There is a current trend to establish complementary and integrative health interventions for chronic pain, for which yoga has been found to have exciting potential. Nevertheless, an important consideration within the field is accessibility to adequate care. Telehealth can be used to provide real-time interactive video conferencing leading to increased access to health care for individuals located remotely or who otherwise have difficulty accessing services, perhaps through issues of mobility or proximity of adequate services. This article assesses the current status and feasibility of implementing tele-yoga for chronic pain. Methodological limitations and recommendations for future research are discussed.

Tele-yoga for Chronic Pain: Current Status and Future Directions

PubMed Central

Mahoney, Louise A; Bayley, Peter J

2018-01-01

Pain is a pervasive, debilitating disorder that is resistant to long-term pharmacological interventions. Although psychological therapies such as cognitive behavior therapy demonstrate moderate efficacy, many individuals continue to have ongoing difficulties following treatment. There is a current trend to establish complementary and integrative health interventions for chronic pain, for which yoga has been found to have exciting potential. Nevertheless, an important consideration within the field is accessibility to adequate care. Telehealth can be used to provide real-time interactive video conferencing leading to increased access to health care for individuals located remotely or who otherwise have difficulty accessing services, perhaps through issues of mobility or proximity of adequate services. This article assesses the current status and feasibility of implementing tele-yoga for chronic pain. Methodological limitations and recommendations for future research are discussed. PMID:29637012

Targeting Antitumor Immune Response for Enhancing the Efficacy of Photodynamic Therapy of Cancer: Recent Advances and Future Perspectives

PubMed Central

2016-01-01

Photodynamic therapy (PDT) is a minimally invasive therapeutic strategy for cancer treatment, which can destroy local tumor cells and induce systemic antitumor immune response, whereas, focusing on improving direct cytotoxicity to tumor cells treated by PDT, there is growing interest in developing approaches to further explore the immune stimulatory properties of PDT. In this review we summarize the current knowledge of the innate and adaptive immune responses induced by PDT against tumors, providing evidence showing PDT facilitated-antitumor immunity. Various immunotherapeutic approaches on different cells are reviewed for their effectiveness in improving the treatment efficiency in concert with PDT. Future perspectives are discussed for further enhancing PDT efficiency via intracellular targetable drug delivery as well as optimized experimental model development associated with the study of antitumor immune response. PMID:27672421

Cell-based therapies and imaging in cardiology.

PubMed

Bengel, Frank M; Schachinger, Volker; Dimmeler, Stefanie

2005-12-01

Cell therapy for cardiac repair has emerged as one of the most exciting and promising developments in cardiovascular medicine. Evidence from experimental and clinical studies is increasing that this innovative treatment will influence clinical practice in the future. But open questions and controversies with regard to the basic mechanisms of this therapy continue to exist and emphasise the need for specific techniques to visualise the mechanisms and success of therapy in vivo. Several non-invasive imaging approaches which aim at tracking of transplanted cells in the heart have been introduced. Among these are direct labelling of cells with radionuclides or paramagnetic agents, and the use of reporter genes for imaging of cell transplantation and differentiation. Initial studies have suggested that these molecular imaging techniques have great potential. Integration of cell imaging into studies of cardiac cell therapy holds promise to facilitate further growth of the field towards a broadly clinically useful application.

Viral Vector-Based Innovative Approaches to Directly Abolishing Tumorigenic Pluripotent Stem Cells for Safer Regenerative Medicine.

PubMed

Mitsui, Kaoru; Ide, Kanako; Takahashi, Tomoyuki; Kosai, Ken-Ichiro

2017-06-16

Human pluripotent stem cells (hPSCs) are a promising source of regenerative material for clinical applications. However, hPSC transplant therapies pose the risk of teratoma formation and malignant transformation of undifferentiated remnants. These problems underscore the importance of developing technologies that completely prevent tumorigenesis to ensure safe clinical application. Research to date has contributed to establishing safe hPSC lines, improving the efficiency of differentiation induction, and indirectly ensuring the safety of products. Despite such efforts, guaranteeing the clinical safety of regenerative medicine products remains a key challenge. Given the intrinsic genome instability of hPSCs, selective growth advantage of cancer cells, and lessons learned through failures in previous attempts at hematopoietic stem cell gene therapy, conventional strategies are unlikely to completely overcome issues related to hPSC tumorigenesis. Researchers have recently embarked on studies aimed at locating and directly treating hPSC-derived tumorigenic cells. In particular, novel approaches to directly killing tumorigenic cells by transduction of suicide genes and oncolytic viruses are expected to improve the safety of hPSC-based therapy. This article discusses the current status and future perspectives of methods aimed at directly eradicating undifferentiated tumorigenic hPSCs, with a focus on viral vector transduction.

Improving Therapy of Chronic Lymphocytic Leukemia (CLL) with Chimeric Antigen Receptor (CAR) T Cells

PubMed Central

Fraietta, Joseph A.; Schwab, Robert D.; Maus, Marcela V.

2016-01-01

Adoptive cell immunotherapy for the treatment of chronic lymphocytic leukemia (CLL) has heralded a new era of synthetic biology. The infusion of genetically-engineered, autologous chimeric antigen receptor (CAR) T cells directed against CD19 expressed by normal and malignant B cells represents a novel approach to cancer therapy. The results of recent clinical trials of CAR T cells in relapsed and refractory CLL have demonstrated long-term disease-free remissions, underscoring the power of harnessing and re-directing the immune system against cancer. This review will briefly summarize T cell therapies in development for CLL disease. We discuss the role of T cell function and phenotype, T cell culture optimization, CAR design, and approaches to potentiate the survival and anti-tumor effects of infused lymphocytes. Future efforts will focus on improving the efficacy of CAR T cells for the treatment of CLL and incorporating adoptive cell immunotherapy into standard medical management of CLL. PMID:27040708

Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (III).

PubMed

Fernández, Óscar; Arnal-García, Carmen; Arroyo-González, Rafael; Brieva, Lluís; Calles-Hernández, M Carmen; Casanova-Estruch, Bonaventura; Comabella, Manuel; de las Heras, Virginia; García-Merino, Juan A; Hernández-Pérez, Miguel A; Izquierdo, Guillermo; Matas, Elisabet; Meca-Lallana, José E; Mendibe-Bilbao, María del Mar; Muñoz-García, Delicias; Olascoaga, Javier; Oreja-Guevara, Celia; Prieto, José M; Ramió-Torrentà, Lluís; Rodríguez-Antigüedad, Alfredo; Saiz, Albert; Téllez, Nieves; Villar, Luisa M; Tintoré, Mar

2013-10-01

The most significant data presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in France in October 2012, have been summarised in the fifth edition of the Post-ECTRIMS Experts Meeting, held in Madrid in October 2012. This led to the drafting of this review, which has been published in three parts. This third part of the Post-ECTRIMS review presents the findings from the latest studies conducted with disease-modifying treatments, more specifically with glatiramer acetate, laquinimod, ponesimod, BG-12, teriflunomide, daclizumab, natalizumab and secukinumab (AIN457). Likewise, we also address the reasons that justify the search for innovative treatments for multiple sclerosis, with antigen-specific therapy, cell therapy and therapy aimed at promoting remyelination being highlighted among other future therapeutic strategies. Access to new pharmacological agents and the complexity of the therapy of multiple sclerosis in the future will require new design strategies and directions in clinical trials, including the use of surrogate markers, new statistical applications, superiority, inferiority or equivalence clinical trials and adaptable designs.

Progress and outlook of inorganic nanoparticles for delivery of nucleic acid sequences related to orthopedic pathologies: a review.

PubMed

Wagner, Darcy E; Bhaduri, Sarit B

2012-02-01

The anticipated growth in the aging population will drastically increase medical needs of society; of which, one of the largest components will undoubtedly be from orthopedic-related pathologies. There are several proposed solutions being investigated to cost-effectively prepare for the future--pharmaceuticals, implant devices, cell and gene therapies, or some combination thereof. Gene therapy is one of the more promising possibilities because it seeks to correct the root of the problem, thereby minimizing treatment duration and cost. Currently, viral vectors have shown the highest efficacies, but immunological concerns remain. Nonviral methods show reduced immune responses but are regarded as less efficient. The nonviral paradigms consist of mechanical and chemical approaches. While organic-based materials have been used more frequently in particle-based methods, inorganic materials capable of delivery have distinct advantages, especially advantageous in orthopedic applications. The inorganic gene therapy field is highly interdisciplinary in nature, and requires assimilation of knowledge across the broad fields of cell biology, biochemistry, molecular genetics, materials science, and clinical medicine. This review provides an overview of the role each area plays in orthopedic gene therapy as well as possible future directions for the field.

The evolution of recombinant thrombolytics: Current status and future directions

PubMed Central

Adivitiya; Khasa, Yogender Pal

2017-01-01

ABSTRACT Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity, hypertension, raised blood lipids, diabetes and age-related risks. The use of classical antiplatelet and anticoagulant therapies combined with surgical intervention helped to clear blood clots during the inceptive years. However, the discovery of streptokinase and urokinase ushered the way of using these enzymes as thrombolytic agents to degrade the fibrin network with an issue of systemic hemorrhage. The development of second generation plasminogen activators like anistreplase and tissue plasminogen activator partially controlled this problem. The third generation molecules, majorly t-PA variants, showed desirable properties of improved stability, safety and efficacy with enhanced fibrin specificity. Plasmin variants are produced as direct fibrinolytic agents as a futuristic approach with targeted delivery of these drugs using liposome technlogy. The novel molecules from microbial, plant and animal origin present the future of direct thrombolytics due to their safety and ease of administration. PMID:27696935

Cost Minimization Analysis of Two Treatment Regimens for Low-Risk Rhabdomyosarcoma in Children: A Report From the Children’s Oncology Group

PubMed Central

Russell, Heidi; Swint, J. Michael; Lal, Lincy; Meza, Jane; Walterhouse, David; Hawkins, Douglas S.; Okcu, M. Fatih

2015-01-01

Background Recent Children’s Oncology Group trials for low-risk rhabdomyosarcoma attempted to reduce therapy while maintaining excellent outcomes. D9602 delivered 45 weeks of outpatient vincristine and dactinomycin (VA) for patients in Subgroup A. ARST0331 reduced the duration of therapy to 22 weeks but added four doses of cyclophosphamide to VA for patients in Subset 1. Failure-free survival was similar. We undertook a cost minimization comparison to help guide future decision-making. Procedure Addressing the costs of treatment from the healthcare perspective we modeled a simple decision-analytic model from aggregate clinical trial data. Medical care inputs and probabilities were estimated from trial reports and focused chart review. Costs of radiation, surgery and off-therapy surveillance were excluded. Unit costs were obtained from literature and national reimbursement and inpatient utilization databases and converted to 2012 US dollars. Model uncertainty was assessed with first-order sensitivity analysis. Results Direct medical costs were $46,393 for D9602 and $43,261 for ARST0331 respectively, making ARST0331 the less costly strategy. Dactinomycin contributed the most to D9602 total costs but varied with age (42–69%). Chemotherapy administration costs accounted for the largest proportion of ARST0331 total costs (39–57%). ARST0331 incurred fewer costs than D9602 under most alternative distributive models and alternative clinical practice assumptions. Conclusions Cost analysis suggests that ARST0331 may incur fewer costs than D9602 from the healthcare system’s perspective. Attention to the services driving the costs provides directions for future efficiency improvements. Future studies should prospectively consider the patient and family’s perspective. PMID:24453105

Cost minimization analysis of two treatment regimens for low-risk rhabdomyosarcoma in children: a report from the Children's Oncology Group.

PubMed

Russell, Heidi; Swint, J Michael; Lal, Lincy; Meza, Jane; Walterhouse, David; Hawkins, Douglas S; Okcu, M Fatih

2014-06-01

Recent Children's Oncology Group trials for low-risk rhabdomyosarcoma attempted to reduce therapy while maintaining excellent outcomes. D9602 delivered 45 weeks of outpatient vincristine and dactinomycin (VA) for patients in Subgroup A. ARST0331 reduced the duration of therapy to 22 weeks but added four doses of cyclophosphamide to VA for patients in Subset 1. Failure-free survival was similar. We undertook a cost minimization comparison to help guide future decision-making. Addressing the costs of treatment from the healthcare perspective we modeled a simple decision-analytic model from aggregate clinical trial data. Medical care inputs and probabilities were estimated from trial reports and focused chart review. Costs of radiation, surgery and off-therapy surveillance were excluded. Unit costs were obtained from literature and national reimbursement and inpatient utilization databases and converted to 2012 US dollars. Model uncertainty was assessed with first-order sensitivity analysis. Direct medical costs were $46,393 for D9602 and $43,261 for ARST0331 respectively, making ARST0331 the less costly strategy. Dactinomycin contributed the most to D9602 total costs but varied with age (42-69%). Chemotherapy administration costs accounted for the largest proportion of ARST0331 total costs (39-57%). ARST0331 incurred fewer costs than D9602 under most alternative distributive models and alternative clinical practice assumptions. Cost analysis suggests that ARST0331 may incur fewer costs than D9602 from the healthcare system's perspective. Attention to the services driving the costs provides directions for future efficiency improvements. Future studies should prospectively consider the patient and family's perspective. © 2014 Wiley Periodicals, Inc.

B Cell-Directed Therapeutics in Multiple Sclerosis: Rationale and Clinical Evidence.

PubMed

Kinzel, Silke; Weber, Martin S

2016-12-01

Over the last decade, evidence condensed that B cells, B cell-derived plasma cells and antibodies play a key role in the pathogenesis and progression of multiple sclerosis (MS). In many patients with MS, peripheral B cells show signs of chronic activation; within the cerebrospinal fluid clonally expanded plasma cells produce oligoclonal immunoglobulins, which remain a hallmark diagnostic finding. Confirming the clinical relevance of these immunological alterations, recent trials testing anti-CD20-mediated depletion of peripheral B cells showed an instantaneous halt in development of new central nervous system lesions and occurrence of relapses. Notwithstanding this enormous success, not all B cells or B cell subsets may contribute in a pathogenic manner, and may, in contrast, exert anti-inflammatory and, thus, therapeutically desirable properties in MS. Naïve B cells, in MS patients similar to healthy controls, are a relevant source of regulatory cytokines such as interleukin-10, which dampens the activity of other immune cells and promotes recovery from acute disease flares in experimental MS models. In this review, we describe in detail pathogenic but also regulatory properties of B and plasma cells in the context of MS and its animal model experimental autoimmune encephalomyelitis. In the second part, we review what impact current and future therapies may have on these B cell properties. Within this section, we focus on the highly encouraging data on anti-CD20 antibodies as future therapy for MS. Lastly, we discuss how B cell-directed therapy in MS could be possibly advanced even further in regard to efficacy and safety by integrating the emerging information on B cell regulation in MS into future therapeutic strategies.

Advancing Cancer Therapy with Present and Emerging Immuno-Oncology Approaches

PubMed Central

Kamta, Jeff; Chaar, Maher; Ande, Anusha; Altomare, Deborah A.; Ait-Oudhia, Sihem

2017-01-01

Immuno-oncology (I-O) is a young and growing field on the frontier of cancer therapy. Contrary to cancer therapies that directly target malignant cells, I-O therapies stimulate the body’s immune system to target and attack the tumor, which is otherwise invisible to, or inhibiting the immune response. To this end, several methods have been developed: First, passive therapies that enable T-cells to fight the tumor without direct manipulation, typically through binding and modifying the intracellular signaling of surface receptors. Checkpoint inhibitors, perhaps the most well known of I-O therapies; are an example of such. These are monoclonal antibodies that block binding of the tumor cell at receptors that inactivate the T-cell. A variety of small molecules can achieve the same effect by affecting metabolic or signaling pathways to boost the immune response or prevent its attenuation. Drugs originally formulated for unrelated disease states are now being used to treat cancer under the I-O approach. Second, active therapies which often involve direct manipulations that occur in vitro and once introduced to the patient will directly attack the tumor. Adoptive cell transfer is the oldest of these methods. It involves the removal of T-cells from the body, which are then expanded and genetically modified for specificity toward tumor-associated antigens (TAAs), and then reintroduced to the patient. A similar approach is taken with cancer vaccines, where TAAs are identified and reintroduced with adjuvants to stimulate an immune response, sometimes in the context of antigen-presenting cells or viral vectors. Oncolytic viruses are genetically modified natural viruses for selectivity toward tumor cells. The resulting cytotoxicity has the potential to elicit an immune response that furthers tumor cell killing. A final active approach is bi-specific T-cell engagers. These modified antibodies act to link a T-cell and tumor cell through surface receptors and thereby forcibly generate immune recognition. The therapies in each of these subfields are all still very new and ongoing clinical trials could provide even further additions. The full therapeutic potential of the aforementioned therapies, alone or in combination, has yet to be realized, but holds great promise for the future of cancer treatment. PMID:28459041

Function of Matrix IGF-1 in Coupling Bone Resorption and Formation

PubMed Central

Crane, Janet L.; Cao, Xu

2013-01-01

Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space and time dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of MSCs and HSCs and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis. PMID:24068256

Function of matrix IGF-1 in coupling bone resorption and formation.

PubMed

Crane, Janet L; Cao, Xu

2014-02-01

Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore, understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space- and time-dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of mesenchymal stem cells and hematopoietic stem cells and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis.

Imaging: Guiding the Clinical Translation of Cardiac Stem Cell Therapy

PubMed Central

Nguyen, Patricia K.; Lan, Feng; Wang, Yongming; Wu, Joseph C.

2011-01-01

Stem cells have been touted as the holy grail of medical therapy with promises to regenerate cardiac tissue, but it appears the jury is still out on this novel therapy. Using advanced imaging technology, scientists have discovered that these cells do not survive nor engraft long-term. In addition, only marginal benefit has been observed in large animal studies and human trials. However, all is not lost. Further application of advanced imaging technology will help scientists unravel the mysteries of stem cell therapy and address the clinical hurdles facing its routine implementation. In this review, we will discuss how advanced imaging technology will help investigators better define the optimal delivery method, improve survival and engraftment, and evaluate efficacy and safety. Insights gained from this review may direct the development of future preclinical investigations and clinical trials. PMID:21960727

Evolution of Endovascular Therapy in Acute Stroke: Implications of Device Development

PubMed Central

Balasubramaian, Adithya; Mitchell, Peter; Dowling, Richard

2015-01-01

Intravenous thrombolysis is an effective treatment for acute ischaemic stroke. However, vascular recanalization rates remain poor especially in the setting of large artery occlusion. On the other hand, endovascular intra-arterial therapy addresses this issue with superior recanalization rates compared with intravenous thrombolysis. Although previous randomized controlled studies of intra-arterial therapy failed to demonstrate superiority, the failings may be attributed to a combination of inferior intra-arterial devices and suboptimal selection criteria. The recent results of several randomized controlled trials have demonstrated significantly improved outcomes, underpinning the advantage of newer intra-arterial devices and superior recanalization rates, leading to renewed interest in establishing intra-arterial therapy as the gold standard for acute ischaemic stroke. The aim of this review is to outline the history and development of different intra-arterial devices and future directions in research. PMID:26060800

The Role of Biomarkers in Detection of Cardio-toxicity.

PubMed

Shah, Kevin S; Yang, Eric H; Maisel, Alan S; Fonarow, Gregg C

2017-06-01

The goal of this paper is to review the current literature on the role of biomarkers in the detection and management of patients with cardio-oncologic disease. The role of biomarker surveillance in patients with known cardiac disease, as a result of chemotherapy or with the potential to develop cardio-toxicity, will be discussed. In addition, the studies surrounding sub-clinical cardiac toxicity monitoring during therapy, identification of high-risk patients prior to therapy, and tailoring oncologic therapies to potential biomarker risk profiles are reviewed. Based on evidence, to date, troponin and natriuretic peptides have the greatest potential to detect sub-clinical cardiac dysfunction and even tailor therapy to prevent progression based on biomarker profiles. Finally, future directions for potential utilization of novel biomarkers for the improvement of care of patients in the field of cardio-oncology are discussed.

In vitro and in vivo studies on laser-activated gold nanorods for applications in photothermal therapies

NASA Astrophysics Data System (ADS)

Pini, Roberto; Ratto, Fulvio; Matteini, Paolo; Centi, Sonia; Rossi, Francesca

2010-04-01

We review our experimental studies on near infrared laser-activated gold nanoparticles in the direct welding of connective tissues. In particular, we discuss the use of gold nanorods excited by diode laser radiation at 810 nm to mediate functional photothermal effects and weld eye's lens capsules and arteries. The preparation of biopolymeric matrices including gold nanorods is described as well, together with preliminary tests for their application in the closure of wounds in vessels and tendons. Finally we mention future perspectives on the use of these nanoparticles for applications in the therapy of cancer.

Advances in evidence-based cancer adoptive cell therapy.

PubMed

Ge, Chunlei; Li, Ruilei; Song, Xin; Qin, Shukui

2017-04-01

Adoptive cell therapy (ACT) has been developed in cancer treatment by transferring/infusing immune cells into cancer patients, which are able to recognize, target, and destroy tumor cells. Recently, sipuleucel-T and genetically-modified T cells expressing chimeric antigen receptors (CAR) show a great potential to control metastatic castration-resistant prostate cancer and hematologic malignancies in clinic. This review summarized some of the major evidence-based ACT and the challenges to improve cell quality and reduce the side effects in the field. This review also provided future research directions to make sure ACT widely available in clinic.

Interferon in chronic myeloid leukaemia: past and future.

PubMed

Guilhot, François; Roy, Lydia; Saulnier, Pierre-Jean; Guilhot, Joëlle

2009-09-01

Imatinib has revolutionized the therapy of chronic myeloid leukaemia. However the complete eradication of leukaemic stem cells is still a matter of discussion. Interferon (IFN) has been used in the past with success. However the proportion of patients who achieved sustained complete cytogenetic response was small. Recently, in addition to its direct antineoplastic effect and immunomodulatory activity, IFN has been shown to stimulate the quiescent leukaemic stem cells. Thus there is now a rational for combining Imatinib and IFN. Large prospective phase III trials are in good progress to demonstrate in humans the usefullness of a combination therapy using Imatinib and IFN.

[Standard Cancer Therapy Are Established by the Investigator-Initiated Post-Marketing Clinical Trials, Not by the Indication-Directed Clinical Trials].

PubMed

Shimada, Yasuhiro

2016-04-01

The financial supports for investigator-initiated post-marketing clinical trial in clinical oncology are reduced after scandals related to the other fields of clinical trials in Japan. These clinical trials are the essential final steps of clinical development in newer cancer therapy, which should be conducted in the investigator-initiated clinical trial groups with well-organized infrastructure and continuous financial supports. The present problems are discussed and summarized. Future perspectives with the national viewpoints needed to be included the idea of "health technology assessment".

Progresses towards safe and efficient gene therapy vectors.

PubMed

Chira, Sergiu; Jackson, Carlo S; Oprea, Iulian; Ozturk, Ferhat; Pepper, Michael S; Diaconu, Iulia; Braicu, Cornelia; Raduly, Lajos-Zsolt; Calin, George A; Berindan-Neagoe, Ioana

2015-10-13

The emergence of genetic engineering at the beginning of the 1970's opened the era of biomedical technologies, which aims to improve human health using genetic manipulation techniques in a clinical context. Gene therapy represents an innovating and appealing strategy for treatment of human diseases, which utilizes vehicles or vectors for delivering therapeutic genes into the patients' body. However, a few past unsuccessful events that negatively marked the beginning of gene therapy resulted in the need for further studies regarding the design and biology of gene therapy vectors, so that this innovating treatment approach can successfully move from bench to bedside. In this paper, we review the major gene delivery vectors and recent improvements made in their design meant to overcome the issues that commonly arise with the use of gene therapy vectors. At the end of the manuscript, we summarized the main advantages and disadvantages of common gene therapy vectors and we discuss possible future directions for potential therapeutic vectors.

Progresses towards safe and efficient gene therapy vectors

PubMed Central

Chira, Sergiu; Jackson, Carlo S.; Oprea, Iulian; Ozturk, Ferhat; Pepper, Michael S.; Diaconu, Iulia; Braicu, Cornelia; Raduly, Lajos-Zsolt; Calin, George A.; Berindan-Neagoe, Ioana

2015-01-01

The emergence of genetic engineering at the beginning of the 1970′s opened the era of biomedical technologies, which aims to improve human health using genetic manipulation techniques in a clinical context. Gene therapy represents an innovating and appealing strategy for treatment of human diseases, which utilizes vehicles or vectors for delivering therapeutic genes into the patients' body. However, a few past unsuccessful events that negatively marked the beginning of gene therapy resulted in the need for further studies regarding the design and biology of gene therapy vectors, so that this innovating treatment approach can successfully move from bench to bedside. In this paper, we review the major gene delivery vectors and recent improvements made in their design meant to overcome the issues that commonly arise with the use of gene therapy vectors. At the end of the manuscript, we summarized the main advantages and disadvantages of common gene therapy vectors and we discuss possible future directions for potential therapeutic vectors. PMID:26362400

Stem cell and genetic therapies for the fetus.

PubMed

Pearson, Erik G; Flake, Alan W

2013-02-01

The prenatal diagnosis and management of congenital disease has made significant progress over the previous decade. Currently, fetal therapy (including open surgery and fetoscopic intervention) provides therapeutic options for a range of congenital anomalies; however, it is restricted to the treatment of fetal pathophysiology. Improvements in prenatal screening and the early diagnosis of genetic disease allow for preemptive treatment of anticipated postnatal disease by stem cell or genetic therapy. While currently awaiting clinical application, in utero stem cell therapy has made significant advances in overcoming the engraftment and immunologic barriers in both murine and pre-clinical large animal models. Likewise, proof in principle for fetal gene therapy has been demonstrated in rodent and large animal systems as a method to prevent the onset of inherited genetic disease; however, safety and ethical risks still need to be addressed prior to human application. In this review, we examine the current status and future direction of stem cell and genetic therapy for the fetus. Copyright © 2013. Published by Elsevier Inc.

Back to the future: therapies for idiopathic nephrotic syndrome.

PubMed

Gibson, Keisha L; Glenn, Dorey; Ferris, Maria E

2015-01-01

Roughly 20-40% of individuals with idiopathic nephrotic syndrome will fail to respond to standard therapies and have a high risk of progression to end stage kidney disease (ESKD). In the last 50 years, no new therapies have been approved specifically for the treatment of these individuals with recalcitrant disease. Recent in vitro, translational, and clinical studies have identified novel targets and pathways that not only expand our understanding of the complex pathophysiology of proteinuric disease but also provide an opportunity to challenge the tradition of relying on histologic classification of nephrotic diseases to make treatment decisions. The traditional methods of directing the care of individuals with nephrotic syndrome by histological classification or deciding second line therapies on the basis of steroid-responsiveness may soon yield customizing therapies based on our expanding understanding of molecular targets. Important non-immunologic mechanisms of widely used immunosuppressive therapies may be just as important in palliating proteinuric disease as proposed immunologic functions. © 2015 S. Karger AG, Basel.

Two preliminary studies on sleep and psychotherapy.

PubMed

Karle, W; Hopper, M; Corriere, R; Hart, J; Switzer, A

1977-09-01

Two preliminary studies were conducted to assess the effects of an intensive outpatient psychotherapy, Feeling Therapy, on sleep. This therapy was chosen because of its demonstrated ability to affect its patients' dreams. In the first study a newly entering female patient was recorded across the first three weeks of intensive daily therapy. In contrast to two control subjects recorded across a similar time period, she demonstrated low REM times and short REM latencies on the average, and considerably greater variability in nearly every parameter. In the second study, two patients were recorded across three days (the middle of which was the day of a therapy session) first when new in therapy and then again after two and one-half years of therapy. It was found that when new in therapy both subjects spent nights of significantly altered sleep the day of the therapy session. One subject showed no REM sleep whatsoever while the other showed a 10 min REM latency and low REM time. The significance of these findings and the direction of future research is discussed.

Cancer and Radiation Therapy: Current Advances and Future Directions

PubMed Central

Baskar, Rajamanickam; Lee, Kuo Ann; Yeo, Richard; Yeoh, Kheng-Wei

2012-01-01

In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. However with its increasing incidence, the clinical management of cancer continues to be a challenge for the 21st century. Treatment modalities comprise of radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Radiation therapy remains an important component of cancer treatment with approximately 50% of all cancer patients receiving radiation therapy during their course of illness; it contributes towards 40% of curative treatment for cancer. The main goal of radiation therapy is to deprive cancer cells of their multiplication (cell division) potential. Celebrating a century of advances since Marie Curie won her second Nobel Prize for her research into radium, 2011 has been designated the Year of Radiation therapy in the UK. Over the last 100 years, ongoing advances in the techniques of radiation treatment and progress made in understanding the biology of cancer cell responses to radiation will endeavor to increase the survival and reduce treatment side effects for cancer patients. In this review, principles, application and advances in radiation therapy with their biological end points are discussed. PMID:22408567

Cancer and radiation therapy: current advances and future directions.

PubMed

Baskar, Rajamanickam; Lee, Kuo Ann; Yeo, Richard; Yeoh, Kheng-Wei

2012-01-01

In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. However with its increasing incidence, the clinical management of cancer continues to be a challenge for the 21st century. Treatment modalities comprise of radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Radiation therapy remains an important component of cancer treatment with approximately 50% of all cancer patients receiving radiation therapy during their course of illness; it contributes towards 40% of curative treatment for cancer. The main goal of radiation therapy is to deprive cancer cells of their multiplication (cell division) potential. Celebrating a century of advances since Marie Curie won her second Nobel Prize for her research into radium, 2011 has been designated the Year of Radiation therapy in the UK. Over the last 100 years, ongoing advances in the techniques of radiation treatment and progress made in understanding the biology of cancer cell responses to radiation will endeavor to increase the survival and reduce treatment side effects for cancer patients. In this review, principles, application and advances in radiation therapy with their biological end points are discussed.

Coping Skills and Exposure Therapy in Panic Disorder and Agoraphobia: Latest Advances and Future Directions

PubMed Central

Meuret, Alicia E.; Wolitzky-Taylor, Kate B.; Twohig, Michael P.; Craske, Michelle G.

2012-01-01

Although cognitive-behavioral treatments for panic disorder have demonstrated efficacy, a considerable number of patients terminate treatment prematurely or remain symtpomatic. Cognitive and biobehavioral coping skills are taught to improve exposure therapy outcomes but evidence for an additive effect is largely lacking. Current methodologies used to study the augmenting effects of coping skills test the degree to which the delivery of coping skills enhances outcomes. However, they do not assess the degree to which acquisition of coping skills and their application during exposure therapy augment outcomes. We examine the extant evidence on the role of traditional coping skills in augmenting exposure for panic disorder, discuss the limitations of existing research, and offer recommendations for methodological advances. PMID:22440065

[The Learning Effectiveness of Nurses Participating in a Simulated Radiation Therapy Skin Care Workshop].

PubMed

Lee, Yu-San; Kao, Yu-Hsiu

2016-08-01

The skin reaction rate is 60-95% in cancer patients that receive radiation therapy. This therapy is likely to cause physical and mental discomfort and prolong treatment for patients. The current emphasis on lectures rather than practice to help nurses learn proper skin care practices likely imposes difficulties for nurses to handle various clinical situations. To investigate the learning effectiveness of a simulated radiation therapy skin care workshop for nurses. A total of 34 nurses at a hospital in one health system in northern Taiwan who had never used radiation therapy to provide care to patients were enrolled in this quasi-experimental study. A single group pretest, posttest and post-posttest (6 weeks after intervention) approach was used. At the simulated radiation therapy skin care workshop, we used teaching strategies including Ausubel's direct instruction teaching method and practice on simulated wounds on pig skins. Outcomes were evaluated using "the questionnaire of radiation therapy skin care" and "direct observation of procedural skills checklist". The results from the simulated radiation therapy skin care workshop were analyzed using GEE (generalized estimating equation). The post-posttest and posttest scores increased significantly; knowledge mean score 3.14 (< .001) vs 2.64 (< .001), attitude mean score 2.06 (p < .05) vs 2.24 (p < .001), and skill mean score 2.79 (p < .001) vs 1.68 (p < .001). The simulated radiation therapy skin care workshop demonstrated significant and positive effects on learning outcomes. Therefore, we recommend incorporating this workshop into clinical nursing education and training strategies in the future.

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions.

PubMed

Sofia, M Anthony; Rubin, David T

2017-04-01

The development of therapeutic antibodies represents a revolutionary change in medical therapy for digestive diseases. Beginning with the initial studies that confirmed the pathogenicity of cytokines in inflammatory bowel disease, the development and application of therapeutic antibodies brought challenges and insights into their potential and optimal use. Infliximab was the first biological drug approved for use in Crohn's disease and ulcerative colitis. The lessons learned from infliximab include the importance of immunogenicity and the influence of pharmacokinetics on disease response and outcomes. Building on this foundation, other therapeutic antibodies achieved approval for inflammatory bowel disease and many more are in development for several digestive diseases. In this review, we reflect on the history of therapeutic antibodies and discuss current practice and future directions for the field.

Identifying therapeutic targets in gastric cancer: the current status and future direction

PubMed Central

Yu, Beiqin; Xie, Jingwu

2016-01-01

Gastric cancer is the third leading cause of cancer-related death worldwide. Our basic understanding of gastric cancer biology falls behind that of many other cancer types. Current standard treatment options for gastric cancer have not changed for the last 20 years. Thus, there is an urgent need to establish novel strategies to treat this deadly cancer. Successful clinical trials with Gleevec in CML and gastrointestinal stromal tumors have set up an example for targeted therapy of cancer. In this review, we will summarize major progress in classification, therapeutic options of gastric cancer. We will also discuss molecular mechanisms for drug resistance in gastric cancer. In addition, we will attempt to propose potential future directions in gastric cancer biology and drug targets. PMID:26373844

JACIE accreditation for blood and marrow transplantation: past, present and future directions of an international model for healthcare quality improvement

PubMed Central

Snowden, J A; McGrath, E; Duarte, R F; Saccardi, R; Orchard, K; Worel, N; Kuball, J; Chabannon, C; Mohty, M

2017-01-01

Blood and marrow transplantation (BMT) is a complex and evolving medical speciality that makes substantial demands on healthcare resources. To meet a professional responsibility to both patients and public health services, the European Society for Blood and Marrow Transplantation (EBMT) initiated and developed the Joint Accreditation Committee of the International Society for Cellular Therapy and EBMT—better known by the acronym, JACIE. Since its inception, JACIE has performed over 530 voluntary accreditation inspections (62% first time; 38% reaccreditation) in 25 countries, representing 40% of transplant centres in Europe. As well as widespread professional acceptance, JACIE has become incorporated into the regulatory framework for delivery of BMT and other haematopoietic cellular therapies in several countries. In recent years, JACIE has been validated using the EBMT registry as an effective means of quality improvement with a substantial positive impact on survival outcomes. Future directions include development of Europe-wide risk-adjusted outcome benchmarking through the EBMT registry and further extension beyond Europe, including goals to faciliate access for BMT programmes in in low- and middle-income economies (LMIEs) via a ‘first-step’ process. PMID:28346416

Cutaneous Scarring: Basic Science, Current Treatments, and Future Directions.

PubMed

Marshall, Clement D; Hu, Michael S; Leavitt, Tripp; Barnes, Leandra A; Lorenz, H Peter; Longaker, Michael T

2018-02-01

Significance: Scarring of the skin from burns, surgery, and injury constitutes a major burden on the healthcare system. Patients affected by major scars, particularly children, suffer from long-term functional and psychological problems. Recent Advances: Scarring in humans is the end result of the wound healing process, which has evolved to rapidly repair injuries. Wound healing and scar formation are well described on the cellular and molecular levels, but truly effective molecular or cell-based antiscarring treatments still do not exist. Recent discoveries have clarified the role of skin stem cells and fibroblasts in the regeneration of injuries and formation of scar. Critical Issues: It will be important to show that new advances in the stem cell and fibroblast biology of scarring can be translated into therapies that prevent and reduce scarring in humans without major side effects. Future Directions: Novel therapies involving the use of purified human cells as well as agents that target specific cells and modulate the immune response to injury are currently undergoing testing. In the basic science realm, researchers continue to refine our understanding of the role that particular cell types play in the development of scar.

Lung capillary injury and repair in left heart disease: a new target for therapy?

PubMed

Azarbar, Sayena; Dupuis, Jocelyn

2014-07-01

The lungs are the primary organs affected in LHD (left heart disease). Increased left atrial pressure leads to pulmonary alveolar-capillary stress failure, resulting in cycles of alveolar wall injury and repair. The reparative process causes the proliferation of MYFs (myofibroblasts) with fibrosis and extracellular matrix deposition, resulting in thickening of the alveolar wall. Although the resultant reduction in vascular permeability is initially protective against pulmonary oedema, the process becomes maladaptive causing a restrictive lung syndrome with impaired gas exchange. This pathological process may also contribute to PH (pulmonary hypertension) due to LHD. Few clinical trials have specifically evaluated lung structural remodelling and the effect of related therapies in LHD. Currently approved treatment for chronic HF (heart failure) may have direct beneficial effects on lung structural remodelling. In the future, novel therapies specifically targeting the remodelling processes may potentially be utilized. In the present review, we summarize data supporting the clinical importance and pathophysiological mechanisms of lung structural remodelling in LHD and propose that this pathophysiological process should be explored further in pre-clinical studies and future therapeutic trials.

Psychotherapy in psychiatry: the current situation and future directions in Germany.

PubMed

Schnell, Knut; Herpertz, Sabine C

2011-11-01

The aim of this article is to review how psychotherapy is dispensed to patients in psychiatric treatment and to render the future perspectives of psychotherapy in psychiatric outpatient and inpatient care in Germany. We demonstrate that--according to the currently available data about healthcare providers, allocation of financial resources and curricular regulations--the presently used definition of the term "psychotherapy" is ambiguous. One major problem for the application of psychotherapy in psychiatry is obviously constituted by the dominance of the major guideline therapies ("Richtlinienverfahren") within psychiatric services. Here, guideline therapies do not meet the needs of a significant proportion of acutely, severely and/or chronically ill psychiatric patients and restrain the application of scientifically approved, disorder-oriented and context compliant interventions in psychiatric practice. As a future perspective, we suggest that the training of psychiatrists should impart profound interpersonal skills and provide the competence to offer psychotherapy within a multimodal, modular, and flexible treatment plan on the background of the self-conception of psychiatry as a medical discipline. Moreover, future concepts of psychiatric psychotherapy should promote an evidence-based selection and application of scientifically approved, disorder-oriented, and integrative treatment methods, which are available in growing number.

Motor rehabilitation in stroke and traumatic brain injury: stimulating and intense.

PubMed

Breceda, Erika Y; Dromerick, Alexander W

2013-12-01

The purpose of this review is to provide an update on the latest neurorehabilitation literature for motor recovery in stroke and traumatic brain injury to assist clinical decision making and assessing future research directions. The emerging approach to motor restoration is now multimodal. It engages the traditional multidisciplinary rehabilitation team, but incorporates highly structured activity-based therapies, pharmacology, brain stimulation and robotics. Clinical trial data support selective serotonin reuptake inhibitors and amantadine to assist motor recovery poststroke and traumatic brain injury, respectively. Similarly, there is continued support for intensity as a key factor in activity-based therapies, across skilled and nonskilled interventions. Aerobic training appears to have multiple benefits; increasing the capacity to meet the demands of hemiparetic gait improves endurance for activities of daily living while promoting cognition and mood. At this time, the primary benefit of robotic therapy lies in the delivery of highly intense and repetitive motor practice. Both transcranial direct current and magnetic stimulation therapies are in early stages, but have promise in motor and language restoration. Advancements in neurorehabilitation have shifted treatment away from nonspecific activity regimens and amphetamines. As the body of knowledge grows, evidence-based practice using interventions targeted at specific subgroups becomes progressively more feasible.

Tumors of the central nervous system: clinical aspects, molecular mechanisms, unanswered questions, and future research directions.

PubMed

Babcock, Michael A; Kostova, Felina V; Guha, Abhijit; Packer, Roger J; Pollack, Ian F; Maria, Bernard L

2008-10-01

Central nervous system tumors are the most common solid tumors in children. Many histological subtypes and biological variants exist. The 2007 Neurobiology of Disease in Children Symposium, held in conjunction with the 36th annual meeting of the Child Neurology Society, aimed to define current knowledge in the field and to develop specific aims for future clinical, translational, and fundamental science. Because of advances in structural and metabolic imaging, surgical technique, and combination therapies, the life expectancy of children with some of the most common tumors, such as cerebellar astrocytomas and medulloblastomas, has improved. Other common tumor types, including diffuse pontine gliomas and malignant embryonal tumors, still have a dismal prognosis. As novel therapies are identified for pediatric central nervous system tumors, long-term survival may be associated with considerable disability. A cooperative effort is crucial to early diagnosis and to translating basic research findings into safe, effective new treatments.

A call for sustainable practice in occupational therapy.

PubMed

Dennis, Carole W; Dorsey, Julie A; Gitlow, Lynn

2015-06-01

The ability of the earth to sustain health among humans and in the natural world is under threat from overpopulation, environmental degradation, and climate change. These global threats are anticipated to harm health and human occupation in many direct and indirect ways. Strategies are needed to mitigate the effects of these threats and to build individual and community capacities to foster resilience. This paper links issues of sustainability with occupational therapy philosophy and discusses how employing a sustainability lens with professional reasoning can help practitioners integrate sustainability into their practice. Human occupation is inseparable from the environments in which people live. Human occupation has caused the current environmental crisis, and targeted human action is required to safeguard future health and well-being. Occupational therapists have an ethical obligation to use professional reasoning strategies that, taken collectively, can help to build a sustainable and resilient future.

mTOR Inhibitors in Children: Current Indications and Future Directions in Neurology.

PubMed

Jeong, Anna; Wong, Michael

2016-12-01

The mammalian/mechanistic target of rapamycin (mTOR) pathway is a key signaling pathway that has been implicated in genetic epilepsy syndromes, neurodegenerative diseases, and conditions associated with autism spectrum disorder and cognitive impairment. The mTOR pathway has become an exciting treatment target for these various disorders, with mTOR inhibitors such as rapamycin being studied for their potential therapeutic applications. In particular, tuberous sclerosis complex (TSC) is a genetic disorder resulting from overactivation of the mTOR pathway, and pharmacologic therapy with mTOR inhibitors has emerged as a viable treatment option for the systemic manifestations of the disease. In this review, we discuss the approved indications for mTOR inhibitors in TSC, the potential future applications of mTOR inhibitors in TSC and other neurological conditions, and the safety considerations applicable to mTOR therapy in the pediatric population.

CRISPR in the Retina: Evaluation of Future Potential.

PubMed

Cho, Galaxy Y; Justus, Sally; Sengillo, Jesse D; Tsang, Stephen H

2017-01-01

Clustered regularly interspaced short palindromic repeats (CRISPR) has been gaining widespread attention for its ability for targeted genome surgery. In treating inherited retinal degenerations, gene therapies have had varied results; the ones effective in restoring eye sight are limited by transiency in its effect. Genome surgery, however, is a solution that could potentially provide the eye with permanent healthy cells. As retinal degenerations are irreversible and the retina has little regenerative potential, permanent healthy cells are vital for vision. Since the retina is anatomically accessible and capable of being monitored in vivo, the retina is a prime location for novel therapies. CRISPR technology can be used to make corrections directly in vivo as well as ex vivo of stem cells for transplantation. Current standard of care includes genetic testing for causative mutations in expectation of this potential. This chapter explores future potential and strategies for retinal degenerative disease correction via CRISPR and its limitations.

Making Better Chimeric Antigen Receptors for Adoptive T-cell Therapy

PubMed Central

Maus, Marcela V.; June, Carl H.

2016-01-01

Chimeric antigen receptors (CARs) are engineered fusion proteins constructed from antigen recognition, signaling, and costimulatory domains that can be expressed in cytotoxic T cells with the purpose of reprograming the T cells to specifically target tumor cells. CAR T-cell therapy uses gene transfer technology to reprogram a patient's own T cells to stably express CARs, thereby combining the specificity of an antibody with the potent cytotoxic and memory functions of a T cell. In early phase clinical trials, CAR T cells targeting CD19 have resulted in sustained complete responses within a population of otherwise refractory patients with B-cell malignancies and, more specifically, have shown complete response rates of ≈90% in patients with relapsed or refractory acute lymphoblastic leukemia. Given this clinical efficacy, preclinical development of CAR T-cell therapy for a number of cancer indications has been actively investigated, and the future of the CAR T-cell field is extensive and dynamic. Several approaches to increase the feasibility and safety of CAR T cells are currently being explored, including investigation into mechanisms regulating the persistence of CAR T cells. Additionally, numerous early-phase clinical trials are now investigating CAR T-cell therapy beyond targeting CD19, especially in solid tumors. Trials investigating combinations of CAR T cells with immune checkpoint blockade therapies are now beginning and results are eagerly awaited. This review evaluates several of the ongoing and future directions of CAR T-cell therapy. PMID:27084741

Mapping the Decision-Making Process for Adjuvant Endocrine Therapy for Breast Cancer: The Role of Decisional Resolve.

PubMed

Beryl, Louise L; Rendle, Katharine A S; Halley, Meghan C; Gillespie, Katherine A; May, Suepattra G; Glover, Jennifer; Yu, Peter; Chattopadhyay, Runi; Frosch, Dominick L

2017-01-01

Studies show adjuvant endocrine therapy increases survival and decreases risk of breast cancer recurrence for hormone receptor-positive tumors. Yet studies also suggest that adherence rates among women taking this therapy may be as low as 50% owing largely to adverse side effects. Despite these rates, research on longitudinal patient decision making regarding this therapy is scant. We sought to map the decision-making process for women considering and initiating adjuvant endocrine therapy, paying particular attention to patterns of uncertainty and decisional change over time. A longitudinal series of semistructured interviews conducted at a multispecialty health care organization in Northern California with 35 newly diagnosed patients eligible for adjuvant endocrine therapy were analyzed. Analysis led to the identification and indexing of 3 new decision-making constructs-decisional phase, decisional direction, and decisional resolve-which were then organized using a visual matrix and examined for patterns characterizing the decision-making process. Our data reveal that most patients do not make a single, discrete decision to take or not take hormone therapy but rather traverse multiple decisional states, characterized by 1) phase, 2) direction, and 3) strength of resolve. Our analysis tracks these decisional states longitudinally using a grayscale-coded matrix. Our data show that decisional resolve wavers not just when considering therapy, as the existing concept of decisional conflict suggests, but even after initiating it, which may signal future decisions to forgo therapy. Adjuvant endocrine therapy, like other chronic care decisions, has a longer decision-making process and implementation period. Thus, theoretical, empirical, and clinical approaches should consider further exploring the new concept and measurement of decisional resolve, as it may help to improve subsequent medication adherence. © The Author(s) 2016.

Achondroplasia: pathogenesis and implications for future treatment.

PubMed

Laederich, Melanie B; Horton, William A

2010-08-01

Although the genetic defect underlying achondroplasia has been known for over a decade, no effective therapies to stimulate bone growth have emerged. Here we review the recent literature and summarize the molecular mechanisms underlying disease pathology and examine their potential as therapeutic targets. Currently used preclinical models are discussed in the context of recent advances with a special focus on C-type natriuretic peptide. Research on the mutation in Fibroblast Growth Factor Receptor 3 (FGFR3) that causes achondroplasia suggests that disease results from increased signal transduction from the mutant receptor. Thus, current therapeutic strategies have focused on reducing signals emanating from FGFR3. First-generation therapies directly targeting FGFR3, such as kinase inhibitors and neutralizing antibodies, designed for targeting FGFR3 in cancer, are still in the preclinical phase and have yet to translate into the management of achondroplasia. Counteracting signal transduction pathways downstream of FGFR3 holds promise with the discovery that administration of C-type natriuretic peptide to achondroplastic mice ameliorates their clinical phenotype. However, more research into long-term effectiveness and safety of this strategy is needed. Direct targeting of therapeutic agents to growth plate cartilage may enhance efficacy and minimize side effects of these and future therapies. Current research into the pathogenesis of achondroplasia has expanded our understanding of the mechanisms of FGFR3-induced disease and has increased the number of approaches that we may use to potentially correct it. Further research is needed to validate these approaches in preclinical models of achondroplasia.

Recent advances in the treatment of hepatitis C.

PubMed

Dhingra, Abhinav; Kapoor, Saloni; Alqahtani, Saleh A

2014-10-01

Hepatitis C virus (HCV) therapeutics is amidst a revolution. With the recent approval of sofosbuvir (Sovaldi) and simeprevir (Olysio), clinicians and patients started to recognize that for the first time in the history, hepatitis C can be cured in a majority of patients without interferon. These new regimens are safe, and have excellent efficacy and minimal adverse events. Sofosbuvir, a nucleotide analogue (NS5B polymerase inhibitor), is a potent drug with excellent tolerability and pan-genotypic activity with a high barrier to resistance. Simeprevir, a second-generation protease inhibitor which inhibits the initial cleavage of the HCV poly-protein by the NS3/4A protease. Simeprevir has been evaluated in clinical trials in combination with interferon and ribavirin based therapy and also in the COSMO trial in combination with sofosbuvir. More directly acting antiviral therapy drugs are in the pipeline with several drugs being expected to be approved by the FDA in late 2014. Although these drugs have excellent efficacy, they are more costly. The price of these drugs limits treatments of many patients in the world especially in countries with limited economic resources. However, with the availability of a variety of excellent directly acting antivirals (DAAs) in the near future, hopefully many patients would be able to afford the treatment. The future in HCV therapy will focus on special groups of patients who were excluded from initial HCV clinical trials such as post-liver transplant HCV recurrence, patients with HCV/HIV co-infection, and patients with advanced cirrhosis.

Chemical genetics and its potential in cardiac stem cell therapy

PubMed Central

Vieira, Joaquim M; Riley, Paul R

2013-01-01

Over the last decade or so, intensive research in cardiac stem cell biology has led to significant discoveries towards a potential therapy for cardiovascular disease; the main cause of morbidity and mortality in humans. The major goal within the field of cardiovascular regenerative medicine is to replace lost or damaged cardiac muscle and coronaries following ischaemic disease. At present, de novo cardiomyocytes can be generated either in vitro, for cell transplantation or disease modelling using directed differentiation of embryonic stem cells or induced pluripotent stem cells, or in vivo via direct reprogramming of resident adult cardiac fibroblast or ectopic stimulation of resident cardiac stem or progenitor cells. A major bottleneck with all of these approaches is the low efficiency of cardiomyocyte differentiation alongside their relative functional immaturity. Chemical genetics, and the application of phenotypic screening with small molecule libraries, represent a means to enhance understanding of the molecular pathways controlling cardiovascular cell differentiation and, moreover, offer the potential for discovery of new drugs to invoke heart repair and regeneration. Here, we review the potential of chemical genetics in cardiac stem cell therapy, highlighting not only the major contributions to the field so far, but also the future challenges. LINKED ARTICLES This article is part of a themed section on Regenerative Medicine and Pharmacology: A Look to the Future. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-2 PMID:22385148

Assessing Patients' Cognitive Therapy Skills: Initial Evaluation of the Competencies of Cognitive Therapy Scale.

PubMed

Strunk, Daniel R; Hollars, Shannon N; Adler, Abby D; Goldstein, Lizabeth A; Braun, Justin D

2014-10-01

In Cognitive Therapy (CT), therapists work to help patients develop skills to cope with negative affect. Most current methods of assessing patients' skills are cumbersome and impractical for clinical use. To address this issue, we developed and conducted an initial psychometric evaluation of self and therapist reported versions of a new measure of CT skills: the Competencies of Cognitive Therapy Scale (CCTS). We evaluated the CCTS at intake and post-treatment in a sample of 67 patients participating in CT. The CCTS correlated with a preexisting measure of CT skills (the Ways of Responding Questionnaire) and was also related to concurrent depressive symptoms. Across CT, self-reported improvements in CT competencies were associated with greater changes in depressive symptoms. These findings offer initial evidence for the validity of the CCTS. We discuss the CCTS in comparison with other measures of CT skills and suggest future research directions.

Use of polyclonal/monoclonal antibody therapies in transplantation.

PubMed

Yeung, Melissa Y; Gabardi, Steven; Sayegh, Mohamed H

2017-03-01

For over thirty years, antibody (mAb)-based therapies have been a standard component of transplant immunosuppression, and yet much remains to be learned in order for us to truly harness their therapeutic capabilities. Current mAbs used in transplant directly target and destroy graft-destructive immune cells, interrupt cytokine and costimulation-dependent T and B cell activation, and prevent down-stream complement activation. Areas covered: This review summarizes our current approaches to using antibody-based therapies to prevent and treat allograft rejection. It also provides examples of promising novel mAb therapies, and discusses the potential for future mAb development in transplantation. Expert opinion: The broad capability of antibodies, in parallel with our growing ability to synthetically modulate them, offers exciting opportunities to develop better biologic therapeutics. In order to do so, we must further our understanding about the basic biology underlying allograft rejection, and gain better appreciation of how characteristics of therapeutic antibodies affect their efficacy.

Assessing Patients’ Cognitive Therapy Skills: Initial Evaluation of the Competencies of Cognitive Therapy Scale

PubMed Central

Strunk, Daniel R.; Hollars, Shannon N.; Adler, Abby D.; Goldstein, Lizabeth A.; Braun, Justin D.

2014-01-01

In Cognitive Therapy (CT), therapists work to help patients develop skills to cope with negative affect. Most current methods of assessing patients’ skills are cumbersome and impractical for clinical use. To address this issue, we developed and conducted an initial psychometric evaluation of self and therapist reported versions of a new measure of CT skills: the Competencies of Cognitive Therapy Scale (CCTS). We evaluated the CCTS at intake and post-treatment in a sample of 67 patients participating in CT. The CCTS correlated with a preexisting measure of CT skills (the Ways of Responding Questionnaire) and was also related to concurrent depressive symptoms. Across CT, self-reported improvements in CT competencies were associated with greater changes in depressive symptoms. These findings offer initial evidence for the validity of the CCTS. We discuss the CCTS in comparison with other measures of CT skills and suggest future research directions. PMID:25408560

Complicated grief therapy as a new treatment approach

PubMed Central

Wetherell, Julie Loebach

2012-01-01

Complicated grief therapy (CGT) is a relatively new psychotherapy model designed to address symptoms of complicated grief. Drawn from attachment theory and with roots in both interpersonal therapy (IPT) and cognitive-behavioral therapy, CGT includes techniques similar to prolonged exposure (repeatedly telling the story of the death and in vivo exposure activities). The treatment also involves focusing on personal goals and relationships. CGT has been demonstrated to be effective in a trial in which participants with complicated grief were randomly assigned to CGT or IPT; individuals receiving CGT responded more quickly and were more likely to respond overall (51 % vs 28%). This article briefly summarizes the conceptual underpinnings of CGT, discusses the empirical evidence for its efficacy, describes its techniques, and presents a case example of a client treated in a 16-session manualized CGT protocol. The article concludes with a description of future research directions for CGT. PMID:22754288

Molecular Targeted Drugs and Biomarkers in NSCLC, the Evolving Role of Individualized Therapy

PubMed Central

Domvri, Kalliopi; Zarogoulidis, Paul; Darwiche, Kaid; Browning, Robert F.; Li, Qiang; Turner, J. Francis; Kioumis, Ioannis; Spyratos, Dionysios; Porpodis, Konstantinos; Papaiwannou, Antonis; Tsiouda, Theodora; Freitag, Lutz; Zarogoulidis, Konstantinos

2013-01-01

Lung cancer first line treatment has been directed from the non-specific cytotoxic doublet chemotherapy to the molecular targeted. The major limitation of the targeted therapies still remains the small number of patients positive to gene mutations. Furthermore, the differentiation between second line and maintenance therapy has not been fully clarified and differs in the clinical practice between cancer centers. The authors present a segregation between maintenance treatment and second line and present a possible definition for the term “maintenance” treatment. In addition, cancer cell evolution induces mutations and therefore either targeted therapies or non-specific chemotherapy drugs in many patients become ineffective. In the present work pathways such as epidermal growth factor, anaplastic lymphoma kinase, met proto-oncogene and PI3K are extensively presented and correlated with current chemotherapy treatment. Future, perspectives for targeted treatment are presented based on the current publications and ongoing clinical trials. PMID:24312144

Targeted polymeric nanoparticles for cancer gene therapy

PubMed Central

Kim, Jayoung; Wilson, David R.; Zamboni, Camila G.; Green, Jordan J.

2015-01-01

In this article, advances in designing polymeric nanoparticles for targeted cancer gene therapy are reviewed. Characterization and evaluation of biomaterials, targeting ligands, and transcriptional elements are each discussed. Advances in biomaterials have driven improvements to nanoparticle stability and tissue targeting, conjugation of ligands to the surface of polymeric nanoparticles enable binding to specific cancer cells, and the design of transcriptional elements has enabled selective DNA expression specific to the cancer cells. Together, these features have improved the performance of polymeric nanoparticles as targeted non-viral gene delivery vectors to treat cancer. As polymeric nanoparticles can be designed to be biodegradable, non-toxic, and to have reduced immunogenicity and tumorigenicity compared to viral platforms, they have significant potential for clinical use. Results of polymeric gene therapy in clinical trials and future directions for the engineering of nanoparticle systems for targeted cancer gene therapy are also presented. PMID:26061296

Update on adjuvant chemotherapy for early breast cancer.

PubMed

Rampurwala, Murtuza M; Rocque, Gabrielle B; Burkard, Mark E

2014-01-01

Breast cancer is the second most common cancer in women worldwide. Although most women are diagnosed with early breast cancer, a substantial number recur due to persistent micro-metastatic disease. Systemic adjuvant chemotherapy improves outcomes and has advanced from first-generation regimens to modern dose-dense combinations. Although chemotherapy is the cornerstone of adjuvant therapy, new biomarkers are identifying patients who can forego such treatment. Neo-adjuvant therapy is a promising platform for drug development, but investigators should recognize the limitations of surrogate endpoints and clinical trials. Previous decades have focused on discovering, developing, and intensifying adjuvant chemotherapy. Future efforts should focus on customizing therapy and reducing chemotherapy for patients unlikely to benefit. In some cases, it may be possible to replace chemotherapy with treatments directed at specific genetic or molecular breast cancer subtypes. Yet, we anticipate that chemotherapy will remain a critical component of adjuvant therapy for years to come.

Cell-based therapeutic strategies for multiple sclerosis

PubMed Central

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A; Atkins, Harold; Banwell, Brenda; Bar-Or, Amit; Bebo, Bruce; Bowen, James; Burt, Richard; Calabresi, Peter; Cohen, Jeffrey; Comi, Giancarlo; Connick, Peter; Cross, Anne; Cutter, Gary; Derfuss, Tobias; Ffrench-Constant, Charles; Freedman, Mark; Galipeau, Jacques; Goldman, Myla; Goldman, Steven; Goodman, Andrew; Green, Ari; Griffith, Linda; Hartung, Hans-Peter; Hemmer, Bernhard; Hyun, Insoo; Iacobaeus, Ellen; Inglese, Matilde; Jubelt, Burk; Karussis, Dimitrios; Küry, Patrick; Landsman, Douglas; Laule, Cornelia; Liblau, Roland; Mancardi, Giovanni; Ann Marrie, Ruth; Miller, Aaron; Miller, Robert; Miller, David; Mowry, Ellen; Muraro, Paolo; Nash, Richard; Ontaneda, Daniel; Pasquini, Marcelo; Pelletier, Daniel; Peruzzotti-Jametti, Luca; Pluchino, Stefano; Racke, Michael; Reingold, Stephen; Rice, Claire; Ringdén, Olle; Rovira, Alex; Saccardi, Riccardo; Sadiq, Saud; Sarantopoulos, Stefanie; Savitz, Sean; Scolding, Neil; Soelberg Sorensen, Per; Pia Sormani, Maria; Stuve, Olaf; Tesar, Paul; Thompson, Alan; Trojano, Maria; Uccelli, Antonio; Uitdehaag, Bernard; Utz, Ursula; Vukusic, Sandra; Waubant, Emmanuelle; Wilkins, Alastair

2017-01-01

Abstract The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. PMID:29053779

Recent Advances in Targeted Therapy for Glioma.

PubMed

Lin, Lin; Cai, Jinquan; Jiang, Chuanlu

2017-01-01

Gliomas are the most common primary malignant brain tumors, which have a universally fatal outcome. Current standard treatment for glioma patients is surgical removal followed by radiotherapy and adjuvant chemotherapy. Due to therapeutic resistance and tumor recurrence, efforts are ongoing to identify the molecules that are fundamental to regulate the tumor progression and provide additional methods for individual treatment of glioma patients. By studying the initiation and maintenance of glioma, studies focused on the targets of tyrosine kinase receptors including EGFR, PDGFR and other crucial signal pathways such as PI3K/AKT and RAS/RAF/MAPK pathway. Furthermore, recent advances in targeting immunotherapy and stem cell therapy also brought numerous strategies to glioma treatment. This article reviewed the researches focused on the advanced strategies of various target therapies for improving the glioma treatment efficacy, and discussed the challenges and future directions for glioma therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Complicated grief therapy as a new treatment approach.

PubMed

Wetherell, Julie Loebach

2012-06-01

Complicated grief therapy (CGT) is a relatively new psychotherapy model designed to address symptoms of complicated grief. Drawn from attachment theory and with roots in both interpersonal therapy (IPT) and cognitive-behavioral therapy, CGT includes techniques similar to prolonged exposure (repeatedly telling the story of the death and in vivo exposure activities). The treatment also involves focusing on personal goals and relationships. CGT has been demonstrated to be effective in a trial in which participants with complicated grief were randomly assigned to CGT or IPT; individuals receiving CGT responded more quickly and were more likely to respond overall (51% vs 28%). This article briefly summarizes the conceptual underpinnings of CGT, discusses the empirical evidence for its efficacy, describes its techniques, and presents a case example of a client treated in a 16-session manualized CGT protocol. The article concludes with a description of future research directions for CGT.

Stem cells in retinal regeneration: past, present and future.

PubMed

Ramsden, Conor M; Powner, Michael B; Carr, Amanda-Jayne F; Smart, Matthew J K; da Cruz, Lyndon; Coffey, Peter J

2013-06-01

Stem cell therapy for retinal disease is under way, and several clinical trials are currently recruiting. These trials use human embryonic, foetal and umbilical cord tissue-derived stem cells and bone marrow-derived stem cells to treat visual disorders such as age-related macular degeneration, Stargardt's disease and retinitis pigmentosa. Over a decade of analysing the developmental cues involved in retinal generation and stem cell biology, coupled with extensive surgical research, have yielded differing cellular approaches to tackle these retinopathies. Here, we review these various stem cell-based approaches for treating retinal diseases and discuss future directions and challenges for the field.

Human Hemato-Lymphoid System Mice: Current Use and Future Potential for Medicine

PubMed Central

Rongvaux, Anthony; Takizawa, Hitoshi; Strowig, Till; Willinger, Tim; Eynon, Elizabeth E.

2014-01-01

To directly study complex human hemato-lymphoid system physiology and respective system-associated diseases in vivo, human-to-mouse xenotransplantation models for human blood and blood-forming cells and organs have been developed over the past three decades. We here review the fundamental requirements and the remarkable progress made over the past few years in improving these systems, the current major achievements reached by use of these models, and the future challenges to more closely model and study human health and disease and to achieve predictive preclinical testing of both prevention measures and potential new therapies. PMID:23330956

Biomarkers and patient selection for PI3K/Akt/mTOR targeted therapies: current status and future directions.

PubMed

Bartlett, John M S

2010-11-01

The phosphatidylinositol 3-kinase (PI3K)/Akt/ mammalian target of rapamycin (mTOR) pathway regulates a broad spectrum of physiologic and pathologic processes. In breast cancer mutation, amplification, deletion, methylation, and posttranslational modifications lead to significant dysregulation of this pathway leading to more aggressive and potentially drug-resistant disease. Multiple novel agents, targeting different nodes within the pathway are currently under development by both commercial and academic partners. The key to the successful validation of these markers is selection of the appropriate patient groups using biomarkers. This article reviews current progress in this area, highlighting the key molecular alterations described in genes within the PI3K/Akt/mTOR pathway that may have an effect on response to current and future therapeutic interventions. Herein, gaps in current knowledge are highlighted and suggestions for future research directions given that may facilitate biomarker development in partnership with current drug development.

Enhancing cell and gene therapy manufacture through the application of advanced fluorescent optical sensors (Review).

PubMed

Harrison, Richard P; Chauhan, Veeren M

2017-12-15

Cell and gene therapies (CGTs) are examples of future therapeutics that can be used to cure or alleviate the symptoms of disease, by repairing damaged tissue or reprogramming defective genetic information. However, despite the recent advancements in clinical trial outcomes, the path to wide-scale adoption of CGTs remains challenging, such that the emergence of a "blockbuster" therapy has so far proved elusive. Manufacturing solutions for these therapies require the application of scalable and replicable cell manufacturing techniques, which differ markedly from the existing pharmaceutical incumbent. Attempts to adopt this pharmaceutical model for CGT manufacture have largely proved unsuccessful. The most significant challenges facing CGT manufacturing are process analytical testing and quality control. These procedures would greatly benefit from improved sensory technologies that allow direct measurement of critical quality attributes, such as pH, oxygen, lactate and glucose. In turn, this would make manufacturing more robust, replicable and standardized. In this review, the present-day state and prospects of CGT manufacturing are discussed. In particular, the authors highlight the role of fluorescent optical sensors, focusing on their strengths and weaknesses, for CGT manufacture. The review concludes by discussing how the integration of CGT manufacture and fluorescent optical sensors could augment future bioprocessing approaches.

Allorecognition pathways in transplant rejection and tolerance.

PubMed

Ali, Jason M; Bolton, Eleanor M; Bradley, J Andrew; Pettigrew, Gavin J

2013-10-27

With the advent of cellular therapies, it has become clear that the success of future therapies in prolonging allograft survival will require an intimate understanding of the allorecognition pathways and effector mechanisms that are responsible for chronic rejection and late graft loss.Here, we consider current understanding of T-cell allorecognition pathways and discuss the most likely mechanisms by which these pathways collaborate with other effector mechanisms to cause allograft rejection. We also consider how this knowledge may inform development of future strategies to prevent allograft rejection.Although both direct and indirect pathway CD4 T cells appear active immediately after transplantation, it has emerged that indirect pathway CD4 T cells are likely to be the dominant alloreactive T-cell population late after transplantation. Their ability to provide help for generating long-lived alloantibody is likely one of the main mechanisms responsible for the progression of allograft vasculopathy and chronic rejection.Recent work has suggested that regulatory T cells may be an effective cellular therapy in transplantation. Given the above, adoptive therapy with CD4 regulatory T cells with indirect allospecificity is a rational first choice in attempting to attenuate the development and progression of chronic rejection; those with additional properties that enable inhibition of germinal center alloantibody responses hold particular appeal.

Treatment of systemic mast cell disorders.

PubMed

Worobec, A S

2000-06-01

The heterogeneous nature of disease manifestations in mastocytosis requires the individualization of therapy to each patient's clinical presentation and prognosis. The mainstay of treatment for most categories of mastocytosis are H1 and H2 antihistamines with the addition of corticosteroids for more severe symptoms. This article presents a summary of treatment strategies for indolent and aggressive forms of mastocytosis along with a discussion of future therapeutic directions.

Beyond BRAF: where next for melanoma therapy?

PubMed Central

Fedorenko, I V; Gibney, G T; Sondak, V K; Smalley, K S M

2015-01-01

In recent years, melanoma has become a poster-child for the development of oncogene-directed targeted therapies. This approach, which has been exemplified by the development of small-molecule BRAF inhibitors and the BRAF/MEK inhibitor combination for BRAF-mutant melanoma, has brought new hope to patients. Despite these successes, treatment failure seems near inevitable in the majority of cases—even in individuals treated with the BRAF/MEK inhibitor doublet. In the current review, we discuss the future of combination strategies for patients with BRAF-mutant melanoma as well as the emerging therapeutic options for patients with NRAS-mutant and BRAF/NRAS-wild-type melanoma. We also outline some of the newest developments in the in-depth personalisation of therapy that should allow melanoma treatment to continue shaping the field precision cancer medicine. PMID:25180764

Key anticipated regulatory issues for clinical use of human induced pluripotent stem cells.

PubMed

Knoepfler, Paul S

2012-09-01

The production of human induced pluripotent stem cells (hiPSCs) has greatly expanded the realm of possible stem cell-based regenerative medicine therapies and has particularly exciting potential for autologous therapies. However, future therapies based on hiPSCs will first have to address not only similar regulatory issues as those facing human embryonic stem cells with the US FDA and international regulatory agencies, but also hiPSCs have raised unique concerns as well. While the first possible clinical use of hiPSCs remains down the road, as a field it would be wise for us to anticipate potential roadblocks and begin formulating solutions. In this article, I discuss the potential regulatory issues facing hiPSCs and propose some potential changes in the direction of the field in response.

Enacting relationships in marriage and family therapy: a conceptual and operational definition of an enactment.

PubMed

Davis, Sean D; Butler, Mark H

2004-07-01

Enactments are a potential common clinical process factor contributing to positive outcomes in many relational therapies. Enactments provide therapists a medium for mediating relationships through simultaneous experiential intervention and change at multiple levels of relationships--including specific relationship disagreements and problems, interaction process surrounding these issues, and underlying emotions and attachment issues confounded with those problems. We propose a model of enactments in marriage and family therapy, consisting of three components--initiation operations, intervention operations, and evaluation operations. We offer a conceptual framework to help clinicians know when and to what purpose to use this model of enactments. We provide an operational description of each component of an enactment, exemplifying them using a hypothetical clinical vignette. Directions for future research are suggested.

Nonviral vectors for cancer gene therapy: prospects for integrating vectors and combination therapies.

PubMed

Ohlfest, John R; Freese, Andrew B; Largaespada, David A

2005-12-01

Gene therapy has the potential to improve the clinical outcome of many cancers by transferring therapeutic genes into tumor cells or normal host tissue. Gene transfer into tumor cells or tumor-associated stroma is being employed to induce tumor cell death, stimulate anti-tumor immune response, inhibit angiogenesis, and control tumor cell growth. Viral vectors have been used to achieve this proof of principle in animal models and, in select cases, in human clinical trials. Nevertheless, there has been considerable interest in developing nonviral vectors for cancer gene therapy. Nonviral vectors are simpler, more amenable to large-scale manufacture, and potentially safer for clinical use. Nonviral vectors were once limited by low gene transfer efficiency and transient or steadily declining gene expression. However, recent improvements in plasmid-based vectors and delivery methods are showing promise in circumventing these obstacles. This article reviews the current status of nonviral cancer gene therapy, with an emphasis on combination strategies, long-term gene transfer using transposons and bacteriophage integrases, and future directions.

Bone morphogenetic protein-2 and bone therapy: successes and pitfalls.

PubMed

Poon, Bonnie; Kha, Tram; Tran, Sally; Dass, Crispin R

2016-02-01

Bone morphogenetic proteins (BMPs), more specifically BMP-2, are being increasingly used in orthopaedic surgery due to advanced research into osteoinductive factors that may enhance and improve bone therapy. There are many areas in therapy that BMP-2 is being applied to, including dental treatment, open tibial fractures, cancer and spinal surgery. Within these areas of treatment, there are many reports of successes and pitfalls. This review explores the use of BMP-2 and its successes, pitfalls and future prospects in bone therapy. The PubMed database was consulted to compile this review. With successes in therapy, there were descriptions of a more rapid healing time with no signs of rejection or infection attributed to BMP-2 treatment. Pitfalls included BMP-2 'off-label' use, which lead to various adverse effects. Our search highlighted that optimising treatment with BMP-2 is a direction that many researchers are exploring, with areas of current research interest including concentration and dose of BMP-2, carrier type and delivery. © 2015 Royal Pharmaceutical Society.

Focus on anorexia nervosa: modern psychological treatment and guidelines for the adolescent patient

PubMed Central

Espie, Jonathan; Eisler, Ivan

2015-01-01

Anorexia nervosa is a serious condition associated with high mortality. Incidence is highest for female adolescents, and prevalence data highlight a pressing unmet need for treatment. While there is evidence that adolescent-onset anorexia has relatively high rates of eventual recovery, the illness is often protracted, and even after recovery from the eating disorder there is an ongoing vulnerability to psychosocial problems in later life. Family therapy for anorexia in adolescence has evolved from a generic systemic treatment into an eating disorder-specific format (family therapy for anorexia nervosa), and this approach has been evidenced as an effective treatment. Individual treatments, including cognitive behavioral therapy, also have some evidence of effectiveness. Most adolescents can be effectively and safely managed as outpatients. Day-patient treatment holds promise as an alternative to inpatient treatment or as an intensive program following a brief medical admission. Evidence is emerging of advantages in detecting and treating adolescent anorexia nervosa in specialist community-based child and adolescent eating-disorder services accessible directly from primary care. Limitations and future directions for modern treatment are considered. PMID:25678834

Therapeutic Efficacy of Neurostimulation for Depression: Techniques, Current Modalities, and Future Challenges.

PubMed

Akhtar, Hafsah; Bukhari, Faiza; Nazir, Misbah; Anwar, Muhammad Nabeel; Shahzad, Adeeb

2016-02-01

Depression is the most prevalent debilitating mental illness; it is characterized as a disorder of mood, cognitive function, and neurovegetative function. About one in ten individuals experience depression at some stage of their lives. Antidepressant drugs are used to reduce the symptoms but relapse occurs in ~20% of patients. However, alternate therapies like brain stimulation techniques have shown promising results in this regard. This review covers the brain stimulation techniques electroconvulsive therapy, transcranial direct current stimulation, repetitive transcranial magnetic stimulation, vagus nerve stimulation, and deep brain stimulation, which are used as alternatives to antidepressant drugs, and elucidates their research and clinical outcomes.

Therapeutic Genome Editing: Prospects and Challenges

PubMed Central

Cox, David Benjamin Turitz; Platt, Randall Jeffrey; Zhang, Feng

2015-01-01

Recent advances in the development of genome editing technologies based on programmable nucleases have significantly improved our ability to make precise changes in the genomes of eukaryotic cells. Genome editing is already broadening our ability to elucidate the contribution of genetics to disease by facilitating the creation of more accurate cellular and animal models of pathological processes. A particularly tantalizing application of programmable nucleases is the potential to directly correct genetic mutations in affected tissues and cells to treat diseases that are refractory to traditional therapies. Here we discuss current progress towards developing programmable nuclease-based therapies as well as future prospects and challenges. PMID:25654603

Improving Collaborative Play Between Children with Autism Spectrum Disorders and Their Siblings: The Effectiveness of a Robot-Mediated Intervention Based on Lego® Therapy.

PubMed

Huskens, Bibi; Palmen, Annemiek; Van der Werff, Marije; Lourens, Tino; Barakova, Emilia

2015-11-01

The aim of the study was to investigate the effectiveness of a brief robot-mediated intervention based on Lego(®) therapy on improving collaborative behaviors (i.e., interaction initiations, responses, and play together) between children with ASD and their siblings during play sessions, in a therapeutic setting. A concurrent multiple baseline design across three child-sibling pairs was in effect. The robot-intervention resulted in no statistically significant changes in collaborative behaviors of the children with ASD. Despite limited effectiveness of the intervention, this study provides several practical implications and directions for future research.

Combination of photodynamic therapy and immunomodulation — current status and future trends

PubMed Central

Qiang, Yong-Gang; Yow, Christine M.N.; Huang, Zheng

2008-01-01

Photodynamic therapy (PDT) has been used for the treatment of non-malignant and malignant diseases from head to toe. Over the last decade its clinical application has gained increasing acceptance around the world. Pre-clinical studies demonstrate that, in addition to the direct local cytotoxicity and vascular effects, PDT can induce various host immune responses. Recent clinical data also show that improved clinical outcomes are obtained through the combination of PDT and immunomodulation. This review will summarize and discuss recent progress in developing innovative regimen of PDT combined with immunomodulation for the treatment of both non-malignant and malignant diseases. PMID:18161883

The Various Applications of 3D Printing in Cardiovascular Diseases.

PubMed

El Sabbagh, Abdallah; Eleid, Mackram F; Al-Hijji, Mohammed; Anavekar, Nandan S; Holmes, David R; Nkomo, Vuyisile T; Oderich, Gustavo S; Cassivi, Stephen D; Said, Sameh M; Rihal, Charanjit S; Matsumoto, Jane M; Foley, Thomas A

2018-05-10

To highlight the various applications of 3D printing in cardiovascular disease and discuss its limitations and future direction. Use of handheld 3D printed models of cardiovascular structures has emerged as a facile modality in procedural and surgical planning as well as education and communication. Three-dimensional (3D) printing is a novel imaging modality which involves creating patient-specific models of cardiovascular structures. As percutaneous and surgical therapies evolve, spatial recognition of complex cardiovascular anatomic relationships by cardiologists and cardiovascular surgeons is imperative. Handheld 3D printed models of cardiovascular structures provide a facile and intuitive road map for procedural and surgical planning, complementing conventional imaging modalities. Moreover, 3D printed models are efficacious educational and communication tools. This review highlights the various applications of 3D printing in cardiovascular diseases and discusses its limitations and future directions.

Irreversible pan-ErbB tyrosine kinase inhibitors and breast cancer: current status and future directions.

PubMed

Ocaña, Alberto; Amir, Eitan

2009-12-01

Aberrant activation of HER2 through overexpression has been shown to play an important role in some breast cancers. Therapies against this receptor including the monoclonal antibody, trastuzumab, or the small tyrosine kinase inhibitor, lapatinib have shown to improve the prognosis of such patients. Despite overexpressing HER2, some patients do not respond to these targeted treatments or progress after a short period of time. Irreversible tyrosine kinase inhibitors have been developed to bypass several pathways that could be involved in this resistance. In vitro, these agents have been shown to be more potent and to prolong target inhibition. Clinical development of these agents is ongoing and early results are promising. This review will describe the biologic rationale that justifies the development of these agents in breast cancer focusing on the current status and future directions.

Targets for Drug Therapy for Autism Spectrum Disorder: Challenges and Future Directions.

PubMed

Lacivita, Enza; Perrone, Roberto; Margari, Lucia; Leopoldo, Marcello

2017-11-22

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests, and activities. Various factors are involved in the etiopathogenesis of ASD, including genetic factors, environmental toxins and stressors, impaired immune responses, mitochondrial dysfunction, and neuroinflammation. The heterogeneity in the phenotype among ASD patients and the complex etiology of the condition have long impeded the advancement of the development of pharmacological therapies. In the recent years, the integration of findings from mouse models to human genetics resulted in considerable progress toward the understanding of ASD pathophysiology. Currently, strategies to treat core symptoms of ASD are directed to correct synaptic dysfunctions, abnormalities in central oxytocin, vasopressin, and serotonin neurotransmission, and neuroinflammation. Here, we present a survey of the studies that have suggested molecular targets for drug development for ASD and the state-of-the-art of medicinal chemistry efforts in related areas.

Parathyroid Gland Function in Primary Aldosteronism.

PubMed

Asbach, E; Bekeran, M; Reincke, M

2015-12-01

Primary aldosteronism (PA) is the most frequent cause of secondary arterial hypertension. Beyond its effects on intravascular volume and blood pressure, PA causes metabolic alterations and a higher cardiovascular morbidity, which is reduced by PA-directed therapy. Experimental studies demonstrated that mineralocorticoid excess may also influence mineral homeostasis. A role in cardiovascular disease has also been attributed to parathyroid hormone (PTH). Increasing evidence supports a bidirectional interaction between aldosterone and PTH.Primary hyperparathyroidism is associated with arterial hypertension and an increased cardiovascular morbidity and mortality, which might be associated to higher aldosterone values; parathyreoidectomy results in lowered aldosterone and blood pressure levels. PA leads to secondary hyperparathyroidism, which is reversible by PA-directed therapy. A lower bone mineral density and a higher fracture rate were also shown to be reversible by PA-directed therapy. There is a suspicion of a bidirectional interaction between aldosterone and PTH, which might lead to a higher cardiovascular risk. There are more and more reports about coincident PA and primary hyperparathyroidism. From a pathophysiologic point of view this constellation is best characterized as tertiary hyperparathyroidism. Future aspects should further clarify the extent of these endocrine interactions and analyze the influence of this interplay on cardiovascular morbidity and mortality and bone health. © Georg Thieme Verlag KG Stuttgart · New York.

Duchenne Muscular Dystrophy Gene Therapy in the Canine Model

PubMed Central

2015-01-01

Abstract Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disease caused by dystrophin deficiency. Gene therapy has significantly improved the outcome of dystrophin-deficient mice. Yet, clinical translation has not resulted in the expected benefits in human patients. This translational gap is largely because of the insufficient modeling of DMD in mice. Specifically, mice lacking dystrophin show minimum dystrophic symptoms, and they do not respond to the gene therapy vector in the same way as human patients do. Further, the size of a mouse is hundredfolds smaller than a boy, making it impossible to scale-up gene therapy in a mouse model. None of these limitations exist in the canine DMD (cDMD) model. For this reason, cDMD dogs have been considered a highly valuable platform to test experimental DMD gene therapy. Over the last three decades, a variety of gene therapy approaches have been evaluated in cDMD dogs using a number of nonviral and viral vectors. These studies have provided critical insight for the development of an effective gene therapy protocol in human patients. This review discusses the history, current status, and future directions of the DMD gene therapy in the canine model. PMID:25710459

The effectiveness of parent participation in occupational therapy for children with developmental delay

PubMed Central

Lin, Chien-Lin; Lin, Chin-Kai; Yu, Jia-Jhen

2018-01-01

Introduction This study aims to explore the impact of Parent Participation Program on the development of developmental delay children. Methods Pretest-posttest equivalent-group experimental design study was used in this paper. A total of 30 pairs of developmental delay children aged 0–72 months and their parents participated into this study. They were divided into two groups, namely control group and experimental group, according to parents’ wishes. The objects of study in control group received 16 courses of direct rehabilitation therapy; those in experimental group received 8 courses of direct rehabilitation therapy and 8 courses of instruction and tracking of Parent Participation Program. The duration of the intervention was 8 weeks. All cases should be evaluated before and after the intervention, to analyze the difference before and after intervention and among groups. The statistical methods in this paper included descriptive analysis, Chi-square test, independent sample t-test, pair-sample t-test. Results and conclusion The intervention of Parent Participation Occupational Program has positive impact on the development of developmental delay children in various fields. Among all the intervention results, the progress of the experimental group is 1.895 times more than that of the control group. With parent involvement, Parent Participation Occupational Therapy can promote the cognitive ability, language ability, action ability (gross and fine movement), social competence and self-care ability of children with developmental delay. Finally, the researcher presents suggestions and directions for future research in accordance with the results. PMID:29503546

The Potential Role of Aerobic Exercise to Modulate Cardiotoxicity of Molecularly Targeted Cancer Therapeutics

PubMed Central

Lakoski, Susan; Mackey, John R.; Douglas, Pamela S.; Haykowsky, Mark J.; Jones, Lee W.

2013-01-01

Molecularly targeted therapeutics (MTT) are the future of cancer systemic therapy. They have already moved from palliative therapy for advanced solid malignancies into the setting of curative-intent treatment for early-stage disease. Cardiotoxicity is a frequent and potentially serious adverse complication of some targeted therapies, leading to a broad range of potentially life-threatening complications, therapy discontinuation, and poor quality of life. Low-cost pleiotropic interventions are therefore urgently required to effectively prevent and/or treat MTT-induced cardiotoxicity. Aerobic exercise therapy has the unique capacity to modulate, without toxicity, multiple gene expression pathways in several organ systems, including a plethora of cardiac-specific molecular and cell-signaling pathways implicated in MTT-induced cardiac toxicity. In this review, we examine the molecular signaling of antiangiogenic and HER2-directed therapies that may underpin cardiac toxicity and the hypothesized molecular mechanisms underlying the cardioprotective properties of aerobic exercise. It is hoped that this knowledge can be used to maximize the benefits of small molecule inhibitors, while minimizing cardiac damage in patients with solid malignancies. PMID:23335619

Biofield therapies: helpful or full of hype? A best evidence synthesis.

PubMed

Jain, Shamini; Mills, Paul J

2010-03-01

Biofield therapies (such as Reiki, therapeutic touch, and healing touch) are complementary medicine modalities that remain controversial and are utilized by a significant number of patients, with little information regarding their efficacy. This systematic review examines 66 clinical studies with a variety of biofield therapies in different patient populations. We conducted a quality assessment as well as a best evidence synthesis approach to examine evidence for biofield therapies in relevant outcomes for different clinical populations. Studies overall are of medium quality, and generally meet minimum standards for validity of inferences. Biofield therapies show strong evidence for reducing pain intensity in pain populations, and moderate evidence for reducing pain intensity hospitalized and cancer populations. There is moderate evidence for decreasing negative behavioral symptoms in dementia and moderate evidence for decreasing anxiety for hospitalized populations. There is equivocal evidence for biofield therapies' effects on fatigue and quality of life for cancer patients, as well as for comprehensive pain outcomes and affect in pain patients, and for decreasing anxiety in cardiovascular patients. There is a need for further high-quality studies in this area. Implications and future research directions are discussed.

Proposed definition of the vaginal cuff and paracolpium clinical target volume in postoperative uterine cervical cancer.

PubMed

Murakami, Naoya; Norihisa, Yoshiki; Isohashi, Fumiaki; Murofushi, Keiko; Ariga, Takuro; Kato, Tomoyasu; Inaba, Koji; Okamoto, Hiroyuki; Ito, Yoshinori; Toita, Takafumi; Itami, Jun

2016-01-01

The aim of this study was to develop an appropriate definition for vaginal cuff and paracolpium clinical target volume (CTV) for postoperative intensity modulated radiation therapy in patients with uterine cervical cancer. A working subgroup was organized within the Radiation Therapy Study Group of the Japan Clinical Oncology Group to develop a definition for the postoperative vaginal cuff and paracolpium CTV in December 2013. The group consisted of 5 radiation oncologists who specialized in gynecologic oncology and a gynecologic oncologist. A comprehensive literature review that included anatomy, surgery, and imaging fields was performed and was followed by multiple discreet face-to-face discussions and e-mail messages before a final consensus was reached. Definitions for the landmark structures in all directions that demarcate the vaginal cuff and paracolpium CTV were decided by consensus agreement of the working group. A table was created that showed boundary structures of the vaginal cuff and paracolpium CTV in each direction. A definition of the postoperative cervical cancer vaginal cuff and paracolpium CTV was developed. It is expected that this definition guideline will serve as a template for future radiation therapy clinical trial protocols, especially protocols involving intensity modulated radiation therapy. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Protecting retinal ganglion cells.

PubMed

Khatib, T Z; Martin, K R

2017-02-01

Retinal ganglion cell degeneration underlies several conditions which give rise to significant visual compromise, including glaucoma, hereditary optic neuropathies, ischaemic optic neuropathies, and demyelinating disease. In this review, we discuss the emerging strategies for neuroprotection specifically in the context of glaucoma, including pharmacological neuroprotection, mesenchymal stem cells, and gene therapy approaches. We highlight potential pitfalls that need to be considered when developing these strategies and outline future directions, including the prospects for clinical trials.

Future of diagnostic microbiology.

PubMed

Khardori, N

2014-01-01

Diagnostic Microbiology is the tool that makes it possible to identify the exact etiology of infectious diseases and the most optimal therapy at the level of individual patients as well as communities. Conventional methods require time to grow the microbes in vitro under specific conditions and not all microbes are easily cultivable. This is followed by biochemical methods for identification which also require hours and sometimes days. Transport of the specimens under less than ideal conditions, prior use of antibiotics and small number of organisms are among the factors that render culture-based methods less reliable. Newer methods depend on amplification of nucleic acids followed by use of probes for identification. This mitigates the need for higher microbial load, presence of metabolically active viable organisms and shortens the time to reporting. These methods can be used to detect antibiotic resistance genes directly from the specimen and help direct targeted therapy. Since these methods will not fulfill all the diagnostic needs, a second approach is being used to shorten the time to identification after the organism has already grown. Mass spectrometry and bioinformatics are the tools making this possible. This review gives a historical perspective on diagnostic microbiology, discusses the pitfalls of current methodology and provides an overview of newer and future methods.

In vivo models in breast cancer research: progress, challenges and future directions

PubMed Central

Holen, Ingunn; Speirs, Valerie; Morrissey, Bethny

2017-01-01

ABSTRACT Research using animal model systems has been instrumental in delivering improved therapies for breast cancer, as well as in generating new insights into the mechanisms that underpin development of the disease. A large number of different models are now available, reflecting different types and stages of the disease; choosing which one to use depends on the specific research question(s) to be investigated. Based on presentations and discussions from leading experts who attended a recent workshop focused on in vivo models of breast cancer, this article provides a perspective on the many varied uses of these models in breast cancer research, their strengths, associated challenges and future directions. Among the questions discussed were: how well do models represent the different stages of human disease; how can we model the involvement of the human immune system and microenvironment in breast cancer; what are the appropriate models of metastatic disease; can we use models to carry out preclinical drug trials and identify pathways responsible for drug resistance; and what are the limitations of patient-derived xenograft models? We briefly outline the areas where the existing breast cancer models require improvement in light of the increased understanding of the disease process, reflecting the drive towards more personalised therapies and identification of mechanisms of drug resistance. PMID:28381598

State of the Art, Unresolved Issues, and Future Research Directions in the Fight against Hepatitis C Virus: Perspectives for Screening, Diagnostics of Resistances, and Immunization

PubMed Central

Ansaldi, Filippo

2016-01-01

Hepatitis C virus (HCV) still represents a major public health threat, with a dramatic burden from both epidemiological and clinical points of view. New generation of direct-acting antiviral agents (DAAs) has been recently introduced in clinical practice promising to cure HCV and to overcome the issues related to the interferon-based therapies. However, the emergence of drug resistance and the suboptimal activity of DAAs therapies against diverse HCV genotypes have been observed, determining treatment failure and hampering an effective control of HCV spread worldwide. Moreover, these treatments remain poorly accessible, particularly in low-income countries. Finally, effective screening strategy is crucial to early identifying and treating all HCV chronically infected patients. For all these reasons, even though new drugs may contribute to impacting HCV spread worldwide a preventive HCV vaccine remains a cornerstone in the road to significantly reduce the HCV spread globally, with the ultimate goal of its eradication. Advances in molecular vaccinology, together with a strong financial, political, and societal support, will enable reaching this fundamental success in the coming years. In this comprehensive review, the state of the art about these major topics in the fight against HCV and the future of research in these fields are discussed. PMID:27843956

Inorganic Nitrite Therapy: Historical perspective and future directions

PubMed Central

Kevil, Christopher G.; Kolluru, Gopi K.; Pattillo, Christopher B.; Giordano, Tony

2015-01-01

Over the past several years, investigators studying nitric oxide (NO) biology and metabolism have come to learn that the one electron oxidation product of NO, nitrite anion, serves as a unique player in modulating tissue NO bioavailability. Numerous studies have examined how this oxidized metabolite of NO can act as a salvage pathway for maintaining NO equivalents through multiple reduction mechanisms in permissive tissue environments. Moreover, it is now clear that nitrite anion production and distribution throughout the body can act in an endocrine manner to augment NO bioavailability that is important for physiological and pathological processes. These discoveries have led to renewed hope and efforts for an effective NO based therapeutic agent through the unique action of sodium nitrite as an NO pro-drug. More recent studies also indicate that sodium nitrate may also increase plasma nitrite levels via the enterosalivary circulatory system resulting in nitrate reduction to nitrite by microorganisms found within the oral cavity. In this review, we discuss the importance of nitrite anion in several disease models along with an appraisal of sodium nitrite therapy in the clinic, potential caveats of such clinical uses, and future possibilities of nitrite based therapies. PMID:21619929

Genomic Alterations in Advanced Esophageal Cancer May Lead to Subtype-Specific Therapies

PubMed Central

Forde, Patrick M.

2013-01-01

The development of targeted agents for metastatic esophageal or gastroesophageal junction (GEJ) tumors has been limited when compared with that for other common tumors. To date, the anti-human epidermal growth factor receptor-2 (HER-2) antibody, trastuzumab, in combination with chemotherapy, is the only approved novel agent for these cancers, and its use is limited to the small population of patients whose tumors overexpress HER-2. Despite recent progress in the field, median overall survival remains only 8–12 months for patients with stage IV esophageal or GEJ cancer. In this article, we examine the molecular aberrations thought to drive the development and spread of esophageal cancer and identify promising targets for specific tumor inhibition. Data from clinical studies of targeted agents are reviewed, including epidermal growth factor receptor antibodies, tyrosine kinase inhibitors, HER-2, and vascular endothelial growth factor-directed therapy. Current and future targets include MET, fibroblast growth factor receptor, and immune-based therapies. Evidence from trials to date suggests that molecularly unselected patient cohorts derive minimal benefit from most target-specific agents, suggesting that future collaborative investigation should focus on preselected molecular subgroups of patients with this challenging heterogeneous disease. PMID:23853247

Toward an integrative understanding of narrative and emotion processes in Emotion-focused therapy of depression: implications for theory, research and practice.

PubMed

Angus, Lynne

2012-01-01

This paper addresses the fundamental contributions of client narrative disclosure in psychotherapy and its importance for the elaboration of new emotional meanings and self understanding in the context of Emotion-focused therapy (EFT) of depression. An overview of the multi-methodological steps undertaken to empirically investigate the contributions of client story telling, emotional differentiation and meaning-making processes (Narrative Processes Coding System; Angus et al., 1999) in EFT treatments of depression is provided, followed by a summary of key research findings that informed the development of a narrative-informed approach to Emotion-focused therapy of depression (Angus & Greenberg, 2011). Finally, the clinical practice and training implications of adopting a research-informed approach to working with narrative and emotion processes in EFT are described, and future research directions discussed.

Renin-angiotensin-aldosterone system (RAAS) pharmacogenomics: implications in heart failure management.

PubMed

Beitelshees, Amber L; Zineh, Issam

2010-05-01

Blockade of the renin-angiotensin-aldosterone system (RAAS) with ACE inhibitors has been a cornerstone of heart failure therapy for over 15 years. More recently, further blockade of RAAS with aldosterone antagonists and angiotensin receptor blockers (ARBs) has been studied. While these therapies have certainly improved outcomes in the treatment of heart failure, morbidity and mortality remain extremely high. Furthermore, polypharmacy and complex regimens of seven medications on average is the norm for management of heart failure. This results in increased costs, patient burden, and uncertainty as to the best course of therapy. The ability to personalize patients' therapeutic regimens using pharmacogenomics has the potential of providing more effective and efficient use of RAAS-modulating medications. This review highlights the implications of major RAAS pharmacogenetic studies, while outlining future directions for translation to practice.

From a Parkinson's disease expert: Rasagiline and the Future of Therapy

PubMed Central

Lakhan, Shaheen E

2007-01-01

John Finberg is a professor of pharmacology at the Faculty of Medicine, Technion – Israel Institute of Technology, home of Israel's two Nobel laureates. He and his colleague Prof. Moussa Youdim were instrumental in the early clinical development of the anti-Parkinson drug rasagiline, which gained UK- and EU-marketing authorization in 2005 and US FDA approval in 2006. In our interview, Finberg reflects on his clinical research to develop rasagiline as a commercial drug and its proposed pharmacological mechanisms of action. Moreover, he elucidates the current state of anti-Parkinson drug discovery and offers direction for future research. PMID:17617893

Theory-based training strategies for modifying practitioner concerns about exposure therapy.

PubMed

Farrell, Nicholas R; Deacon, Brett J; Dixon, Laura J; Lickel, James J

2013-12-01

Despite the well-established efficacy of exposure therapy in the treatment of pathological anxiety, many therapists believe this treatment carries an unacceptably high risk for harm, is intolerable for patients, and poses a number of ethical quandaries. These beliefs have been shown to account for two related problems: (a) underutilization of exposure therapy, and (b) overly cautious and suboptimal delivery the treatment, which likely attenuates treatment outcomes. At present, there is little guidance for those who train exposure therapists to address these concerns. This article reviews therapist negative beliefs about exposure therapy and discusses their modification based on findings from social and cognitive psychology pertinent to belief change, including dual-processing in reasoning, the need for cognition and affect, and attitude inoculation. A number of strategies are offered for augmenting training in exposure therapy in order to promote positive beliefs about the treatment. These strategies involve: (a) therapists engaging in simulated exposure therapy exercises and presenting arguments in defense of exposure's safety, tolerability, and ethicality, and (b) training therapists using emotion-based appeals (e.g., case examples) to supplement research findings. Directions for future research on practitioner concerns about exposure therapy are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Concept Analysis: Music Therapy.

PubMed

Murrock, Carolyn J; Bekhet, Abir K

2016-01-01

Down through the ages, music has been universally valued for its therapeutic properties based on the psychological and physiological responses in humans. However, the underlying mechanisms of the psychological and physiological responses to music have been poorly identified and defined. Without clarification, a concept can be misused, thereby diminishing its importance for application to nursing research and practice. The purpose of this article was for the clarification of the concept of music therapy based on Walker and Avant's concept analysis strategy. A review of recent nursing and health-related literature covering the years 2007-2014 was performed on the concepts of music, music therapy, preferred music, and individualized music. As a result of the search, the attributes, antecedents, and consequences of music therapy were identified, defined, and used to develop a conceptual model of music therapy. The conceptual model of music therapy provides direction for developing music interventions for nursing research and practice to be tested in various settings to improve various patient outcomes. Based on Walker and Avant's concept analysis strategy, model and contrary cases are included. Implications for future nursing research and practice to use the psychological and physiological responses to music therapy are discussed.

miRNAs as potential therapeutic targets for age-related macular degeneration.

PubMed

Wang, Shusheng; Koster, Kyle M; He, Yuguang; Zhou, Qinbo

2012-03-01

Since their recent discovery, miRNAs have been shown to play critical roles in a variety of pathophysiological processes. Such processes include pathological angiogenesis, the oxidative stress response, immune response and inflammation, all of which have been shown to have important and interdependent roles in the pathogenesis and progression of age-related macular degeneration (AMD). Here we present a brief review of the pathological processes involved in AMD and review miRNAs and other noncoding RNAs involved in regulating these processes. Specifically, we discuss several candidate miRNAs that show promise as AMD therapeutic targets due to their direct involvement in choroidal neovascularization or retinal pigment epithelium atrophy. We discuss potential miRNA-based therapeutics and delivery methods for AMD and provide future directions for the field of miRNA research with respect to AMD. We believe the future of miRNAs in AMD therapy is promising.

Mindfulness Meditation Training for Attention-Deficit/Hyperactivity Disorder in Adulthood: Current Empirical Support, Treatment Overview, and Future Directions

PubMed Central

Mitchell, John T.; Zylowska, Lidia; Kollins, Scott H.

2015-01-01

Research examining nonpharmacological interventions for adults diagnosed with attention-deficit/hyperactivity disorder (ADHD) has expanded in recent years and provides patients with more treatment options. Mindfulness-based training is an example of an intervention that is gaining promising preliminary empirical support and is increasingly administered in clinical settings. The aim of this review is to provide a rationale for the application of mindfulness to individuals diagnosed with ADHD, describe the current state of the empirical basis for mindfulness training in ADHD, and summarize a treatment approach specific to adults diagnosed with ADHD: the Mindful Awareness Practices (MAPs) for ADHD Program. Two case study examples are provided to demonstrate relevant clinical issues for practitioners interested in this approach. Directions for future research, including mindfulness meditation as a standalone treatment and as a complementary approach to cognitive-behavioral therapy, are provided. PMID:25908900

Treatment of renal cell carcinoma: Current status and future directions.

PubMed

Barata, Pedro C; Rini, Brian I

2017-11-01

Answer questions and earn CME/CNE Over the past 12 years, medical treatment for renal cell carcinoma (RCC) has transitioned from a nonspecific immune approach (in the cytokine era), to targeted therapy against vascular endothelial growth factor (VEGF), and now to novel immunotherapy agents. Multiple agents-including molecules against vascular endothelial growth factor, platelet-derived growth factor, and related receptors; inhibitors of other targets, such as the mammalian target of rapamycin and the MET and AXL tyrosine-protein kinase receptors; and an immune-checkpoint inhibitor-have been approved based on significant activity in patients with advanced RCC. Despite these advances, important questions remain regarding biomarkers of efficacy, patient selection, and the optimal combination and sequencing of agents. The purpose of this review is to summarize present management and future directions in the treatment of metastatic RCC. CA Cancer J Clin 2017;67:507-524. © 2017 American Cancer Society. © 2017 American Cancer Society.

Australian radiation therapy – Part two: Reflections of the past, the present, the future

DOE Office of Scientific and Technical Information (OSTI.GOV)

Merchant, Susan; Curtin Health Innovative Research Institute, Curtin University, Perth, WA; Halkett, Georgia

2014-02-15

Introduction: Documentation on the history of Australian radiotherapy is limited. This study provides radiation therapists' (RTs) perspectives of the people, workplace, and work practices in Australian radiotherapy centres from 1960 onwards. It provides a follow-up to our previous study: Australian radiation therapy: An overview – Part one, which outlines the history and development of radiotherapy from conception until present day. Methods: Four focus groups were conducted on separate occasions in 2010, one in South Australia and three in Victoria, Australia. Participants who worked in radiotherapy were purposively selected to ensure a range of experience, age, and years of work. Results:more » From a RT perspective, radiotherapy has evolved from a physically demanding ‘hands-on’ work environment, often with unpleasant sights and smells of disease, to a more technology-driven workplace. Conclusion: Understanding these changes and their subsequent effects on the role of Australian RTs will assist future directions in advanced role development.« less

Selective mutism: a review of etiology, comorbidities, and treatment.

PubMed

Wong, Priscilla

2010-03-01

Selective mutism is a rare and multidimensional childhood disorder that typically affects children entering school age. It is characterized by the persistent failure to speak in select social settings despite possessing the ability to speak and speak comfortably in more familiar settings. Many theories attempt to explain the etiology of selective mutism.Comorbidities and treatment. Selective mutism can present a variety of comorbidities including enuresis, encopresis, obsessive-compulsive disorder, depression, premorbid speech and language abnormalities, developmental delay, and Asperger's disorders. The specific manifestations and severity of these comorbidities vary based on the individual. Given the multidimensional manifestations of selective mutism, treatment options are similarly diverse. They include individual behavioral therapy, family therapy, and psychotherapy with antidepressants and anti-anxiety medications.Future directions. While studies have helped to elucidate the phenomenology of selective mutism, limitations and gaps in knowledge still persist. In particular, the literature on selective mutism consists primarily of small sample populations and case reports. Future research aims to develop an increasingly integrated, multidimensional framework for evaluating and treating children with selective mutism.

Selective Mutism

PubMed Central

2010-01-01

Selective mutism is a rare and multidimensional childhood disorder that typically affects children entering school age. It is characterized by the persistent failure to speak in select social settings despite possessing the ability to speak and speak comfortably in more familiar settings. Many theories attempt to explain the etiology of selective mutism. Comorbidities and treatment. Selective mutism can present a variety of comorbidities including enuresis, encopresis, obsessive-compulsive disorder, depression, premorbid speech and language abnormalities, developmental delay, and Asperger's disorders. The specific manifestations and severity of these comorbidities vary based on the individual. Given the multidimensional manifestations of selective mutism, treatment options are similarly diverse. They include individual behavioral therapy, family therapy, and psychotherapy with antidepressants and anti-anxiety medications. Future directions. While studies have helped to elucidate the phenomenology of selective mutism, limitations and gaps in knowledge still persist. In particular, the literature on selective mutism consists primarily of small sample populations and case reports. Future research aims to develop an increasingly integrated, multidimensional framework for evaluating and treating children with selective mutism. PMID:20436772

The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection.

PubMed

Lake, Jordan E

2017-12-01

The aim of this review is to summarize knowledge of the prevalence, relevant physiology, and consequences of obesity and visceral adiposity in HIV-infected adults, including highlighting gaps in current knowledge and future research directions. Similar to the general population, obesity prevalence is increasing among HIV-infected persons, and obesity and visceral adiposity are associated with numerous metabolic and inflammatory sequelae. However, HIV- and antiretroviral therapy (ART)-specific factors may contribute to fat gain and fat quality in treated HIV infection, particularly to the development of visceral adiposity, and sex differences may exist. Obesity and visceral adiposity commonly occur in HIV-infected persons and have significant implications for morbidity and mortality. Future research should aim to better elucidate the HIV- and ART-specific contributors to obesity and visceral adiposity in treated HIV infection, with the goal of developing targeted therapies for the prevention and treatment of obesity and visceral adiposity in the modern ART era.

Anti-Angiogenics: Current Situation and Future Perspectives.

PubMed

Zirlik, Katja; Duyster, Justus

2018-01-01

Angiogenesis, the process leading to the formation of new blood vessels, is one of the hallmarks of cancer. Extensive studies established that i) vascular endothelial growth factor (VEGF) is a key driver of sprouting angiogenesis, ii) VEGF is overexpressed in most solid cancers, and iii) inhibition of VEGF can suppress tumor growth in animal models. This has led to the development of pharmacological agents for anti-angiogenesis to disrupt the vascular supply and starve the tumor of nutrients and oxygen, primarily through the blockade of VEGF/VEGF receptor signaling. This effort has resulted in 11 anti-VEGF drugs approved for certain advanced cancers, either alone or in combination with chemotherapy and other targeted therapies. However, inhibition of VEGF signaling is not effective in all cancers, and anti-angiogenics have often only limited impact on overall survival of cancer patients. This review focuses on the current status of FDA-approved anti-angiogenic antibodies and tyrosine kinase inhibitors and summarizes the progress and future directions of VEGF-targeted therapy. © 2018 S. Karger GmbH, Freiburg.

Clinical trials needed to evaluate compression therapy in breast cancer related lymphedema (BCRL). Proposals from an expert group.

PubMed

Partsch, H; Stout, N; Forner-Cordero, I; Flour, M; Moffatt, C; Szuba, A; Milic, D; Szolnoky, G; Brorson, H; Abel, M; Schuren, J; Schingale, F; Vignes, S; Piller, N; Döller, W

2010-10-01

A mainstay of lymphedema management involves the use of compression therapy. Compression therapy application is variable at different levels of disease severity. Evidence is scant to direct clinicians in best practice regarding compression therapy use. Further, compression clinical trials are fragmented and poorly extrapolable to the greater population. An ideal construct for conducting clinical trials in regards to compression therapy will promote parallel global initiatives based on a standard research agenda. The purpose of this article is to review current evidence in practice regarding compression therapy for BCRL management and based on this evidence, offer an expert consensus recommendation for a research agenda and prescriptive trials. Recommendations herein focus solely on compression interventions. This document represents the proceedings of a session organized by the International Compression Club (ICC) in June 2009 in Ponzano (Veneto, Italy). The purpose of the meeting was to enable a group of experts to discuss the existing evidence for compression treatment in breast cancer related lymphedema (BCRL) concentrating on areas where randomized controlled trials (RCTs) are lacking. The current body of research suggests efficacy of compression interventions in the treatment and management of lymphedema. However, studies to date have failed to adequately address various forms of compression therapy and their optimal application in BCRL. We offer recommendations for standardized compression research trials for prophylaxis of arm lymphedema and for the management of chronic BCRL. Suggestions are also made regarding; inclusion and exclusion criteria, measurement methodology and additional variables of interest for researchers to capture. This document should inform future research trials in compression therapy and serve as a guide to clinical researchers, industry researchers and lymphologists regarding the strengths, weaknesses and shortcomings of the current literature. By providing this construct for research trials, the authors aim to support evidence-based therapy interventions, promote a cohesive, standardized and informative body of literature to enhance clinical outcomes, improve the quality of future research trials, inform industry innovation and guide policy related to BCRL.

Stroke Treatment Academic Industry Roundtable

PubMed Central

Jovin, Tudor G.; Albers, Gregory W.; Liebeskind, David S.

2017-01-01

Background and Purpose The STAIR (Stroke Treatment Academic Industry Roundtable) meeting aims to advance acute stroke therapy development through collaboration between academia, industry, and regulatory institutions. In pursuit of this goal and building on recently available level I evidence of benefit from endovascular therapy (ET) in large vessel occlusion stroke, STAIR IX consensus recommendations were developed that outline priorities for future research in ET. Methods Three key directions for advancing the field were identified: (1) development of systems of care for ET in large vessel occlusion stroke, (2) development of therapeutic approaches adjunctive to ET, and (3) exploring clinical benefit of ET in patient population insufficiently studied in recent trials. Methodological issues such as optimal trial design and outcome measures have also been addressed. Results Development of systems of care strategies should be geared both toward ensuring broad access to ET for eligible patients and toward shortening time to reperfusion to the minimum possible. Adjunctive therapy development includes neuroprotective approaches, adjuvant microcirculatory/collateral enhancing strategies, and periprocedural management. Future research priorities seeking to expand the eligible patient population are to determine benefit of ET in patients presenting beyond conventional time windows, in patients with large baseline ischemic core lesions, and in other important subgroups. Conclusions Research priorities in ET for large vessel occlusion stroke are to improve systems of care, investigate effective adjuvant therapies, and explore whether patient eligibility could be expanded. PMID:27586682

Review article: Medical decision models of Helicobacter pylori therapy to prevent gastric cancer.

PubMed

Sonnenberg, A; Inadomi, J M

1998-02-01

The aim of the present article is to study the utility of Helicobacter pylori eradication programmes in decreasing the incidence of gastric cancer. Three types of decision models are employed to pursue this aim, i.e. decision tree, present value, and declining exponential approximation of life expectancy (DEALE). 1) A decision tree allows one to model the interaction of multiple variables in great detail and to calculate the marginal cost, as well as the marginal cost-benefit ratio, of a preventive strategy. The cost of gastric cancer, the efficacy of H. pylori therapy in preventing cancer, and the cumulative probability of developing gastric cancer exert the largest influence on the marginal cost of cancer prevention. The high cost of future gastric cancer and a high efficacy of therapy make screening for H. pylori and its eradication the preferred strategy. 2) The present value is an economic method to adjust future costs or benefits to their current value using a discount rate and the length of time between now and a given time point in the future. It accounts for the depreciation of money and all material values over time. During childhood, the present value of future gastric cancer is very low. Vaccination of children to prevent gastric cancer would need to be very inexpensive to be practicable. Cancer prevention becomes a feasible option, only if the time period between the preventive measures and the occurrence of gastric cancer can be made relatively short. 3) The DEALE provides a means to calculate the increase in life expectancy that would occur, if death from a particular disease became preventable. Life expectancy of the general population is hardly affected by gastric cancer. For life expectancy to increase appreciably by vaccination or antibiotic therapy directed against H. pylori infection, these interventions would need to be focused towards a sub-population with an a priori high risk for gastric cancer.

Asthma pharmacogenetics and the development of genetic profiles for personalized medicine

PubMed Central

Ortega, Victor E; Meyers, Deborah A; Bleecker, Eugene R

2015-01-01

Human genetics research will be critical to the development of genetic profiles for personalized or precision medicine in asthma. Genetic profiles will consist of gene variants that predict individual disease susceptibility and risk for progression, predict which pharmacologic therapies will result in a maximal therapeutic benefit, and predict whether a therapy will result in an adverse response and should be avoided in a given individual. Pharmacogenetic studies of the glucocorticoid, leukotriene, and β2-adrenergic receptor pathways have focused on candidate genes within these pathways and, in addition to a small number of genome-wide association studies, have identified genetic loci associated with therapeutic responsiveness. This review summarizes these pharmacogenetic discoveries and the future of genetic profiles for personalized medicine in asthma. The benefit of a personalized, tailored approach to health care delivery is needed in the development of expensive biologic drugs directed at a specific biologic pathway. Prior pharmacogenetic discoveries, in combination with additional variants identified in future studies, will form the basis for future genetic profiles for personalized tailored approaches to maximize therapeutic benefit for an individual asthmatic while minimizing the risk for adverse events. PMID:25691813

Targeting EGFR in lung cancer: Lessons learned and future perspectives

PubMed Central

Steuer, Conor E.; Ramalingam, Suresh S.

2016-01-01

The development of individualized therapies has become the focus of current oncology research. Precision medicine has demonstrated great potential for bringing safe and effective drugs to those patients stricken with cancer, and is becoming a reality as more oncogenic drivers of malignancy are discovered. The discovery of Epidermal Growth Factor Receptor (EGFR) mutations as a driving mutation in non-small cell lung cancer (NSCLC) and the subsequent success of the tyrosine kinase inhibitors (TKI) have led the way for NSCLC to be at the forefront of biomarker-based drug development. However, this direction was not always so clear, and this article describes the lessons learned in targeted therapy development from EGFR in NSCLC. PMID:26022942

Entrepreneurs: leading the way to pharmacy's future.

PubMed

Martin, Caren McHenry

2011-12-01

Entrepreneurship has always been central to the practice of pharmacy. Whether opening a new retail store, setting up a unique clinic practice, or researching a novel therapy, pharmacists are continually looking forward and following their visions of how pharmacy can be part of a new direction in health care. In 2011, the American Society of Consultant Pharmacists (ASCP) Foundation--itself the product of entrepreneurship--awarded grants to three entrepreneurs who are seeking to establish a fee-for-service component of their senior care pharmacy practices in the community. The grant recipients, while differing in their approaches, share the common goal of providing safe, effective, and cost-justified medication therapy and education to ambulatory older adults.

Manufacturing Cell Therapies Using Engineered Biomaterials.

PubMed

Abdeen, Amr A; Saha, Krishanu

2017-10-01

Emerging manufacturing processes to generate regenerative advanced therapies can involve extensive genomic and/or epigenomic manipulation of autologous or allogeneic cells. These cell engineering processes need to be carefully controlled and standardized to maximize safety and efficacy in clinical trials. Engineered biomaterials with smart and tunable properties offer an intriguing tool to provide or deliver cues to retain stemness, direct differentiation, promote reprogramming, manipulate the genome, or select functional phenotypes. This review discusses the use of engineered biomaterials to control human cell manufacturing. Future work exploiting engineered biomaterials has the potential to generate manufacturing processes that produce standardized cells with well-defined critical quality attributes appropriate for clinical testing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Advances in the diagnosis and treatment of cystic fibrosis.

PubMed

Martiniano, Stacey L; Hoppe, Jordana E; Sagel, Scott D; Zemanick, Edith T

2014-08-01

CF is a genetic, life-shortening, multisystem disease that is most commonly diagnosed through newborn screen performed in all 50 states in the United States. In the past, therapies for CF lung disease have primarily targeted the downstream effects of a dysfunctional CFTR protein. Newer CFTR modulator therapies, targeting the basic defect in CF, are available for a limited group of people with CF, and offer the hope of improved treatment options for many more people with CF in the near future. Best practice is directed by consensus clinical care guidelines from the CFF and is provided with a multidisciplinary approach by the team at the CF care center and the primary care office.

Depression and prospection.

PubMed

Roepke, Ann Marie; Seligman, Martin E P

2016-03-01

Prospection, the mental representation of possible futures, is usually adaptive. When it goes awry, however, it disrupts emotion and motivation. A negative view of the future is typically seen as one symptom of depression, but we suggest that such negative prospection is the core causal element of depression. Here, we describe the empirical evidence supporting this framework, and we explore the implications for clinical interventions. We integrate several literatures: Using the database PsycInfo, we retrieved empirical studies with the keywords prospection, prediction, expectation, pessimism, mental simulation, future-thinking, future-directed thinking, foresight, and/or mental time travel, in conjunction with depression, depressed, or depressive. Three kinds of faulty prospection, taken together, could drive depression: Poor generation of possible futures, poor evaluation of possible futures, and negative beliefs about the future. Depressed mood and poor functioning, in turn, may maintain faulty prospection and feed a vicious cycle. Future-oriented treatment strategies drawn from cognitive-behavioural therapy help to fix poor prospection, and they deserve to be developed further. Prospection-based techniques may lead to transdiagnostic treatment strategies for depression and other disorders. © 2015 The British Psychological Society.

NCI support for particle therapy: past, present, future.

PubMed

Deye, James A

2012-11-01

In light of the rising worldwide interest in particle therapy, and proton therapy specifically in the United States, the National Cancer Institute (NCI) is being asked more often about funding for such research and facilities. Many of the questions imply that NCI is naive to the exciting possibilities inherent in particle therapies, and thus they wish to encourage NCI to initiate and underwrite such programs. In fact, NCI has a long track record of support for the translation of hadrons from the physics laboratory to the therapy clinic by way of technology development and scientific investigations of physical and biological processes as well as clinical outcomes. Early work has included continuous funding since 1961 of proton treatments for more than 15,000 patients and facility construction at the Harvard/Massachusetts General Hospital (MGH) site; treatment of 227 patients with the pi-meson facility at Los Alamos between 1974 and 1981; funding of more than $69M for seven neutron therapy centers between 1971 and 1989; many funded projects in boron neutron capture radiation therapy through the present time; and numerous radiobiology projects over the past 50 y. NCI continues to play an active role in the incorporation of protons into randomized clinical trials through the Children's Oncology Group, Radiation Therapy Oncology Group, and the Program Project Grant (P01), which is co-directed by the MGH and MD Anderson Cancer Center. This has required funding development and implementation of guidelines that enable intercomparison of dosimetry and treatment between facilities. NCI has also funded recent efforts to develop new physical processes for the production of particles such as protons. With regard to the future, while it is true that there are no specific funding opportunity announcements directed to particle therapy research, it is also true that NCI remains open to reviewing any research that is compatible with an established mechanism. However, given the very substantial resources that these facilities currently require along with the highly competitive economic environment that now exists, it is clear that scientific review of such grant applications will look to leverage the scientific pursuits that are the NCI mandate with the reality of the clinical practices, just as is the case for photon radiation research. Such leveraging should be enhanced by the growing opportunities and need for international collaborations. On the other hand, these collaborations are complicated by the fact that these particle therapies are now fully reimbursable modalities, which makes it difficult to separate research (the NCI mission) from clinical practice development. This paper seeks to illuminate these new realities in order to encourage the pursuit and funding of the scientific underpinnings of physical methods, radiobiology, and clinical practice with particle therapy.

Future directions in treatment of brain metastases

PubMed Central

Barani, Igor J.; Larson, David A.; Berger, Mitchel S.

2013-01-01

Background: Brain metastases affect up to 30% of patients with cancer. Management of brain metastases continues to evolve with ever increasing focus on cognitive preservation and quality of life. This manuscript reviews current state of brain metastases management and discusses various treatment controversies with focus on future clinical trials. Stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are discussed in context of multiple (4+ brain metastases) as well as new approaches combining radiation and targeted agents. A brief discussion of modified WBRT approaches, including hippocampal-avoidance WBRT (HA-WBRT) is included as well as a section on recently presented results of Radiation Therapy Oncology Group (RTOG) 0614, a randomized, double-blind, placebo-controlled trial of menantine for prevention of neurocognitive injury after WBRT. Methods: A search of selected studies relevant to management of brain metastases was performed in PubMed as well as in various published meeting abstracts. This data was collated and analyzed in context of contemporary management and future clinical trial plans. This data is presented in tabular form and discussed extensively in the text. Results: The published data demonstrate continued evolution of clinical trials and management strategies designed to minimize and/or prevent cognitive decline following radiation therapy management of brain metastases. Hippocampal avoidance whole-brain radiation therapy (HA-WBRT) and radiosurgery treatments for multiple brain metastases are discussed along with preliminary results of RTOG 0614, a trial of memantine therapy to prevent cognitive decline following WBRT. Trial results appear to support the use of memantine for prevention of cognitive decline. Conclusions: Different management strategies for multiple brain metastases (>4 brain metastases) are currently being evaluated in prospective clinical trials to minimize the likelihood of cognitive decline following WBRT. PMID:23717793

Future directions in treatment of brain metastases.

PubMed

Barani, Igor J; Larson, David A; Berger, Mitchel S

2013-01-01

Brain metastases affect up to 30% of patients with cancer. Management of brain metastases continues to evolve with ever increasing focus on cognitive preservation and quality of life. This manuscript reviews current state of brain metastases management and discusses various treatment controversies with focus on future clinical trials. Stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are discussed in context of multiple (4+ brain metastases) as well as new approaches combining radiation and targeted agents. A brief discussion of modified WBRT approaches, including hippocampal-avoidance WBRT (HA-WBRT) is included as well as a section on recently presented results of Radiation Therapy Oncology Group (RTOG) 0614, a randomized, double-blind, placebo-controlled trial of menantine for prevention of neurocognitive injury after WBRT. A search of selected studies relevant to management of brain metastases was performed in PubMed as well as in various published meeting abstracts. This data was collated and analyzed in context of contemporary management and future clinical trial plans. This data is presented in tabular form and discussed extensively in the text. The published data demonstrate continued evolution of clinical trials and management strategies designed to minimize and/or prevent cognitive decline following radiation therapy management of brain metastases. Hippocampal avoidance whole-brain radiation therapy (HA-WBRT) and radiosurgery treatments for multiple brain metastases are discussed along with preliminary results of RTOG 0614, a trial of memantine therapy to prevent cognitive decline following WBRT. Trial results appear to support the use of memantine for prevention of cognitive decline. Different management strategies for multiple brain metastases (>4 brain metastases) are currently being evaluated in prospective clinical trials to minimize the likelihood of cognitive decline following WBRT.

Protecting retinal ganglion cells

PubMed Central

Khatib, T Z; Martin, K R

2017-01-01

Retinal ganglion cell degeneration underlies several conditions which give rise to significant visual compromise, including glaucoma, hereditary optic neuropathies, ischaemic optic neuropathies, and demyelinating disease. In this review, we discuss the emerging strategies for neuroprotection specifically in the context of glaucoma, including pharmacological neuroprotection, mesenchymal stem cells, and gene therapy approaches. We highlight potential pitfalls that need to be considered when developing these strategies and outline future directions, including the prospects for clinical trials. PMID:28085136

Sensitivity of Salivary Glands to Radiation

PubMed Central

Grundmann, O.; Mitchell, G.C.; Limesand, K.H.

2009-01-01

Radiation therapy for head and neck cancer causes significant secondary side-effects in normal salivary glands, resulting in diminished quality of life for these individuals. Salivary glands are exquisitely sensitive to radiation and display acute and chronic responses to radiotherapy. This review will discuss clinical implications of radiosensitivity in normal salivary glands, compare animal models used to investigate radiation-induced salivary gland damage, address therapeutic advances, and project future directions in the field. PMID:19783796

Psoriasis

PubMed Central

Di Meglio, Paola; Villanova, Federica; Nestle, Frank O.

2014-01-01

Psoriasis is a common chronic inflammatory skin disease with a spectrum of clinical phenotypes and results from the interplay of genetic, environmental, and immunological factors. Four decades of clinical and basic research on psoriasis have elucidated many of the pathogenic mechanisms underlying disease and paved the way to effective targeted therapies. Here, we review this progress and identify future directions of study that are supported by a more integrative research approach and aim at further improving the patients' life. PMID:25085957

Workshop on challenges, insights, and future directions for mouse and humanized models in cancer immunology and immunotherapy: a report from the associated programs of the 2016 annual meeting for the Society for Immunotherapy of cancer.

PubMed

Zloza, Andrew; Karolina Palucka, A; Coussens, Lisa M; Gotwals, Philip J; Headley, Mark B; Jaffee, Elizabeth M; Lund, Amanda W; Sharpe, Arlene H; Sznol, Mario; Wainwright, Derek A; Wong, Kwok-Kin; Bosenberg, Marcus W

2017-09-19

Understanding how murine models can elucidate the mechanisms underlying antitumor immune responses and advance immune-based drug development is essential to advancing the field of cancer immunotherapy. The Society for Immunotherapy of Cancer (SITC) convened a workshop titled, "Challenges, Insights, and Future Directions for Mouse and Humanized Models in Cancer Immunology and Immunotherapy" as part of the SITC 31st Annual Meeting and Associated Programs on November 10, 2016 in National Harbor, MD. The workshop focused on key issues in optimizing models for cancer immunotherapy research, with discussions on the strengths and weaknesses of current models, approaches to improve the predictive value of mouse models, and advances in cancer modeling that are anticipated in the near future. This full-day program provided an introduction to the most common immunocompetent and humanized models used in cancer immunology and immunotherapy research, and addressed the use of models to evaluate immune-targeting therapies. Here, we summarize the workshop presentations and subsequent panel discussion.

Implications for managed care and specialty pharmacy in rheumatoid arthritis.

PubMed

Cardarelli, William J

2012-12-01

Treatment of rheumatoid arthritis (RA) can be very costly. Cost-effectiveness studies provide insight into the value of treatment from a number of perspectives (eg, societal, healthcare). In most cases, the indirect costs of RA can offset the direct costs in 2 ways. Prevention of disease progression can limit future costs, such as those related to surgery and hospitalization. When disease progression is minimized, patients feel better and can have improved work productivity. Disease control of RA has improved over time, and this is attributed primarily to the introduction of more effective therapies. Despite the effectiveness of new therapies, there are a number of barriers to optimal treatment. Barriers include lack of education for patients and practitioners about RA, poor patient-provider communication, uncertainty regarding which treatments to choose, cost, and lack of adherence. Specialty pharmacy and disease therapy management programs can assist patients by providing structure, education, and mechanisms to improve treatment adherence and persistence to optimize therapy.

Achievements and obstacles of remyelinating therapies in multiple sclerosis.

PubMed

Stangel, Martin; Kuhlmann, Tanja; Matthews, Paul M; Kilpatrick, Trevor J

2017-12-01

Remyelination in the CNS is the natural process of damage repair in demyelinating diseases such as multiple sclerosis (MS). However, remyelination becomes inadequate in many people with MS, which results in axonal degeneration and clinical disability. Enhancement of remyelination is a logical therapeutic goal; nevertheless, all currently licensed therapies for MS are immunomodulatory and do not support remyelination directly. Several molecular pathways have been identified as potential therapeutic targets to induce remyelination, and some of these have now been assessed in proof-of-concept clinical trials. However, trial design faces several obstacles: optimal clinical or paraclinical outcome measures to assess remyelination remain ill-defined, and identification of the ideal timing of therapy is also a crucial issue. In addition, realistic expectations are needed concerning the probable benefits of such therapies. Nevertheless, approaches that enhance remyelination are likely to be protective for axons and so could prevent long-term neurodegeneration. Future MS treatment paradigms, therefore, are likely to comprise a combinatorial approach that involves both immunomodulatory and regenerative treatments.

Chinese medicine protein and peptide in gene and cell therapy.

PubMed

Feng, Yinglu; Yin, Zifei; Zhang, Daniel; Srivastava, Arun; Ling, Chen

2018-06-11

The success of gene and cell therapy in clinic during the past two decades as well as our expanding ability to manipulate these biomaterials are leading to new therapeutic options for a wide range of inherited and acquired diseases. Combining conventional therapies with this emerging field is a promising strategy to treat those previously-thought untreatable diseases. Traditional Chinese medicine (TCM) has evolved for thousands of years in China and still plays an important role in human health. As part of the active ingredients of TCM, proteins and peptides have attracted long-term enthusiasm of researchers. More recently, they have been utilized in gene and cell therapy, resulting in promising novel strategies to treat both cancer and non-cancer diseases. This manuscript presents a critical review on this field, accompanied with perspectives on the challenges and new directions for future research in this emerging frontier. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cell-based therapeutic strategies for multiple sclerosis.

PubMed

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A

2017-11-01

The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

[Lung and kidney failure. Pathogenesis, interactions, and therapy].

PubMed

John, S; Willam, C

2015-09-01

The lungs and kidneys represent the most often affected organs (acute respiratory distress syndrome, ARDS or kidney failure) in multiple organ failure (MOF) due to shock, trauma, or sepsis with a still unacceptable high mortality for both organ failures. Although the exact pathophysiological mechanisms of MOF are not completely elucidated, it appears that the lungs and kidneys share several pathophysiologic pathways and have the potential to further harm each other (kidney-lung crosstalk). Inflammatory signals in both directions and volume overload with consecutive edema formation in both organs may play a key role in this crosstalk. The organ replacement therapies used in both organ failures have the potential to further injure the other organ (ventilator trauma, dialyte trauma). On the other hand, renal replacement therapy can have positive effects on lung injury by restoring volume and acid-base homeostasis. The new development of "low-flow" extracorporeal CO2 removal on renal replacement therapy platforms may further help to decrease ventilator trauma in the future.

New therapeutic directions for advanced pancreatic cancer: cell cycle inhibitors, stromal modifiers and conjugated therapies.

PubMed

Matera, Robert; Saif, Muhammad Wasif

2017-09-01

Pancreatic adenocarcinoma is a devastating malignancy with an extremely poor prognosis. These tumors progress rapidly and somewhat silently with few specific symptoms and are relatively resistant to chemotherapeutic agents. Many agents, including cell cycle inhibitors, are under development for the treatment of this cancer for which there are disappointingly few treatment options. Areas covered: Here we outline the existing approved treatments for advanced pancreatic disease and discuss a range of novel therapies currently under development including cell cycle inhibitors, stromal modifiers and conjugated therapies. We also describe the current state of the pancreatic cancer therapeutics market both past and future. Expert opinion: Despite the recent explosion of novel therapies with an array of unique targets, the core treatment of pancreatic cancer still with traditional cytotoxic agents with a few exceptions. However, as these novel treatments move through the pipeline, we are hopeful that there will soon be a number of effective options for patients with advanced pancreatic cancer.

Cancer metabolism: strategic diversion from targeting cancer drivers to targeting cancer suppliers.

PubMed

Kim, Soo-Youl

2015-03-01

Drug development groups are close to discovering another pot of gold-a therapeutic target-similar to the success of imatinib (Gleevec) in the field of cancer biology. Modern molecular biology has improved cancer therapy through the identification of more pharmaceutically viable targets, and yet major problems and risks associated with late-phase cancer therapy remain. Presently, a growing number of reports have initiated a discussion about the benefits of metabolic regulation in cancers. The Warburg effect, a great discovery approximately 70 years ago, addresses the "universality" of cancer characteristics. For instance, most cancer cells prefer aerobic glycolysis instead of mitochondrial respiration. Recently, cancer metabolism has been explained not only by metabolites but also through modern molecular and chemical biological techniques. Scientists are seeking context-dependent universality among cancer types according to metabolic and enzymatic pathway signatures. This review presents current cancer metabolism studies and discusses future directions in cancer therapy targeting bio-energetics, bio-anabolism, and autophagy, emphasizing the important contribution of cancer metabolism in cancer therapy.

Effects of robotic-aided rehabilitation on recovery of upper extremity function in chronic stroke: a single case study.

PubMed

Flinn, Nancy A; Smith, Jennifer L; Tripp, Christopher J; White, Matthew W

2009-01-01

The objective of the study was to examine the results of robotic therapy in a single client. A 48-year-old female client 15 months post-stroke, with right hemiparesis, received robotic therapy as an outpatient in a large Midwestern rehabilitation hospital. Robotic therapy was provided three times a week for 6 weeks. Robotic therapy consisted of goal-directed, robotic-aided reaching tasks to exercise the hemiparetic shoulder and elbow. No other therapeutic intervention for the affected upper extremity was provided during the study or 3 months follow-up period. The outcome measures included the Fugl-Meyer, graded Wolf motor function test (GWMFT), motor activity log, active range of motion and Canadian occupational performance measure. The participant made gains in active movement; performance; and satisfaction of functional tasks, GWMFT and functional use. Limitations involved in this study relate to the generalizability of the sample size, effect of medications, expense of robotic technologies and the impact of aphasia. Future research should incorporate functional use training along with robotic therapy.

Teaching of direct posterior resin composite restorations in UK dental therapy training programmes.

PubMed

Lynch, C D; Wilson, N H F

2010-05-08

With the numbers of dental therapists involved in the delivery of dental care within the UK on the increase, and the trend towards the use of direct resin composites (composites) for the restoration of posterior teeth, this study was undertaken to describe the teaching of posterior composites in dental therapy training programmes in the UK. A secondary aim was to identify differences in techniques for posterior composites taught within these dental therapy training programmes. In 2008/9, a questionnaire seeking information on the teaching of posterior composites was distributed by email to 13 centres with dental therapy training programmes in the UK. This questionnaire sought information relating to the teaching of direct posterior composites to dental therapy students, including the amounts of preclinical and clinical teaching in respect of deciduous and permanent teeth, numbers of restorations placed, contraindications to placement, and details in respect of operative techniques. Ten completed responses were received (response rate = 77%). In ten programmes, student dental therapists received clinical training in the placement of composite restorations in the occlusal surfaces of premolar and permanent molar teeth, and nine programmes included such training for two and three surface occlusoproximal restorations. The mean proportions of posterior restorations placed clinically by the trainee dental therapists in permanent teeth using dental amalgam and composite were 52% and 46% respectively (range: amalgam = 20-95%; composite = 5-70%). With the exception of one programme, the teaching of posterior composites is a well established element of dental therapy training. Some variations were noted in the teaching of clinical techniques between respondent training centres. It is suggested that to ensure harmony in approaches to treatments provided by graduated therapists that training centres look to relevant consensus documents, such as those of the British Association for the Teaching of Conservative Dentistry. The findings of our study are important for the future provision of oral healthcare, given the growing evidence base in favour of minimally invasive dentistry.

Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part II. Prognosis, management, and future directions.

PubMed

Jawed, Sarah I; Myskowski, Patricia L; Horwitz, Steven; Moskowitz, Alison; Querfeld, Christiane

2014-02-01

Both mycosis fungoides (MF) and Sézary syndrome (SS) have a chronic, relapsing course, with patients frequently undergoing multiple, consecutive therapies. Treatment is aimed at the clearance of skin disease, the minimization of recurrence, the prevention of disease progression, and the preservation of quality of life. Other important considerations are symptom severity, including pruritus and patient age/comorbidities. In general, for limited patch and plaque disease, patients have excellent prognosis on ≥1 topical formulations, including topical corticosteroids and nitrogen mustard, with widespread patch/plaque disease often requiring phototherapy. In refractory early stage MF, transformed MF, and folliculotropic MF, a combination of skin-directed therapy plus low-dose immunomodulators (eg, interferon or bexarotene) may be effective. Patients with advanced and erythrodermic MF/SS can have profound immunosuppression, with treatments targeting tumor cells aimed for immune reconstitution. Biologic agents or targeted therapies either alone or in combination--including immunomodulators and histone-deacetylase inhibitors--are tried first, with more immunosuppressive therapies, such as alemtuzumab or chemotherapy, being generally reserved for refractory or rapidly progressive disease or extensive lymph node and metastatic involvement. Recently, an increased understanding of the pathogenesis of MF and SS with identification of important molecular markers has led to the development of new targeted therapies that are currently being explored in clinical trials in advanced MF and SS. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Review of the progress toward achieving heat confinement-the holy grail of photothermal therapy

NASA Astrophysics Data System (ADS)

Sheng, Wangzhong; He, Sha; Seare, William J.; Almutairi, Adah

2017-08-01

Photothermal therapy (PTT) involves the application of normally benign light wavelengths in combination with efficient photothermal (PT) agents that convert the absorbed light to heat to ablate selected cancers. The major challenge in PTT is the ability to confine heating and thus direct cellular death to precisely where PT agents are located. The dominant strategy in the field has been to create large libraries of PT agents with increased absorption capabilities and to enhance their delivery and accumulation to achieve sufficiently high concentrations in the tissue targets of interest. While the challenge of material confinement is important for achieving "heat and lethality confinement," this review article suggests another key prospective strategy to make this goal a reality. In this approach, equal emphasis is placed on selecting parameters of light exposure, including wavelength, duration, power density, and total power supplied, based on the intrinsic properties and geometry of tissue targets that influence heat dissipation, to truly achieve heat confinement. This review highlights significant milestones researchers have achieved, as well as examples that suggest future research directions, in this promising technique, as it becomes more relevant in clinical cancer therapy and other noncancer applications.

Immune-directed therapy for type 1 diabetes at the clinical level: the Immune Tolerance Network (ITN) experience.

PubMed

Ehlers, Mario R; Nepom, Gerald T

2012-01-01

Reestablishing immune tolerance in type 1 diabetes (T1D), a chronic autoimmune disease, is a major goal. The Immune Tolerance Network (ITN) has initiated eight clinical trials of immunomodulatory therapies in recent-onset T1D over the past decade. Results have been mixed in terms of clinical efficacy, but the studies have provided valuable mechanistic insight that are enhancing our understanding of the disease and guiding the design of future trials. Trials of non-Fc-binding anti-CD3 mAbs have revealed that modulation of this target leads to partial responses, and ITN's AbATE trial led to identification of a robust responder group that could be distinguished from non-responders by baseline metabolic and immunologic features. A pilot study of the combination of IL-2 and rapamycin gave the first demonstration that frequency and function of regulatory T cells (Tregs) can be enhanced in T1D subjects, although the therapy triggered the activation of effectors with transient β-cell dysfunction. Similarly, therapy with anti-thymocyte globulin led to substantial lymphocyte depletion, but also to the activation of the acute-phase response with no clinical benefit during preliminary analyses. These and other results provide mechanistic tools that can be used as biomarkers for safety and efficacy in future trials. Furthermore, our results, together with those of other organizations, notably TrialNet, delineate the roles of the major components of the immune response in T1D. This information is setting the stage for future combination therapy trials. The development of disease-relevant biomarkers will also enable the implementation of innovative trial designs, notably adaptive trials, which will increase efficiencies in terms of study duration and sample size, and which will expedite the conduct of trials in which there are uncertainties about dose response and effect size.

Systemic family psychotherapy in China: a qualitative analysis of therapy process.

PubMed

Liu, Liang; Miller, John K; Zhao, Xudong; Ma, Xiquan; Wang, Jikun; Li, Wentian

2013-12-01

Although the procedure of systemic family therapy has been extensively researched in Western culture, few studies on this subject have been conducted in China. The aim of this study was to specify the therapy-delivered interventions in Chinese systemic family therapy and to explore how Western-imported systemic therapy model is delivered in Chinese culture. A qualitative and exploratory research approach was taken in which thematic analysis was used to analyse the transcribed psychotherapy videotapes with Chinese families. Twenty-six hours of video-recorded systemic family therapy sessions from 14 Chinese family cases were sampled. Thematic analysis was used to analyse the transcriptions of therapy sessions and identify therapist-generated interventions in therapy. Frequencies of different interventions were counted, and correspondence analysis (CA) was used to reveal the corresponding relationships between different interventions. Analysis led to two main themes related to therapists-delivered interventions: Therapist's intention and therapy technique. Results revealed 15 types of therapist's intentions and 16 categories of therapy techniques. CA indicated that therapists' intentions changed across different therapy stages and specific techniques were used to achieve corresponding intentions. Interventions delivered in Chinese systemic therapy are mainly adherent with Milan and post-Milan systemic models. Due to the shortage in systemic therapy service in China and Chinese culture advocating reverence to authority, components of psycho-education, guidance, and metaphor are adopted in Chinese systemic practice. Some directions for future research are suggested. © 2012 The British Psychological Society.

Future Directions in Medical Physics

NASA Astrophysics Data System (ADS)

Jeraj, Robert

Medical Physics is a highly interdisciplinary field at the intersection between physics and medicine and biology. Medical Physics is aiming at development of novel applications of physical processes and techniques in various areas of medicine and biology. Medical Physics had and continues to have profound impact by developing improved imaging and treatment technologies, and helping to advance our understanding of the complexity of the disease. The general trend in medicine towards personalized therapy, and emphasis on accelerated translational research is having a profound impact on medical physics as well. In the traditional stronghold for medical physicists - radiation therapy - the new reality is shaping in the form of biologically conformal and combination therapies, as well as advanced particle therapy approaches, such as proton and ion therapies. Rapid increase in faster and more informative multi-modality medical imaging is bringing a wealth of information that is being complemented with data obtained from genomic profiling and other biomarkers. Novel data analysis and data mining approaches are proving grounds for employment of various artificial intelligence methods that will help further improving clinical decision making for optimization of various therapies as well as better understanding of the disease properties and disease evolution, ultimately leading to improved clinical outcomes.

Realising the Mass Public Benefit of Evidence-Based Psychological Therapies: The IAPT Program

PubMed Central

Clark, David M

2018-01-01

Empirically supported psychological therapies have been developed for many mental health conditions. However, in most countries only a small proportion of the public benefit from these advances. The English Improving Access to Psychological Therapies (IAPT) program aims to bridge the gap between research and practice by training over 10,500 new psychological therapists in empirically supported treatments and deploying them in new services for the treatment of depression and anxiety disorders. Currently IAPT treats over 560,000 patients per year, obtains clinical outcome data on 98.5% of these individuals and places this information in the public domain. Around 50% of patients treated in IAPT services recover and two-thirds show worthwhile benefits. The clinical and economic arguments on which IAPT is based are presented, along with details of the service model, how the program was implemented, and recent findings about service organization. Limitations and future directions are outlined. PMID:29350997

Cognitive-behavioral therapy for anxiety disorders: an update on the empirical evidence

PubMed Central

Kaczkurkin, Antonia N.; Foa, Edna B.

2015-01-01

A large amount of research has accumulated on the efficacy and effectiveness of cognitive-behavioral therapy (CBT) for anxiety disorders including posttraumatic stress disorder, obsessive-compulsive disorder, panic disorder, generalized anxiety disorder, social anxiety disorder, and specific phobia. The purpose of the current article is to provide an overview of two of the most commonly used CBT methods used to treat anxiety disorders (exposure and cognitive therapy) and to summarize and discuss the current empirical research regarding the usefulness of these techniques for each anxiety disorder. Additionally, we discuss the difficulties that arise when comparing active CBT treatments, and we suggest directions for future research. Overall, CBT appears to be both efficacious and effective in the treatment of anxiety disorders, but dismantling studies are needed to determine which specific treatment components lead to beneficial outcomes and which patients are most likely to benefit from these treatment components. PMID:26487814

Non-genetic engineering of cells for drug delivery and cell-based therapy.

PubMed

Wang, Qun; Cheng, Hao; Peng, Haisheng; Zhou, Hao; Li, Peter Y; Langer, Robert

2015-08-30

Cell-based therapy is a promising modality to address many unmet medical needs. In addition to genetic engineering, material-based, biochemical, and physical science-based approaches have emerged as novel approaches to modify cells. Non-genetic engineering of cells has been applied in delivering therapeutics to tissues, homing of cells to the bone marrow or inflammatory tissues, cancer imaging, immunotherapy, and remotely controlling cellular functions. This new strategy has unique advantages in disease therapy and is complementary to existing gene-based cell engineering approaches. A better understanding of cellular systems and different engineering methods will allow us to better exploit engineered cells in biomedicine. Here, we review non-genetic cell engineering techniques and applications of engineered cells, discuss the pros and cons of different methods, and provide our perspectives on future research directions. Copyright © 2014 Elsevier B.V. All rights reserved.

Evolving lessons on nanomaterial-coated viral vectors for local and systemic gene therapy

PubMed Central

Kasala, Dayananda; Yoon, A-Rum; Hong, Jinwoo; Kim, Sung Wan; Yun, Chae-Ok

2016-01-01

Viral vectors are promising gene carriers for cancer therapy. However, virus-mediated gene therapies have demonstrated insufficient therapeutic efficacy in clinical trials due to rapid dissemination to nontarget tissues and to the immunogenicity of viral vectors, resulting in poor retention at the disease locus and induction of adverse inflammatory responses in patients. Further, the limited tropism of viral vectors prevents efficient gene delivery to target tissues. In this regard, modification of the viral surface with nanomaterials is a promising strategy to augment vector accumulation at the target tissue, circumvent the host immune response, and avoid nonspecific interactions with the reticuloendothelial system or serum complement. In the present review, we discuss various chemical modification strategies to enhance the therapeutic efficacy of viral vectors delivered either locally or systemically. We conclude by highlighting the salient features of various nanomaterial-coated viral vectors and their prospects and directions for future research. PMID:27348247

Cancer immunotherapy-targeted glypican-3 or neoantigens.

PubMed

Shimizu, Yasuhiro; Suzuki, Toshihiro; Yoshikawa, Toshiaki; Tsuchiya, Nobuhiro; Sawada, Yu; Endo, Itaru; Nakatsura, Tetsuya

2018-03-01

Immune checkpoint inhibitors have ushered in a new era in cancer therapy, although other therapies or combinations thereof are still needed for many patients for whom these drugs are ineffective. In this light, we have identified glypican-3 an HLA-24, HLA-A2 restriction peptide with extreme cancer specificity. In this paper, we summarize results from a number of related clinical trials showing that glypican-3 peptide vaccines induce specific CTLs in most patients (UMIN Clinical Trials Registry: UMIN000001395, UMIN000005093, UMIN000002614, UMN000003696, and UMIN000006357). We also describe the current state of personalized cancer immunotherapy based on neoantigens, and assess, based on our own research and experience, the potential of such therapy to elicit cancer regression. Finally, we discuss the future direction of cancer immunotherapy. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

50 years of rational‐emotive and cognitive‐behavioral therapy: A systematic review and meta‐analysis

PubMed Central

Cotet, Carmen; Matu, Silviu; Mogoase, Cristina; Stefan, Simona

2017-01-01

Objective Rational emotive behavior therapy (REBT), introduced by Albert Ellis in the late 1950s, is one of the main pillars of cognitive‐behavioral therapy. Existing reviews on REBT are overdue by 10 years or more. We aimed to summarize the effectiveness and efficacy of REBT since its beginnings and investigate the alleged mechanisms of change. Method Systematic search identified 84 articles, out of which 68 provided data for between‐group analyses and 39 for within‐group analyses. Results We found a medium effect size of REBT compared to other interventions on outcomes (d = 0.58) and on irrational beliefs (d = 0.70), at posttest. For the within‐group analyses, we obtained medium effects for both outcomes (d = 0.56) and irrational beliefs (d = 0.61). Several significant moderators emerged. Conclusion REBT is a sound psychological intervention. Directions for future studies are outlined, stemming from the limitations of existing ones. PMID:28898411

Induced pluripotent stem cells for the treatment of stroke: the potential and the pitfalls.

PubMed

Yu, Fenggang; Li, Yingying; Morshead, Cindi M

2013-09-01

The extraordinary discovery of induced pluripotent stem cells (iPSCs) has led to the very real possibility that patient-specific cell therapy can be realized. The potential to develop cell replacement therapies outside the ethical and legal limitations, has initiated a new era of hope for regenerative strategies to treat human neurological disease including stroke. In this article, we will review and compare the current approaches to derive iPSCs from different somatic cells, and the induction into neuronal phenotypes, considering the advantages and disadvantages to the methodologies of derivation. We will highlight the work relating to the use of iPSC-based therapies in models of stroke and their potential use in clinical trials. Finally, we will consider future directions and areas of exploration which may promote the realization of iPSC-based cell replacement strategies for the treatment of stroke.

Current status of intratumoral therapy for glioblastoma.

PubMed

Mehta, Ankit I; Linninger, Andreas; Lesniak, Maciej S; Engelhard, Herbert H

2015-10-01

With emerging drug delivery technologies becoming accessible, more options are expected to become available to patients with glioblastoma (GBM) in the near future. It is important for clinicians to be familiar with the underlying mechanisms and limitations of intratumoral drug delivery, and direction of recent research efforts. Tumor-adjacent brain is an extremely complex living matrix that creates challenges with normal tissue intertwining with tumor cells. For convection-enhanced delivery (CED), the role of tissue anisotropy for better predicting the biodistribution of the infusate has recently been studied. Computational predictive methods are now available to better plan CED therapy. Catheter design and placement—in addition to the agent being used—are critical components of any protocol. This paper overviews intratumoral therapies for GBM, highlighting key anatomic and physiologic perspectives, selected agents (especially immunotoxins), and some new developments such as the description of the glymphatic system.

The Potential for Tumor Suppressor Gene Therapy in Head and Neck Cancer

PubMed Central

Birkeland, Andrew C.; Ludwig, Megan L.; Spector, Matthew E.; Brenner, J. Chad

2016-01-01

Head and neck squamous cell carcinoma remains a highly morbid and fatal disease. Importantly, genomic sequencing of head and neck cancers has identified frequent mutations in tumor suppressor genes. While targeted therapeutics increasingly are being investigated in head and neck cancer, the majority of these agents are against overactive/overexpressed oncogenes. Therapy to restore lost tumor suppressor gene function remains a key and under-addressed niche in trials for head and neck cancer. Recent advances in gene editing have captured the interest of both the scientific community and the public. As our technology for gene editing and gene expression modulation improves, addressing lost tumor suppressor gene function in head and neck cancers is becoming a reality. This review will summarize new techniques, challenges to implementation, future directions, and ethical ramifications of gene therapy in head and neck cancer. PMID:26896601

Emerging drugs for the treatment of wound healing.

PubMed

Zielins, Elizabeth R; Brett, Elizabeth A; Luan, Anna; Hu, Michael S; Walmsley, Graham G; Paik, Kevin; Senarath-Yapa, Kshemendra; Atashroo, David A; Wearda, Taylor; Lorenz, H Peter; Wan, Derrick C; Longaker, Michael T

2015-06-01

Wound healing can be characterized as underhealing, as in the setting of chronic wounds, or overhealing, occurring with hypertrophic scar formation after burn injury. Topical therapies targeting specific biochemical and molecular pathways represent a promising avenue for improving and, in some cases normalizing, the healing process. A brief overview of both normal and pathological wound healing has been provided, along with a review of the current clinical guidelines and treatment modalities for chronic wounds, burn wounds and scar formation. Next, the major avenues for wound healing drugs, along with drugs currently in development, are discussed. Finally, potential challenges to further drug development, and future research directions are discussed. The large body of research concerning wound healing pathophysiology has provided multiple targets for topical therapies. Growth factor therapies with the ability to be targeted for localized release in the wound microenvironment are most promising, particularly when they modulate processes in the proliferative phase of wound healing.

The molecular genetics of eyelid tumors: recent advances and future directions.

PubMed

Milman, Tatyana; McCormick, Steven A

2013-02-01

Unprecedented recent advances in the molecular genetics of cutaneous malignancies have markedly improved our ability to diagnose, treat, and counsel patients with skin tumors. This review provides an update on molecular genetics of periocular cutaneous basal cell carcinoma, squamous cell carcinoma, sebaceous carcinoma, Merkel cell carcinoma, and malignant melanoma and describes how the knowledge of molecular genetics is translated into clinical practice. A literature search of peer-reviewed and indexed publications from 1965 to 2012 using the PubMed search engine was performed. Key terms included: molecular genetics, eyelid, basal cell carcinoma, squamous cell carcinoma, sebaceous adenoma, sebaceous epithelioma, sebaceoma, sebaceous carcinoma, Merkel cell carcinoma, and melanoma. Seminal articles prior to 1965 were selected from primary sources and reviews from the initial search. Articles were chosen based on pertinence to clinical, genetic, and therapeutic topics reviewed in this manuscript. We reviewed the literature regarding the advances in molecular genetics of cutaneous basal cell carcinoma, squamous cell carcinoma, sebaceous neoplasia, Merkel cell carcinoma, and malignant melanoma, and possible future directions towards diagnosing and treating cutaneous tumors at the genetic level. Cell culture experiments, animal models, and molecular genetic studies on the patients' tumor tissues helped to elucidate genetic aberrations in these lesions. Cell culture experiments, animal studies and, ultimately, clinical trials provided means to test and develop novel therapeutic strategies, namely targeted therapy directed at specific molecular genetic defects. While remarkable progress has been made in this process, the complexity of the molecular genetics of skin tumors makes complete elucidation of the genetic mechanisms and the search for ideal therapies challenging. The recent studies focusing on molecular genetics of cutaneous malignancies show promising results, thereby improving our ability to diagnose, treat and counsel patients with these lesions. Future studies will hopefully help unravel further molecular mechanisms involved in cutaneous neoplasia and provide insights into novel preventative and therapeutic modalities.

Treating Alopecia Areata: Current Practices Versus New Directions.

PubMed

Gupta, Aditya K; Carviel, Jessie; Abramovits, William

2017-02-01

Alopecia areata (AA) is non-scarring hair loss resulting from an autoimmune disorder. Severity varies from patchy hair loss that often spontaneously resolves to severe and chronic cases that can progress to total loss of scalp and body hair. Many treatments are available; however, the efficacy of these treatments has not been confirmed, especially in severe cases, and relapse rates are high. First-line treatment often includes corticosteroids such as intralesional or topical steroids for mild cases and systemic steroids or topical immunotherapy with diphenylcyclopropenone or squaric acid dibutylester in severe cases. Minoxidil and bimatoprost may also be recommended, usually in combination with another treatment. Ongoing research and new insights into mechanisms have led to proposals of innovative therapies. New directions include biologics targeting immune response as well as lasers and autologous platelet-rich plasma therapy. Preliminary data are encouraging, and it is hoped this research will translate into new options for the treatment of AA in the near future.

Cell cycle proteins as promising targets in cancer therapy.

PubMed

Otto, Tobias; Sicinski, Piotr

2017-01-27

Cancer is characterized by uncontrolled tumour cell proliferation resulting from aberrant activity of various cell cycle proteins. Therefore, cell cycle regulators are considered attractive targets in cancer therapy. Intriguingly, animal models demonstrate that some of these proteins are not essential for proliferation of non-transformed cells and development of most tissues. By contrast, many cancers are uniquely dependent on these proteins and hence are selectively sensitive to their inhibition. After decades of research on the physiological functions of cell cycle proteins and their relevance for cancer, this knowledge recently translated into the first approved cancer therapeutic targeting of a direct regulator of the cell cycle. In this Review, we focus on proteins that directly regulate cell cycle progression (such as cyclin-dependent kinases (CDKs)), as well as checkpoint kinases, Aurora kinases and Polo-like kinases (PLKs). We discuss the role of cell cycle proteins in cancer, the rationale for targeting them in cancer treatment and results of clinical trials, as well as the future therapeutic potential of various cell cycle inhibitors.

Optimizing hydroxyurea therapy for sickle cell anemia.

PubMed

Ware, Russell E

2015-01-01

Hydroxyurea has proven efficacy in numerous clinical trials as a disease-modifying treatment for patients with sickle cell anemia (SCA) but is currently under-used in clinical practice. To improve the effectiveness of hydroxyurea therapy, efforts should be directed toward broadening the clinical treatment indications, optimizing the daily dosage, and emphasizing the benefits of early and extended treatment. Here, various issues related to hydroxyurea treatment are discussed, focusing on both published evidence and clinical experience. Specific guidance is provided regarding important but potentially unfamiliar aspects of hydroxyurea treatment for SCA, such as escalating to maximum tolerated dose, treating in the setting of cerebrovascular disease, switching from chronic transfusions to hydroxyurea, and using serial phlebotomy to alleviate iron overload. Future research directions to optimize hydroxyurea therapy are also discussed, including personalized dosing based on pharmacokinetic modeling, prediction of fetal hemoglobin responses based on pharmacogenomics, and the risks and benefits of hydroxyurea for non-SCA genotypes and during pregnancy/lactation. Another critical initiative is the introduction of hydroxyurea safely and effectively into global regions that have a high disease burden of SCA but limited resources, such as sub-Saharan Africa, the Caribbean, and India. Final considerations emphasize the long-term goal of optimizing hydroxyurea therapy, which is to help treatment become accepted as standard of care for all patients with SCA. © 2015 by The American Society of Hematology. All rights reserved.

Future of human mitochondrial DNA editing technologies.

PubMed

Verechshagina, N; Nikitchina, N; Yamada, Y; Harashima, Н; Tanaka, M; Orishchenko, K; Mazunin, I

2018-05-15

ATP and other metabolites, which are necessary for the development, maintenance, and functioning of bodily cells are all synthesized in the mitochondria. Multiple copies of the genome, present within the mitochondria, together with its maternal inheritance, determine the clinical manifestation and spreading of mutations in mitochondrial DNA (mtDNA). The main obstacle in the way of thorough understanding of mitochondrial biology and the development of gene therapy methods for mitochondrial diseases is the absence of systems that allow to directly change mtDNA sequence. Here, we discuss existing methods of manipulating the level of mtDNA heteroplasmy, as well as the latest systems, that could be used in the future as tools for human mitochondrial genome editing.

Novel biomarkers for cardiovascular risk assessment: current status and future directions.

PubMed

MacNamara, James; Eapen, Danny J; Quyyumi, Arshed; Sperling, Laurence

2015-09-01

Cardiovascular disease (CVD) is the leading cause of mortality in the modern world. Traditional risk algorithms may miss up to 20% of CVD events. Therefore, there is a need for new cardiac biomarkers. Many fields of research are dedicated to improving cardiac risk prediction, including genomics, transcriptomics and proteomics. To date, even the most promising biomarkers have only demonstrated modest associations and predictive ability. Few have undergone randomized control trials. A number of biomarkers are targets to new therapies aimed to reduce cardiovascular risk. Currently, some of the most promising risk prediction has been demonstrated with panels of multiple biomarkers. This article reviews the current state and future of proteomic biomarkers and aggregate biomarker panels.

Acquired resistance to EGFR targeted therapy in non-small cell lung cancer: Mechanisms and therapeutic strategies.

PubMed

Lim, Sun Min; Syn, Nicholas L; Cho, Byoung Chul; Soo, Ross A

2018-04-01

The tyrosine kinase inhibitors (TKIs) directed at sensitizing mutations in the epidermal growth factor receptor (EGFR) gene represents a critical pillar in non-small cell lung cancer treatment. Despite the excellent disease control with initial EGFR TKI therapy, acquired resistance is ubiquitous and remains a key challenge. Investigations into the mechanisms which foster resistance to EGFR TKIs has led to the discovery of novel biomarkers and drug targets, and in turn has enabled the development of third-generation TKIs and proposals for rational therapeutic combinations. The threonine-to-methionine substitution mutation at position 790 (T790M) is clinically validated to engender refractoriness to first- and second-generation TKIs, and is a standard-of-care predictive biomarker used in therapeutic stratification. Clinical use of liquid biopsy approaches for assessment of T790M mutations continues to increase, with growing advocacy for serial monitoring of tumor evolution. For patients who are T790M-negative, cytotoxic chemotherapy or protracted EGFR TKI treatment are acceptable treatment standards after disease progression, although combinations of targeted therapies and checkpoint blockade immunotherapy may offer promising alternatives in the future. Among T790M-positive patients, the third-generation EGFR TKI, osimertinib, has shown superiority over both platinum-doublet chemotherapy and 1st generation EGFR TKI in randomized clinical trials, and exhibits enhanced in vitro selectivity for mutant EGFR receptors and pharmacokinetics compared to earlier-generation TKIs. This article appraises the key literature on the contemporary management of non-small cell lung cancer patients with acquired resistance to EGFR TKIs, and envisions future directions in translational and clinical research. Copyright © 2018 Elsevier Ltd. All rights reserved.

Antithrombotic Strategies in Endovascular Interventions: Current Status and Future Directions.

PubMed

Shishehbor, Mehdi H; Katzen, Barry T

2013-10-01

Despite increasing numbers of endovascular interventions to treat arterial and venous disease, scant level 1 evidence is available regarding the role of antithrombotic and antiplatelet therapy in patients undergoing these procedures. The current practice in this regard is heterogeneous and has mainly been driven by data from coronary artery disease and percutaneous coronary intervention. This article discusses the role of antithrombotic and antiplatelet agents for endovascular intervention. Copyright © 2013 Elsevier Inc. All rights reserved.

Current and future treatment options for gonorrhoea.

PubMed

Ison, Catherine A; Deal, Carolyn; Unemo, Magnus

2013-12-01

The delivery of effective antimicrobial therapy is essential for public health control of gonorrhoea, in the absence of a suitable vaccine. The antimicrobial agent chosen should have high efficacy and quality, lack toxicity and give >95% success when given empirically. Guidelines, which are informed by surveillance data, are used to aid clinicians in their choice of appropriate agent. Historically, gonorrhoea treatment has been delivered as a single, directly observed dose but this has resulted in failure of successive antimicrobial agents which have been replaced by a new antimicrobial to which resistance has been rare or non-existing. Following the drift towards decreased susceptibility and treatment failure to the extended spectrum cephalosporins, and the lack of 'new' alternative antimicrobials, the threat of difficult to treat or untreatable gonorrhoea has emerged. The challenge of maintaining gonorrhoea as a treatable infection has resulted in national, regional and global response or action plans. This review discusses different approaches to the future treatment of gonorrhoea including; use of ceftriaxone, the injectable cephalosporin at increased dosage; dual antimicrobial therapy; use of drugs developed for other infections and use of older agents, directed by rapid point of care tests, to susceptible infections. Finally, it is considered whether the time is right to readdress the possibility of developing an effective gonococcal vaccine, given the major advances in our understanding of natural infection, molecular pathogenesis and the revolution in molecular biology techniques.

Use of Targeted Therapeutics in Epithelial Ovarian Cancer: A Review of Current Literature and Future Directions.

PubMed

Vetter, Monica Hagan; Hays, John L

2018-03-01

Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer death in the United States. Most patients will ultimately fail platinum-based chemotherapy and have the disease recur. Interest is increasing in the use of targeted therapies in the treatment of EOC. This review focuses on the current use of targeted therapeutics in EOC as well as future directions. A literature search of Medline and PubMed was conducted (January 2000-October 2017) to identify recent reports of targeted drugs in EOC. A wide range of targeted therapeutics is currently being used as both monotherapy and in combination in the treatment of EOC. Clinically, the most commonly used classes of drugs currently are antiangiogenics and poly (ADP-ribose) polymerase inhibitors. However, a number of drugs in varying stages in development target a wide range of biochemical pathways. Activity and response rates of these drugs vary greatly. Questions continue about combination drug therapy and appropriate patient selection. The use of targeted therapeutics in the treatment of EOC, both as monotherapy and in combination, will continue to expand as more mechanisms of tumorigenesis are identified. Multiple clinical trials of a wide range of targeted therapeutics are currently ongoing. Evidence-based selection of drug targets and appropriate patient populations will allow strategic application of targeted therapeutics. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

Intra-articular therapies for osteoarthritis.

PubMed

Yu, Shirley P; Hunter, David J

2016-10-01

Conventional medical therapies for osteoarthritis are mainly palliative in nature, aiming to control pain and symptoms. Traditional intra-articular therapies are not recommended in guidelines as first line therapy, but are potential alternatives, when conventional therapies have failed. Current and future intra-articular drug therapies for osteoarthritis are highlighted, including corticosteroids, hyaluronate, and more controversial treatments marketed commercially, namely platelet rich plasma and mesenchymal cell therapy. Intraarticular disease modifying osteoarthritis drugs are the future of osteoarthritis treatments, aiming at structural modification and altering the disease progression. Interleukin-1β inhibitor, bone morphogenic protein-7, fibroblast growth factor 18, bradykinin B2 receptor antagonist, human serum albumin, and gene therapy are discussed in this review. The evolution of drug development in osteoarthritis is limited by the ability to demonstrate effect. High quality trials are required to justify the use of existing intra-articular therapies and to advocate for newer, promising therapies. Challenges in osteoarthritis therapy research are fundamentally related to the complexity of the pathological mechanisms of osteoarthritis. Novel drugs offer hope in a disease with limited medical therapy options. Whether these future intra-articular therapies will provide clinically meaningful benefits, remains unknown.

Cognitive behavioural therapy in pain and psychological disorders: Towards a hybrid future.

PubMed

Tang, Nicole K Y

2017-03-08

Cognitive Behavioural Therapy (CBT) is a form of evidence-based talking therapy that emphasises the importance of behaviour and conscious thoughts in shaping our emotional experiences. As pain becomes increasingly accepted as not only a sensory but also an emotional experience, success in using CBT to treat emotional disorders has resulted in the incorporation of cognitive-behavioural principles into the management of chronic pain. Outcomes of CBT-informed interdisciplinary pain management programmes are modest at best, despite rapid methodological improvements in trial design and implementation. Whilst the field searches for new treatment directions, a hybrid CBT approach that seeks to simultaneously tackle pain and its comorbidities shows promise in optimising treatment effectiveness and flexibility. This article provides a brief description of the core characteristics of CBT and the transformation this therapeutic model has brought to our understanding and management of chronic pain. Current evidence on efficacy of CBT for chronic pain is then reviewed, followed by a critical consideration of the advantages and disadvantages of the new hybrid treatment approach that conceptualises and treats chronic pain in connection with its comorbidities. Recent progress made in the area of pain and insomnia is highlighted as an example to project therapeutic innovations in the near future. Copyright © 2017 Elsevier Inc. All rights reserved.

Gene therapy delivery systems for enhancing viral and nonviral vectors for cardiac diseases: current concepts and future applications.

PubMed

Katz, Michael G; Fargnoli, Anthony S; Williams, Richard D; Bridges, Charles R

2013-11-01

Gene therapy is one of the most promising fields for developing new treatments for the advanced stages of ischemic and monogenetic, particularly autosomal or X-linked recessive, cardiomyopathies. The remarkable ongoing efforts in advancing various targets have largely been inspired by the results that have been achieved in several notable gene therapy trials, such as the hemophilia B and Leber's congenital amaurosis. Rate-limiting problems preventing successful clinical application in the cardiac disease area, however, are primarily attributable to inefficient gene transfer, host responses, and the lack of sustainable therapeutic transgene expression. It is arguable that these problems are directly correlated with the choice of vector, dose level, and associated cardiac delivery approach as a whole treatment system. Essentially, a delicate balance exists in maximizing gene transfer required for efficacy while remaining within safety limits. Therefore, the development of safe, effective, and clinically applicable gene delivery techniques for selected nonviral and viral vectors will certainly be invaluable in obtaining future regulatory approvals. The choice of gene transfer vector, dose level, and the delivery system are likely to be critical determinants of therapeutic efficacy. It is here that the interactions between vector uptake and trafficking, delivery route means, and the host's physical limits must be considered synergistically for a successful treatment course.

Role of Helicobacter pylori infection in gastric carcinogenesis: Current knowledge and future directions

PubMed Central

Sokic-Milutinovic, Aleksandra; Alempijevic, Tamara; Milosavljevic, Tomica

2015-01-01

Helicobacter pylori (H. pylori) plays a role in the pathogenesis of gastric cancer. The outcome of the infection depends on environmental factors and bacterial and host characteristics. Gastric carcinogenesis is a multistep process that is reversible in the early phase of mucosal damage, but the exact point of no return has not been identified. Therefore, two main therapeutic strategies could reduce gastric cancer incidence: (1) eradication of the already present infection; and (2) immunization (prior to or during the course of the infection). The success of a gastric cancer prevention strategy depends on timing because the prevention strategy must be introduced before the point of no return in gastric carcinogenesis. Although the exact point of no return has not been identified, infection should be eradicated before severe atrophy of the gastric mucosa develops. Eradication therapy rates remain suboptimal due to increasing H. pylori resistance to antibiotics and patient noncompliance. Vaccination against H. pylori would reduce the cost of eradication therapies and lower gastric cancer incidence. A vaccine against H. pylori is still a research challenge. An effective vaccine should have an adequate route of delivery, appropriate bacterial antigens and effective and safe adjuvants. Future research should focus on the development of rescue eradication therapy protocols until an efficacious vaccine against the bacterium becomes available. PMID:26556993

Current advances in T-cell-based cancer immunotherapy

PubMed Central

Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

2015-01-01

Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy. PMID:25524383

Halo naevi, vitiligo and diffuse alopecia areata associated with tocilizumab therapy

PubMed Central

Nadesalingam, Kavitha; Goodfield, Mark; Emery, Paul

2016-01-01

We present a follow-up case report of a 33-year-old lady with juvenile onset arthritis who developed halo naevi while on treatment with tocilizumab. This case report describes the development of halo naevi, vitiligo and diffuse alopecia areata associated with tocilizumab therapy following infection with Methicillin-resistant Staphylococcus aureus (MRSA) and Panton–Valentine leukocidin positivity. This is the first case that describes these events and supports previous theories on cellular and humoral immunity as causative factors. The regression of melanocytes during treatment with tocilizumab could also implicate IL-6 and sIL-6R as future targets in the treatment of melanoma through its direct effect of melanocytic cytotoxicity, which supports previous studies. PMID:27516894

New insights into huperzine A for the treatment of Alzheimer's disease

PubMed Central

Zhang, Hai-yan

2012-01-01

Huperzine A, an active Lycopodium alkaloid extracted from traditional Chinese herb, is a potent, selective and reversible acetylcholinesterase (AChE) inhibitor and has been widely used in China for the treatment of Alzheimer's disease (AD). Accordingly, some new mechanisms of action for huperzine A have been discovered over the past decades. In addition to its AChE inhibitory effect, potent multifaceted neuroprotective effect through activating cholinergic system and directly acting on mitochondria have been explored. Moreover, in order to maximize the efficacy and safety of huperzine A therapy, great efforts have been made to optimize drug delivery system. In the present article, an attempt is made to discuss the current progress and future perspective for huperzine A therapy in AD. PMID:22941287

Molecular mechanisms in therapy of acid-related diseases

PubMed Central

Shin, J. M.; Vagin, O.; Munson, K.; Kidd, M.; Modlin, I. M.; Sachs, G.

2011-01-01

Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration; therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell hydrogen-potassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities. Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of a novel class of agents, the acid pump antagonists. PMID:17928953

Are inner context factors related to implementation outcomes in cognitive-behavioral therapy for youth anxiety?

PubMed Central

Edmunds, Julie; Ditty, Matthew; Watkins, Jessica; Walsh, Lucia; Marcus, Steven; Kendall, Philip

2013-01-01

Among the challenges facing the mental health field are the dissemination and implementation of evidence-based practices. The present study investigated the relationships between inner context variables (i.e., adopter characteristics and individual perceptions of intra-organizational factors) and two implementation outcomes – independently rated therapist fidelity on a performance-based role-play (i.e., adherence and skill) and self-reported penetration of cognitive behavioral therapy for youth anxiety following training. A significant relationship was found between inner context variables and fidelity. Specifically, adopter characteristics were associated with adherence and skill; individual perceptions of intra-organizational factors were associated with adherence. Inner context variables were not associated with penetration. Future directions are discussed. PMID:24202067

Current advances in T-cell-based cancer immunotherapy.

PubMed

Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

2014-01-01

Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy.

Optimization of Bone Health in Children before and after Renal Transplantation: Current Perspectives and Future Directions

PubMed Central

Sgambat, Kristen; Moudgil, Asha

2014-01-01

The accrual of healthy bone during the critical period of childhood and adolescence sets the stage for lifelong skeletal health. However, in children with chronic kidney disease (CKD), disturbances in mineral metabolism and endocrine homeostasis begin early on, leading to alterations in bone turnover, mineralization, and volume, and impairing growth. Risk factors for CKD–mineral and bone disorder (CKD–MBD) include nutritional vitamin D deficiency, secondary hyperparathyroidism, increased fibroblast growth factor 23 (FGF-23), altered growth hormone and insulin-like growth factor-1 axis, delayed puberty, malnutrition, and metabolic acidosis. After kidney transplantation, nutritional vitamin D deficiency, persistent hyperparathyroidism, tertiary FGF-23 excess, hypophosphatemia, hypomagnesemia, immunosuppressive therapy, and alteration of sex hormones continue to impair bone health and growth. As function of the renal allograft declines over time, CKD–MBD associated changes are reactivated, further impairing bone health. Strategies to optimize bone health post-transplant include healthy diet, weight-bearing exercise, correction of vitamin D deficiency and acidosis, electrolyte abnormalities, steroid avoidance, and consideration of recombinant human growth hormone therapy. Other drug therapies have been used in adult transplant recipients, but there is insufficient evidence for use in the pediatric population at the present time. Future therapies to be explored include anti-FGF-23 antibodies, FGF-23 receptor blockers, and treatments targeting the colonic microbiota by reduction of generation of bacterial toxins and adsorption of toxic end products that affect bone mineralization. PMID:24605319

Advances in Bone Marrow Stem Cell Therapy for Retinal Dysfunction

PubMed Central

Park, Susanna S.; Moisseiev, Elad; Bauer, Gerhard; Anderson, Johnathon D.; Grant, Maria B.; Zam, Azhar; Zawadzki, Robert J.; Werner, John S.; Nolta, Jan A.

2016-01-01

The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue. Since the paracrine trophic effects can have regenerative effects on multiple cells in the retina, the use of this cell therapy is not limited to a particular retinal condition. Autologous bone marrow-derived stem cells are being explored in early clinical trials as therapy for various retinal conditions. These bone marrow stem cells include mesenchymal stem cells, mononuclear cells and CD34+ cells. Autologous therapy requires no systemic immunosuppression or donor matching. Intravitreal delivery of CD34+ cells and mononuclear cells appears to be tolerated and is being explored since some of these cells can home into the damaged retina after intravitreal administration. The safety of intravitreal delivery of mesenchymal stem cells has not been well established. This review provides an update of the current evidence in support of the use of bone marrow stem cells as treatment for retinal dysfunction. The potential limitations and complications of using certain forms of bone marrow stem cells as therapy are discussed. Future directions of research include methods to optimize the therapeutic potential of these stem cells, non-cellular alternatives using extracellular vesicles, and in vivo high-resolution retinal imaging to detect cellular changes in the retina following cell therapy. PMID:27784628

Goal-directed Fluid Therapy Does Not Reduce Primary Postoperative Ileus after Elective Laparoscopic Colorectal Surgery: A Randomized Controlled Trial.

PubMed

Gómez-Izquierdo, Juan C; Trainito, Alessandro; Mirzakandov, David; Stein, Barry L; Liberman, Sender; Charlebois, Patrick; Pecorelli, Nicolò; Feldman, Liane S; Carli, Franco; Baldini, Gabriele

2017-07-01

Inadequate perioperative fluid therapy impairs gastrointestinal function. Studies primarily evaluating the impact of goal-directed fluid therapy on primary postoperative ileus are missing. The objective of this study was to determine whether goal-directed fluid therapy reduces the incidence of primary postoperative ileus after laparoscopic colorectal surgery within an Enhanced Recovery After Surgery program. Randomized patient and assessor-blind controlled trial conducted in adult patients undergoing laparoscopic colorectal surgery within an Enhanced Recovery After Surgery program. Patients were assigned randomly to receive intraoperative goal-directed fluid therapy (goal-directed fluid therapy group) or fluid therapy based on traditional principles (control group). Primary postoperative ileus was the primary outcome. One hundred twenty-eight patients were included and analyzed (goal-directed fluid therapy group: n = 64; control group: n = 64). The incidence of primary postoperative ileus was 22% in the goal-directed fluid therapy and 22% in the control group (relative risk, 1; 95% CI, 0.5 to 1.9; P = 1.00). Intraoperatively, patients in the goal-directed fluid therapy group received less intravenous fluids (mainly less crystalloids) but a greater volume of colloids. The increase of stroke volume and cardiac output was more pronounced and sustained in the goal-directed fluid therapy group. Length of hospital stay, 30-day postoperative morbidity, and mortality were not different. Intraoperative goal-directed fluid therapy compared with fluid therapy based on traditional principles does not reduce primary postoperative ileus in patients undergoing laparoscopic colorectal surgery in the context of an Enhanced Recovery After Surgery program. Its previously demonstrated benefits might have been offset by advancements in perioperative care.

Treatment of persistent post-concussion syndrome due to mild traumatic brain injury: current status and future directions.

PubMed

Hadanny, Amir; Efrati, Shai

2016-08-01

Persistent post-concussion syndrome caused by mild traumatic brain injury has become a major cause of morbidity and poor quality of life. Unlike the acute care of concussion, there is no consensus for treatment of chronic symptoms. Moreover, most of the pharmacologic and non-pharmacologic treatments have failed to demonstrate significant efficacy on both the clinical symptoms as well as the pathophysiologic cascade responsible for the permanent brain injury. This article reviews the pathophysiology of PCS, the diagnostic tools and criteria, the current available treatments including pharmacotherapy and different cognitive rehabilitation programs, and promising new treatment directions. A most promising new direction is the use of hyperbaric oxygen therapy, which targets the basic pathological processes responsible for post-concussion symptoms; it is discussed here in depth.

Chasing Tics in the Human Brain: Development of Open, Scheduled and Closed Loop Responsive Approaches to Deep Brain Stimulation for Tourette Syndrome

PubMed Central

Martinez-Ramirez, Daniel; Rossi, Peter J.; Peng, Zhongxing; Gunduz, Aysegul; Okun, Michael S.

2015-01-01

Tourette syndrome is a childhood-onset disorder characterized by a combination of motor and vocal tics, often associated with psychiatric comorbidities including attention deficit and hyperactivity disorder and obsessive-compulsive disorder. Despite an onset early in life, half of patients may present symptoms in adulthood, with variable degrees of severity. In select cases, the syndrome may lead to significant physical and social impairment, and a worrisome risk for self injury. Evolving research has provided evidence supporting the idea that the pathophysiology of Tourette syndrome is directly related to a disrupted circuit involving the cortex and subcortical structures, including the basal ganglia, nucleus accumbens, and the amygdala. There has also been a notion that a dysfunctional group of neurons in the putamen contributes to an abnormal facilitation of competing motor responses in basal ganglia structures ultimately underpinning the generation of tics. Surgical therapies for Tourette syndrome have been reserved for a small group of patients not responding to behavioral and pharmacological therapies, and these therapies have been directed at modulating the underlying pathophysiology. Lesion therapy as well as deep brain stimulation has been observed to suppress tics in at least some of these cases. In this article, we will review the clinical aspects of Tourette syndrome, as well as the evolution of surgical approaches and we will discuss the evidence and clinical responses to deep brain stimulation in various brain targets. We will also discuss ongoing research and future directions as well as approaches for open, scheduled and closed loop feedback-driven electrical stimulation for the treatment of Tourette syndrome. PMID:25851890

Impact of Pharmacogenetics on Efficacy and Safety of Statin Therapy for Dyslipidemia.

PubMed

Maxwell, Whitney D; Ramsey, Laura B; Johnson, Samuel G; Moore, Kate G; Shtutman, Michael; Schoonover, John H; Kawaguchi-Suzuki, Marina

2017-09-01

Interindividual variability in response to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, with regard to both efficacy and safety is an obvious target for pharmacogenetic research. Many genes have been identified as possible contributors to variability in statin response and safety. Genetic polymorphisms may alter the structure or expression of coded proteins, with potential impacts on lipid and statin absorption, distribution, metabolism, and elimination as well as response pathways related to the pharmacologic effect. Many studies have explored the variation in statins' pharmacokinetic and pharmacodynamic parameters; however, to our knowledge, few have established definitive relationships between the genetic polymorphisms and patient outcomes, such as cardiovascular events. In this review article, we provide a statin-based summary of available evidence describing pharmacogenetic associations that may be of clinical relevance in the future. Although currently available studies are often small or retrospective, and may have conflicting results, they may be useful in providing direction for future confirmatory studies and may point to associations that could be confirmed in the future when more patient outcomes-based studies are available. We also summarize the clinically relevant evidence currently available to assist clinicians with providing personalized pharmacotherapy for patients requiring statin therapy. © 2017 Pharmacotherapy Publications, Inc.

Early management of patients with acute heart failure: state of the art and future directions. A consensus document from the society for academic emergency medicine/heart failure society of America acute heart failure working group.

PubMed

Collins, Sean; Storrow, Alan B; Albert, Nancy M; Butler, Javed; Ezekowitz, Justin; Felker, G Michael; Fermann, Gregory J; Fonarow, Gregg C; Givertz, Michael M; Hiestand, Brian; Hollander, Judd E; Lanfear, David E; Levy, Phillip D; Pang, Peter S; Peacock, W Frank; Sawyer, Douglas B; Teerlink, John R; Lenihan, Daniel J

2015-01-01

Heart failure (HF) afflicts nearly 6 million Americans, resulting in one million emergency department (ED) visits and over one million annual hospital discharges. An aging population and improved survival from cardiovascular diseases is expected to further increase HF prevalence. Emergency providers play a significant role in the management of patients with acute heart failure (AHF). It is crucial that emergency physicians and other providers involved in early management understand the latest developments in diagnostic testing, therapeutics and alternatives to hospitalization. Further, clinical trials must be conducted in the ED in order to improve the evidence base and drive optimal initial therapy for AHF. Should ongoing and future studies suggest early phenotype-driven therapy improves in-hospital and post-discharge outcomes, ED treatment decisions will need to evolve accordingly. The potential impact of future studies which incorporate risk-stratification into ED disposition decisions cannot be underestimated. Predictive instruments that identify a cohort of patients safe for ED discharge, while simultaneously addressing barriers to successful outpatient management, have the potential to significantly impact quality of life and resource expenditures. Copyright © 2015 Elsevier Inc. All rights reserved.

Redox-Modulated Phenomena and Radiation Therapy: The Central Role of Superoxide Dismutases

PubMed Central

Holley, Aaron K.; Miao, Lu; St. Clair, Daret K.

2014-01-01

Abstract Significance: Ionizing radiation is a vital component in the oncologist's arsenal for the treatment of cancer. Approximately 50% of all cancer patients will receive some form of radiation therapy as part of their treatment regimen. DNA is considered the major cellular target of ionizing radiation and can be damaged directly by radiation or indirectly through reactive oxygen species (ROS) formed from the radiolysis of water, enzyme-mediated ROS production, and ROS resulting from altered aerobic metabolism. Recent Advances: ROS are produced as a byproduct of oxygen metabolism, and superoxide dismutases (SODs) are the chief scavengers. ROS contribute to the radioresponsiveness of normal and tumor tissues, and SODs modulate the radioresponsiveness of tissues, thus affecting the efficacy of radiotherapy. Critical Issues: Despite its prevalent use, radiation therapy suffers from certain limitations that diminish its effectiveness, including tumor hypoxia and normal tissue damage. Oxygen is important for the stabilization of radiation-induced DNA damage, and tumor hypoxia dramatically decreases radiation efficacy. Therefore, auxiliary therapies are needed to increase the effectiveness of radiation therapy against tumor tissues while minimizing normal tissue injury. Future Directions: Because of the importance of ROS in the response of normal and cancer tissues to ionizing radiation, methods that differentially modulate the ROS scavenging ability of cells may prove to be an important method to increase the radiation response in cancer tissues and simultaneously mitigate the damaging effects of ionizing radiation on normal tissues. Altering the expression or activity of SODs may prove valuable in maximizing the overall effectiveness of ionizing radiation. Antioxid. Redox Signal. 20, 1567–1589. PMID:24094070

Stimulating effect of thyroid hormones in peripheral nerve regeneration: research history and future direction toward clinical therapy

PubMed Central

Barakat-Walter, I.; Kraftsik, R.

2018-01-01

Injury to peripheral nerves is often observed in the clinic and severe injuries may cause loss of motor and sensory functions. Despite extensive investigation, testing various surgical repair techniques and neurotrophic molecules, at present, a satisfactory method to ensuring successful recovery does not exist. For successful molecular therapy in nerve regeneration, it is essential to improve the intrinsic ability of neurons to survive and to increase the speed of axonal outgrowth. Also to induce Schwann cell phenotypical changes to prepare the local environment favorable for axonal regeneration and myelination. Therefore, any molecule that regulates gene expression of both neurons and Schwann cells could play a crucial role in peripheral nerve regeneration. Clinical and experimental studies have reported that thyroid hormones are essential for the normal development and function of the nervous system, so they could be candidates for nervous system regeneration. This review provides an overview of studies devoted to testing the effect of thyroid hormones on peripheral nerve regeneration. Also it emphasizes the importance of combining biodegradable tubes with local administration of triiodothyronine for future clinical therapy of human severe injured nerves. We highlight that the local and single administration of triiodothyronine within biodegradable nerve guide improves significantly the regeneration of severed peripheral nerves, and accelerates functional recovering. This technique provides a serious step towards future clinical application of triiodothyronine in human severe injured nerves. The possible regulatory mechanism by which triiodothyronine stimulates peripheral nerve regeneration is a rapid action on both axotomized neurons and Schwann cells. PMID:29722302

A New Era for Cancer Target Therapies: Applying Systems Biology and Computer-Aided Drug Design to Cancer Therapies.

PubMed

Wong, Yung-Hao; Chiu, Chia-Chiun; Lin, Chih-Lung; Chen, Ting-Shou; Jheng, Bo-Ren; Lee, Yu-Ching; Chen, Jeremy; Chen, Bor-Sen

In recent years, many systems biology approaches have been used with various cancers. The materials described here can be used to build bases to discover novel cancer therapy targets in connection with computer-aided drug design (CADD). A deeper understanding of the mechanisms of cancer will provide more choices and correct strategies in the development of multiple target drug therapies, which is quite different from the traditional cancer single target therapy. Targeted therapy is one of the most powerful strategies against cancer and can also be applied to other diseases. Due to the large amount of progress in computer hardware and the theories of computational chemistry and physics, CADD has been the main strategy for developing novel drugs for cancer therapy. In contrast to traditional single target therapies, in this review we will emphasize the future direction of the field, i.e., multiple target therapies. Structure-based and ligand-based drug designs are the two main topics of CADD. The former needs both 3D protein structures and ligand structures, while the latter only needs ligand structures. Ordinarily it is estimated to take more than 14 years and 800 million dollars to develop a new drug. Many new CADD software programs and techniques have been developed in recent decades. We conclude with an example where we combined and applied systems biology and CADD to the core networks of four cancers and successfully developed a novel cocktail for drug therapy that treats multiple targets.

Understanding Microbiome Effect on Immune Checkpoint Inhibition in Lung Cancer: Placing the Puzzle Pieces Together.

PubMed

Swami, Umang; Zakharia, Yousef; Zhang, Jun

2018-05-17

Over the past couple of years, human microbiome has received increasing attention as a regulator and predictor of response to the therapies of various diseases. It is speculated that manipulating gut microbiome can modify response to cancer immunotherapies as well. Through this review, we have critically analyzed our current understanding of gut microbiome as a modulator of immunotherapies in lung cancer, explained conflicting data, evaluated current gaps and extrapolated our present knowledge to generate directions for future investigations.

Immunotherapy for Infectious Diseases: Past, Present, and Future.

PubMed

Manohar, Akshay; Ahuja, Jasmine; Crane, John K

2015-01-01

Passive immunotherapy for established infections, as opposed to active immunization to prevent disease, remains a tiny niche in the world of antimicrobial therapies. Many of the passive immunotherapies currently available are directed against bacterial toxins, such as botulism, or are intended for agents of bioterrorism such as anthrax, which fortunately has remained rare. The emergence of Ebola virus and multi-drug resistant pathogens, however, may breathe new life into the immunotherapy field as researchers seek non-antibiotic interventions for infectious diseases.

Psoriasis.

PubMed

Di Meglio, Paola; Villanova, Federica; Nestle, Frank O

2014-08-01

Psoriasis is a common chronic inflammatory skin disease with a spectrum of clinical phenotypes and results from the interplay of genetic, environmental, and immunological factors. Four decades of clinical and basic research on psoriasis have elucidated many of the pathogenic mechanisms underlying disease and paved the way to effective targeted therapies. Here, we review this progress and identify future directions of study that are supported by a more integrative research approach and aim at further improving the patients' life. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

The Management of Hypertension in Pregnancy

PubMed Central

Kattah, Andrea G.; Garovic, Vesna D.

2014-01-01

Hypertensive pregnancy disorders complicate 6–8% of pregnancies and cause significant maternal and fetal morbidity and mortality. The goal of treatment is to prevent significant cerebrovascular and cardiovascular events in the mother, without compromising fetal well-being. Current guidelines differentiate between the treatment of women with acute hypertensive syndromes of pregnancy and women with preexisting chronic hypertension in pregnancy. This review will address the management of hypertension in pregnancy, review the various pharmacologic therapies, and discuss the future directions in this field. PMID:23928387

RNA interference in the clinic: challenges and future directions

PubMed Central

Pecot, Chad V.; Calin, George A.; Coleman, Robert L.; Lopez-Berestein, Gabriel; Sood, Anil K.

2011-01-01

Inherent difficulties with blocking many desirable targets using conventional approaches have prompted many to consider using RNA interference (RNAi) as a therapeutic approach. Although exploitation of RNAi has immense potential as a cancer therapeutic, many physiological obstacles stand in the way of successful and efficient delivery. This Review explores current challenges to the development of synthetic RNAi-based therapies and considers new approaches to circumvent biological barriers, to avoid intolerable side effects and to achieve controlled and sustained release. PMID:21160526

A new prospect in cancer therapy: targeting cancer stem cells to eradicate cancer.

PubMed

Chen, Li-Sha; Wang, An-Xin; Dong, Bing; Pu, Ke-Feng; Yuan, Li-Hua; Zhu, Yi-Min

2012-12-01

According to the cancer stem cell theory, cancers can be initiated by cancer stem cells. This makes cancer stem cells prime targets for therapeutic intervention. Eradicating cancer stem cells by efficient targeting agents may have the potential to cure cancer. In this review, we summarize recent breakthroughs that have improved our understanding of cancer stem cells, and we discuss the therapeutic strategy of targeting cancer stem cells, a promising future direction for cancer stem cell research.

Disease management: remote monitoring in heart failure patients with implantable defibrillators, resynchronization devices, and haemodynamic monitors.

PubMed

Abraham, William T

2013-06-01

Heart failure represents a major public health concern, associated with high rates of morbidity and mortality. A particular focus of contemporary heart failure management is reduction of hospital admission and readmission rates. While optimal medical therapy favourably impacts the natural history of the disease, devices such as cardiac resynchronization therapy devices and implantable cardioverter defibrillators have added incremental value in improving heart failure outcomes. These devices also enable remote patient monitoring via device-based diagnostics. Device-based measurement of physiological parameters, such as intrathoracic impedance and heart rate variability, provide a means to assess risk of worsening heart failure and the possibility of future hospitalization. Beyond this capability, implantable haemodynamic monitors have the potential to direct day-to-day management of heart failure patients to significantly reduce hospitalization rates. The use of a pulmonary artery pressure measurement system has been shown to significantly reduce the risk of heart failure hospitalization in a large randomized controlled study, the CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients (CHAMPION) trial. Observations from a pilot study also support the potential use of a left atrial pressure monitoring system and physician-directed patient self-management paradigm; these observations are under further investigation in the ongoing LAPTOP-HF trial. All these devices depend upon high-intensity remote monitoring for successful detection of parameter deviations and for directing and following therapy.

Gastrointestinal Neuroendocrine Tumors: Pancreatic Endocrine Tumors

PubMed Central

Metz, David C.

2008-01-01

Pancreatic endocrine tumors (PETs) have long fascinated clinicians and investigators despite their relative rarity. Their clinical presentation varies depending upon whether the tumor is functional or not and also according to the specific hormonal syndrome produced. Tumors may be sporadic or inherited but little is known about their molecular pathology, especially the sporadic forms. Chromogranin A appears to be the most useful serum marker for diagnosis, staging and monitoring. Initially, therapy should be directed at the hormonal syndrome as this has the major initial impact on the patient's health. Most PETs are relatively indolent but ultimately malignant, except for insulinomas which are predominantly benign. Surgery is the only modality that offers the possibility of cure although it is generally noncurative in patients with Zollinger-Ellison syndrome or nonfunctional PETs with MEN1. Preoperative staging of disease extent is necessary to determine the likelihood of complete resection though debulking surgery is often felt to be useful in unresectable patients. Once metastatic, biotherapy is usually the first modality employed because it is generally well tolerated. Systemic or regional therapies are generally reserved until symptoms occur or tumor growth is rapid. Recently a number of newer agents, as well as receptor-directed radiotherapy, are being evalulated for patients with advanced disease. This review addresses a number of recent advances regarding the molecular pathology, diagnosis, localization and management of PETs including discussion of peptide receptor radionuclide therapy and other novel antitumor approaches. We conclude with a discussion of future directions and unsettled problems in the field. PMID:18703061

DIAGNOSTIC IMAGING IN A DIRECT-ACCESS SPORTS PHYSICAL THERAPY CLINIC: A 2-YEAR RETROSPECTIVE PRACTICE ANALYSIS.

PubMed

Crowell, Michael S; Dedekam, Erik A; Johnson, Michael R; Dembowski, Scott C; Westrick, Richard B; Goss, Donald L

2016-10-01

While advanced diagnostic imaging is a large contributor to the growth in health care costs, direct-access to physical therapy is associated with decreased rates of diagnostic imaging. No study has systematically evaluated with evidence-based criteria the appropriateness of advanced diagnostic imaging, including magnetic resonance imaging (MRI), when ordered by physical therapists. The primary purpose of this study was to describe the appropriateness of magnetic resonance imaging (MRI) or magnetic resonance arthrogram (MRA) exams ordered by physical therapists in a direct-access sports physical therapy clinic. Retrospective observational study of practice. Greater than 80% of advanced diagnostic imaging orders would have an American College of Radiology (ACR) Appropriateness Criteria rating of greater than 6, indicating an imaging order that is usually appropriate. A 2-year retrospective analysis identified 108 MRI/MRA examination orders from four physical therapists. A board-certified radiologist determined the appropriateness of each order based on ACR appropriateness criteria. The principal investigator and co-investigator radiologist assessed agreement between the clinical diagnosis and MRI/surgical findings. Knee (31%) and shoulder (25%) injuries were the most common. Overall, 55% of injuries were acute. The mean ACR rating was 7.7; scores from six to nine have been considered appropriate orders and higher ratings are better. The percentage of orders complying with ACR appropriateness criteria was 83.2%. Physical therapist's clinical diagnosis was confirmed by MRI/MRA findings in 64.8% of cases and was confirmed by surgical findings in 90% of cases. Physical therapists providing musculoskeletal primary care in a direct-access sports physical therapy clinic appropriately ordered advanced diagnostic imaging in over 80% of cases. Future research should prospectively compare physical therapist appropriateness and utilization to other groups of providers and explore the effects of physical therapist imaging privileging on outcomes. Diagnosis, Level 3.

Light Therapy and Alzheimer’s Disease and Related Dementia: Past, Present, and Future

PubMed Central

Hanford, Nicholas; Figueiro, Mariana

2012-01-01

Sleep disturbances are common in persons with Alzheimer’s disease or related dementia (ADRD), resulting in a negative impact on the daytime function of the affected person and on the wellbeing of caregivers. The sleep/wake pattern is directly driven by the timing signals generated by a circadian pacemaker, which may or may not be perfectly functioning in those with ADRD. A 24-hour light/dark pattern incident on the retina is the most efficacious stimulus for entraining the circadian system to the solar day. In fact, a carefully orchestrated light/dark pattern has been shown in several controlled studies of older populations, with and without ADRD, to be a powerful non-pharmacological tool to improve sleep efficiency and consolidation. Discussed here are research results from studies looking at the effectiveness of light therapy in improving sleep, depression, and agitation in older adults with ADRD. A 24-hour lighting scheme to increase circadian entrainment, improve visibility, and reduce the risk of falls in those with ADRD is proposed, and future research needs are discussed. PMID:23099814

Light therapy and Alzheimer's disease and related dementia: past, present, and future.

PubMed

Hanford, Nicholas; Figueiro, Mariana

2013-01-01

Sleep disturbances are common in persons with Alzheimer's disease or related dementia (ADRD), resulting in a negative impact on the daytime function of the affected person and on the wellbeing of caregivers. The sleep/wake pattern is directly driven by the timing signals generated by a circadian pacemaker, which may or may not be perfectly functioning in those with ADRD. A 24-hour light/dark pattern incident on the retina is the most efficacious stimulus for entraining the circadian system to the solar day. In fact, a carefully orchestrated light/dark pattern has been shown in several controlled studies of older populations, with and without ADRD, to be a powerful non-pharmacological tool to improve sleep efficiency and consolidation. Discussed here are research results from studies looking at the effectiveness of light therapy in improving sleep, depression, and agitation in older adults with ADRD. A 24-hour lighting scheme to increase circadian entrainment, improve visibility, and reduce the risk of falls in those with ADRD is proposed, and future research needs are discussed.

Antimalarial drug policy in India: past, present & future.

PubMed

Anvikar, Anupkumar R; Arora, Usha; Sonal, G S; Mishra, Neelima; Shahi, Bharatendu; Savargaonkar, Deepali; Kumar, Navin; Shah, Naman K; Valecha, Neena

2014-02-01

The use of antimalarial drugs in India has evolved since the introduction of quinine in the 17 th century. Since the formal establishment of a malaria control programme in 1953, shortly after independence, treatments provided by the public sector ranged from chloroquine, the mainstay drug for many decades, to the newer, recently introduced artemisinin based combination therapy. The complexity of considerations in antimalarial treatment led to the formulation of a National Antimalarial Drug Policy to guide procurement as well as communicate best practices to both public and private healthcare providers. Challenges addressed in the policy include the use of presumptive treatment, the introduction of alternate treatments for drug-resistant malaria, the duration of primaquine therapy to prevent relapses of vivax malaria, the treatment of malaria in pregnancy, and the choice of drugs for chemoprophylaxis. While data on antimalarial drug resistance and both public and private sector treatment practices have been recently reviewed, the policy process of setting national standards has not. In this perspective on antimalarial drug policy, this review highlights its relevant history, analyzes the current policy, and examines future directions.

Optimal Management of Metastatic Melanoma: Current Strategies and Future Directions

PubMed Central

Batus, Marta; Waheed, Salman; Ruby, Carl; Petersen, Lindsay; Bines, Steven D.; Kaufman, Howard L.

2013-01-01

Melanoma is increasing in incidence and remains a major public health threat. Although the disease may be curable when identified early, advanced melanoma is characterized by widespread metastatic disease and a median survival of less than 10 months. In recent years, however, major advances in our understanding of the molecular nature of melanoma and the interaction of melanoma cells with the immune system have resulted in several new therapeutic strategies that are showing significant clinical benefit. Current therapeutic approaches include surgical resection of metastatic disease, chemotherapy, immunotherapy, and targeted therapy. Dacarbazine, interleukin-2, ipilimumab, and vemurafenib are now approved for the treatment of advanced melanoma. In addition, new combination chemotherapy regimens, monoclonal antibodies blocking the programmed death-1 (PD-1)/PD-ligand 1 pathway, and targeted therapy against CKIT, mitogen-activated protein/extracellular signal-regulated kinase (MEK), and other putative signaling pathways in melanoma are beginning to show promise in early-phase clinical trials. Further research on these modalities alone and in combination will likely be the focus of future clinical investigation and may impact the outcomes for patients with advanced melanoma. PMID:23677693

Biomarkers in systemic lupus erythematosus: challenges and prospects for the future

PubMed Central

Kao, Amy H.; Manzi, Susan; Ahearn, Joseph M.

2013-01-01

The search for lupus biomarkers to diagnose, monitor, stratify, and predict individual response to therapy is currently more intense than ever before. This effort is essential for several reasons. First, epidemic overdiagnosis and underdiagnosis of lupus, even by certified rheumatologists, leads to errors in therapy with concomitant side effects which may be more serious than the disease itself. Second, identification of lupus flares remains as much an art as it is a science. Third, the capacity to stratify patients so as to predict those who will develop specific patterns of organ involvement is not currently possible but would potentially lead to preventive therapeutic strategies. Fourth, only one new drug for the treatment of lupus has been approved by the US Food and Drug Administration in over 50 years. A major obstacle in this pipeline is the dearth of biomarkers available to prove a patient has responded to an experimental therapeutic intervention. This review will summarize the challenges faced in the discovery and validation of lupus biomarkers, the most promising lupus biomarkers identified to date, and the promise of future directions. PMID:23904865

Targeting Gas6/TAM in cancer cells and tumor microenvironment.

PubMed

Wu, Guiling; Ma, Zhiqiang; Cheng, Yicheng; Hu, Wei; Deng, Chao; Jiang, Shuai; Li, Tian; Chen, Fulin; Yang, Yang

2018-01-31

Growth arrest-specific 6, also known as Gas6, is a human gene encoding the Gas6 protein, which was originally found to be upregulated in growth-arrested fibroblasts. Gas6 is a member of the vitamin K-dependent family of proteins expressed in many human tissues and regulates several biological processes in cells, including proliferation, survival and migration, by binding to its receptors Tyro3, Axl and Mer (TAM). In recent years, the roles of Gas6/TAM signalling in cancer cells and the tumour microenvironment have been studied, and some progress has made in targeted therapy, providing new potential directions for future investigations of cancer treatment. In this review, we introduce the Gas6 and TAM receptors and describe their involvement in different cancers and discuss the roles of Gas6 in cancer cells, the tumour microenvironment and metastasis. Finally, we introduce recent studies on Gas6/TAM targeting in cancer therapy, which will assist in the experimental design of future analyses and increase the potential use of Gas6 as a therapeutic target for cancer.

Direct Reprogramming—The Future of Cardiac Regeneration?

PubMed Central

Doppler, Stefanie A.; Deutsch, Marcus-André; Lange, Rüdiger; Krane, Markus

2015-01-01

Today, the only available curative therapy for end stage congestive heart failure (CHF) is heart transplantation. This therapeutic option is strongly limited by declining numbers of available donor hearts and by restricted long-term performance of the transplanted graft. The disastrous prognosis for CHF with its restricted therapeutic options has led scientists to develop different concepts of alternative regenerative treatment strategies including stem cell transplantation or stimulating cell proliferation of different cardiac cell types in situ. However, first clinical trials with overall inconsistent results were not encouraging, particularly in terms of functional outcome. Among other approaches, very promising ongoing pre-clinical research focuses on direct lineage conversion of scar fibroblasts into functional myocardium, termed “direct reprogramming” or “transdifferentiation.” This review seeks to summarize strategies for direct cardiac reprogramming including the application of different sets of transcription factors, microRNAs, and small molecules for an efficient generation of cardiomyogenic cells for regenerative purposes. PMID:26230692

REM Sleep Behavior Disorder: Updated Review of the Core Features, the RBD-Neurodegenerative Disease Association, Evolving Concepts, Controversies, and Future Directions

PubMed Central

Boeve, Bradley F.

2010-01-01

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia manifested by vivid, often frightening dreams associated with simple or complex motor behavior during REM sleep. Patients appear to “act out their dreams,” in which the exhibited behaviors mirror the content of the dreams, and the dream content often involves a chasing or attacking theme. The polysomnographic features of RBD include increased electromyographic tone +/- dream enactment behavior during REM sleep. Management with counseling and pharmacologic measures is usually straight-forward and effective. In this review, the terminology, clinical and polysomnographic features, demographic and epidemiologic features, diagnostic criteria, differential diagnosis, and management strategies are discussed. Recent data on the suspected pathophysiologic mechanisms of RBD are also reviewed. The literature and our institutional experience on RBD are next discussed, with an emphasis on the RBD-neurodegenerative disease association and particularly the RBD-synucleinopathy association. Several issues relating to evolving concepts, controversies, and future directions are then reviewed, with an emphasis on idiopathic RBD representing an early feature of a neurodegenerative disease and particularly an evolving synucleinopathy. Planning for future therapies that impact patients with idiopathic RBD is reviewed in detail. PMID:20146689

The Efficacy of Equine-Assisted Activities and Therapies on Improving Physical Function.

PubMed

Rigby, B Rhett; Grandjean, Peter W

2016-01-01

To summarize the physical benefits of therapeutic horseback riding and hippotherapy and suggest directions for future research. Review of databases for peer-reviewed articles related to equine-assisted activities and therapies. Databases included MEDLINE via EBSCO, Web of Science, PubMed, Google Scholar, and Academic Search Complete. Articles were limited to those with full-text access published in English since 1987. Acute and residual improvements in physical benefits, such as gross motor function (e.g., walking, running, jumping), spasticity, muscle symmetry, posture, balance, and gait occur in adults and children with varying disabilities. The benefits appear to be greatest following multiweek interventions with one or more sessions per week. Modest acute cardiovascular responses are observed during equine-assisted activities and therapies with little or no evidence for training improvements in heart rate or blood pressure at rest or during riding. The present body of literature provides evidence that equine-assisted activities and therapies are an effective means of improving many measures of physical health. However, more controlled trials are urgently needed to strengthen the current knowledge base, establish dose-response characteristics of equine-assisted activities and therapies, and explore the physiologic basis for the promising results suggested from the literature.

Image-guided ultrasound phased arrays are a disruptive technology for non-invasive therapy

NASA Astrophysics Data System (ADS)

Hynynen, Kullervo; Jones, Ryan M.

2016-09-01

Focused ultrasound offers a non-invasive way of depositing acoustic energy deep into the body, which can be harnessed for a broad spectrum of therapeutic purposes, including tissue ablation, the targeting of therapeutic agents, and stem cell delivery. Phased array transducers enable electronic control over the beam geometry and direction, and can be tailored to provide optimal energy deposition patterns for a given therapeutic application. Their use in combination with modern medical imaging for therapy guidance allows precise targeting, online monitoring, and post-treatment evaluation of the ultrasound-mediated bioeffects. In the past there have been some technical obstacles hindering the construction of large aperture, high-power, densely-populated phased arrays and, as a result, they have not been fully exploited for therapy delivery to date. However, recent research has made the construction of such arrays feasible, and it is expected that their continued development will both greatly improve the safety and efficacy of existing ultrasound therapies as well as enable treatments that are not currently possible with existing technology. This review will summarize the basic principles, current statures, and future potential of image-guided ultrasound phased arrays for therapy.

Image-guided ultrasound phased arrays are a disruptive technology for non-invasive therapy.

PubMed

Hynynen, Kullervo; Jones, Ryan M

2016-09-07

Focused ultrasound offers a non-invasive way of depositing acoustic energy deep into the body, which can be harnessed for a broad spectrum of therapeutic purposes, including tissue ablation, the targeting of therapeutic agents, and stem cell delivery. Phased array transducers enable electronic control over the beam geometry and direction, and can be tailored to provide optimal energy deposition patterns for a given therapeutic application. Their use in combination with modern medical imaging for therapy guidance allows precise targeting, online monitoring, and post-treatment evaluation of the ultrasound-mediated bioeffects. In the past there have been some technical obstacles hindering the construction of large aperture, high-power, densely-populated phased arrays and, as a result, they have not been fully exploited for therapy delivery to date. However, recent research has made the construction of such arrays feasible, and it is expected that their continued development will both greatly improve the safety and efficacy of existing ultrasound therapies as well as enable treatments that are not currently possible with existing technology. This review will summarize the basic principles, current statures, and future potential of image-guided ultrasound phased arrays for therapy.

Targeted alpha therapy using Radium-223: From physics to biological effects.

PubMed

Marques, I A; Neves, A R; Abrantes, A M; Pires, A S; Tavares-da-Silva, E; Figueiredo, A; Botelho, M F

2018-05-25

With the advance of the use of ionizing radiation in therapy, targeted alpha therapy (TAT) has assumed an important role around the world. This kind of therapy can potentially reduce side effects caused by radiation in normal tissues and increased destructive radiobiological effects in tumor cells. However, in many countries, the use of this therapy is still in a pioneering phase. Radium-223 ( 223 Ra), an alpha-emitting radionuclide, has been the first of its kind to be approved for the treatment of bone metastasis in metastatic castration-resistant prostate cancer. Nevertheless, the interaction mechanism and the direct effects of this radiopharmaceutical in tumor cells are not fully understood neither characterized at a molecular level. In fact, the ways how TAT is linked to radiobiological effects in cancer is not yet revised. Therefore, this review introduces some physical properties of TAT that leads to biological effects and links this information to the hallmarks of cancer. The authors also collected the studies developed with 223 Ra to correlate with the three categories reviewed - properties of TAT, 5 R's of radiobiology and hallmarks of cancer- and with the promising future to this radiopharmaceutical. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evidence-based psychosocial treatments for child and adolescent depression.

PubMed

David-Ferdon, Corinne; Kaslow, Nadine J

2008-01-01

The evidence-base of psychosocial treatment outcome studies for depressed youth conducted since 1998 is examined. All studies for depressed children meet Nathan and Gorman's (2002) criteria for Type 2 studies whereas the adolescent protocols meet criteria for both Type 1 and Type 2 studies. Based on the Task Force on the Promotion and Dissemination of Psychological Procedures guidelines, the cognitive-behavioral therapy (CBT) based specific programs of Penn Prevention Program, Self-Control Therapy, and Coping with Depression-Adolescent are probably efficacious. Interpersonal Therapy-Adolescent, which falls under the theoretical category of interpersonal therapy (IPT), also is a probably efficacious treatment. CBT provided through the modalities of child group only and child group plus parent components are well-established intervention approaches for depressed children. For adolescents, two modalities are well-established (CBT adolescent only group, IPT individual), and three are probably efficacious (CBT adolescent group plus parent component, CBT individual, CBT individual plus parent/family component). From the broad theoretical level, CBT has well-established efficacy and behavior therapy meets criteria for a probably efficacious intervention for childhood depression. For adolescent depression, both CBT and IPT have well-established efficacy. Future research directions and best practices are offered.

Image-guided ultrasound phased arrays are a disruptive technology for non-invasive therapy

PubMed Central

Hynynen, Kullervo; Jones, Ryan M.

2016-01-01

Focused ultrasound offers a non-invasive way of depositing acoustic energy deep into the body, which can be harnessed for a broad spectrum of therapeutic purposes, including tissue ablation, the targeting of therapeutic agents, and stem cell delivery. Phased array transducers enable electronic control over the beam geometry and direction, and can be tailored to provide optimal energy deposition patterns for a given therapeutic application. Their use in combination with modern medical imaging for therapy guidance allows precise targeting, online monitoring, and post-treatment evaluation of the ultrasound-mediated bioeffects. In the past there have been some technical obstacles hindering the construction of large aperture, high-power, densely-populated phased arrays and, as a result, they have not been fully exploited for therapy delivery to date. However, recent research has made the construction of such arrays feasible, and it is expected that their continued development will both greatly improve the safety and efficacy of existing ultrasound therapies as well as enable treatments that are not currently possible with existing technology. This review will summarize the basic principles, current statures, and future potential of image-guided ultrasound phased arrays for therapy. PMID:27494561

Biomarker Guided Therapy in Chronic Heart Failure

PubMed Central

Bektas, Sema

2015-01-01

This review article addresses the question of whether biomarker-guided therapy is ready for clinical implementation in chronic heart failure. The most well-known biomarkers in heart failure are natriuretic peptides, namely B-type natriuretic peptide (BNP) and N-terminal pro-BNP. They are well-established in the diagnostic process of acute heart failure and prediction of disease prognosis. They may also be helpful in screening patients at risk of developing heart failure. Although studied by 11 small- to medium-scale trials resulting in several positive meta-analyses, it is less well-established whether natriuretic peptides are also helpful for guiding chronic heart failure therapy. This uncertainty is expressed by differences in European and American guideline recommendations. In addition to reviewing the evidence surrounding the use of natriuretic peptides to guide chronic heart failure therapy, this article gives an overview of the shortcomings of the trials, how the results may be interpreted and the future directions necessary to fill the current gaps in knowledge. Therapy guidance in chronic heart failure using other biomarkers has not been prospectively tested to date. Emerging biomarkers, such as galectin-3 and soluble ST2, might be useful in this regard, as suggested by several post-hoc analyses. PMID:28785440

[Stem cell therapy in cardiovascular diseases].

PubMed

Vértesaljai, Márton; Piróth, Zsolt; Fontos, Géza; Andréka, Gyórgy; Font, Gusztáv; Szánthó, Gergely; Réti, Marienn; Masszi, Tamás; Andréka, Peter

2005-11-20

Myocardial infarction is the leading cause of congestive heart failure in the industrialized world. Current treatments fail to address the underlying scarring and cell loss, which are the causes of ischaemic heart failure. Recent interest has focused on stem cells, which are undifferentiated and pluripotent cells that can proliferate, potentially self-renew, and differentiate into cardiomyocytes and endothelial cells. Myocardial regeneration is the most widely studied and debated example of stem cell plasticity. Early reports from animal and clinical investigations disagree on the extent of myocardial renewal in adults, but evidence indicates that cardiomyocytes were generated in what was previously considered a postmitotic organ. So far, candidates for cardiac stem cell therapy have been limited to patients with acute myocardial infarction and chronic ischaemic heart failure. Currently, bone marrow stem cells seem to be the most attractive cell type for these patients. The cells may be delivered by means of direct surgical injection, intracoronary infusion, retrograde venous infusion, and transendocardial infusion. Stem cells may directly increase cardiac contractility or passively limit infarct expansion and remodeling. Early phase I clinical studies indicate that stem cell transplantation is feasible and may have beneficial effects on ventricular remodeling after myocardial infarction. Future randomized clinical trials will establish the magnitude of benefit and the effect on mortality after stem cell therapy.

Folate-targeted nanoparticles for rheumatoid arthritis therapy.

PubMed

Nogueira, Eugénia; Gomes, Andreia C; Preto, Ana; Cavaco-Paulo, Artur

2016-05-01

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting almost 1% of the world population. Although the cause of RA remains unknown, the complex interaction between immune mediators (cytokines and effector cells) is responsible for the joint damage that begins at the synovial membrane. Activated macrophages are critical in the pathogenesis of RA and showed specifically express a receptor for the vitamin folic acid (FA), folate receptor β (FRβ). This particular receptor allows internalization of FA-coupled cargo. In this review we will address the potential of nanoparticles as an effective drug delivery system for therapies that will directly target activated macrophages. Special attention will be given to stealth degree of the nanoparticles as a strategy to avoid clearance by macrophages of the mononuclear phagocytic system (MPS). This review summarizes the application of FA-target nanoparticles as drug delivery systems for RA and proposes prospective future directions. Rheumatoid arthritis is a debilitating autoimmune disease of the joints which affects many people worldwide. Up till now, there is a lack of optimal therapy against this disease. In this review article, the authors outlined in depth the current mechanism of disease for rheumatoid arthritis and described the latest research in using folic acid-targeted nanoparticles to target synovial macrophages in the fight against rheumatoid arthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

[Immunotherapy for refractory viral infections].

PubMed

Morio, Tomohiro; Fujita, Yuriko; Takahashi, Satoshi

Various antiviral agents have been developed, which are sometimes associated with toxicity, development of virus-resistant strain, and high cost. Virus-specific T-cell (VST) therapy provides an alternative curative therapy that can be effective for a prolonged time without eliciting drug resistance. VSTs can be directly separated using several types of capture devices and can be obtained by stimulating peripheral blood mononuclear cells with viral antigens (virus, protein, or peptide) loaded on antigen-presenting cells (APC). APC can be transduced with virus-antigen coding plasmid or pulsed with overlapping peptides. VST therapy has been studied in drug non-responsive viral infections after hematopoietic cell transplantation (HCT). Several previous studies have demonstrated the efficacy of VST therapy without significant severe GVHD. In addition, VSTs from a third-party donor have been prepared and administered for post-HCT viral infection. Although target viruses of VSTs include herpes virus species and polyomavirus species, a wide variety of pathogens, such as papillomavirus, intracellular bacteria, and fungi, can be treated by pathogen-specific T-cells. Perhaps, these specific T-cells could be used for opportunistic infections in other immunocompromised hosts in the near future.

Changing strategies for target therapy in gastric cancer.

PubMed

Lee, Suk-Young; Oh, Sang Cheul

2016-01-21

In spite of a worldwide decrease in the incidence of gastric cancer, this malignancy still remains one of the leading causes of cancer mortality. Great efforts have been made to improve treatment outcomes in patients with metastatic gastric cancer, and the introduction of trastuzumab has greatly improved the overall survival. The trastuzumab treatment took its first step in opening the era of molecular targeted therapy, however several issues still need to be resolved to increase the efficacy of targeted therapy. Firstly, many patients with metastatic gastric cancer who receive trastuzumab in combination with chemotherapeutic agents develop resistance to the targeted therapy. Secondly, many clinical trials testing novel molecular targeted agents with demonstrated efficacy in other malignancies have failed to show benefit in patients with metastatic gastric cancer, suggesting the importance of the selection of appropriate indications according to molecular characteristics in application of targeted agents. Herein, we review the molecular targeted agents currently approved and in use, and clinical trials in patients with metastatic gastric cancer, and demonstrate the limitations and future direction in treatment of advanced gastric cancer.

Stress in multiple sclerosis: review of new developments and future directions.

PubMed

Lovera, Jesus; Reza, Tara

2013-11-01

In the experimental autoimmune encephalitis model of multiple sclerosis, the effects of stress on disease severity depend on multiple factors, including the animal's genetics and the type of stressor. The studies in humans relating stress to the risk of developing multiple sclerosis have found discordant results. The studies looking at the association of stress with relapses show a fairly consistent association, where higher stress is associated with a higher risk of relapse. Higher stress levels also appear to increase the risk of development of gadolinium-enhancing lesions. A recent randomized trial shows that reducing stress using stress management therapy (SMT), a cognitive-behavioral therapy approach, results in a statistically significant reduction in new magnetic resonance imaging lesions. The magnitude of this effect is large and comparable to the effects of existent disease-modifying therapies, but no data exist yet proving that SMT reduces relapses or clinical progression; the effect of SMT appears to be short-lived. Additional work is needed to improve the duration of this effect and make this therapy more widely accessible.

New developments in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Pontari, Michel; Giusto, Laura

2013-11-01

To describe new developments in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome (CPPS). Symptoms in men with chronic prostatitis/CPPS appear to cluster into a group with primarily pelvic or localized disease, and a group with more systemic symptoms. Several other chronic pain conditions can be associated with chronic prostatitis/CPPS, including irritable bowel syndrome, fibromyalgia, and chronic fatigue syndrome. Markers of neurologic inflammation and autoimmune disease parallel changes in symptoms after treatment. Treatment options include new alpha-blockers, psychological intervention, and prostate-directed therapy. The areas of acupuncture and pelvic floor physical therapy/myofascial release have received increased recent attention and appear to be good options in these patients. Future therapy may include antibodies to mediators of neurogenic inflammation and even treatment of bacteria in the bowel. The diagnosis of chronic prostatitis/CPPS must include conditions traditionally outside the scope of urologic practice but important for the care of men with chronic pelvic pain. The treatment is best done using multiple simultaneous therapies aimed at the different aspects of the condition.

Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases. Comprehensive Review of the Recent Literature 2010–2012

PubMed Central

2013-01-01

A conference, “Stem Cells and Cell Therapies in Lung Biology and Lung Diseases,” was held July 25 to 28, 2011 at the University of Vermont to review the current understanding of the role of stem and progenitor cells in lung repair after injury and to review the current status of cell therapy and ex vivo bioengineering approaches for lung diseases. These are rapidly expanding areas of study that provide further insight into and challenge traditional views of mechanisms of lung repair after injury and pathogenesis of several lung diseases. The goals of the conference were to summarize the current state of the field, to discuss and debate current controversies, and to identify future research directions and opportunities for basic and translational research in cell-based therapies for lung diseases. The goal of this article, which accompanies the formal conference report, is to provide a comprehensive review of the published literature in lung regenerative medicine from the last conference report through December 2012. PMID:23869446

Synthetic lethality in DNA repair network: A novel avenue in targeted cancer therapy and combination therapeutics.

PubMed

Bhattacharjee, Sonali; Nandi, Saikat

2017-12-01

Synthetic lethality refers to a lethal phenotype that results from the simultaneous disruptions of two genes, while the disruption of either gene alone is viable. Many DNA double strand break repair (DSBR) genes have synthetic lethal relationships with oncogenes and tumor suppressor genes, which can be exploited for targeted cancer therapy, an approach referred to as combination therapy. DNA double-strand breaks (DSBs) are one of the most toxic lesions to a cell and can be repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). HR and NHEJ genes are particularly attractive targets for cancer therapy because these genes have altered expression patterns in cancer cells when compared with normal cells and these genetic abnormalities can be targeted for selectively killing cancer cells. Here, we review recent advances in the development of small molecule inhibitors against HR and NHEJ genes to induce synthetic lethality and address the future directions and clinical relevance of this approach. © 2017 IUBMB Life, 69(12):929-937, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Adjuvant therapy for resected colon cancer 2017, including the IDEA analysis.

PubMed

Tang, Monica; Price, Timothy Jay; Shapiro, Jeremy; Gibbs, Peter; Haller, Daniel G; Arnold, Dirk; Peeters, Marc; Segelov, Eva; Roy, Amitesh; Tebbutt, Niall; Pavlakis, Nick; Karapetis, Chris; Burge, Matthew

2018-04-01

Oxaliplatin-based adjuvant chemotherapy has been the standard of care for resected early colon cancer for over a decade. Recent results from the IDEA meta-analysis attempt to address the question of whether 3 or 6 months of adjuvant chemotherapy is preferable in Stage III colon cancer. Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of adjuvant therapy for resected early colon cancers. This article reviews the current evidence for adjuvant treatment of Stage II and III colon cancer, as well as up-to-date data regarding optimal duration of therapy. This article reviews the evidence for lifestyle modifications in the management of early colorectal cancer and other future directions for research in early colon cancer. Expert commentary: In recent years, there have been no advances in the development of novel agents for adjuvant therapy in colorectal cancer. Although the IDEA meta-analysis was negative for its primary non-inferiority endpoint, the detailed results provide valuable information that allows personalisation of treatment regimen and duration.

Treatment of obsessive morbid jealousy with cognitive analytic therapy: An adjudicated hermeneutic single-case efficacy design evaluation.

PubMed

Curling, Louise; Kellett, Stephen; Totterdell, Peter; Parry, Glenys; Hardy, Gillian; Berry, Katherine

2018-03-01

The evidence base for the treatment of morbid jealousy with integrative therapies is thin. This study explored the efficacy of cognitive analytic therapy (CAT). An adjudicated hermeneutic single-case efficacy design evaluated the cognitive analytic treatment of a patient meeting diagnostic criteria for obsessive morbid jealousy. A rich case record was developed using a matrix of nomothetic and ideographic quantitative and qualitative outcomes. This record was then debated by sceptic and affirmative research teams. Experienced psychotherapy researchers acted as judges, assessed the original case record, and heard the affirmative-versus-sceptic debate. Judges pronounced an opinion regarding the efficacy of the therapy. The efficacy of CAT was supported by all three judges. Each ruled that change had occurred due to the action of the therapy, beyond any level of reasonable doubt. This research demonstrates the potential usefulness of CAT in treating morbid jealousy and suggests that CAT is conceptually well suited. Suggestions for future clinical and research directions are provided. The relational approach of CAT makes it a suitable therapy for morbid jealousy. The narrative reformulation component of CAT appears to facilitate early change in chronic jealousy patterns. It is helpful for therapists during sessions to use CAT theory to diagrammatically spell out the patterns maintaining jealousy. © 2017 The British Psychological Society.

Viral vectors for therapy of neurologic diseases

PubMed Central

Choudhury, Sourav R.; Hudry, Eloise; Maguire, Casey A.; Sena-Esteves, Miguel; Breakefield, Xandra O.; Grandi, Paola

2018-01-01

Neurological disorders – disorders of the brain, spine and associated nerves – are a leading contributor to global disease burden with a shockingly large associated economic cost. Various treatment approaches – pharmaceutical medication, device-based therapy, physiotherapy, surgical intervention, among others – have been explored to alleviate the resulting extent of human suffering. In recent years, gene therapy using viral vectors – encoding a therapeutic gene or inhibitory RNA into a “gutted” viral capsid and supplying it to the nervous system – has emerged as a clinically viable option for therapy of brain disorders. In this Review, we provide an overview of the current state and advances in the field of viral vector-mediated gene therapy for neurological disorders. Vector tools and delivery methods have evolved considerably over recent years, with the goal of providing greater and safer genetic access to the central nervous system. Better etiological understanding of brain disorders has concurrently led to identification of improved therapeutic targets. We focus on the vector technology, as well as preclinical and clinical progress made thus far for brain cancer and various neurodegenerative and neurometabolic disorders, and point out the challenges and limitations that accompany this new medical modality. Finally, we explore the directions that neurological gene therapy is likely to evolve towards in the future. PMID:26905292

Pharmacogenetics of novel oral anticoagulants: a review of identified gene variants & future perspectives.

PubMed

Ašić, Adna; Marjanović, Damir; Mirat, Jure; Primorac, Dragan

2018-05-16

Novel oral anticoagulants (NOACs) are becoming a therapy of choice in everyday clinical practice after almost 50 years during which warfarin and related coumarin derivatives were used as the main anticoagulants. Advantages of NOACs over standard anticoagulants include their predictable pharmacodynamics and pharmacokinetics, stable plasma concentrations and less drug-drug and food-drug interactions. However, pharmacogenetics has its place in administration of NOACs, as considerable interindividual variations have been detected. In this review, previous findings in pharmacogenetics of dabigatran, rivaroxaban, apixaban and edoxaban are summarized, along with recommendations for studying genes encoding metabolically important enzymes for four selected NOACs. Future directions include identification of clinically relevant SNPs, and change in optimum dosage for patients who are carriers of significant variants.

Sulfur mustard skin lesions: A systematic review on pathomechanisms, treatment options and future research directions.

PubMed

Rose, Dorothee; Schmidt, Annette; Brandenburger, Matthias; Sturmheit, Tabea; Zille, Marietta; Boltze, Johannes

2018-09-01

Sulfur mustard (SM) is a chemical warfare, which has been used for one hundred years. However, its exact pathomechanisms are still incompletely understood and there is no specific therapy available so far. In this systematic review, studies published between January 2000 and July 2017 involving pathomechanisms and experimental treatments of SM-induced skin lesions were analyzed to summarize current knowledge on SM pathology, to provide an overview on novel treatment options, and to identify promising targets for future research to more effectively counter SM effects. We suggest that future studies should focus on (I) systemic effects of SM intoxication due to its distribution throughout the body, (II) removal of SM depots that continuously release active compound contributing to chronic skin damage, and (III) therapeutic options that counteract the pleiotropic effects of SM. Copyright © 2017 Elsevier B.V. All rights reserved.

Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy.

PubMed

Rose, Jason J; Wang, Ling; Xu, Qinzi; McTiernan, Charles F; Shiva, Sruti; Tejero, Jesus; Gladwin, Mark T

2017-03-01

Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. The clinical presentation runs a spectrum, ranging from headache and dizziness to coma and death, with a mortality rate ranging from 1 to 3%. A significant number of patients who survive CO poisoning suffer from long-term neurological and affective sequelae. The neurologic deficits do not necessarily correlate with blood CO levels but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation, and free radical generation, especially in the brain and heart. Long-term neurocognitive deficits occur in 15-40% of patients, whereas approximately one-third of moderate to severely poisoned patients exhibit cardiac dysfunction, including arrhythmia, left ventricular systolic dysfunction, and myocardial infarction. Imaging studies reveal cerebral white matter hyperintensities, with delayed posthypoxic leukoencephalopathy or diffuse brain atrophy. Management of these patients requires the identification of accompanying drug ingestions, especially in the setting of intentional poisoning, fire-related toxic gas exposures, and inhalational injuries. Conventional therapy is limited to normobaric and hyperbaric oxygen, with no available antidotal therapy. Although hyperbaric oxygen significantly reduces the permanent neurological and affective effects of CO poisoning, a portion of survivors still have substantial morbidity. There has been some early success in therapies targeting the downstream inflammatory and oxidative effects of CO poisoning. New methods to directly target the toxic effect of CO, such as CO scavenging agents, are currently under development.

Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy

PubMed Central

Xu, Qinzi; Shiva, Sruti

2017-01-01

Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. The clinical presentation runs a spectrum, ranging from headache and dizziness to coma and death, with a mortality rate ranging from 1 to 3%. A significant number of patients who survive CO poisoning suffer from long-term neurological and affective sequelae. The neurologic deficits do not necessarily correlate with blood CO levels but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation, and free radical generation, especially in the brain and heart. Long-term neurocognitive deficits occur in 15–40% of patients, whereas approximately one-third of moderate to severely poisoned patients exhibit cardiac dysfunction, including arrhythmia, left ventricular systolic dysfunction, and myocardial infarction. Imaging studies reveal cerebral white matter hyperintensities, with delayed posthypoxic leukoencephalopathy or diffuse brain atrophy. Management of these patients requires the identification of accompanying drug ingestions, especially in the setting of intentional poisoning, fire-related toxic gas exposures, and inhalational injuries. Conventional therapy is limited to normobaric and hyperbaric oxygen, with no available antidotal therapy. Although hyperbaric oxygen significantly reduces the permanent neurological and affective effects of CO poisoning, a portion of survivors still have substantial morbidity. There has been some early success in therapies targeting the downstream inflammatory and oxidative effects of CO poisoning. New methods to directly target the toxic effect of CO, such as CO scavenging agents, are currently under development. PMID:27753502

Carcinomatous meningitis: Leptomeningeal metastases in solid tumors

PubMed Central

Le Rhun, Emilie; Taillibert, Sophie; Chamberlain, Marc C.

2013-01-01

Leptomeningeal metastasis (LM) results from metastatic spread of cancer to the leptomeninges, giving rise to central nervous system dysfunction. Breast cancer, lung cancer, and melanoma are the most frequent causes of LM among solid tumors in adults. An early diagnosis of LM, before fixed neurologic deficits are manifest, permits earlier and potentially more effective treatment, thus leading to a better quality of life in patients so affected. Apart from a clinical suspicion of LM, diagnosis is dependent upon demonstration of cancer in cerebrospinal fluid (CSF) or radiographic manifestations as revealed by neuraxis imaging. Potentially of use, though not commonly employed, today are use of biomarkers and protein profiling in the CSF. Symptomatic treatment is directed at pain including headache, nausea, and vomiting, whereas more specific LM-directed therapies include intra-CSF chemotherapy, systemic chemotherapy, and site-specific radiotherapy. A special emphasis in the review discusses novel agents including targeted therapies, that may be promising in the future management of LM. These new therapies include anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib in nonsmall cell lung cancer, anti-HER2 monoclonal antibody trastuzumab in breast cancer, anti-CTLA4 ipilimumab and anti-BRAF tyrosine kinase inhibitors such as vermurafenib in melanoma, and the antivascular endothelial growth factor monoclonal antibody bevacizumab are currently under investigation in patients with LM. Challenges of managing patients with LM are manifold and include determining the appropriate patients for treatment as well as the optimal route of administration of intra-CSF drug therapy. PMID:23717798

Making it stick: chasing the optimal stem cells for cardiac regeneration

PubMed Central

Quijada, Pearl; Sussman, Mark A

2014-01-01

Despite the increasing use of stem cells for regenerative-based cardiac therapy, the optimal stem cell population(s) remains in a cloud of uncertainty. In the past decade, the field has witnessed a surge of researchers discovering stem cell populations reported to directly and/or indirectly contribute to cardiac regeneration through processes of cardiomyogenic commitment and/or release of cardioprotective paracrine factors. This review centers upon defining basic biological characteristics of stem cells used for sustaining cardiac integrity during disease and maintenance of communication between the cardiac environment and stem cells. Given the limited successes achieved so far in regenerative therapy, the future requires development of unprecedented concepts involving combinatorial approaches to create and deliver the optimal stem cell(s) that will enhance myocardial healing. PMID:25340282

The Application of Microencapsulation Techniques in the Treatment of Endodontic and Periodontal Disease

PubMed Central

Álvarez, Asteria Luzardo; Espinar, Francisco Otero; Méndez, José Blanco

2011-01-01

In the treatment of intracanal and periodontal infections, the local application of antibiotics and other therapeutic agents in the root canal or in periodontal pockets may be a promising approach to achieve sustained drug release, high antimicrobial activity and low systemic side effects. Microparticles made from biodegradable polymers have been reported to be an effective means of delivering antibacterial drugs in endodontic and periodontal therapy. The aim of this review article is to assess recent therapeutic strategies in which biocompatible microparticles are used for effective management of periodontal and endodontic diseases. In vitro and in vivo studies that have investigated the biocompatibility or efficacy of certain microparticle formulations and devices are presented. Future directions in the application of microencapsulation techniques in endodontic and periodontal therapies are discussed. PMID:24310596

An introduction to minimally invasive therapy.

PubMed

Wickham, J E

1993-01-01

Minimally invasive therapy (MIT) has as its basic premise the reduction of iatrogenic trauma to the patient by surgeon, physician or radiologist. This approach must also imply that the therapeutic procedure succeeds in its aim of cure in a manner no less effective than is currently achievable by established methods of treatment. Acceptance of this principal has many identifiable sequelae, including profound changes in hospital design, increasingly expensive technological instrumentation, more sophisticated teaching and learning patterns, and a massive redirection of health care financial resources. These changes cannot be contemplated at leisure, because they are dynamically imperative and progressing with relentless rapidity, being directly driven by the consumer. It is vital that this shift in clinical emphasis should be appreciated so that future planning can be undertaken with some rationality.

Recent Developments of Liposomes as Nanocarriers for Theranostic Applications

PubMed Central

Xing, Hang; Hwang, Kevin; Lu, Yi

2016-01-01

Liposomes are nanocarriers comprised of lipid bilayers encapsulating an aqueous core. The ability of liposomes to encapsulate a wide variety of diagnostic and therapeutic agents has led to significant interest in utilizing liposomes as nanocarriers for theranostic applications. In this review, we highlight recent progress in developing liposomes as nanocarriers for a) diagnostic applications to detect proteins, DNA, and small molecule targets using fluorescence, magnetic resonance, ultrasound, and nuclear imaging; b) therapeutic applications based on small molecule-based therapy, gene therapy and immunotherapy; and c) theranostic applications for simultaneous detection and treatment of heavy metal toxicity and cancers. In addition, we summarize recent studies towards understanding of interactions between liposomes and biological components. Finally, perspectives on future directions in advancing the field for clinical translations are also discussed. PMID:27375783

Management of patients with pulmonary arterial hypertension due to congenital heart disease: recent advances and future directions.

PubMed

Blok, Ilja M; van Riel, Annelieke C M J; Mulder, Barbara J M; Bouma, Berto J

2015-12-01

Pulmonary arterial hypertension is a serious complication of adult congenital heart disease associated with systemic-to-pulmonary shunts. Although early shunt closure restricts development of pulmonary arterial hypertension, patients remain at risk even after repair. The development of pulmonary arterial hypertension is associated with a markedly increased morbidity and mortality. It is important to identify patients with a poor prognosis using disease specific markers. Echocardiography and biomarkers arise as practical tools to determine the risk of mortality. Although pulmonary arterial hypertension cannot be cured, four classes of disease-targeting therapies are currently available and several promising therapies are being studied. There is a shift in drug studies towards more clinically relevant endpoints such as time to clinical worsening and morbidity and mortality events.

Anti-EGFR Agents: Current Status, Forecasts and Future Directions.

PubMed

Kwapiszewski, Radoslaw; Pawlak, Sebastian D; Adamkiewicz, Karolina

2016-12-01

The epidermal growth factor receptor (EGFR) is one of the most important and attractive targets for specific anticancer therapies. It is a robust regulator of pathways involved in cancer pathogenesis and progression. Thus far, clinical trials have demonstrated the benefits of monoclonal antibodies and synthetic tyrosine kinase inhibitors in targeting this receptor; however, novel strategies are still being developed. This article reviews the current state of efforts in targeting the EGFR in cancer therapy. Following a brief characterization of EGFR, we will present a complete list of anti-EGFR agents that are already approved, and available in clinical practice. Aside from the indications, we will present the sales forecasts and expiry dates of product patents for the selected agents. Finally, we discuss the novel anti-EGFR strategies that are currently in preclinical development.

Occlusion dose monitoring in amblyopia therapy: status, insights, and future directions.

PubMed

Stewart, Catherine E; Moseley, Merrick J; Georgiou, Pantelis; Fielder, Alistair R

2017-10-01

Occlusion therapy remains the mainstay treatment of amblyopia, but its outcome is not assured or universally excellent. Many factors are known to influence treatment outcome, among which compliance is foremost. The occlusion dose monitor (ODM) removes one variable from the treatment equation, because it records the occlusion actually received by-rather than prescribed for-the child. Improvement observed can thus be quantitatively related to the patching received. This review summarizes the insights the ODM has provided to date particularly in elucidating the dose-response relationship. We are entering the era of personalized ophthalmology in which treatments will be tailored to the needs of the individual child and facilitated by the use of wearable monitors. Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

Direct access compared with referred physical therapy episodes of care: a systematic review.

PubMed

Ojha, Heidi A; Snyder, Rachel S; Davenport, Todd E

2014-01-01

Evidence suggests that physical therapy through direct access may help decrease costs and improve patient outcomes compared with physical therapy by physician referral. The purpose of this study was to conduct a systematic review of the literature on patients with musculoskeletal injuries and compare health care costs and patient outcomes in episodes of physical therapy by direct access compared with referred physical therapy. Ovid MEDLINE, CINAHL (EBSCO), Web of Science, and PEDro were searched using terms related to physical therapy and direct access. Included articles were hand searched for additional references. Included studies compared data from physical therapy by direct access with physical therapy by physician referral, studying cost, outcomes, or harm. The studies were appraised using the Centre for Evidence-Based Medicine (CEBM) levels of evidence criteria and assigned a methodological score. Of the 1,501 articles that were screened, 8 articles at levels 3 to 4 on the CEBM scale were included. There were statistically significant and clinically meaningful findings across studies that satisfaction and outcomes were superior, and numbers of physical therapy visits, imaging ordered, medications prescribed, and additional non-physical therapy appointments were less in cohorts receiving physical therapy by direct access compared with referred episodes of care. There was no evidence for harm. There is evidence across level 3 and 4 studies (grade B to C CEBM level of recommendation) that physical therapy by direct access compared with referred episodes of care is associated with improved patient outcomes and decreased costs. Primary limitations were lack of group randomization, potential for selection bias, and limited generalizability. Physical therapy by way of direct access may contain health care costs and promote high-quality health care. Third-party payers should consider paying for physical therapy by direct access to decrease health care costs and incentivize optimal patient outcomes.

The experience of adjusting to a diagnosis of non-epileptic attack disorder (NEAD) and the subsequent process of psychological therapy.

PubMed

Wyatt, Caroline; Laraway, Alec; Weatherhead, Stephen

2014-10-01

Research suggests psychological therapy as the treatment of choice for individuals diagnosed with NEAD. This study explored the experience of adjusting to a diagnosis of NEAD and engagement with therapy through a qualitative methodology. Semi-structured interviews were conducted with 6 people with a diagnosis of NEAD and analysed using thematic analysis. Six master-themes were generated, with four discussed. Two themes were not discussed due to previous coverage in the literature and their less direct relevance to the service context. Theme 1: 'understanding NEAD' incorporated participants' evolving understanding of the diagnosis and their reflections on this. Theme 2: 'I can't deal with you' centres on participants' accounts of relationships with professionals in the context of NEAD. Theme 3: 'experiences of psychological therapy' reflected participants' experience of being referred to psychology and gaining a deeper understanding of themselves through therapy. Theme 4: 'adjusting to life with NEAD' explores participants' views on living with NEAD and their expectations for the future. This study extended previous research by highlighting the impact of how the diagnosis is received and understood on engagement in therapy. Improving awareness of NEAD amongst healthcare professionals is of key importance in reducing stigma and encouraging engagement in therapy. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Microdosimetry in ion-beam therapy

NASA Astrophysics Data System (ADS)

Magrin, Giulio; Mayer, Ramona

2015-06-01

The information of the dose is not sufficiently describing the biological effects of ions on tissue since it does not express the radiation quality, i.e. the heterogeneity of the processes due to the slowing-down and the fragmentation of the particles when crossing a target. Depending on different circumstances, the radiation quality can be determined using measurements, calculations, or simulations. Microdosimeters are the primary tools used to provide the experimental information of the radiation quality and their role is becoming crucial for the recent clinical developments in particular with carbon ion therapy. Microdosimetry is strongly linked to the biological effectiveness of the radiation since it provides the physical parameters which explicitly distinguish the radiation for its capability of damaging cells. In the framework of ion-beam therapy microdosimetry can be used in the preparation of the treatment to complement radiobiological experiments and to analyze the modification of the radiation quality in phantoms. A more ambitious goal is to perform the measurements during the irradiation procedure to determine the non-targeted radiation and, more importantly, to monitor the modification of the radiation quality inside the patient. These procedures provide the feedback of the treatment directly beneficial for the single patient but also for the characterization of the biological effectiveness in general with advantages for all future treatment. Traditional and innovative tools are currently under study and an outlook of present experience and future development is presented here.

Image-guided surgery and therapy: current status and future directions

NASA Astrophysics Data System (ADS)

Peters, Terence M.

2001-05-01

Image-guided surgery and therapy is assuming an increasingly important role, particularly considering the current emphasis on minimally-invasive surgical procedures. Volumetric CT and MR images have been used now for some time in conjunction with stereotactic frames, to guide many neurosurgical procedures. With the development of systems that permit surgical instruments to be tracked in space, image-guided surgery now includes the use of frame-less procedures, and the application of the technology has spread beyond neurosurgery to include orthopedic applications and therapy of various soft-tissue organs such as the breast, prostate and heart. Since tracking systems allow image- guided surgery to be undertaken without frames, a great deal of effort has been spent on image-to-image and image-to- patient registration techniques, and upon the means of combining real-time intra-operative images with images acquired pre-operatively. As image-guided surgery systems have become increasingly sophisticated, the greatest challenges to their successful adoption in the operating room of the future relate to the interface between the user and the system. To date, little effort has been expended to ensure that the human factors issues relating to the use of such equipment in the operating room have been adequately addressed. Such systems will only be employed routinely in the OR when they are designed to be intuitive, unobtrusive, and provide simple access to the source of the images.

Tissue engineering: current strategies and future directions.

PubMed

Olson, Jennifer L; Atala, Anthony; Yoo, James J

2011-04-01

Novel therapies resulting from regenerative medicine and tissue engineering technology may offer new hope for patients with injuries, end-stage organ failure, or other clinical issues. Currently, patients with diseased and injured organs are often treated with transplanted organs. However, there is a shortage of donor organs that is worsening yearly as the population ages and as the number of new cases of organ failure increases. Scientists in the field of regenerative medicine and tissue engineering are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that can restore and maintain normal function in diseased and injured tissues. In addition, the stem cell field is a rapidly advancing part of regenerative medicine, and new discoveries in this field create new options for this type of therapy. For example, new types of stem cells, such as amniotic fluid and placental stem cells that can circumvent the ethical issues associated with embryonic stem cells, have been discovered. The process of therapeutic cloning and the creation of induced pluripotent cells provide still other potential sources of stem cells for cell-based tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous, adult cells have already entered the clinical setting, indicating that regenerative medicine holds much promise for the future.

Gene Therapy Delivery Systems for Enhancing Viral and Nonviral Vectors for Cardiac Diseases: Current Concepts and Future Applications

PubMed Central

Katz, Michael G.; Fargnoli, Anthony S.; Williams, Richard D.

2013-01-01

Abstract Gene therapy is one of the most promising fields for developing new treatments for the advanced stages of ischemic and monogenetic, particularly autosomal or X-linked recessive, cardiomyopathies. The remarkable ongoing efforts in advancing various targets have largely been inspired by the results that have been achieved in several notable gene therapy trials, such as the hemophilia B and Leber's congenital amaurosis. Rate-limiting problems preventing successful clinical application in the cardiac disease area, however, are primarily attributable to inefficient gene transfer, host responses, and the lack of sustainable therapeutic transgene expression. It is arguable that these problems are directly correlated with the choice of vector, dose level, and associated cardiac delivery approach as a whole treatment system. Essentially, a delicate balance exists in maximizing gene transfer required for efficacy while remaining within safety limits. Therefore, the development of safe, effective, and clinically applicable gene delivery techniques for selected nonviral and viral vectors will certainly be invaluable in obtaining future regulatory approvals. The choice of gene transfer vector, dose level, and the delivery system are likely to be critical determinants of therapeutic efficacy. It is here that the interactions between vector uptake and trafficking, delivery route means, and the host's physical limits must be considered synergistically for a successful treatment course. PMID:24164239

Image-guided radiation therapy in lymphoma management

PubMed Central

Eng, Tony

2015-01-01

Image-guided radiation therapy (IGRT) is a process of incorporating imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), Positron emission tomography (PET), and ultrasound (US) during radiation therapy (RT) to improve treatment accuracy. It allows real-time or near real-time visualization of anatomical information to ensure that the target is in its position as planned. In addition, changes in tumor volume and location due to organ motion during treatment can be also compensated. IGRT has been gaining popularity and acceptance rapidly in RT over the past 10 years, and many published data have been reported on prostate, bladder, head and neck, and gastrointestinal cancers. However, the role of IGRT in lymphoma management is not well defined as there are only very limited published data currently available. The scope of this paper is to review the current use of IGRT in the management of lymphoma. The technical and clinical aspects of IGRT, lymphoma imaging studies, the current role of IGRT in lymphoma management and future directions will be discussed. PMID:26484299

Stem cell therapy for retinal diseases

PubMed Central

Garcia, José Mauricio; Mendonça, Luisa; Brant, Rodrigo; Abud, Murilo; Regatieri, Caio; Diniz, Bruno

2015-01-01

In this review, we discuss about current knowledge about stem cell (SC) therapy in the treatment of retinal degeneration. Both human embryonic stem cell and induced pluripotent stem cell has been growth in culture for a long time, and started to be explored in the treatment of blinding conditions. The Food and Drug Administration, recently, has granted clinical trials using SC retinal therapy to treat complex disorders, as Stargardt’s dystrophy, and patients with geographic atrophy, providing good outcomes. This study’s intent is to overview the critical regeneration of the subretinal anatomy through retinal pigment epithelium transplantation, with the goal of reestablish important pathways from the retina to the occipital cortex of the brain, as well as the differentiation from pluripotent quiescent SC to adult retina, and its relationship with a primary retinal injury, different techniques of transplantation, management of immune rejection and tumorigenicity, its potential application in improving patients’ vision, and, finally, approaching future directions and challenges for the treatment of several conditions. PMID:25621115

The Gene Therapy Resource Program: A Decade of Dedication to Translational Research by the National Heart, Lung, and Blood Institute.

PubMed

Flotte, Terence R; Daniels, Eric; Benson, Janet; Bevett-Rose, Jeneé M; Cornetta, Kenneth; Diggins, Margaret; Johnston, Julie; Sepelak, Susan; van der Loo, Johannes C M; Wilson, James M; McDonald, Cheryl L

2017-12-01

Over a 10-year period, the Gene Therapy Resource Program (GTRP) of the National Heart Lung and Blood Institute has provided a set of core services to investigators to facilitate the clinical translation of gene therapy. These services have included a preclinical (research-grade) vector production core; current Good Manufacturing Practice clinical-grade vector cores for recombinant adeno-associated virus and lentivirus vectors; a pharmacology and toxicology core; and a coordinating center to manage program logistics and to provide regulatory and financial support to early-phase clinical trials. In addition, the GTRP has utilized a Steering Committee and a Scientific Review Board to guide overall progress and effectiveness and to evaluate individual proposals. These resources have been deployed to assist 82 investigators with 172 approved service proposals. These efforts have assisted in clinical trial implementation across a wide range of genetic, cardiac, pulmonary, and blood diseases. Program outcomes and potential future directions of the program are discussed.

Chimeric Antigen Receptor-Modified T Cells for Solid Tumors: Challenges and Prospects

PubMed Central

Guo, Yelei; Wang, Yao; Han, Weidong

2016-01-01

Recent studies have highlighted the successes of chimeric antigen receptor-modified T- (CART-) cell-based therapy for B-cell malignancies, and early phase clinical trials have been launched in recent years. The few published clinical studies of CART cells in solid tumors have addressed safety and feasibility, but the clinical outcome data are limited. Although antitumor effects were confirmed in vitro and in animal models, CART-cell-based therapy still faces several challenges when directed towards solid tumors, and it has been difficult to achieve the desired outcomes in clinical practice. Many studies have struggled to improve the clinical responses to and benefits of CART-cell treatment of solid tumors. In this review, the status quo of CART cells and their clinical applications for solid tumors will be summarized first. Importantly, we will suggest improvements that could increase the therapeutic effectiveness of CART cells for solid tumors and their future clinical applications. These interventions will make treatment with CART cells an effective and routine therapy for solid tumors. PMID:26998495

Future directions in lipid therapies.

PubMed

Ansell, Benjamin

2002-01-01

Cholesterol management to reduce the burden of cardiovascular disease is a major public health concern. Despite widespread recognition of lipid abnormalities as cardiovascular risk factors, significant cardiovascular event reductions with cholesterol-lowering therapies, and dissemination of treatment guidelines, most high-risk patients are not at target lipid levels. In addition to lifestyle changes, four major drug classes are available to modify lipid levels: fibrates, niacin, resins, and statins. High efficacy and tolerability in clinical trials make statins the most widely prescribed of these agents. Newer, more potent members of this class and novel formulations of niacin and resins may provide more effective therapy for dyslipidemia with fewer side effects. Several agents in development (cholesterol-absorption inhibitors and ACAT inhibitors) exploit mechanisms of action complementary to those of current treatments and combined with statins may produce greater improvements in lipid profiles than are now possible. These innovations should enable a greater number of patients to achieve more aggressive cholesterol goals, thereby reducing the risk of cardiovascular events.

50 years of rational-emotive and cognitive-behavioral therapy: A systematic review and meta-analysis.

PubMed

David, Daniel; Cotet, Carmen; Matu, Silviu; Mogoase, Cristina; Stefan, Simona

2018-03-01

Rational emotive behavior therapy (REBT), introduced by Albert Ellis in the late 1950s, is one of the main pillars of cognitive-behavioral therapy. Existing reviews on REBT are overdue by 10 years or more. We aimed to summarize the effectiveness and efficacy of REBT since its beginnings and investigate the alleged mechanisms of change. Systematic search identified 84 articles, out of which 68 provided data for between-group analyses and 39 for within-group analyses. We found a medium effect size of REBT compared to other interventions on outcomes (d = 0.58) and on irrational beliefs (d = 0.70), at posttest. For the within-group analyses, we obtained medium effects for both outcomes (d = 0.56) and irrational beliefs (d = 0.61). Several significant moderators emerged. REBT is a sound psychological intervention. Directions for future studies are outlined, stemming from the limitations of existing ones. © 2017 The Authors. Journal of Clinical Psychology published by Wiley Periodicals, Inc.

ALS Biomarkers for Therapy Development: State of the Field & Future Directions

PubMed Central

Benatar, Michael; Boylan, Kevin; Jeromin, Andreas; Rutkove, Seward B.; Berry, James; Atassi, Nazem; Bruijn, Lucie

2015-01-01

Biomarkers have become the focus of intense research in the field of amyotrophic lateral sclerosis (ALS), with the hope that they might aid therapy development efforts. Notwithstanding the discovery of many candidate biomarkers, none have yet emerged as validated tools for drug development. In this review we present a nuanced view of biomarkers based on the perspective of the FDA; highlight the distinction between discovery and validation; describe existing and emerging resources; review leading biological fluid-based, electrophysiological and neuroimaging candidates relevant to therapy development efforts; discuss lessons learned from biomarker initiatives in related neurodegenerative diseases; and outline specific steps that we, as a field, might take in order to hasten the development and validation of biomarkers that will prove useful in enhancing efforts to develop effective treatments for ALS patients. Most important among these perhaps is the proposal to establish a federated ALS Biomarker Consortium (ABC) in which all interested and willing stakeholders may participate with equal opportunity to contribute to the broader mission of biomarker development and validation. PMID:26574709

Gene Therapy for Hemophilia.

PubMed

Nienhuis, Arthur W; Nathwani, Amit C; Davidoff, Andrew M

2017-05-03

The X-linked bleeding disorder hemophilia causes frequent and exaggerated bleeding that can be life-threatening if untreated. Conventional therapy requires frequent intravenous infusions of the missing coagulation protein (factor VIII [FVIII] for hemophilia A and factor IX [FIX] for hemophilia B). However, a lasting cure through gene therapy has long been sought. After a series of successes in small and large animal models, this goal has finally been achieved in humans by in vivo gene transfer to the liver using adeno-associated viral (AAV) vectors. In fact, multiple recent clinical trials have shown therapeutic, and in some cases curative, expression. At the same time, cellular immune responses against the virus have emerged as an obstacle in humans, potentially resulting in loss of expression. Transient immune suppression protocols have been developed to blunt these responses. Here, we provide an overview of the clinical development of AAV gene transfer for hemophilia, as well as an outlook on future directions. Copyright © 2017. Published by Elsevier Inc.

Targeted Therapies for Advanced Oesophagogastric Cancer: Recent Progress and Future Directions.

PubMed

Young, Kate; Chau, Ian

2016-01-01

The genomic landscape of oesophagogastric (OG) cancer is highly complex. The recent elucidation of some of the pathways involved has suggested a number of novel targets for therapy. This therapy is urgently required as with conventional chemotherapy regimens patients with advanced OG cancer still have a median overall survival of under a year. This review outlines the rationale for the current treatment of OG cancer with chemotherapy and describes both previously conducted and ongoing clinical trials of novel agents in this area. The targets and associated treatments discussed include HER-2, EGFR, VEGF, c-Met, FGFR-2, PI3K, mTOR andIGF-1. To date only two targeted treatments, trastuzumab and ramucirumab, have become part of the treatment paradigm for OG cancer, partly due to difficulties in defining predictive biomarkers in this disease. However, there are a number of promising drugs in the pipeline and this article seeks to describe these and other potential novel approaches including targeting DNA repair deficiencies and the immune system.

Improving therapy of chronic lymphocytic leukemia with chimeric antigen receptor T cells.

PubMed

Fraietta, Joseph A; Schwab, Robert D; Maus, Marcela V

2016-04-01

Adoptive cell immunotherapy for the treatment of chronic lymphocytic leukemia (CLL) has heralded a new era of synthetic biology. The infusion of genetically engineered, autologous chimeric antigen receptor (CAR) T cells directed against CD19 expressed by normal and malignant B cells represents a novel approach to cancer therapy. The results of recent clinical trials of CAR T cells in relapsed and refractory CLL have demonstrated long-term disease-free remissions, underscoring the power of harnessing and redirecting the immune system against cancer. This review will briefly summarize T-cell therapies in development for CLL disease. We discuss the role of T-cell function and phenotype, T-cell culture optimization, CAR design, and approaches to potentiate the survival and anti-tumor effects of infused lymphocytes. Future efforts will focus on improving the efficacy of CAR T cells for the treatment of CLL and incorporating adoptive cell immunotherapy into standard medical management of CLL. Copyright © 2016 Elsevier Inc. All rights reserved.

The therapeutic and diagnostic potential of the prostate specific membrane antigen/glutamate carboxypeptidase II (PSMA/GCPII) in cancer and neurological disease

PubMed Central

Evans, James C; Malhotra, Meenakshi; Cryan, John F

2016-01-01

Prostate specific membrane antigen (PSMA) otherwise known as glutamate carboxypeptidase II (GCPII) is a membrane bound protein that is highly expressed in prostate cancer and in the neovasculature of a wide variety of tumours including glioblastomas, breast and bladder cancers. This protein is also involved in a variety of neurological diseases including schizophrenia and ALS. In recent years, there has been a surge in the development of both diagnostics and therapeutics that take advantage of the expression and activity of PSMA/GCPII. These include gene therapy, immunotherapy, chemotherapy and radiotherapy. In this review, we discuss the biological roles that PSMA/GCPII plays, both in normal and diseased tissues, and the current therapies exploiting its activity that are at the preclinical stage. We conclude by giving an expert opinion on the future direction of PSMA/GCPII based therapies and diagnostics and hurdles that need to be overcome to make them effective and viable. PMID:27526115

Personalized Medicine for Chronic Respiratory Infectious Diseases: Tuberculosis, Nontuberculous Mycobacterial Pulmonary Diseases, and Chronic Pulmonary Aspergillosis.

PubMed

Salzer, Helmut J F; Wassilew, Nasstasja; Köhler, Niklas; Olaru, Ioana D; Günther, Gunar; Herzmann, Christian; Kalsdorf, Barbara; Sanchez-Carballo, Patricia; Terhalle, Elena; Rolling, Thierry; Lange, Christoph; Heyckendorf, Jan

2016-01-01

Chronic respiratory infectious diseases are causing high rates of morbidity and mortality worldwide. Tuberculosis, a major cause of chronic pulmonary infection, is currently responsible for approximately 1.5 million deaths per year. Although important advances in the fight against tuberculosis have been made, the progress towards eradication of this disease is being challenged by the dramatic increase in multidrug-resistant bacilli. Nontuberculous mycobacteria causing pulmonary disease and chronic pulmonary aspergillosis are emerging infectious diseases. In contrast to other infectious diseases, chronic respiratory infections share the trait of having highly variable treatment outcomes despite longstanding antimicrobial therapy. Recent scientific progress indicates that medicine is presently at a transition stage from programmatic to personalized management. We explain current state-of-the-art management concepts of chronic pulmonary infectious diseases as well as the underlying methods for therapeutic decisions and their implications for personalized medicine. Furthermore, we describe promising biomarkers and techniques with the potential to serve future individual treatment concepts in this field of difficult-to-treat patients. These include candidate markers to improve individual risk assessment for disease development, the design of tailor-made drug therapy regimens, and individualized biomarker-guided therapy duration to achieve relapse-free cure. In addition, the use of therapeutic drug monitoring to reach optimal drug dosing with the smallest rate of adverse events as well as candidate agents for future host-directed therapies are described. Taken together, personalized medicine will provide opportunities to substantially improve the management and treatment outcome of difficult-to-treat patients with chronic respiratory infections. © 2016 S. Karger AG, Basel.

Quantitative imaging as cancer biomarker

NASA Astrophysics Data System (ADS)

Mankoff, David A.

2015-03-01

The ability to assay tumor biologic features and the impact of drugs on tumor biology is fundamental to drug development. Advances in our ability to measure genomics, gene expression, protein expression, and cellular biology have led to a host of new targets for anticancer drug therapy. In translating new drugs into clinical trials and clinical practice, these same assays serve to identify patients most likely to benefit from specific anticancer treatments. As cancer therapy becomes more individualized and targeted, there is an increasing need to characterize tumors and identify therapeutic targets to select therapy most likely to be successful in treating the individual patient's cancer. Thus far assays to identify cancer therapeutic targets or anticancer drug pharmacodynamics have been based upon in vitro assay of tissue or blood samples. Advances in molecular imaging, particularly PET, have led to the ability to perform quantitative non-invasive molecular assays. Imaging has traditionally relied on structural and anatomic features to detect cancer and determine its extent. More recently, imaging has expanded to include the ability to image regional biochemistry and molecular biology, often termed molecular imaging. Molecular imaging can be considered an in vivo assay technique, capable of measuring regional tumor biology without perturbing it. This makes molecular imaging a unique tool for cancer drug development, complementary to traditional assay methods, and a potentially powerful method for guiding targeted therapy in clinical trials and clinical practice. The ability to quantify, in absolute measures, regional in vivo biologic parameters strongly supports the use of molecular imaging as a tool to guide therapy. This review summarizes current and future applications of quantitative molecular imaging as a biomarker for cancer therapy, including the use of imaging to (1) identify patients whose tumors express a specific therapeutic target; (2) determine whether the drug reaches the target; (3) identify an early response to treatment; and (4) predict the impact of therapy on long-term outcomes such as survival. The manuscript reviews basic concepts important in the application of molecular imaging to cancer drug therapy, in general, and will discuss specific examples of studies in humans, and highlight future directions, including ongoing multi-center clinical trials using molecular imaging as a cancer biomarker.

THE MOVEMENT SYSTEM IN EDUCATION.

PubMed

Hoogenboom, Barbara J; Sulavik, Mark

2017-11-01

Although many physical therapists have begun to focus on movement and function in clinical practice, a significant number continue to focus on impairments or pathoanatomic models to direct interventions. This paradigm may be driven by the current models used to direct and guide curricula used for physical therapist education. The methods by which students are educated may contribute to a focus on independent systems, rather than viewing the body as a functional whole. Students who enter practice must be able to integrate information across multiple systems that affect a patient or client's movement and function. Such integration must be taught to students and it is the responsibility of those in physical therapist education to embrace and teach the next generation of students this identifying professional paradigm of the movement system. The purpose of this clinical commentary is to describe the current state of the movement system in physical therapy education, suggest strategies for enhancing movement system focus in entry level education, and envision the future of physical therapy education related to the movement system. Contributions by a student author offer depth and perspective to the ideas and suggestions presented. 5.

Paenibacillus larvae-Directed Bacteriophage HB10c2 and Its Application in American Foulbrood-Affected Honey Bee Larvae.

PubMed

Beims, Hannes; Wittmann, Johannes; Bunk, Boyke; Spröer, Cathrin; Rohde, Christine; Günther, Gabi; Rohde, Manfred; von der Ohe, Werner; Steinert, Michael

2015-08-15

Paenibacillus larvae is the causative agent of American foulbrood (AFB), the most serious honey bee brood bacterial disease. We isolated and characterized P. larvae-directed bacteriophages and developed criteria for safe phage therapy. Whole-genome analysis of a highly lytic virus of the family Siphoviridae (HB10c2) provided a detailed safety profile and uncovered its lysogenic nature and a putative beta-lactamase-like protein. To rate its antagonistic activity against the pathogens targeted and to specify potentially harmful effects on the bee population and the environment, P. larvae genotypes ERIC I to IV, representatives of the bee gut microbiota, and a broad panel of members of the order Bacillales were analyzed for phage HB10c2-induced lysis. Breeding assays with infected bee larvae revealed that the in vitro phage activity observed was not predictive of the real-life scenario and therapeutic efficacy. On the basis of the disclosed P. larvae-bacteriophage coevolution, we discuss the future prospects of AFB phage therapy. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Overview of recent trends in diagnosis and management of leptomeningeal multiple myeloma.

PubMed

Yellu, Mahender R; Engel, Jessica M; Ghose, Abhimanyu; Onitilo, Adedayo A

2016-03-01

Neurological complications related to multiple myeloma (MM) are not uncommon; however, direct involvement of the central nervous system (CNS) is extremely rare and represents a diagnostic and therapeutic challenge. Significant survival difference has been noted with the introduction of novel therapy in patients with MM, but their effect on the incidence and their use for management of leptomeningeal myeloma (LMM) is uncertain. Analysis of published data demonstrates its recent increased incidence, median time to CNS presentation, and slight improvement in median survival after diagnosis of LMM. Less common MM isotypes have been overrepresented in LMM. CNS relapse occurred mostly in patients with Durie-Salmon stage III MM. Despite treatments, standard or experimental, the survival rates of LMM remain dismal. Monitoring high risk patients closely, even after achieving complete remission, may be useful in early detection of LMM. As we gain better understanding of LMM, we recommend that future research and clinical care focus on earlier diagnosis and development of more efficient CNS-directed therapy to improve survival in this patient population. Copyright © 2014 John Wiley & Sons, Ltd.

Paenibacillus larvae-Directed Bacteriophage HB10c2 and Its Application in American Foulbrood-Affected Honey Bee Larvae

PubMed Central

Beims, Hannes; Wittmann, Johannes; Bunk, Boyke; Spröer, Cathrin; Rohde, Christine; Günther, Gabi; Rohde, Manfred; von der Ohe, Werner

2015-01-01

Paenibacillus larvae is the causative agent of American foulbrood (AFB), the most serious honey bee brood bacterial disease. We isolated and characterized P. larvae-directed bacteriophages and developed criteria for safe phage therapy. Whole-genome analysis of a highly lytic virus of the family Siphoviridae (HB10c2) provided a detailed safety profile and uncovered its lysogenic nature and a putative beta-lactamase-like protein. To rate its antagonistic activity against the pathogens targeted and to specify potentially harmful effects on the bee population and the environment, P. larvae genotypes ERIC I to IV, representatives of the bee gut microbiota, and a broad panel of members of the order Bacillales were analyzed for phage HB10c2-induced lysis. Breeding assays with infected bee larvae revealed that the in vitro phage activity observed was not predictive of the real-life scenario and therapeutic efficacy. On the basis of the disclosed P. larvae-bacteriophage coevolution, we discuss the future prospects of AFB phage therapy. PMID:26048941

The influence of program acceptability on the effectiveness of public health policy: a study of directly observed therapy for tuberculosis.

PubMed Central

Heymann, S J; Sell, R; Brewer, T F

1998-01-01

OBJECTIVES: This study examined how patient acceptability influences the effectiveness of directly observed therapy for tuberculosis. METHODS: Decision and sensitivity analyses were used in assessing influences. RESULTS: If mandatory directly observed therapy discourages 6% of initial tuberculosis patients (range: 4% to 10%) from seeking care, then such therapy will be less effective than self-administered therapy. Directly observed therapy is more effective than repeated self-administered therapy for patients failing to complete initial treatment unless 32% (range: 27% to 38%) of patients avoid seeking care. CONCLUSIONS: Patient acceptability must be taken into consideration before selecting public health strategies. PMID:9518978

Success of nutrition-therapy interventions in persons with type 2 diabetes: challenges and future directions.

PubMed

Franz, Marion J; MacLeod, Janice

2018-01-01

A systematic review was conducted by the Academy of Nutrition and Dietetics to determine the evidence for the effectiveness of individualized nutrition therapy provided by a dietitian nutritionist and evidence-based (EB) nutrition-therapy interventions in adults with diabetes. This article briefly reviews the systematic process used and summarizes the effectiveness evidence and intervention recommendations. In persons with type 2 diabetes (T2D), 18 studies met study criteria for the effectiveness question. A 0.3%-2.0% decrease from baseline in glycated hemoglobin was reported at 3 months in 13 study arms, a 0.3%-1.8% decrease at 6 months in 12 study arms, a 0.3%-1.6% decrease at 12 months with ongoing support in six study arms, and a 0.6%-1.8% decrease at >12 months in four study arms. An initial series of encounters with follow-up visits and implementation of a variety of nutrition-therapy interventions, all of which reduced energy intake, were reported. Nutrition therapy also significantly decreased doses or number of glucose-lowering medications used and resulted in improvements in quality of life. Mixed effects on cardiovascular risk factors and body weight were reported. Fourteen questions were identified related to nutrition-therapy interventions. A total of 38 studies met study criteria for the nutrition-intervention questions, from which 30 conclusion statements and 19 nutrition-practice guideline recommendations for T2D were written. Three additional NPG recommendations for T2D were written based on evidence reviewed by the American Diabetes Association. The 22 nutrition-intervention recommendations for T2D are summarized. How to implement nutrition-practice guideline recommendations effectively by health care providers and individuals with T2D remains challenging. Of importance, it is recognized that identifying and integrating EB digital health-technology tools into clinical practice are major challenges for future management of diabetes, self-management education, and support.

CRISPR-Cas9 for in vivo Gene Therapy: Promise and Hurdles.

PubMed

Dai, Wei-Jing; Zhu, Li-Yao; Yan, Zhong-Yi; Xu, Yong; Wang, Qi-Long; Lu, Xiao-Jie

2016-01-01

Owing to its easy-to-use and multiplexing nature, the genome editing tool CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats (CRISPR) associated nuclease 9) is revolutionizing many areas of medical research and one of the most amazing areas is its gene therapy potentials. Previous explorations into the therapeutic potentials of CRISPR-Cas9 were mainly conducted in vitro or in animal germlines, the translatability of which, however, is either limited (to tissues with adult stem cells amenable to culture and manipulation) or currently impermissible (due to ethic concerns). Recently, important progresses have been made on this regard. Several studies have demonstrated the ability of CRISPR-Cas9 for in vivo gene therapy in adult rodent models of human genetic diseases delivered by methods that are potentially translatable to human use. Although these recent advances represent a significant step forward to the eventual application of CRISPR-Cas9 to the clinic, there are still many hurdles to overcome, such as the off-target effects of CRISPR-Cas9, efficacy of homology-directed repair, fitness of edited cells, immunogenicity of therapeutic CRISPR-Cas9 components, as well as efficiency, specificity, and translatability of in vivo delivery methods. In this article, we introduce the mechanisms and merits of CRISPR-Cas9 in genome editing, briefly retrospect the applications of CRISPR-Cas9 in gene therapy explorations and highlight recent advances, later we discuss in detail the challenges lying ahead in the way of its translatability, propose possible solutions, and future research directions. Copyright © 2016 Official journal of the American Society of Gene & Cell Therapy. Published by Elsevier Inc. All rights reserved.

[Effects of functional electrical therapy on upper extremity functional motor recovery in patients after stroke--our experience and future directions].

PubMed

Plavsić, Aleksandra; Svirtlih, Laslo; Stefanović, Aleksandra; Jović, Stevan; Durović, Aleksandar; Popović, Mirjana

2011-01-01

New neurorehabilitation together with conventional techniques provide methods and technologies for maximizing what is preserved from the sensory motor system after cerebrovascular insult. The rehabilitation technique named functional electrical therapy was investigated in more than 60 patients in acute, subacute and chronic phase after cerebrovascular insult. The functional sensory information generated by functional electrical therapy was hypothesized to result in the intensive functional brain training of the activities performed. Functional electrical therapy is a combination of functional exercise and electrical therapy. The functional electrical therapy protocol comprises voluntary movement of the paretic arm in synchrony with the electrically assisted hand functions in order to perform typical daily activities. The daily treatment of 30 minutes lasts three weeks. The outcome measures include several tests for the evaluation of arm/hand functionality: upper extremity function test, drawing test, modified Aschworth scale, motor activity log and passive range of movement. Results from our several clinical studies showed that functional electrical therapy, if applied in acute and subacute stroke patients, leads to faster and greater improvement of functioning of the hemiplegic arm/hand compared to the control group. The outcomes were significantly superior at all times after the treatment for the higher functioning group. Additional well-planned clinical studies are needed to determine the adequate dose of treatment (timing, duration, intensity) with functional electrical therapy regarding the patient's status. A combination with other techniques should be further investigated.

Importance of holographic light in the emerging field of mind-body healing

NASA Astrophysics Data System (ADS)

Booth, Roberta

2000-10-01

Healing with color has been researched and documented worldwide for centuries. Every single part of the brain and every cell in the body is effected by light. Chinese and Russian scientists demonstrated that the acupuncture meridians transmit light. Dr. Peter Mandel, German chiropractic physician and acupuncturist, states that the acupuncture points are especially sensitive to electromagnetic waves within the spectrum of visible light and microwave energy, and all cells constantly emit and absorb small pockets of electromagnetic radiation or light, called biophotons. The harmony or disharmony of cells has been documented. Kirlian photography, to photography the aura was invented by Russians Semyon and Valentina Kirlian. Photo therapy and light research are being practiced worldwide. In the United States, Dr. Jacob Lieberman has written an influential book Light Medicine of the Future. In 1992 the first Light Years Ahead conference was held. (#5 1996) Dr. Brian Breiling and Dr. Lee Hartley brought together experts in the field to discuss the many potentials of light therapy. My present research in this area has focused on narrow band frequencies through the use of holography. Its therapeutic applications of color healing in this research are both critical and fundamental. My current work, The Chakras, seven reflection holograms on silver halide, relate to the wheels of light described in the earliest recorded Indian history. I will discus the chakras, this ancient metaphysical system under the new light of popular western metaphors and visionary art, how the chakras relate to the seven colors of the rainbow, the electromagnetic waves, and the connection to color holography in healing light therapy. I will be citing concurrent research in color healing, and the important areas of research that are necessary to have significant impact on future directions. Holography in the future will constitute a major frontier in discovery.

New Treatment Strategies of Depression: Based on Mechanisms Related to Neuroplasticity

PubMed Central

Lane, Hsien-Yuan

2017-01-01

Major depressive disorder is a severe and complex mental disorder. Impaired neurotransmission and disrupted signalling pathways may influence neuroplasticity, which is involved in the brain dysfunction in depression. Traditional neurobiological theories of depression, such as monoamine hypothesis, cannot fully explain the whole picture of depressive disorders. In this review, we discussed new treatment directions of depression, including modulation of glutamatergic system and noninvasive brain stimulation. Dysfunction of glutamatergic neurotransmission plays an important role in the pathophysiology of depression. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has rapid and lasting antidepressive effects in previous studies. In addition to ketamine, other glutamatergic modulators, such as sarcosine, also show potential antidepressant effect in animal models or clinical trials. Noninvasive brain stimulation is another new treatment strategy beyond pharmacotherapy. Growing evidence has demonstrated that superficial brain stimulations, such as transcranial magnetic stimulation, transcranial direct current stimulation, cranial electrotherapy stimulation, and magnetic seizure therapy, can improve depressive symptoms. The antidepressive effect of these brain stimulations may be through modulating neuroplasticity. In conclusion, drugs that modulate neurotransmission via NMDA receptor and noninvasive brain stimulation may provide new directions of treatment for depression. Furthermore, exploring the underlying mechanisms will help in developing novel therapies for depression in the future. PMID:28491480

Manual Therapy: The Historical, Current, and Future Role in the Treatment of Pain

PubMed Central

Smith, A. Russell

2007-01-01

Manual therapy has been an approach in the management of patients with various disorders dating back to ancient times and continues to play a significant role in current health care. The future role of manual therapy in health care is an important area of research. This paper reviews the history of manual therapy, examines the current literature related to the use of manual techniques (including manipulation, massage, and nerve manipulation), and discusses future research topics. The literature related to manual therapy has historically been anecdotal and theoretical, and current research tends to have a generic approach with broad definitions of manual therapy and inconsistencies in the classification of specific disorders. Systematic reviews of various types of manual therapy have differed on their conclusions regarding the effectiveness of this treatment modality. The current demand in health care for evidence-based practice necessitates a movement towards more specificity in the research of the effectiveness of manual therapy, with emphasis on specific patient signs and symptoms and specific manual techniques that result in effective care. PMID:17334604

Emerging Regenerative Approaches for Periodontal Reconstruction: A Consensus Report From the AAP Regeneration Workshop

PubMed Central

Cochran, David L.; Cobb, Charles M.; Bashutski, Jill D.; Chun, Yong-Hee Patricia; Lin, Zhao; Mandelaris, George A.; McAllister, Bradley S.; Murakami, Shinya; Rios, Hector F.

2015-01-01

Background Historically, periodontal regeneration has focused predominantly on bone substitutes and/or barrier membrane application to provide for defect fill and/or selected cell repopulation of the lesion. More recently, a number of technologies have evolved that can be viewed as emerging therapeutic approaches for periodontal regeneration, and these technologies were considered in the review paper and by the consensus group. The goal of this consensus report on emerging regenerative approaches for periodontal hard and soft tissue reconstruction was to develop a consensus document based on the accompanying review paper and on additional materials submitted before and at the consensus group session. Methods The review paper was sent to all the consensus group participants in advance of the consensus conference. In addition and also before the conference, individual consensus group members submitted additional material for consideration by the group. At the conference, each consensus group participant introduced themselves and provided disclosure of any potential conflicts of interest. The review paper was briefly presented by two of the authors and discussed by the consensus group. A discussion of each of the following topics then occurred based on the content of the review: a general summary of the topic, implications for patient-reported outcomes, and suggested research priorities for the future. As each topic was discussed based on the review article, supplemental information was then added that the consensus group agreed on. Last, an updated reference list was created. Results The application of protein and peptide therapy, cell-based therapy, genetic therapy, application of scaffolds, bone anabolics, and lasers were found to be emerging technologies for periodontal regeneration. Other approaches included the following: 1) therapies directed at the resolution of inflammation; 2) therapies that took into account the influence of the microbiome; 3) therapies involving the local regulation of phosphate and pyrophosphate metabolism; and 4) approaches directed at harnessing current therapies used for other purposes. The results indicate that, with most emerging technologies, the specific mechanisms of action are not well understood nor are the specific target cells identified. Patient-related outcomes were typically not addressed in the literature. Numerous recommendations can bemade for future research priorities for both basic science and clinical application of emerging therapies. The need to emphasize the importance of regeneration of a functional periodontal organ system was noted. The predictability and efficacy of outcomes, as well as safety concerns and the cost-to-benefit ratio were also identified as key factors for emerging technologies. Conclusions A number of technologies appear viable as emerging regenerative approaches for periodontal hard and soft tissue regeneration and are expanding the potential of reconstructing the entire periodontal organ system. The cost-to-benefit ratio and safety issues are important considerations for any new emerging therapies. Clinical Recommendation At this time, there is insufficient evidence on emerging periodontal regenerative technologies to warrant definitive clinical recommendations. PMID:25317603

Photosensitized singlet oxygen generation and detection: Recent advances and future perspectives in cancer photodynamic therapy.

PubMed

Li, Buhong; Lin, Lisheng; Lin, Huiyun; Wilson, Brian C

2016-12-01

Photodynamic therapy (PDT) uses photosensitizers and visible light in combination with molecular oxygen to produce reactive oxygen species (ROS) that kill malignant cells by apoptosis and/or necrosis, shut down the tumor microvasculature and stimulate the host immune system. The excited singlet state of oxygen ( 1 O 2 ) is recognized to be the main cytotoxic ROS generated during PDT for the majority of photosensitizers used clinically and for many investigational new agents, so that maximizing its production within tumor cells and tissues can improve the therapeutic response, and several emerging and novel approaches for this are summarized. Quantitative techniques for 1 O 2 production measurement during photosensitization are also of immense importance of value for both preclinical research and future clinical practice. In this review, emerging strategies for enhanced photosensitized 1 O 2 generation are introduced, while recent advances in direct detection and imaging of 1 O 2 luminescence are summarized. In addition, the correlation between cumulative 1 O 2 luminescence and PDT efficiency will be highlighted. Meanwhile, the validation of 1 O 2 luminescence dosimetry for PDT application is also considered. This review concludes with a discussion on future demands of 1 O 2 luminescence detection for PDT dosimetry, with particular emphasis on clinical translation. Eye-catching color image for graphical abstract. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nonstatin therapies for management of dyslipidemia: a review.

PubMed

Sando, Karen R; Knight, Michelle

2015-10-01

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Recently published cholesterol treatment guidelines emphasize the use of statins as the preferred treatment strategy for both primary and secondary prevention of CVD. However, the optimal treatment strategy for patients who cannot tolerate statin therapy or those who need additional lipid-lowering therapy is unclear in light of recent evidence that demonstrates a lack of improved cardiovascular outcomes with combination therapy. The purpose of this review is to summarize and interpret evidence that evaluates nonstatin drug classes in reducing cardiovascular outcomes, to provide recommendations for use of nonstatin therapies in clinical practice, and to review emerging nonstatin therapies for management of dyslipidemia. Relevant articles were identified through searches of PubMed, International Pharmaceutical Abstracts, and the Cochrane Database of Systematic Reviews by using the terms niacin, omega-3 fatty acids (FAs), clofibrate, fibrate, fenofibrate, fenofibric acid, gemfibrozil, cholestyramine, colestipol, colesevelam, ezetimibe, proprotein convertase subtilisin/kexin 9 (PCSK9), cholesteryl ester transfer protein (CETP), and cardiovascular outcomes. Only English language, human clinical trials, meta-analyses, and systematic reviews were included. Additional references were identified from citations of published articles. Niacin may reduce cardiovascular events as monotherapy; however, recent trials in combination with statins have failed to show a benefit. Trials with omega-3 FAs have failed to demonstrate significant reductions in cardiovascular outcomes. Fibrates may improve cardiovascular outcomes as monotherapy; however, trials in combination with statins have failed to show a benefit, except in those with elevated triglycerides (>200 mg/dL) or low HDL-C (<40 mg/dL). There is a lack of data that evaluates bile acid sequestrant in combination with statin therapy on reducing cardiovascular events. Ezetimibe-statin combination therapy can reduce cardiovascular outcomes in those with chronic kidney disease and following vascular surgery or acute coronary syndrome. Long-term effects of emerging nonstatin therapies (CETP and PCSK9 inhibitors) are currently being evaluated in ongoing Phase III trials. Nonstatin therapies have a limited role in reducing cardiovascular events in those maintained on guideline-directed statin therapy. In certain clinical situations, such as patients who are unable to tolerate statin therapy or recommended intensities of statin therapy, those with persistent severe elevations in triglycerides, or patients with high cardiovascular risk, some nonstatin therapies may be useful in reducing cardiovascular events. Future research is needed to evaluate the role of nonstatin therapies in those who are unable to tolerate guideline-directed statin doses. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Cushing's disease: current medical therapies and molecular insights guiding future therapies.

PubMed

Lau, Darryl; Rutledge, Caleb; Aghi, Manish K

2015-02-01

OBJECT Cushing's disease (CD) can lead to significant morbidity secondary to hormonal sequelae or mass effect from the pituitary tumor. A transsphenoidal approach to resection of the adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is the first-line treatment. However, in the setting in which patients are unable to undergo surgery, have acute hypercortisolism, or have recurrent disease, medical therapy can play an important role. The authors performed a systematic review to highlight the efficacy of medical treatment of CD and discuss novel molecular insights that could guide the development of future medical treatments of CD. METHODS A search on current medical therapies for CD was performed. After individual medical therapeutic agents for CD were identified, each agent underwent a formal systematic search. The phrase "(name of agent) and Cushing's" was used as a search term in PubMed for all years up to 2014. The abstract of each article was reviewed for studies that evaluated the efficacy of medical treatment of CD. Only studies that enrolled at least 20 patients were included in the review. RESULTS A total of 11 articles on 6 individual agents were included in this review. Specific medical therapies were categorized based on the level of action: pituitary directed (cabergoline and pasireotide), adrenal/steroidogenesis directed (ketoconazole, metyrapone, and mitotane), and end-tissue directed/cortisol receptors (mifepristone). The studies identified consisted of a mix of retrospective reviews and small clinical trials. Only pasireotide and mifepristone have undergone Phase III clinical trials, from which they garnered FDA approval for the treatment of patients with CD. Overall, agents targeting ACTH secretion and steroidogenesis were found to be quite effective in reducing urine free cortisol (UFC) to levels near normal. A significant reduction in UFC was observed in 45%-100% of patients and a majority of patients gained clinical improvement. Similarly, inhibition at the end-tissue level led to clinical improvement in 87% of patients. However, side-effect rates associated with these drugs are high (up to 88%). Ketoconazole has been shown to enhance tumor appearance on MRI to facilitate pituitary resection. Promising molecular targets have been identified, including epidermal growth factor receptor, retinoic acid receptors, and cyclin dependent kinases. These pathways have been linked to the regulation of pro-opiomelanocortin expression, ACTH secretion, and tumor growth. CONCLUSIONS Despite encouraging Phase III clinical trials leading to FDA approval of 2 agents for treatment of patients with CD, no agent has yet produced results comparable to resection. As a result, the molecular insights gained into CD pathogenesis will need to continue to be expanded until they can lead to the development of medical therapies for CD with a favorable side-effect profile and efficacy comparable to resection. Ideally these agents should also reduce tumor size, which could potentially permit their eventual discontinuation.

Transcranial direct current stimulation over left inferior frontal cortex improves speech fluency in adults who stutter.

PubMed

Chesters, Jennifer; Möttönen, Riikka; Watkins, Kate E

2018-04-01

See Crinion (doi:10.1093/brain/awy075) for a scientific commentary on this article.Stuttering is a neurodevelopmental condition affecting 5% of children, and persisting in 1% of adults. Promoting lasting fluency improvement in adults who stutter is a particular challenge. Novel interventions to improve outcomes are of value, therefore. Previous work in patients with acquired motor and language disorders reported enhanced benefits of behavioural therapies when paired with transcranial direct current stimulation. Here, we report the results of the first trial investigating whether transcranial direct current stimulation can improve speech fluency in adults who stutter. We predicted that applying anodal stimulation to the left inferior frontal cortex during speech production with temporary fluency inducers would result in longer-lasting fluency improvements. Thirty male adults who stutter completed a randomized, double-blind, controlled trial of anodal transcranial direct current stimulation over left inferior frontal cortex. Fifteen participants received 20 min of 1-mA stimulation on five consecutive days while speech fluency was temporarily induced using choral and metronome-timed speech. The other 15 participants received the same speech fluency intervention with sham stimulation. Speech fluency during reading and conversation was assessed at baseline, before and after the stimulation on each day of the 5-day intervention, and at 1 and 6 weeks after the end of the intervention. Anodal stimulation combined with speech fluency training significantly reduced the percentage of disfluent speech measured 1 week after the intervention compared with fluency intervention alone. At 6 weeks after the intervention, this improvement was maintained during reading but not during conversation. Outcome scores at both post-intervention time points on a clinical assessment tool (the Stuttering Severity Instrument, version 4) also showed significant improvement in the group receiving transcranial direct current stimulation compared with the sham group, in whom fluency was unchanged from baseline. We conclude that transcranial direct current stimulation combined with behavioural fluency intervention can improve fluency in adults who stutter. Transcranial direct current stimulation thereby offers a potentially useful adjunct to future speech therapy interventions for this population, for whom fluency therapy outcomes are currently limited.

Small Accelerators for the Next Generation of BNCT Irradiation Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kobayashi, T.; Tanaka, K.; Bengua, G.

2005-01-15

The neutron irradiation system for boron neutron capture therapy (BNCT) using compact accelerators installed at hospitals was mainly investigated for the usage of direct neutrons from near-threshold {sup 7}Li(p,n){sup 7}Be, and moderated neutrons from 2.5 MeV {sup 7}Li(p,n){sup 7}Be reactions and other reactions. This kind of system can supply the medical doctors and patients with convenience to carry out BNCT in hospitals. The accelerator system would be regarded as the next-generation of BNCT in the near future.

Single Case Evaluation of an Intensive Cognitive Behavioral Treatment for Generalized Social Anxiety Disorder

PubMed Central

Stoddard, Jill A.; Rosellini, Anthony J.; Hofmann, Stefan G.

2008-01-01

The present study investigated the efficacy of an 8-day, 6-session, intensive individual cognitive behavioral therapy protocol for social anxiety disorder using a multiple baseline across subjects design with 1, 2, and 3 months follow-up assessments. Participants were 5 outpatients with generalized social anxiety disorder. The intervention had variable effects on clinician-rated and self-report measures of anxiety and depression. The results question the efficacy of intensive psychotherapy as a general therapeutic strategy for social anxiety disorder. Directions for future research are discussed. PMID:19169365

Wireless endoscopy in 2020: Will it still be a capsule?

PubMed Central

Koulaouzidis, Anastasios; Iakovidis, Dimitris K; Karargyris, Alexandros; Rondonotti, Emanuele

2015-01-01

Currently, the major problem of all existing commercial capsule devices is the lack of control of movement. In the future, with an interface application, the clinician will be able to stop and direct the device into points of interest for detailed inspection/diagnosis, and therapy delivery. This editorial presents current commercially-available new designs, European projects and delivery capsule and gives an overview of the progress required and progress that will be achieved -according to the opinion of the authors- in the next 5 year leading to 2020. PMID:25954085

Quantitative comparison of cognitive behavioral therapy and music therapy research: a methodological best-practices analysis to guide future investigation for adult psychiatric patients.

PubMed

Silverman, Michael J

2008-01-01

While the music therapy profession is relatively young and small in size, it can treat a variety of clinical populations and has established a diverse research base. However, although the profession originated working with persons diagnosed with mental illnesses, there is a considerable lack of quantitative research concerning the effects of music therapy with this population. Music therapy clinicians and researchers have reported on this lack of evidence and the difficulty in conducting psychosocial research on their interventions (Choi, 1997; Silverman, 2003a). While published studies have provided suggestions for future research, no studies have provided detailed propositions for the methodology and design of meticulous high quality randomized controlled psychiatric music therapy research. How do other psychotherapies accomplish their databases and could the music therapy field borrow from their rigorous "methodological best practices" to strengthen its own literature base? Therefore, as the National Institutes of Mental Health state the treatment of choice for evidence-based psychotherapy is cognitive behavioral therapy (CBT), aspects of this psychotherapy's literature base were analyzed. The purpose of this literature analysis was to (a) analyze and identify components of high-quality quantitative CBT research for adult psychiatric consumers, (b) analyze and identify the variables and other elements of existing quantitative psychiatric music therapy research for adult consumers, and (c) compare the two data sets to identify the best methodological designs and variables for future quantitative music therapy research with the mental health population. A table analyzing randomized and thoroughly controlled studies involving the use of CBT for persons with severe mental illnesses is included to determine chief components of high-quality experimental research designs and implementation of quantitative clinical research. The table also shows the same analyzed components for existing quantitative psychiatric music therapy research with adult consumers, thus highlighting potential areas and elements for future investigations. A second table depicts a number of potential dependent measures and their sources to be evaluated in future music therapy studies. A third table providing suggestions for future research is derived from a synthesis of the tables and is included to guide researchers and encourage the advancement and expansion of the current literature base. The body of the paper is a discussion of the results of the literature analysis derived from the tables, meta-analyses, and reviews of literature. It is hoped that this report will lead to the addition of future high-quality quantitative research to the psychiatric music therapy literature base and thus provide evidence-based services to as many persons with mental illnesses as possible.

Recent findings and future directions for interpolar mitotic kinesin inhibitors in cancer therapy

PubMed Central

Myers, Stephanie M.; Collins, Ian

2016-01-01

The kinesin class of microtubule-associated motor proteins present attractive anti-cancer targets owing to their roles in key functions in dividing cells. Two interpolar mitotic kinesins Eg5 and HSET have opposing motor functions in mitotic spindle assembly with respect to microtubule movement, but both offer opportunities to develop cancer selective therapeutic agents. Here, we summarize the progress to date in developing inhibitors of Eg5 and HSET, with an emphasis on structural biology insights into the binding modes of allosteric inhibitors, compound selectivity and mechanisms of action of different chemical scaffolds. We discuss translation of preclinical studies to clinical experience with Eg5 inhibitors, recent findings on potential resistance mechanisms, and explore the implications for future anticancer drug development against these targets. PMID:26976726

Management of Nasopharyngeal Carcinoma: Current Practice and Future Perspective.

PubMed

Lee, Anne W M; Ma, Brigette B Y; Ng, Wai Tong; Chan, Anthony T C

2015-10-10

Nasopharyngeal carcinoma of the undifferentiated subtype is endemic to southern China, and patient prognosis has improved significantly over the past three decades because of advances in disease management, diagnostic imaging, radiotherapy technology, and broader application of systemic therapy. Despite the excellent local control with modern radiotherapy, distant failure remains a key challenge. Advances in molecular technology have helped to decipher the molecular pathogenesis of nasopharyngeal carcinoma as well as its etiologic association with the Epstein-Barr virus. This in turn has led to the discovery of novel biomarkers and drug targets, rendering this cancer site a current focus for new drug development. This article reviews and appraises the key literature on the current management of nasopharyngeal carcinoma and future directions in clinical research. © 2015 by American Society of Clinical Oncology.

Recent findings and future directions for interpolar mitotic kinesin inhibitors in cancer therapy.

PubMed

Myers, Stephanie M; Collins, Ian

2016-01-01

The kinesin class of microtubule-associated motor proteins present attractive anticancer targets owing to their roles in key functions in dividing cells. Two interpolar mitotic kinesins Eg5 and HSET have opposing motor functions in mitotic spindle assembly with respect to microtubule movement, but both offer opportunities to develop cancer selective therapeutic agents. Here, we summarize the progress to date in developing inhibitors of Eg5 and HSET, with an emphasis on structural biology insights into the binding modes of allosteric inhibitors, compound selectivity and mechanisms of action of different chemical scaffolds. We discuss translation of preclinical studies to clinical experience with Eg5 inhibitors, recent findings on potential resistance mechanisms and explore the implications for future anticancer drug development against these targets.

To CRISPR and beyond: the evolution of genome editing in stem cells

PubMed Central

Chen, Kuang-Yui; Knoepfler, Paul S

2016-01-01

The goal of editing the genomes of stem cells to generate model organisms and cell lines for genetic and biological studies has been pursued for decades. There is also exciting potential for future clinical impact in humans. While recent, rapid advances in targeted nuclease technologies have led to unprecedented accessibility and ease of gene editing, biology has benefited from past directed gene modification via homologous recombination, gene traps and other transgenic methodologies. Here we review the history of genome editing in stem cells (including via zinc finger nucleases, transcription activator-like effector nucleases and CRISPR–Cas9), discuss recent developments leading to the implementation of stem cell gene therapies in clinical trials and consider the prospects for future advances in this rapidly evolving field. PMID:27905217

To CRISPR and beyond: the evolution of genome editing in stem cells.

PubMed

Chen, Kuang-Yui; Knoepfler, Paul S

2016-12-01

The goal of editing the genomes of stem cells to generate model organisms and cell lines for genetic and biological studies has been pursued for decades. There is also exciting potential for future clinical impact in humans. While recent, rapid advances in targeted nuclease technologies have led to unprecedented accessibility and ease of gene editing, biology has benefited from past directed gene modification via homologous recombination, gene traps and other transgenic methodologies. Here we review the history of genome editing in stem cells (including via zinc finger nucleases, transcription activator-like effector nucleases and CRISPR-Cas9), discuss recent developments leading to the implementation of stem cell gene therapies in clinical trials and consider the prospects for future advances in this rapidly evolving field.

Stem cell therapy in the management of shoulder rotator cuff disorders

PubMed Central

Mora, Maria Valencia; Ibán, Miguel A Ruiz; Heredia, Jorge Díaz; Laakso, Raul Barco; Cuéllar, Ricardo; Arranz, Mariano García

2015-01-01

Rotator cuff tears are frequent shoulder problems that are usually dealt with surgical repair. Despite improved surgical techniques, the tendon-to-bone healing rate is unsatisfactory due to difficulties in restoring the delicate transitional tissue between bone and tendon. It is essential to understand the molecular mechanisms that determine this failure. The study of the molecular environment during embryogenesis and during normal healing after injury is key in devising strategies to get a successful repair. Mesenchymal stem cells (MSC) can differentiate into different mesodermal tissues and have a strong paracrine, anti-inflammatory, immunoregulatory and angiogenic potential. Stem cell therapy is thus a potentially effective therapy to enhance rotator cuff healing. Promising results have been reported with the use of autologous MSC of different origins in animal studies: they have shown to have better healing properties, increasing the amount of fibrocartilage formation and improving the orientation of fibrocartilage fibers with less immunologic response and reduced lymphocyte infiltration. All these changes lead to an increase in biomechanical strength. However, animal research is still inconclusive and more experimental studies are needed before human application. Future directions include expanded stem cell therapy in combination with growth factors or different scaffolds as well as new stem cell types and gene therapy. PMID:26029341

The Combination of Laser Therapy and Metal Nanoparticles in Cancer Treatment Originated From Epithelial Tissues: A Literature Review

PubMed Central

Fekrazad, Reza; Naghdi, Nafiseh; Nokhbatolfoghahaei, Hanieh; Bagheri, Hossein

2016-01-01

Several methods have been employed for cancer treatment including surgery, chemotherapy and radiation therapy. Today, recent advances in medical science and development of new technologies, have led to the introduction of new methods such as hormone therapy, Photodynamic therapy (PDT), treatments using nanoparticles and eventually combinations of lasers and nanoparticles. The unique features of LASERs such as photo-thermal properties and the particular characteristics of nanoparticles, given their extremely small size, may provide an interesting combined therapeutic effect. The purpose of this study was to review the simultaneous application of lasers and metal nanoparticles for the treatment of cancers with epithelial origin. A comprehensive search in electronic sources including PubMed, Google Scholar and Science Direct was carried out between 2000 and 2013. Among the initial 400 articles, 250 articles applied nanoparticles and lasers in combination, in which more than 50 articles covered the treatment of cancer with epithelial origin. In the future, the combination of laser and nanoparticles may be used as a new or an alternative method for cancer therapy or diagnosis. Obviously, to exclude the effect of laser’s wavelength and nanoparticle’s properties more animal studies and clinical trials are required as a lack of perfect studies PMID:27330701

Therapeutic Management of Familial Hypercholesterolemia: Current and Emerging Drug Therapies.

PubMed

Patel, Roshni S; Scopelliti, Emily M; Savelloni, Julie

2015-12-01

Familial hypercholesterolemia (FH) is a genetic disorder characterized by significantly elevated low-density lipoprotein cholesterol (LDL-C) concentrations that result from mutations of the LDL receptor, apolipoprotein B (apo B-100), and proprotein convertase subtilisin/kexin type 9 (PCSK9). Early and aggressive treatment can prevent premature atherosclerotic cardiovascular disease in these high-risk patients. Given that the cardiovascular consequences of FH are similar to typical hypercholesterolemia, traditional therapies are utilized to decrease LDL-C levels. Patients with FH should receive statins as first-line treatment; high-potency statins at high doses are often required. Despite the use of statins, additional treatments are often necessary to achieve appropriate LDL-C lowering in this patient population. Novel drug therapies that target the pathophysiologic defects of the condition are continuously emerging. Contemporary therapies including mipomersen (Kynamro, Genzyme), an oligonucleotide inhibitor of apo B-100 synthesis; lomitapide (Juxtapid, Aegerion), a microsomal triglyceride transfer protein inhibitor; and alirocumab (Praluent, Sanofi-Aventis/Regeneron) and evolocumab (Repatha, Amgen), PCSK9 inhibitors, are currently approved by the U.S. Food and Drug Administration for use in FH. This review highlights traditional as well as emerging contemporary therapies with supporting clinical data to evaluate current recommendations and discuss the future direction of FH management. © 2015 Pharmacotherapy Publications, Inc.

Lessons Learned from Gemcitabine: Impact of Therapeutic Carrier Systems and Gemcitabine's Drug Conjugates on Cancer Therapy.

PubMed

Dyawanapelly, Sathish; Kumar, Animesh; Chourasia, Manish K

2017-01-01

Currently, drug delivery systems have a high impact in cancer therapy and are receiving more attention than conventional cancer treatment modalities. Compared with current cancer therapies, gemcitabine (2', 2'-difluoro-2'-deoxycytidine) has been proven to be an effective chemotherapeutic agent against pancreatic, colon, bladder, breast, ovarian, non-small-cell lung, and head and neck cancers in combination with other anticancer agents. To improve the safety and efficacy of cytotoxic drugs, several drug delivery systems have been explored. This review outlines the recent work directed toward gemcitabine delivery systems for cancer therapy, including aerosols, polymeric nanoparticles, liposomes, microparticles, carbon nanotubes, and multifunctional theranostic nanomedicines. It also provides insight into the design and development of gemcitabine conjugation for safe and effective cancer therapy. Despite the clinical promises of gemcitabine, many therapeutic challenges remain. Specifically, its therapeutic use in cancer chemotherapy is impeded by a short biological half-life, caused by its rapid metabolism, and resistance due to increased expression of ribonucleotide reductase. In our opinion, many research investigations have contributed to improve the selectivity and efficacy of gemcitabine. This combined approach of drug delivery systems and gemcitabine conjugates has shown promising efficacy in preclinical models and significant potential for future clinical cancer-therapeutic applications. Also, these strategies overcome most of the aforementioned limits of gemcitabine.

The spiritual meaning of pre-loss music therapy to bereaved caregivers of advanced cancer patients.

PubMed

Magill, Lucanne

2009-03-01

The aim of this study was to learn how music therapy sessions, held prior to the death of a loved one, impact spirituality in surviving caregivers of advanced cancer patients. The method of naturalistic inquiry was used to investigate the spiritual meaning of pre-loss music therapy sessions. Bereaved caregivers of seven different patients, who had been receiving music therapy through a home-based hospice program, participated in individual open-ended interviews. Interviews were recorded, transcribed, and coded. Themes were organized as they emerged. As caregivers reflected on their experiences in music therapy, they reported autonomous joy (music therapy affected the caregiver directly) and empathic joy (caregivers' joy was based in remembering seeing the patient happy in music therapy). They also noted feelings of empowerment due to the ways they felt they had contributed in the care of the patients through music therapy. The caregivers were found to engage in processes of reflection that inspired these spiritual themes: reflection on the present (connectedness), reflection on the past (remembrance), and reflection on the future (hope). They referred to the ways that the music therapy sessions helped them find connection with self, others (through bringing their loved ones "back to life" and have a "renewal of self"), and the "beyond"; and that times in music therapy brought them happy memories and sentiments of hope. Meaning through transcendence was found to be the overarching trend in this study, as caregivers were lifted from remorse into heightened sense of meaning and gained "airplane views" of their lives. Pre-loss music therapy can potentially assist caregivers during times of bereavement, as they retain memories of joy and empowerment, rather than memories of pain and distress, and find meaning through transcendence.

Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy.

PubMed

Dai, Hanren; Wang, Yao; Lu, Xuechun; Han, Weidong

2016-07-01

The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy. © The Author 2016. Published by Oxford University Press.

Admission prevention in COPD: non-pharmacological management.

PubMed

Suh, Eui-Sik; Mandal, Swapna; Hart, Nicholas

2013-11-20

Exacerbations of chronic obstructive pulmonary disease (COPD) are one of the commonest causes of hospital admission in Europe, Australasia, and North America. These adverse events have a large effect on the health status of the patients and impose a heavy burden on healthcare systems. While we acknowledge the contribution of pharmacotherapies to exacerbation prevention, our interpretation of the data is that exacerbations continue to be a major burden to individuals and healthcare systems, therefore, there remains great scope for other therapies to influence exacerbation frequency and preservation of quality of life. In this review, the benefits and limitations of pulmonary rehabilitation, non-invasive ventilation, smoking cessation, and long-term oxygen therapy are discussed. In addition, supported discharge, advanced care coordination, and telehealth programs to improve clinical outcome are reviewed as future directions for the management of COPD.

Complement, a target for therapy in inflammatory and degenerative diseases.

PubMed

Morgan, B Paul; Harris, Claire L

2015-12-01

The complement system is a key innate immune defence against infection and an important driver of inflammation; however, these very properties can also cause harm. Inappropriate or uncontrolled activation of complement can cause local and/or systemic inflammation, tissue damage and disease. Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. Drug design is facilitated by the increasingly detailed structural understanding of the molecules involved in the complement system. Only two anti-complement drugs are currently on the market, but many more are being developed for diseases that include infectious, inflammatory, degenerative, traumatic and neoplastic disorders. In this Review, we describe the history, current landscape and future directions for anti-complement therapies.

Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy

PubMed Central

Dai, Hanren; Wang, Yao; Lu, Xuechun

2016-01-01

The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy. PMID:26819347

Psychological aspects of tinnitus and the application of cognitive-behavioral therapy.

PubMed

Andersson, Gerhard

2002-09-01

This article presents an overview of tinnitus (ringing or buzzing in the ears), its psychological effects, and the application of cognitive-behavioral therapy (CBT) for its treatment. Several studies have confirmed an association between psychological factors, such as anxiety and depression, and severe tinnitus and preliminary reports suggest that a proportion of tinnitus patients suffer from mental illness. Assessment strategies used in CBT for tinnitus include structured interviews, daily diary ratings, and validated self-report questionnaires. The treatment approach described in this article includes applied relaxation, imagery and distraction techniques, advice regarding environmental sounds, management of sleep, cognitive restructuring of thoughts and beliefs associated with tinnitus, and relapse prevention. The literature pertinent to CBT approaches to treating tinnitus is reviewed, and it is concluded that CBT shows promise as a treatment of tinnitus-related distress. Future research directions are discussed.

Physical insights into the blood-brain barrier translocation mechanisms

NASA Astrophysics Data System (ADS)

Theodorakis, Panagiotis E.; Müller, Erich A.; Craster, Richard V.; Matar, Omar K.

2017-08-01

The number of individuals suffering from diseases of the central nervous system (CNS) is growing with an aging population. While candidate drugs for many of these diseases are available, most of these pharmaceutical agents cannot reach the brain rendering most of the drug therapies that target the CNS inefficient. The reason is the blood-brain barrier (BBB), a complex and dynamic interface that controls the influx and efflux of substances through a number of different translocation mechanisms. Here, we present these mechanisms providing, also, the necessary background related to the morphology and various characteristics of the BBB. Moreover, we discuss various numerical and simulation approaches used to study the BBB, and possible future directions based on multi-scale methods. We anticipate that this review will motivate multi-disciplinary research on the BBB aiming at the design of effective drug therapies.

Anti-arrhythmic strategies for atrial fibrillation

PubMed Central

Grandi, Eleonora; Maleckar, Mary M.

2016-01-01

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with increased risk of cerebrovascular stroke, and with several other pathologies, including heart failure. Current therapies for AF are targeted at reducing risk of stroke (anticoagulation) and tachycardia-induced cardiomyopathy (rate or rhythm control). Rate control, typically achieved by atrioventricular nodal blocking drugs, is often insufficient to alleviate symptoms. Rhythm control approaches include antiarrhythmic drugs, electrical cardioversion, and ablation strategies. Here, we offer several examples of how computational modeling can provide a quantitative framework for integrating multi scale data to: (a) gain insight into multi-scale mechanisms of AF; (b) identify and test pharmacological and electrical therapy and interventions; and (c) support clinical decisions. We review how modeling approaches have evolved and contributed to the research pipeline and preclinical development and discuss future directions and challenges in the field. PMID:27612549

Predicting response to EGFR inhibitors in metastatic colorectal cancer: current practice and future directions.

PubMed

Shankaran, Veena; Obel, Jennifer; Benson, Al B

2010-01-01

The identification of KRAS mutational status as a predictive marker of response to antibodies against the epidermal growth factor receptor (EGFR) has been one of the most significant and practice-changing recent advances in colorectal cancer research. Recently, data suggesting a potential role for other markers (including BRAF mutations, loss of phosphatase and tension homologue deleted on chromosome ten expression, and phosphatidylinositol-3-kinase-AKT pathway mutations) in predicting response to anti-EGFR therapy have emerged. Ongoing clinical trials and correlative analyses are essential to definitively identify predictive markers and develop therapeutic strategies for patients who may not derive benefit from anti-EGFR therapy. This article reviews recent clinical trials supporting the predictive role of KRAS, recent changes to clinical guidelines and pharmaceutical labeling, investigational predictive molecular markers, and newer clinical trials targeting patients with mutated KRAS.

Parent–Child Interaction Therapy: current perspectives

PubMed Central

Lieneman, Corey C; Brabson, Laurel A; Highlander, April; Wallace, Nancy M; McNeil, Cheryl B

2017-01-01

Parent–Child Interaction Therapy (PCIT) is an empirically supported intervention originally developed to treat disruptive behavior problems in children between the ages of 2 and 7 years. Since its creation over 40 years ago, PCIT has been studied internationally with various populations and has been found to be an effective intervention for numerous behavioral and emotional issues. This article summarizes progress in the PCIT literature over the past decade (2006–2017) and outlines future directions for this important work. Recent PCIT research related to treatment effectiveness, treatment components, adaptations for specific populations (age groups, cultural groups, military families, individuals diagnosed with specific disorders, trauma survivors, and the hearing-impaired), format changes (group and home-based), teacher–child interaction training (TCIT), intensive PCIT (I-PCIT), treatment as prevention (for externalizing problems, child maltreatment, and developmental delays), and implementation are discussed. PMID:28790873

Directly administered antiretroviral therapy for HIV-infected drug users does not have an impact on antiretroviral resistance: results from a randomized controlled trial.

PubMed

Maru, Duncan Smith-Rohrberg; Kozal, Michael J; Bruce, R Douglas; Springer, Sandra A; Altice, Frederick L

2007-12-15

Directly administered antiretroviral therapy (DAART) is an effective intervention that improves clinical outcomes among HIV-infected drug users. Its effects on antiretroviral drug resistance, however, are unknown. We conducted a community-based, prospective, randomized controlled trial of DAART compared with self-administered therapy (SAT). We performed a modified intention-to-treat analysis among 115 subjects who provided serum samples for HIV genotypic resistance testing at baseline and at follow-up. The main outcomes measures included total genotypic sensitivity score, future drug options, number of new drug resistance mutations (DRMs), and number of new major International AIDS Society (IAS) mutations. The adjusted probability of developing at least 1 new DRM did not differ between the 2 arms (SAT: 0.41 per person-year [PPY], DAART: 0.49 PPY; adjusted relative risk [RR] = 1.04; P = 0.90), nor did the number of new mutations (SAT: 0.76 PPY, DAART: 0.83 PPY; adjusted RR = 0.99; P = 0.99) or the probability of developing new major IAS new drug mutations (SAT: 0.30 PPY, DAART: 0.33 PPY; adjusted RR = 1.12; P = 0.78). On measures of GSS and FDO, the 2 arms also did not differ. In this trial, DAART provided on-treatment virologic benefit for HIV-infected drug users without affecting the rate of development of antiretroviral medication resistance.

CRISPR-Cas9: a new and promising player in gene therapy.

PubMed

Xiao-Jie, Lu; Hui-Ying, Xue; Zun-Ping, Ke; Jin-Lian, Chen; Li-Juan, Ji

2015-05-01

First introduced into mammalian organisms in 2013, the RNA-guided genome editing tool CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9) offers several advantages over conventional ones, such as simple-to-design, easy-to-use and multiplexing (capable of editing multiple genes simultaneously). Consequently, it has become a cost-effective and convenient tool for various genome editing purposes including gene therapy studies. In cell lines or animal models, CRISPR-Cas9 can be applied for therapeutic purposes in several ways. It can correct the causal mutations in monogenic disorders and thus rescue the disease phenotypes, which currently represents the most translatable field in CRISPR-Cas9-mediated gene therapy. CRISPR-Cas9 can also engineer pathogen genome such as HIV for therapeutic purposes, or induce protective or therapeutic mutations in host tissues. Moreover, CRISPR-Cas9 has shown potentials in cancer gene therapy such as deactivating oncogenic virus and inducing oncosuppressor expressions. Herein, we review the research on CRISPR-mediated gene therapy, discuss its advantages, limitations and possible solutions, and propose directions for future research, with an emphasis on the opportunities and challenges of CRISPR-Cas9 in cancer gene therapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Biofield Therapies: Helpful or Full of Hype? A Best Evidence Synthesis

PubMed Central

Mills, Paul J.

2009-01-01

Background Biofield therapies (such as Reiki, therapeutic touch, and healing touch) are complementary medicine modalities that remain controversial and are utilized by a significant number of patients, with little information regarding their efficacy. Purpose This systematic review examines 66 clinical studies with a variety of biofield therapies in different patient populations. Method We conducted a quality assessment as well as a best evidence synthesis approach to examine evidence for biofield therapies in relevant outcomes for different clinical populations. Results Studies overall are of medium quality, and generally meet minimum standards for validity of inferences. Biofield therapies show strong evidence for reducing pain intensity in pain populations, and moderate evidence for reducing pain intensity hospitalized and cancer populations. There is moderate evidence for decreasing negative behavioral symptoms in dementia and moderate evidence for decreasing anxiety for hospitalized populations. There is equivocal evidence for biofield therapies' effects on fatigue and quality of life for cancer patients, as well as for comprehensive pain outcomes and affect in pain patients, and for decreasing anxiety in cardiovascular patients. Conclusion There is a need for further high-quality studies in this area. Implications and future research directions are discussed. Electronic supplementary material The online version of this article (doi:10.1007/s12529-009-9062-4) contains supplementary material, which is available to authorized users. PMID:19856109

Novel Approaches for the Treatment of Familial Hypercholesterolemia: Current Status and Future Challenges.

PubMed

Jiang, Long; Wang, Lu-Ya; Cheng, Xiao-Shu

2018-06-13

Familial hypercholesterolemia (FH) is an autosomal-dominant disorder that is characterized by high plasma low-density lipoprotein cholesterol (LDL-c) levels and an increased risk of cardiovascular disease. Despite the use of high-dose statins and the recent addition of proprotein convertase subtilisin/kexin type 9 inhibitors as a treatment option, many patients with homozygous FH fail to achieve optimal reductions of LDL-c levels. Gene therapy has become one of the most promising research directions for contemporary life sciences and is a potential treatment option for FH. Recent studies have confirmed the efficacy of a recombinant adeno-associated virus 8 vector expressing the human LDL-c receptor gene in a mouse model, and this vector is currently in phase 2 clinical trials. Much progress has also been achieved in the fields of antisense oligonucleotide- and small interfering RNA-based gene therapies, which are in phase 1-2 clinical trials. In addition, novel approaches, such as the use of minicircle DNA vectors, microRNAs, long non-coding RNAs, and the CRISPR/Cas9 gene-editing system, have shown great potential for FH therapy. However, the delivery system, immunogenicity, accuracy, and specificity of gene therapies limit their clinical applications. In this article, we discuss the current status of gene therapy and recent advances that will likely affect the clinical application of gene therapy for the treatment of FH.

Research Priorities in Limb and Task-Specific Dystonias.

PubMed

Pirio Richardson, Sarah; Altenmüller, Eckart; Alter, Katharine; Alterman, Ron L; Chen, Robert; Frucht, Steven; Furuya, Shinichi; Jankovic, Joseph; Jinnah, H A; Kimberley, Teresa J; Lungu, Codrin; Perlmutter, Joel S; Prudente, Cecília N; Hallett, Mark

2017-01-01

Dystonia, which causes intermittent or sustained abnormal postures and movements, can present in a focal or a generalized manner. In the limbs, focal dystonia can occur in either the upper or lower limbs and may be task-specific causing abnormal motor performance for only a specific task, such as in writer's cramp, runner's dystonia, or musician's dystonia. Focal limb dystonia can be non-task-specific and may, in some circumstances, be associated with parkinsonian disorders. The true prevalence of focal limb dystonia is not known and is likely currently underestimated, leaving a knowledge gap and an opportunity for future research. The pathophysiology of focal limb dystonia shares some commonalities with other dystonias with a loss of inhibition in the central nervous system and a loss of the normal regulation of plasticity, called homeostatic plasticity. Functional imaging studies revealed abnormalities in several anatomical networks that involve the cortex, basal ganglia, and cerebellum. Further studies should focus on distinguishing cause from effect in both physiology and imaging studies to permit focus on most relevant biological correlates of dystonia. There is no specific therapy for the treatment of limb dystonia given the variability in presentation, but off-label botulinum toxin therapy is often applied to focal limb and task-specific dystonia. Various rehabilitation techniques have been applied and rehabilitation interventions may improve outcomes, but small sample size and lack of direct comparisons between methods to evaluate comparative efficacy limit conclusions. Finally, non-invasive and invasive therapeutic modalities have been explored in small studies with design limitations that do not yet clearly provide direction for larger clinical trials that could support new clinical therapies. Given these gaps in our clinical, pathophysiologic, and therapeutic knowledge, we have identified priorities for future research including: the development of diagnostic criteria for limb dystonia, more precise phenotypic characterization and innovative clinical trial design that considers clinical heterogeneity, and limited available number of participants.

Research Priorities in Limb and Task-Specific Dystonias

PubMed Central

Pirio Richardson, Sarah; Altenmüller, Eckart; Alter, Katharine; Alterman, Ron L.; Chen, Robert; Frucht, Steven; Furuya, Shinichi; Jankovic, Joseph; Jinnah, H. A.; Kimberley, Teresa J.; Lungu, Codrin; Perlmutter, Joel S.; Prudente, Cecília N.; Hallett, Mark

2017-01-01

Dystonia, which causes intermittent or sustained abnormal postures and movements, can present in a focal or a generalized manner. In the limbs, focal dystonia can occur in either the upper or lower limbs and may be task-specific causing abnormal motor performance for only a specific task, such as in writer’s cramp, runner’s dystonia, or musician’s dystonia. Focal limb dystonia can be non-task-specific and may, in some circumstances, be associated with parkinsonian disorders. The true prevalence of focal limb dystonia is not known and is likely currently underestimated, leaving a knowledge gap and an opportunity for future research. The pathophysiology of focal limb dystonia shares some commonalities with other dystonias with a loss of inhibition in the central nervous system and a loss of the normal regulation of plasticity, called homeostatic plasticity. Functional imaging studies revealed abnormalities in several anatomical networks that involve the cortex, basal ganglia, and cerebellum. Further studies should focus on distinguishing cause from effect in both physiology and imaging studies to permit focus on most relevant biological correlates of dystonia. There is no specific therapy for the treatment of limb dystonia given the variability in presentation, but off-label botulinum toxin therapy is often applied to focal limb and task-specific dystonia. Various rehabilitation techniques have been applied and rehabilitation interventions may improve outcomes, but small sample size and lack of direct comparisons between methods to evaluate comparative efficacy limit conclusions. Finally, non-invasive and invasive therapeutic modalities have been explored in small studies with design limitations that do not yet clearly provide direction for larger clinical trials that could support new clinical therapies. Given these gaps in our clinical, pathophysiologic, and therapeutic knowledge, we have identified priorities for future research including: the development of diagnostic criteria for limb dystonia, more precise phenotypic characterization and innovative clinical trial design that considers clinical heterogeneity, and limited available number of participants. PMID:28515706

Current options and new developments in the treatment of haemophilia.

PubMed

Wong, Trisha; Recht, Michael

2011-02-12

Haemophilia A and B are X-linked bleeding disorders due to the inherited deficiency of factor VIII or factor IX, respectively. Of the approximately 1 per 5000-10000 male births affected by haemophilia, 80% are deficient in factor VIII and 20% are deficient in factor IX. Haemophilia is characterized by spontaneous and provoked joint, muscle, gastrointestinal and CNS bleeding leading to major morbidity and even mortality if left untreated or under-treated. The evolution of haemophilia management has been marked by tragedy and triumph over recent decades. Clotting factors and replacement strategies continue to evolve for patients without inhibitors. For patients with an inhibitor, factor replacement for acute bleeding episodes and immune tolerance, immune modulation and extracorporeal methods for inhibitor reduction are the cornerstone of care. In addition, adjuvant therapies such as desmopressin, antifibrinolytics and topical agents also contribute to improved outcomes for patients with and without inhibitors. The future direction of haemophilia care is promising with new longer-acting clotting factors and genetic therapies, including gene transfer and premature termination codon suppressors. With these current and future treatment modalities, the morbidity and mortality rates in patients with haemophilia certainly will continue to improve.

The impact of chronic kidney disease on medication choice and pharmacologic management in patients with heart failure.

PubMed

Shah, Syed Raza; Winchester, David E

2018-05-21

In the past few years, medical community, including doctors, have become increasingly aware of the fact that chronic kidney disease (CK) and heart failure (HF) have common risk factors which impacts one another in terms of choice of therapy. Areas covered: Management of these two diseases has been a challenge for physicians. The treatment goals for HF patients in CK are very important. They serve as the end-point in using a specific treatment for management and treatment of CK patients hence, decreasing mortality rates. In this review, we discuss the pharmacological approaches to managing patients with HF and CK, discussing current evidence based uptodate management strategies and guidelines in the general population with HF and CK. Expert Commentary: Newer novel drugs targeting specific signaling pathways are approaching the stages of clinical investigation including the direct renin inhibitors. They have been a highly attractive concept for the future in the management of these patients. However, while advances in technology elucidated many aspects of these diseases, many mysteries still remain. With continued research, we can expect more cost- effective and patient-friendly drug therapies to be developed in the near future.

MRI-Guided Selection of Patients for Acute Ischemic Stroke Treatment

PubMed Central

Leigh, Richard; Krakauer, John W.

2014-01-01

Purpose of review To summarize what is known about the use of MRI in acute stroke treatments (predominantly thrombolysis), to examine the assumptions and theories behind the interpretation of MR images of acute stroke and how they are used to select patients for therapies, and to suggest directions for future research. Recent findings Recent studies have been contradictory about the usefulness of MRI in selecting patients for treatment. New MRI models for selecting patients have emerged that focus not only on the ischemic penumbra but also the core infarct. Fixed time-window selection parameters are being replaced by individualized MRI features. New ways to interpret traditional MRI sequences are emerging. Summary Although the efficacy of acute stroke treatment is time dependent, the use of fixed time-windows does not account for individual differences in infarct evolution, which could be detected with MRI. While MRI shows promise for identifying patients who should be treated, as well as exclude patients who should not be treated, definitive evidence is still lacking. Future research should focus on validating the use of MRI to select patients for IV therapies in extended time windows. PMID:24978637

Construction of orthogonal synchronized bi-directional field to enhance heating efficiency of magnetic nanoparticles.

PubMed

Chen, Shih-Wei; Lai, Jr-Jie; Chiang, Chen-Li; Chen, Cheng-Lung

2012-06-01

Magnetic hyperthermia using magnetic nanoparticles (MNPs) has attracted considerable attention as one of the promising tumor therapy. The study has been developed under single magnetic field. Recently, we found that the immobile MNP may generate more heat under two synchronous ac magnetic fields than traditional single and circular polarized fields based on model simulation result. According to this finding we constructed an orthogonal synchronized bi-directional field (OSB field). The system contained two LC resonant inverters (L: inductor, C: capacitor) and both vertical and transverse ac magnetic fields were generated by two Helmholtz coils. To reduce the interference, the axis directional of two coils were arranged orthogonally. The experiments showed that the heating ability of aggregated MNPs is greatly enhanced under this newly designed OSB field without increasing the strength of magnetic field. The OSB field system provides a promising way for future clinical hyperthermia.

Construction of orthogonal synchronized bi-directional field to enhance heating efficiency of magnetic nanoparticles

NASA Astrophysics Data System (ADS)

Chen, Shih-Wei; Lai-Jie, Jr.; Chiang, Chen-Li; Chen, Cheng-Lung

2012-06-01

Magnetic hyperthermia using magnetic nanoparticles (MNPs) has attracted considerable attention as one of the promising tumor therapy. The study has been developed under single magnetic field. Recently, we found that the immobile MNP may generate more heat under two synchronous ac magnetic fields than traditional single and circular polarized fields based on model simulation result. According to this finding we constructed an orthogonal synchronized bi-directional field (OSB field). The system contained two LC resonant inverters (L: inductor, C: capacitor) and both vertical and transverse ac magnetic fields were generated by two Helmholtz coils. To reduce the interference, the axis directional of two coils were arranged orthogonally. The experiments showed that the heating ability of aggregated MNPs is greatly enhanced under this newly designed OSB field without increasing the strength of magnetic field. The OSB field system provides a promising way for future clinical hyperthermia.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Joe Y., E-mail: jychang@mdanderson.org; Jabbour, Salma K.; De Ruysscher, Dirk

Radiation dose escalation has been shown to improve local control and survival in patients with non–small cell lung cancer in some studies, but randomized data have not supported this premise, possibly owing to adverse effects. Because of the physical characteristics of the Bragg peak, proton therapy (PT) delivers minimal exit dose distal to the target volume, resulting in better sparing of normal tissues in comparison to photon-based radiation therapy. This is particularly important for lung cancer given the proximity of the lung, heart, esophagus, major airways, large blood vessels, and spinal cord. However, PT is associated with more uncertainty becausemore » of the finite range of the proton beam and motion for thoracic cancers. PT is more costly than traditional photon therapy but may reduce side effects and toxicity-related hospitalization, which has its own associated cost. The cost of PT is decreasing over time because of reduced prices for the building, machine, maintenance, and overhead, as well as newer, shorter treatment programs. PT is improving rapidly as more research is performed particularly with the implementation of 4-dimensional computed tomography–based motion management and intensity modulated PT. Given these controversies, there is much debate in the oncology community about which patients with lung cancer benefit significantly from PT. The Particle Therapy Co-operative Group (PTCOG) Thoracic Subcommittee task group intends to address the issues of PT indications, advantages and limitations, cost-effectiveness, technology improvement, clinical trials, and future research directions. This consensus report can be used to guide clinical practice and indications for PT, insurance approval, and clinical or translational research directions.« less

Past, present and future of cyanide antagonism research: From the early remedies to the current therapies.

PubMed

Petrikovics, Ilona; Budai, Marianna; Kovacs, Kristof; Thompson, David E

2015-06-26

This paper reviews milestones in antidotal therapies for cyanide (CN) spanning early remedies, current antidotal systems and research towards next generation therapies. CN has been a part of plant defense mechanisms for millions of years. It became industrially important in the nineteenth century with the advent of CN assisted gold mining and the use of CN as a pest control agent. The biochemical basis of CN poisoning was actively studied and key mechanisms were understood as early as 1929. These fundamental studies led to a variety of antidotes, including indirect CN binders that generate methemoglobin, direct CN binders such as hydroxocobalamin, and sulfur donors that convert CN to the less toxic thiocyanate. Research on blood gases at the end of the twentieth century shed new light on the role of nitric oxide (NO) in the body. The discovery of NO's ability to compete with CN for enzymatic binding sites provided a previously missed explanation for the rapid efficacy of NO generating antidotes such as the nitrites. Presently used CN therapies include: methemoglobin/NO generators (e.g., sodium nitrite, amyl nitrite, and dimethyl aminophenol), sulfur donors (e.g., sodium thiosulfate and glutathione), and direct binding agents [(e.g., hydroxocobalamin and dicobalt salt of ethylenediaminetetraacetic acid (dicobalt edetate)]. A strong effort is being made to explore novel antidotal systems and to formulate them for rapid administration at the point of intoxication in mass casualty scenarios. New antidotes, formulations, and delivery systems are enhancing bioavailability and efficacy and hold promise for a new generation of improved CN countermeasures.

Future directions in inflammatory bowel disease management.

PubMed

D'Haens, Geert R; Sartor, R Balfour; Silverberg, Mark S; Petersson, Joel; Rutgeerts, Paul

2014-08-01

Clinical management of inflammatory bowel diseases (IBD), new treatment modalities and the potential impact of personalised medicine remain topics of intense interest as our understanding of the pathophysiology of IBD expands. Potential future strategies for IBD management are discussed, based on recent preclinical and clinical research. A top-down approach to medical therapy is increasingly being adopted for patients with risk factors for severe inflammation or an unfavourable disease course in an attempt to halt the inflammatory process as early as possible, prevent complications and induce mucosal healing. In the future, biological therapies for IBD are likely to be used more selectively based on personalised benefit/risk assessment, determined through reliable biomarkers and tissue signatures, and will probably be optimised throughout the course of treatment. Biologics with different mechanisms of action will be available; when one drug fails, patients will be able to switch to another and even combination biologics may become a reality. The role of biotherapeutic products that are similar to currently licensed biologics in terms of quality, safety and efficacy - i.e. biosimilars - is at an early stage and requires further experience. Other therapeutic strategies may involve manipulation of the microbiome using antibiotics, probiotics, prebiotics, diet and combinations of all these approaches. Faecal microbiota transplantation is also a potential option in IBD although controlled data are lacking. The future of classifying, prognosticating and managing IBD involves an outcomes-based approach to identify biomarkers reflecting various biological processes that can be matched with clinically important endpoints. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Noise-induced cochlear synaptopathy: Past findings and future studies.

PubMed

Kobel, Megan; Le Prell, Colleen G; Liu, Jennifer; Hawks, John W; Bao, Jianxin

2017-06-01

For decades, we have presumed the death of hair cells and spiral ganglion neurons are the main cause of hearing loss and difficulties understanding speech in noise, but new findings suggest synapse loss may be the key contributor. Specifically, recent preclinical studies suggest that the synapses between inner hair cells and spiral ganglion neurons with low spontaneous rates and high thresholds are the most vulnerable subcellular structures, with respect to insults during aging and noise exposure. This cochlear synaptopathy can be "hidden" because this synaptic loss can occur without permanent hearing threshold shifts. This new discovery of synaptic loss opens doors to new research directions. Here, we review a number of recent studies and make suggestions in two critical future research directions. First, based on solid evidence of cochlear synaptopathy in animal models, it is time to apply molecular approaches to identify the underlying molecular mechanisms; improved understanding is necessary for developing rational, effective therapies against this cochlear synaptopathy. Second, in human studies, the data supporting cochlear synaptopathy are indirect although rapid progress has been made. To fully identify changes in function that are directly related this hidden synaptic damage, we argue that a battery of tests including both electrophysiological and behavior tests should be combined for diagnosis of "hidden hearing loss" in clinical studies. This new approach may provide a direct link between cochlear synaptopathy and perceptual difficulties. Copyright © 2016 Elsevier B.V. All rights reserved.

Psychological treatment of attention deficit hyperactivity disorder in adults: a systematic review.

PubMed

Vidal-Estrada, Raquel; Bosch-Munso, Rosa; Nogueira-Morais, Mariana; Casas-Brugue, Miquel; Ramos-Quiroga, Josep A

2012-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder of childhood onset. The disorder persists into adulthood in most cases, significantly affecting patient function. Although the firstline choice of treatment for ADHD is pharmacological, drug treatments are not always sufficient. All the published studies on the psychological treatment of ADHD were systematically reviewed for the present article. The MEDLINE and PsychINFO electronic databases were searched using the terms psychological treatment OR psychotherapy OR psychosocial treatment AND ADHD. Patient age was restricted to adults (all adult:19+ years). Eighteen published studies met inclusion criteria for the review. Fifteen efficacy studies of psychological treatment were selected (cognitive behavioral therapy, metacognitive therapy, dialectical behavior therapy, coaching, cognitive remediation) and three previous reviews. The results indicate that cognitive behavioral therapy is the most effective psychological treatment for ADHD symptoms in adults and the comorbid symptoms of anxiety and depression, which have an important functional impact on the daily life of patients. However, more research is needed to know the differential effects of each psychological approach in relation to improved ADHD symptoms in adults. Finally, future directions for the psychosocial treatment of ADHD problems of adults are suggested.

Proteomic Investigations into Hemodialysis Therapy

PubMed Central

Bonomini, Mario; Sirolli, Vittorio; Pieroni, Luisa; Felaco, Paolo; Amoroso, Luigi; Urbani, Andrea

2015-01-01

The retention of a number of solutes that may cause adverse biochemical/biological effects, called uremic toxins, characterizes uremic syndrome. Uremia therapy is based on renal replacement therapy, hemodialysis being the most commonly used modality. The membrane contained in the hemodialyzer represents the ultimate determinant of the success and quality of hemodialysis therapy. Membrane’s performance can be evaluated in terms of removal efficiency for unwanted solutes and excess fluid, and minimization of negative interactions between the membrane material and blood components that define the membrane’s bio(in)compatibility. Given the high concentration of plasma proteins and the complexity of structural functional relationships of this class of molecules, the performance of a membrane is highly influenced by its interaction with the plasma protein repertoire. Proteomic investigations have been increasingly applied to describe the protein uremic milieu, to compare the blood purification efficiency of different dialyzer membranes or different extracorporeal techniques, and to evaluate the adsorption of plasma proteins onto hemodialysis membranes. In this article, we aim to highlight investigations in the hemodialysis setting making use of recent developments in proteomic technologies. Examples are presented of why proteomics may be helpful to nephrology and may possibly affect future directions in renal research. PMID:26690416

[Proteins support stem cells - use of protein therapeutics in hematopoietic stem cell transplantation].

PubMed

Meyer, Sara Christina; Stern, Martin

2011-11-01

Hematopoietic stem cell transplantation (HSCT) has evolved from a largely experimental therapeutic approach three decades ago to a well-established therapy today for many malignant and non-malignant disorders of the hematopoietic and the immune system. Although it is per se a therapy by transmission of cells, protein therapeutics such as growth factors and antibodies are relevant in all phases of a HSCT and substantially contribute to the success of this often only curative treatment. This review discusses HSCT with a particular focus on the protein therapeutics involved. Granulocyte colony stimulating factor (G-CSF) for mobilization of stem cells to the peripheral blood, the polyclonal anti-T-cell globulin (ATG) and the monoclonal antibodies alemtuzumab and etanercept for prophylaxis and therapy of graft versus host disease (GvHD) are highlighted. Also rituximab, palivizumab and polyclonal intravenous immunoglobulins for treating infections in post-transplant patients are discussed. Since our understanding of cell surface receptors, cytokine and signaling pathways is increasing, there will emerge new targets for directed therapy by proteins in the future. They may have the potential to further improve the success and to widen theapplication of HSCT.

Technological Approaches for Neurorehabilitation: From Robotic Devices to Brain Stimulation and Beyond.

PubMed

Semprini, Marianna; Laffranchi, Matteo; Sanguineti, Vittorio; Avanzino, Laura; De Icco, Roberto; De Michieli, Lorenzo; Chiappalone, Michela

2018-01-01

Neurological diseases causing motor/cognitive impairments are among the most common causes of adult-onset disability. More than one billion of people are affected worldwide, and this number is expected to increase in upcoming years, because of the rapidly aging population. The frequent lack of complete recovery makes it desirable to develop novel neurorehabilitative treatments, suited to the patients, and better targeting the specific disability. To date, rehabilitation therapy can be aided by the technological support of robotic-based therapy, non-invasive brain stimulation, and neural interfaces. In this perspective, we will review the above methods by referring to the most recent advances in each field. Then, we propose and discuss current and future approaches based on the combination of the above. As pointed out in the recent literature, by combining traditional rehabilitation techniques with neuromodulation, biofeedback recordings and/or novel robotic and wearable assistive devices, several studies have proven it is possible to sensibly improve the amount of recovery with respect to traditional treatments. We will then discuss the possible applied research directions to maximize the outcome of a neurorehabilitation therapy, which should include the personalization of the therapy based on patient and clinician needs and preferences.

Community-acquired pneumonia requiring hospitalization: rational decision making and interpretation of guidelines.

PubMed

Postma, Douwe F; van Werkhoven, Cornelis H; Oosterheert, Jan Jelrik

2017-05-01

This review focuses on the evidence base for guideline recommendations on the diagnosis, the optimal choice, timing and duration of empirical antibiotic therapy, and the use of microbiological tests for patients hospitalized with community-acquired pneumonia (CAP): issues for which guidelines are frequently used as a quick reference. Furthermore, we will discuss possibilities for future research in these topics. Many national and international guideline recommendations, even on critical elements of CAP management, are based on low-to-moderate quality evidence. The diagnosis and management of CAP has hardly changed for decades. The recommendation to cover atypical pathogens in all hospitalized CAP patients is based on observational studies only and is challenged by two recent trials. The following years, improved diagnostic testing, radiologically by low-dose Computed Tomography or ultrasound and/or microbiologically by point-of-care multiplex PCR, has the potential to largely influence the choice and start of antibiotic therapy in hospitalized CAP patients. Rapid microbiological testing will hopefully improve antibiotic de-escalation or early pathogen-directed therapy, both potent ways of reducing broad-spectrum antibiotic use. Current guideline recommendations on the timing and duration of antibiotic therapy are based on limited evidence, but will be hard to improve.

Investigational drug therapies for coeliac disease - where to from here?

PubMed

Haridy, James; Lewis, Diana; Newnham, Evan D

2018-03-01

Despite decades of research and a detailed knowledge of the immunopathological basis of coeliac disease (CD), adherence to a lifelong gluten-free diet (GFD) remains the single proven and available treatment. The increasing prevalence of CD combined with variable adherence to the GFD in a significant proportion of patients demands new therapeutic strategies. Areas covered: Trial registries, clinicaltrials.gov, pharmaceutical company website searches as well as published data from PubMed and conference proceedings were used to extract the most recent outcomes for CD therapeutics. This article aims to review the available therapies from a pathophysiological approach, and propose future directions in this interesting yet largely unfulfilled area of research. Expert opinion: Increasingly, the GFD is being challenged by its availability, palatability, practicality and now even efficacy in some populations. Whilst the causative antigens have been well described, it is clear that treatment based on the removal of these immunostimulatory peptides from the diet is far more complex than early experience in CD treatment implied. Despite burgeoning interest and research in experimental therapies for CD over the past twenty years, the only therapy showing promise as a true alternative to a GFD is that of the induction of tolerance via a vaccine.

Management of menopause-associated vasomotor symptoms: Current treatment options, challenges and future directions

PubMed Central

Pachman, Deirdre R; Jones, Jason M; Loprinzi, Charles L

2010-01-01

Hot flashes are one of the most common and distressing symptoms associated with menopause, occurring in more than 75% of postmenopausal women. They are especially problematic in breast cancer patients since some breast cancer therapies can induce hot flashes. For mild hot flashes, it is proposed that behavioral modifications are the first step in management. Hormonal therapies, including estrogens and progestogens, are the most well known effective agents in relieving hot flashes; however, the safety of these agents is controversial. There is an increasing amount of literature on nonhormonal agents for the treatment of hot flashes. The most promising data regard newer antidepressant agents such as venlafaxine, which reduces hot flashes by about 60%. Gabapentin is another nonhormonal agent that is effective in reducing hot flashes. While many complimentary therapies, including phytoestrogens, black cohosh, and dehydroepiandrosterone, have been explored for the treatment of hot flashes; none can be recommended at this time. Furthermore, there is a lack of strong evidence to support exercise, yoga, or relaxation for the treatment of hot flashes. Paced respirations and hypnosis appear to be promising enough to warrant further investigation. Another promising nonpharmacological therapy, currently under investigation, involves a stellate ganglion block. PMID:21072305

Cell-Based Therapies in Vascularized Composite Allotransplantation.

PubMed

Vyas, Krishna S; Mohan, Anita T; Morrison, Shane D; Tran, Duy C; Mardini, Samir

2018-06-26

 Dendritic cells (DCs) are bone marrow-derived, professional antigen-presenting cells with tolerogenic function. The ability of DCs to regulate alloantigen-specific T cell responses and to promote tolerance has aligned them ideally for a role in vascularized composite allotransplantation (VCA). In this study, we summarize the current evidence for DC therapies for tolerance induction to alleviate the requirement for chronic immunosuppression.  A comprehensive and structured review of manuscripts published on VCA was performed using the MEDLINE and PubMed databases. All eligible studies published from the year 2000 to 2017 were included in the final results.  Nineteen original preclinical and clinical studies that employed cell therapy for VCA were included in this review. In vivo DC therapy was found to direct the alloimmune response toward either transplant rejection or tolerance in VCA models. While injection of mature DCs rapidly increases T-cell activity in humans and promotes transplant rejection, the injection of immature DCs acts as an immunosuppressant and inhibits T-cell activity. In addition to immature DCs, mesenchymal stem cells were also found to have a positive effect on allotransplantation of solid organs and bone marrow via cytokine expression which decreases the alloreactive effector lymphocytes and increases CD4+/CD25+/FoxP3 Tregs. Despite the promising findings, the efficacy of cell-based therapies varies greatly across studies, partly due to different methods of cell isolation and purification techniques, source, route and timing of administration, and combination immunosuppressive therapy.  Additional research is needed to evaluate the efficacy and safety of DC and other cell-based therapeutic measures in human allotransplant recipients. Future direction will focus on the development of novel methods to reduce immunosuppression and develop more individualized management, as well as the clinical application of basic research in the mechanisms of immunologic tolerance. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Fluorescence detection, enumeration and characterization of single circulating cells in vivo: technology, applications and future prospects

NASA Astrophysics Data System (ADS)

Hartmann, Carolin; Patil, Roshani; Lin, Charles P.; Niedre, Mark

2018-01-01

There are many diseases and biological processes that involve circulating cells in the bloodstream, such as cancer metastasis, immunology, reproductive medicine, and stem cell therapies. This has driven significant interest in new technologies for the study of circulating cells in small animal research models and clinically. Most currently used methods require drawing and enriching blood samples from the body, but these suffer from a number of limitations. In contrast, ‘in vivo flow cytometry’ (IVFC) refers to set of technologies that allow study of cells directly in the bloodstream of the organism in vivo. In recent years the IVFC field has grown significantly and new techniques have been developed, including fluorescence microscopy, multi-photon, photo-acoustic, and diffuse fluorescence IVFC. In this paper we review recent technical advances in IVFC, with emphasis on instrumentation, contrast mechanisms, and detection sensitivity. We also describe key applications in biomedical research, including cancer research and immunology. Last, we discuss future directions for IVFC, as well as prospects for broader adoption by the biomedical research community and translation to humans clinically.

Fluorescence detection, enumeration and characterization of single circulating cells in vivo: technology, applications and future prospects.

PubMed

Hartmann, Carolin; Patil, Roshani; Lin, Charles P; Niedre, Mark

2017-12-14

There are many diseases and biological processes that involve circulating cells in the bloodstream, such as cancer metastasis, immunology, reproductive medicine, and stem cell therapies. This has driven significant interest in new technologies for the study of circulating cells in small animal research models and clinically. Most currently used methods require drawing and enriching blood samples from the body, but these suffer from a number of limitations. In contrast, 'in vivo flow cytometry' (IVFC) refers to set of technologies that allow study of cells directly in the bloodstream of the organism in vivo. In recent years the IVFC field has grown significantly and new techniques have been developed, including fluorescence microscopy, multi-photon, photo-acoustic, and diffuse fluorescence IVFC. In this paper we review recent technical advances in IVFC, with emphasis on instrumentation, contrast mechanisms, and detection sensitivity. We also describe key applications in biomedical research, including cancer research and immunology. Last, we discuss future directions for IVFC, as well as prospects for broader adoption by the biomedical research community and translation to humans clinically.

Childhood Ataxia: Clinical Features, Pathogenesis, Key Unanswered Questions, and Future Directions

PubMed Central

Ashley, Claire N.; Hoang, Kelly D.; Lynch, David R.; Perlman, Susan L.; Maria, Bernard L.

2013-01-01

Childhood ataxia is characterized by impaired balance and coordination primarily due to cerebellar dysfunction. Friedreich ataxia, a form of childhood ataxia, is the most common multisystem autosomal recessive disease. Most of these patients are homozygous for the GAA repeat expansion located on the first intron of the frataxin gene on chromosome 9. Mutations in the frataxin gene impair mitochondrial function, increase reactive oxygen species, and trigger redistribution of iron in the mitochondria and cytosol. Targeted therapies for Friedreich ataxia are undergoing testing. In addition, a centralized database, patient registry, and natural history study have been launched to support clinical trials in Friedreich ataxia. The 2011 Neurobiology of Disease in Children symposium, held in conjunction with the 40th annual Child Neurology Society meeting, aimed to (1) describe clinical features surrounding Friedreich ataxia, including cardiomyopathy and genetics; (2) discuss recent advances in the understanding of the pathogenesis of Friedreich ataxia and developments of clinical trials; (3) review new investigations of characteristic symptoms; (4) establish clinical and biochemical overlaps in neurodegenerative diseases and possible directions for future basic, translational, and clinical studies. PMID:22859693

Direct versus indirect and individual versus group modes of language therapy for children with primary language impairment: principal outcomes from a randomized controlled trial and economic evaluation.

PubMed

Boyle, James M; McCartney, Elspeth; O'Hare, Anne; Forbes, John

2009-01-01

Many school-age children with language impairments are enrolled in mainstream schools and receive indirect language therapy, but there have been, to the authors' knowledge, no previous controlled studies comparing the outcomes and costs of direct and indirect intervention delivered by qualified therapists and therapy assistants, and each delivery mode offered to children individually or in groups. To investigate the relative effectiveness of indirect and direct intervention therapy modes delivered individually or in groups for children with primary language impairment. A multi-centre randomized controlled trial investigated 161 children with primary language impairment aged 6-11 years randomized to a usual-therapy control group or to direct individual, indirect individual, direct group or indirect group therapy modes. Intervention was delivered three times a week for 30-40-min sessions in mainstream schools over 15 weeks. Language performance was assessed at baseline, post-therapy and at 12 months. Cost analysis was based on salary and travel costs for intervention modes and usual therapy. Compared with controls, children receiving project therapy made short-term improvements in expressive (p = 0.031), but not receptive, language immediately following intervention. Children with specific expressive language delay were more likely to show improvement than those with mixed receptive-expressive difficulties. The four project therapy modes did not differ on primary language outcomes (all p-values>0.392) and there were no further improvements evident at follow-up. Indirect group therapy was the least costly mode, with direct individual therapy the most costly. Intervention in this age group can be effective for expressive language and can be delivered equally effectively though speech and language therapy assistants and to children in groups.

Practice, progress and future directions for physical therapies in Huntingtons disease.

PubMed

Busse, Monica; Khalil, Hanan; Brooks, Simon; Quinn, Lori; Rosser, Anne

2012-01-01

Physical therapies and exercise may have potential as a disease modifying agent in Huntington's disease (HD) and in recent years, there have been several small scale feasibility studies that have shown benefit as a result of physical interventions. When evaluating complex physical interventions, a phased approach using mixed methodology designs that report specific intervention components, adherence, acceptability, adverse events and defined intervention protocols is important for replication and planning of future trials and to ensure potential for implementation in clinical practice. A narrative review of the available literature related to physical activity, physical therapy and exercise in people with HD was performed using a population, intervention, comparison and outcome (PICO) approach. Eight studies met specific inclusion criteria and were reviewed in terms of their systematic conduct and reporting standards. All of the studies (n = 8) provided details of intervention including location and duration. The majority of interventions included balance training activities in combination with other complex activities of daily living that required therapist supervision. Two of the interventions were home based, the remainder were facility or hospital based. None of the studies reported adverse events whilst only 3/8 reported adherence rates which were ranging from 60-80%. In general, limited detail was provided on the specific individual components of the interventions. This review of primary publications and conference proceedings, suggests that researchers working in the field need to focus on clearer reporting of intervention protocols so as to generate a clearer understanding of the impact of exercise and physical therapies on the symptoms of HD, as well as any potential synergistic role alongside the impending disease-modifying interventions.

Liver transplantation for hepatocellular carcinoma: a surgical perspective.

PubMed

Fortune, Brett E; Umman, Veysel; Gilliland, Thomas; Emre, Sukru

2013-07-01

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in the world. Early detection and timely treatment of HCC is critical for better patient outcomes. Curative therapy consists of surgical hepatic resection or liver transplantation (LTx); however, both are restricted to explicit selective criteria. Liver resection is the gold standard of treatment for noncirrhotic patients but can be done in only a small fraction of cirrhotic patients depending on synthetic dysfunction, degree of portal hypertension, and number and location(s) of tumor(s). Therefore, the best treatment modality in cirrhotic patients with HCC is LTx as it will cure both HCC and the underlying cirrhosis. The limitation to offer transplant to all cirrhotic patients with HCC is the shortage of available donor organs. While these patients are waiting for transplant, their tumors may progress and develop distant metastases and may lead to patients losing their candidacy for LTx. Various ablation therapies can be used to treat HCC, prevent tumor progression, and thus, avoid patients losing the option of LTx. Future directions to improve HCC patient outcomes include advancement in tumor gene analysis and histopathology for better prediction of tumor behavior, improved immunosuppression regimens to reduce tumor recurrence in the posttransplant setting, and efficient use of an expanded donor pool that includes living donor organs. This paper will review the current methods of HCC diagnosis, selection for either hepatic resection or LTx, and will also summarize posttreatment outcomes. We will suggest future directions for the field as we strive to improve outcomes for our HCC patients.

Creating state of the art, next-generation Virtual Reality exposure therapies for anxiety disorders using consumer hardware platforms: design considerations and future directions.

PubMed

Lindner, Philip; Miloff, Alexander; Hamilton, William; Reuterskiöld, Lena; Andersson, Gerhard; Powers, Mark B; Carlbring, Per

2017-09-01

Decades of research and more than 20 randomized controlled trials show that Virtual Reality exposure therapy (VRET) is effective in reducing fear and anxiety. Unfortunately, few providers or patients have had access to the costly and technical equipment previously required. Recent technological advances in the form of consumer Virtual Reality (VR) systems (e.g. Oculus Rift and Samsung Gear), however, now make widespread use of VRET in clinical settings and as self-help applications possible. In this literature review, we detail the current state of VR technology and discuss important therapeutic considerations in designing self-help and clinician-led VRETs, such as platform choice, exposure progression design, inhibitory learning strategies, stimuli tailoring, gamification, virtual social learning and more. We illustrate how these therapeutic components can be incorporated and utilized in VRET applications, taking full advantage of the unique capabilities of virtual environments, and showcase some of these features by describing the development of a consumer-ready, gamified self-help VRET application for low-cost commercially available VR hardware. We also raise and discuss challenges in the planning, development, evaluation, and dissemination of VRET applications, including the need for more high-quality research. We conclude by discussing how new technology (e.g. eye-tracking) can be incorporated into future VRETs and how widespread use of VRET self-help applications will enable collection of naturalistic "Big Data" that promises to inform learning theory and behavioral therapy in general.

Delays in Initiation of Disease-Modifying Therapy in Rheumatoid Arthritis Patients: Data from a US-Based Registry.

PubMed

Pappas, Dimitrios A; Kent, Jeffrey D; Greenberg, Jeffrey D; Mason, Marc A; Kremer, Joel M; Holt, Robert J

2015-12-01

The goal of this study was to evaluate how frequently rheumatoid arthritis (RA) therapy is instituted promptly and to describe the characteristics of patients who are not treated early upon diagnosis. The percentage of patients who at the time of enrollment in the Corrona registry were not receiving any RA-directed therapy was evaluated and their characteristics were summarized. The time to subsequent initiation of any RA-directed therapy was also estimated. Among 35,485 patients enrolled in Corrona, 34,735 (97.9%) were on appropriate therapy for RA and 750 (2.1%) had no history of any RA-directed therapy at time of enrollment. Among patients without any history of RA-directed therapy, the overall disease duration was 5.5 ± 9.0 years, with only 50.7% of patients having early disease (duration ≤1 year). Patients with no history of directed RA therapy did not have lower disease activity at enrollment compared with those receiving therapy. Clinical Disease Activity Index (CDAI) was 18.3 ± 15.0; 34% of patients had high and 27.6% moderate disease activity by CDAI. Patients were followed for a median (95% CI) time of 29.5 months (24.6-33.8). During the follow-up period, 372 out of 750 (49.6%) patients initiated RA-directed therapy. The median time to initiation of any RA-directed therapy was 12.1 months (95% CI 9.3-14.8). In this registry analysis, approximately 98% of patients were on appropriate RA therapy for their RA. However, a minority of patients with RA did not have a history of receiving disease-modifying therapy within a mean of approximately 5 years of RA onset and approximately 50% of them did not initiate any therapy within 12 months of registry follow-up. This delay in therapy did not appear to be related to a better controlled, or lower, RA disease activity state at the time of enrollment in the registry. Corrona, LLC.

Induction chemotherapy in acute myeloid leukaemia: origins and emerging directions.

PubMed

Upadhyay, Vivek A; Fathi, Amir T

2018-03-01

This review summarizes the hallmark developments in induction chemotherapy for acute myeloid leukaemia and further describes future directions in its evolution. We describe the origin of induction chemotherapy. We also describe notable modifications and adjustments to 7+3 induction chemotherapy since its development. Finally, we describe new efforts to modify and add new agents to induction therapy, including '7+3 Plus' combinations. Induction chemotherapy remains the standard of care for the majority of patients with acute myeloid leukaemia. However, its success is limited in a subset of patients by toxicity, failure to achieve remission and potential for subsequent relapse. Novel agents such as mutant fms like tyrosine kinase 3 inhibitors, mutant isocitrate dehydrogenase inhibitors, CD33-antibody drug conjugates and liposomal formulations have demonstrated significant potential as modifications to traditional induction chemotherapy.

Low-level Light Therapy for Treatment of Diabetic Foot Ulcer: A Review of Clinical Experiences.

PubMed

Tchanque-Fossuo, Catherine N; Ho, Derek; Dahle, Sara E; Koo, Eugene; Isseroff, R Rivkah; Jagdeo, Jared

2016-07-01

Diabetic foot ulcers (DFU) represent a significant complication of diabetes mellitus (DM). DFU affect one in four patients with DM and treatments of DFU are limited and challenging. The management of DFU remains a significant healthcare and socioeconomic burden ($245 billion). There is a wide range of advanced therapies for DFU, but these are costly and have demonstrated only minimal efficacy in limited published studies. An emerging treatment modality to improve DFU and optimize wound healing is the use of low-level light therapy (LLLT). LLLT involves the use of light in the form of low-level or low-power laser or light emitting diodes to alter biochemical pathways, which may result in changes to cell shape, cell migration, and cell signaling.
To review published clinical experiences (case series and case reports) using LLLT for treatment of DFU, and provide evidence-based recommendations and future directions on the potential of LLLT as a therapeutic modality for DFU.
On January 16, 2016 we searched the published literature using databases: PubMed, EMBASE, CINAHL, and Web of Science with key terms: "diabetic foot" AND ("low level laser therapy" OR "low level light therapy" OR "LLLT" OR "light emitting diode" OR "phototherapy" OR "laser").
After screening of titles, abstracts and/or full-text, 7 original articles were suitable in our review. Our review contains 5 case series and 2 case reports that evaluated LLLT for treatment of DFU, and all reviewed studies have shown positive improvement of DFU using LLLT with no adverse events, albeit with limitations that may be minimized with future RCTs.
LLLT is an emerging and promising treatment modality to current alternatives that are costly and have shown limited success. Based upon the published evidence, we envision additional research may allow for stronger recommendation with LLLT for treatment of DFU.

J Drugs Dermatol. 2016;15(7):843-848.

Rationale, design, and methodology of a trial evaluating three models of care for HCV treatment among injection drug users on opioid agonist therapy.

PubMed

Akiyama, Matthew J; Agyemang, Linda; Arnsten, Julia H; Heo, Moonseong; Norton, Brianna L; Schackman, Bruce R; Linas, Benjamin P; Litwin, Alain H

2018-02-09

People who inject drugs (PWID) constitute 60% of the approximately 5 million people in the U.S. infected with hepatitis C virus (HCV). Treatment of PWID is complex due to addiction, mental illness, poverty, homelessness, lack of positive social support, poor adherence-related skills, low motivation and knowledge, and poor access to and trust in the health care system. New direct-acting antiviral medications are available for HCV with high cure rates and few side effects. The life expectancy and economic benefits of new HCV treatments will not be realized unless we determine optimal models of care for the majority of HCV-infected patients. The purpose of this study is to evaluate the effectiveness of directly observed therapy and group treatment compared with self-administered individual treatment in a large, urban opioid agonist therapy clinic setting in the Bronx, New York. In this randomized controlled trial 150 PWID with chronic HCV were recruited from opioid agonist treatment (OAT) clinics and randomized to one of three models of onsite HCV treatment in OAT: 1) modified directly observed therapy; 2) group treatment; or 3) control - self-administered individual treatment. Participants were age 18 or older, HCV genotype 1, English or Spanish speaking, treatment naïve (or treatment experienced after 12/3/14), willing to receive HCV treatment onsite, receiving methadone or buprenorphine at the medication window at least once per week, and able to provide informed consent. Outcomes of interest include adherence (as measured by self-report and electronic blister packs), HCV treatment completion, sustained virologic response, drug resistance, and cost-effectiveness. This paper describes the design and rationale of a randomized controlled trial comparing three models of care for HCV therapy delivered in an opioid agonist treatment program. Our trial will be critical to rigorously identify models of care that result in high adherence and cure rates. Use of blister pack technology will help us determine the role of adherence in successful cure of HCV. Moreover, the trial methodology outlined here can serve as a template for the development of future programs and studies among HCV-infected drug users receiving opioid agonist therapy, as well as the cost-effectiveness of such programs. This trial was registered with ClinicalTrials.gov ( NCT01857245 ). Trial registration was obtained prospectively on May 20th, 2013.

Costs of bronchoalveolar lavage-directed therapy in the first 5 years of life for children with cystic fibrosis.

PubMed

Moodie, Marj; Lal, Anita; Vidmar, Suzanna; Armstrong, David S; Byrnes, Catherine A; Carlin, John B; Cheney, Joyce; Cooper, Peter J; Grimwood, Keith; Robertson, Colin F; Tiddens, Harm A; Wainwright, Claire E

2014-09-01

To determine whether bronchoalveolar lavage (BAL)-directed therapy for infants and young children with cystic fibrosis (CF), rather than standard therapy, was justified on the grounds of a decrease in average costs and whether the use of BAL reduced treatment costs associated with hospital admissions. Costs were assessed in a randomized controlled trial conducted in Australia and New Zealand on infants diagnosed with CF after newborn screening and assigned to receive either BAL-directed or standard therapy until they reached 5 years of age. A health care funder perspective was adopted. Resource use measurement was based on standardized data collection forms administered for patients across all sites. Unit costs were obtained primarily from government schedules. Mean costs per child during the study period were Australian dollars (AUD)92 860 in BAL-directed therapy group and AUD90 958 in standard therapy group (mean difference AUD1902, 95% CI AUD-27 782 to 31 586, P = .90). Mean hospital costs per child during the study period were AUD57 302 in the BAL-directed therapy group and AUD66 590 in the standard therapy group (mean difference AUD-9288; 95% CI AUD-35 252 to 16 676, P = .48). BAL-directed therapy did not result in either lower mean hospital admission costs or mean costs overall compared with managing patients with CF by a standard protocol based upon clinical features and oropharyngeal culture results alone. Following on our previous findings that BAL-directed treatment offers no clinical advantage over standard therapy at age 5 years, flexible bronchoscopy with BAL cannot be recommended for the routine management of preschool children with CF on the basis of overall cost savings. Copyright © 2014 Elsevier Inc. All rights reserved.

Efficacy of Skin-Directed Therapy for Cutaneous Metastases From Advanced Cancer: A Meta-Analysis

PubMed Central

Spratt, Daniel E.; Gordon Spratt, Elizabeth A.; Wu, Shenhong; DeRosa, Antonio; Lee, Nancy Y.; Lacouture, Mario E.; Barker, Christopher A.

2014-01-01

Purpose To perform the first meta-analysis of the efficacy of skin-directed therapies for cutaneous metastases. Methods MEDLINE, EMBASE, The Cochrane Library, and ClinicalTrials.gov databases were searched for reports of prospective clinical studies published between 1960 and 2013 that assessed the response of skin-directed therapy for cutaneous metastases (47 of 2,955 unique studies were selected). Primary end points of the study were complete and objective response rates. Secondary analyses were preplanned and included subgroup analyses by skin-directed therapy, histology, and recurrence rates. Meta-analyses were performed with random-effect modeling, and extent of heterogeneity between studies was determined with the Cochran Q and I2 tests. Results After applying exclusion criteria, 47 prospective studies of 4,313 cutaneous metastases were assessed. Five skin-directed therapies were identified: electrochemotherapy, photodynamic therapy, radiotherapy, intralesional therapy, and topical therapy. Among all cutaneous metastases, complete response rate was 35.5% (95% CI, 27.6% to 44.3%) and objective response rate was 60.2% (95% CI, 50.6% to 69.0%). Overall recurrence rate was estimated to be 9.2% (95% CI, 3.7% to 21.2%). Melanoma and breast carcinoma comprised 96.8% of all cutaneous metastases studied and had similar objective response rates (54.5% [95% CI, 48.3% to 60.7%] and 54.0% [95% CI, 48.3% to 59.7%], respectively). Grade ≥ 3 toxicity was reported in less than 6% of patients. Conclusion Response to skin-directed therapy for cutaneous metastases is high but heterogeneous across treatment modalities, with low rates of recurrence post-treatment. Treatment was generally well tolerated and conferred improvements in quality of life. Standardization of response criteria for cutaneous metastases and treatment algorithms to optimally use the available skin-directed therapies are needed. PMID:25154827

Cardio-supportive devices (VRD & DCC device) and patches for advanced heart failure: A review, summary of state of the art and future directions.

PubMed

Naveed, Muhammad; Han, Lei; Khan, Ghulam Jilany; Yasmeen, Sufia; Mikrani, Reyaj; Abbas, Muhammad; Cunyu, Li; Xiaohui, Zhou

2018-06-01

Congestive heart failure (CHF) is a complicated pathophysiological syndrome, leading cause of hospitalization as well as mortalities in developed countries wherein an irregular function of the heart leads to the insufficient blood supply to the body organs. It is an accumulative slackening of various complications including myocardial infarction (MI), coronary heart disease (CAD), hypertension, valvular heart disease (VHD) and cardiomyopathy; its hallmarks include hypertrophy, increased interstitial fibrosis and loss of myocytes. The etiology of CHF is very complex and despite the rapid advancement in pharmacological and device-based interventional therapies still, a single therapy may not be sufficient to meet the demand for coping with the diseases. Total artificial hearts (TAH) and ventricular assist devices (VADs) have been widely used clinically to assist patients with severe HF. Unfortunately, direct contact between the patient's blood and device leads to thromboembolic events, and then coagulatory factors, as well as, infection contribute significantly to complicate the situation. There is no effective treatment of HF except cardiac transplantation, however, genetic variations, tissue mismatch; differences in certain immune response and socioeconomic crisis are an important concern with cardiac transplantation suggesting an alternate bridge to transplant (BTT) or destination therapies (DT). For these reasons, researchers have turned to mechanically driven compression devices, ventricular restraint devices (VRD) and heart patches. The ASD is a combination of all operational patches and cardiac support devices (CSD) by delivering biological agents and can restrain or compress the heart. Present study summarizes the accessible peer-reviewed literature focusing on the mechanism of Direct Cardiac Compression (DCC) devices, VRD and patches and their acquaintance to optimize the therapeutic efficacy in a synergistic way. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The future of pharmaceutical manufacturing in the context of the scientific, social, technological and economic evolution.

PubMed

Stegemann, Sven

2016-07-30

Healthcare provision is one of the import elements of modern societies. Life sciences and technology has made substantial progress over the past century and is continuing to evolve exponentially in many different areas. The use of genotypic and phenotypic information in drug discovery and drug therapy, the increasing wealth around the world, growing patient involvement through information and communication technology and finally innovations in pharmaceutical manufacturing technology are transforming the provision of healthcare. The adoption of this new science and technology is going to happen due to the synergistic effects and visible benefits for the society and healthcare systems. The different aspects driving advanced pharmaceutical manufacturing are reviewed to identify future research direction to assure overall acceptance and adoption into healthcare practice. Copyright © 2015 Elsevier B.V. All rights reserved.

[Progress of perioperative goal-directed fluid therapy on prognosis of patients].

PubMed

Zhao, J; Yu, Y H

2016-12-01

Fluid therapy is an important part of perioperative period, also one of the most controversial issues. Having reviewed the relevant research in recent years as well as the large-scale meta-analysis, the perioperative goal-directed fluid therapy has been discussed from the aspects of evaluating indicators, new methods and latest progress, and the impact on the prognosis. It manifests that the development of goal-directed fluid therapy makes a better prognosis than traditional fluid therapy, therefore it has also became an important perioperative treatment strategy.

The future of hemodialysis membranes.

PubMed

Humes, H D; Fissell, W H; Tiranathanagul, K

2006-04-01

Hemodialytic treatment of patients with either acute or chronic renal failure has had a dramatic impact on the mortality rates of these patients. Unfortunately, this membrane-based therapy is still incomplete renal replacement, as the mortality and morbidity of these patients remain unacceptably high. Much progress must be made to improve the biocompatibility of hemodialysis membranes as well as their hydraulic and permselective properties to remove small solutes and 'middle molecules' in compact cartridges. The next directions of development will leverage materials and mechanical engineering technology, including microfluidics and nanofabrication, to further improve the clearance functions of the kidney to replicate glomerular permselectivity while retaining high rates of hydraulic permeability. The extension of membrane technology to biohybrid devices utilizing progenitor/stem cells will be another substantive advance for renal replacement therapy. The ability to not only replace solute and water clearance but also active reabsorptive transport and metabolic activity will add additional benefit to the therapy of patients suffering from renal failure. This area of translational research is rich in creative opportunities to improve the unmet medical needs of patients with either chronic or acute renal failure.

Photodynamic therapy: a promising alternative in oncology

NASA Astrophysics Data System (ADS)

Nelius, Thomas; de Riese, Werner T. W.; Filleur, Stephanie

2004-07-01

Photodynamic Therapy (PDT) is a treatment modality that is based on the administration of a photosensitizer and the following application of light in a wavelength range matching the absorption spectrum of the photosensitizer. Ideally the photosensitizer retains in the tumor tissue more than in normal tissue and thus allows targeted destruction of cancerous tissue. The use of PDT is slowly being accepted as a standard treatment for certain types of cancer. This includes mainly treatment strategies with only palliative intentions (obstructive esophageal cancer and advanced lung cancer) while for certain malignant conditions new applications exists that are already intended for cure (e.g. early stage of lung cancer). The main advantage of PDT is that the treatment can be repeated multiple times safely without major side effects. PDT can be safely combined with already established treatment options like surgery, chemotherapy or radiotherapy. A disadvantage of PDT is the only localized effect of the therapy, which usually cannot significantly alter the outcome of a systemic disease. In this paper we review the history of PDT as well as current clinical applications in oncology and future directions.

Pharmacotherapy of Scleritis: Current Paradigms and Future Directions

PubMed Central

Beardsley, Robert M.; Suhler, Eric B.; Rosenbaum, James T.; Lin, Phoebe

2013-01-01

Introduction Scleritis is an inflammatory condition affecting the eye wall that may be associated with a number of systemic inflammatory diseases. Because scleritis can be refractory to standard treatment, knowledge of the body of available and emerging therapies is paramount and is reviewed here. Areas Covered This review focuses on both traditional and emerging therapies for non-infectious scleritis. We will cover the mechanisms of action and potential adverse effects of each of the treatment modalities. Additionally, a summary of the significant MEDLINE indexed literature under the subject heading “scleritis,” “treatment,” “immunomodulator” will be provided on each therapy, including commentary on appropriate use and relative contraindications. Lastly, novel treatments and potential drug candidates that are currently being evaluated in clinical trials with therapeutic potential will also be reviewed. Expert Opinion While oral non-steroidal anti-inflammatory drugs (NSAIDs) and oral corticosteroids are widely used, effective, first-line agents for inflammatory scleritis, refractory cases require anti-metabolites, T cell inhibitors, or biologic response modifiers. In particular, there is emerging evidence for the use of targeted biologic response modifiers, and potentially, for local drug delivery. PMID:23425055

Internet-Based Cognitive Behavioral Therapy for Adults With ADHD in Outpatient Psychiatric Care.

PubMed

Pettersson, Richard; Söderström, Staffan; Edlund-Söderström, Kerstin; Nilsson, Kent W

2017-04-01

The purpose of the study was to evaluate an Internet-based cognitive behavioral therapy (iCBT) program targeting difficulties and impairments associated with adult ADHD. Forty-five adults diagnosed with ADHD were randomized to either self-help (iCBT self-help format [iCBT-S]), self-help with weekly group sessions (iCBT group-therapy format [iCBT-G]), or a waiting-list control group. Treatment efficacy was measured at pre- and posttreatment and at 6-month follow-up. Intention-to-treat (ITT) analysis showed a significant reduction in ADHD symptoms for the iCBT-S group in comparison with the waiting-list controls at posttreatment, with a between-group effect size of d = 1.07. The result was maintained at 6-month follow-up. No significant difference was found at posttreatment or 6-month follow-up between the iCBT-S and iCBT-G groups. The findings show that a CBT treatment program administered through the Internet can be a promising treatment for adult ADHD. Limitations of the study design and directions for future research are discussed.

Costs, quality of life and treatment compliance associated with antibiotic therapies in patients with cystic fibrosis: a review of the literature.

PubMed

Weiner, Jennifer R; Toy, Edmond L; Sacco, Patricia; Duh, Mei Sheng

2008-04-01

Cystic fibrosis is the most common incurable hereditary disease in the US. Persistent respiratory infection is the leading cause of morbidity and mortality in cystic fibrosis patients. This study aimed to review the literature on economic and quality of life outcomes and treatment compliance associated with antibiotic therapies for cystic fibrosis patients. A systematic literature review was conducted using keyword searches of the MEDLINE database and selected conference abstracts. The review covered studies published between January 1990 and May 2007. Evidence suggests that inhaled tobramycin, a key chronic suppressive therapy, can reduce other healthcare costs. The main determinants of the cost of care include disease severity and respiratory infection. Costs vary widely by country. There is evidence that inhaled tobramycin and oral azithromycin improve quality of life and that treatment setting and patient convenience may also impact on quality of life. Antibiotic treatment compliance varied significantly and depended on the method of measurement, with more subjective measures tending to be higher. This review concludes by offering directions for future research.

Role of Reactive Oxygen Species in Neonatal Pulmonary Vascular Disease

PubMed Central

Steinhorn, Robin H.

2014-01-01

Abstract Significance: Abnormal lung development in the perinatal period can result in severe neonatal complications, including persistent pulmonary hypertension (PH) of the newborn and bronchopulmonary dysplasia. Reactive oxygen species (ROS) play a substantive role in the development of PH associated with these diseases. ROS impair the normal pulmonary artery (PA) relaxation in response to vasodilators, and ROS are also implicated in pulmonary arterial remodeling, both of which can increase the severity of PH. Recent Advances: PA ROS levels are elevated when endogenous ROS-generating enzymes are activated and/or when endogenous ROS scavengers are inactivated. Animal models have provided valuable insights into ROS generators and scavengers that are dysregulated in different forms of neonatal PH, thus identifying potential therapeutic targets. Critical Issues: General antioxidant therapy has proved ineffective in reversing PH, suggesting that it is necessary to target specific signaling pathways for successful therapy. Future Directions: Development of novel selective pharmacologic inhibitors along with nonantioxidant therapies may improve the treatment outcomes of patients with PH, while further investigation of the underlying mechanisms may enable earlier detection of the disease. Antioxid. Redox Signal. 21, 1926–1942. PMID:24350610

Functional Tooth Regeneration Using a Bioengineered Tooth Unit as a Mature Organ Replacement Regenerative Therapy

PubMed Central

Imamura, Aya; Ogawa, Miho; Yasukawa, Masato; Yamazaki, Hiromichi; Morita, Ritsuko; Ikeda, Etsuko; Nakao, Kazuhisa; Takano-Yamamoto, Teruko; Kasugai, Shohei; Saito, Masahiro; Tsuji, Takashi

2011-01-01

Donor organ transplantation is currently an essential therapeutic approach to the replacement of a dysfunctional organ as a result of disease, injury or aging in vivo. Recent progress in the area of regenerative therapy has the potential to lead to bioengineered mature organ replacement in the future. In this proof of concept study, we here report a further development in this regard in which a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone, was successfully transplanted into a properly-sized bony hole in the alveolar bone through bone integration by recipient bone remodeling in a murine transplantation model system. The bioengineered tooth unit restored enough the alveolar bone in a vertical direction into an extensive bone defect of murine lower jaw. Engrafted bioengineered tooth displayed physiological tooth functions such as mastication, periodontal ligament function for bone remodeling and responsiveness to noxious stimulations. This study thus represents a substantial advance and demonstrates the real potential for bioengineered mature organ replacement as a next generation regenerative therapy. PMID:21765896

Cell therapy, 3D culture systems and tissue engineering for cardiac regeneration.

PubMed

Emmert, Maximilian Y; Hitchcock, Robert W; Hoerstrup, Simon P

2014-04-01

Ischemic Heart Disease (IHD) still represents the "Number One Killer" worldwide accounting for the death of numerous patients. However the capacity for self-regeneration of the adult heart is very limited and the loss of cardiomyocytes in the infarcted heart leads to continuous adverse cardiac-remodeling which often leads to heart-failure (HF). The concept of regenerative medicine comprising cell-based therapies, bio-engineering technologies and hybrid solutions has been proposed as a promising next-generation approach to address IHD and HF. Numerous strategies are under investigation evaluating the potential of regenerative medicine on the failing myocardium including classical cell-therapy concepts, three-dimensional culture techniques and tissue-engineering approaches. While most of these regenerative strategies have shown great potential in experimental studies, the translation into a clinical setting has either been limited or too rapid leaving many key questions unanswered. This review summarizes the current state-of-the-art, important challenges and future research directions as to regenerative approaches addressing IHD and resulting HF. Copyright © 2014 Elsevier B.V. All rights reserved.

Biomedical HIV Prevention Including Pre-exposure Prophylaxis and Opiate Agonist Therapy for Women Who Inject Drugs: State of Research and Future Directions.

PubMed

Page, Kimberly; Tsui, Judith; Maher, Lisa; Choopanya, Kachit; Vanichseni, Suphak; Mock, Philip A; Celum, Connie; Martin, Michael

2015-06-01

Women who inject drugs (WWID) are at higher risk of HIV compared with their male counterparts as a result of multiple factors, including biological, behavioral, and sociostructural factors, yet comparatively little effort has been invested in testing and delivering prevention methods that directly target this group. In this article, we discuss the need for expanded prevention interventions for WWID, focusing on 2 safe, effective, and approved, yet underutilized biomedical prevention methods: opiate agonist therapy (OAT) and oral pre-exposure prophylaxis (PrEP). Although both interventions are well researched, they have not been well examined in the context of gender. We discuss the drivers of women injectors' higher HIV risk, review the effectiveness of OAT and PrEP interventions among women, and explain why these new HIV prevention tools should be prioritized for WWID. There is substantial potential for impact of OAT and PrEP programs for WWID in the context of broader gender-responsive HIV prevention initiatives. Although awaiting efficacy data on other biomedical approaches in the HIV prevention research "pipeline," we propose that the scale-up and implementation of these proven, safe, and effective interventions are needed now.

Recent directions in personalised acute respiratory distress syndrome medicine.

PubMed

Jabaudon, Matthieu; Blondonnet, Raiko; Audard, Jules; Fournet, Marianne; Godet, Thomas; Sapin, Vincent; Constantin, Jean-Michel

2018-06-01

Acute respiratory distress syndrome (ARDS) is heterogeneous by definition and patient response varies depending on underlying biology and their severity of illness. Although ARDS subtypes have been identified with different prognoses in past studies, the concept of phenotypes or endotypes does not extend to the clinical definition of ARDS. This has possibly hampered the development of therapeutic interventions that target select biological mechanisms of ARDS. Recently, a major advance may have been achieved as it may now be possible to identify ARDS subtypes that may confer different responses to therapy. The aim of personalised medicine is to identify, select, and test therapies that are most likely to be associated with a favourable outcome in a specific patient. Several promising approaches to ARDS subtypes capable of predicting therapeutic response, and not just prognosis, are highlighted in this perspective paper. An overview is also provided of current and future directions regarding the provision of personalised ARDS medicine. The importance of delivering the right care, at the right time, to the right patient, is emphasised. Copyright © 2018 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Current concepts of severe asthma

PubMed Central

Raundhal, Mahesh; Oriss, Timothy B.; Ray, Prabir; Wenzel, Sally E.

2016-01-01

The term asthma encompasses a disease spectrum with mild to very severe disease phenotypes whose traditional common characteristic is reversible airflow limitation. Unlike milder disease, severe asthma is poorly controlled by the current standard of care. Ongoing studies using advanced molecular and immunological tools along with improved clinical classification show that severe asthma does not identify a specific patient phenotype, but rather includes patients with constant medical needs, whose pathobiologic and clinical characteristics vary widely. Accordingly, in recent clinical trials, therapies guided by specific patient characteristics have had better outcomes than previous therapies directed to any subject with a diagnosis of severe asthma. However, there are still significant gaps in our understanding of the full scope of this disease that hinder the development of effective treatments for all severe asthmatics. In this Review, we discuss our current state of knowledge regarding severe asthma, highlighting different molecular and immunological pathways that can be targeted for future therapeutic development. PMID:27367183

Feasibility and Effectiveness of Parent-Child Interaction Therapy with Victims of Domestic Violence: A Pilot Study

PubMed Central

Herschell, Amy D.; Scudder, Ashley B.; Schaffner, Kristen F.; Slagel, Leslie A.

2016-01-01

Parent-Child Interaction Therapy (PCIT) is an evidence-based treatment for young children (aged 2.5 to 7 years) with externalizing behavior problems. Since its development, PCIT has been applied to a wide array of childhood problems and has a significant evidence base for families with histories of child physical abuse. The current study extended the existing literature by testing the effectiveness and feasibility of PCIT in an urban domestic violence shelter with community-based clinicians delivering the treatment. Seven clinicians implemented PCIT with parent-child dyads which included 21 preschool (M = 4.57 years; SD = 1.50) children. Families completed assessments at baseline, mid-treatment, and post-treatment. Nine families completed PCIT (43%). Completion of PCIT was associated with improved child behavior, parenting practices, and mental health symptoms. Considerations for treatment delivery and future directions are discussed. PMID:28503060

Tissue engineering and cell-based therapy toward integrated strategy with artificial organs.

PubMed

Gojo, Satoshi; Toyoda, Masashi; Umezawa, Akihiro

2011-09-01

Research in order that artificial organs can supplement or completely replace the functions of impaired or damaged tissues and internal organs has been underway for many years. The recent clinical development of implantable left ventricular assist devices has revolutionized the treatment of patients with heart failure. The emerging field of regenerative medicine, which uses human cells and tissues to regenerate internal organs, is now advancing from basic and clinical research to clinical application. In this review, we focus on the novel biomaterials, i.e., fusion protein, and approaches such as three-dimensional and whole-organ tissue engineering. We also compare induced pluripotent stem cells, directly reprogrammed cardiomyocytes, and somatic stem cells for cell source of future cell-based therapy. Integrated strategy of artificial organ and tissue engineering/regenerative medicine should give rise to a new era of medical treatment to organ failure.

Concurrent Treatment of Substance Abuse, Child Neglect, Bipolar Disorder, Post-Traumatic Stress Disorder, and Domestic Violence: A Case Examination Involving Family Behavior Therapy

PubMed Central

Donohue, Brad C.; Romero, Valerie; Herdzik, Karen; Lapota, Holly; Al, Ruwida Abdel; Allen, Daniel N.; Azrin, Nathan H.; Van Hasselt, Vincent B.

2012-01-01

High rates of co-occurrence between substance abuse and child neglect have been well documented and especially difficult to treat. As a first step in developing a comprehensive evidence-based treatment for use in this population, the present case examination underscores Family Behavior Therapy (FBT) in the treatment of a mother who evidenced Substance Dependence, child neglect, Post-Traumatic Stress Disorder, Bipolar I Disorder, and domestic violence. Utilizing psychometrically validated self-report inventories and objective urinalysis, treatment was found to result in the cessation of substance use, lower risk of child maltreatment, improved parenting attitudes and practices, and reduced instances of violence in the home. The importance of utilizing validity scales in the assessment of referrals from child welfare settings is discussed, and future directions are reported in light of the results. PMID:23457426

Targeted therapy in biliary tract cancers-current limitations and potentials in the future.

PubMed

Sahu, Selley; Sun, Weijing

2017-04-01

Biliary tract cancers (BTC)/Cholangiocarcinoma (CCA) is an aggressive biliary tract epithelial malignancy from varying locations within the biliary tree with cholangiocyte depreciation., including intrahepatic cholangiocarcinoma (iCCA) (iCCA), extrahepatic cholangiocarcinoma (eCCA) and gallbladder carcinoma (GBC). The disease is largely heterogeneous in etiology, epidemiology, and molecular profile. There are limited treatment options and low survival rates for those patients with advanced or metastatic disease. Systemic treatment is confined to cytotoxic chemotherapy with the combination of gemcitabine and cisplatin. Lack of a stereotype genetic signature makes difficult in identification of potential actionable target directly, which may also explain lack of obvious clinic benefit with target oriented agents from current studies. It is crucial to understand of BTC carcinogenesis, tumor-stroma interactions, and key molecular pathways, and herald to establish targeted, individualized therapies for the heterogeneous disease, and eventually to improve the survival and overall outcome of patients.

Scaffold-based Anti-infection Strategies in Bone Repair

PubMed Central

Johnson, Christopher T.; García, Andrés J.

2014-01-01

Bone fractures and non-union defects often require surgical intervention where biomaterials are used to correct the defect, and approximately 10% of these procedures are compromised by bacterial infection. Currently, treatment options are limited to sustained, high doses of antibiotics and surgical debridement of affected tissue, leaving a significant, unmet need for the development of therapies to combat device-associated biofilm and infections. Engineering implants to prevent infection is a desirable material characteristic. Tissue engineered scaffolds for bone repair provide a means to both regenerate bone and serve as a base for adding antimicrobial agents. Incorporating anti-infection properties into regenerative medicine therapies could improve clinical outcomes and reduce the morbidity and mortality associated with biomaterial implant-associated infections. This review focuses on current animal models and technologies available to assess bone repair in the context of infection, antimicrobial agents to fight infection, the current state of antimicrobial scaffolds, and future directions in the field. PMID:25476163

Testing the Effectiveness of Cognitive Analytic Therapy for Hypersexuality Disorder: An Intensive Time-Series Evaluation.

PubMed

Kellett, Stephen; Simmonds-Buckley, Mel; Totterdell, Peter

2017-08-18

The evidence base for treatment of hypersexuality disorder (HD) has few studies with appropriate methodological rigor. This study therefore conducted a single case experiment of cognitive analytic therapy (CAT) for HD using an A/B design with extended follow-up. Cruising, pornography usage, masturbation frequency and associated cognitions and emotions were measured daily in a 231-day time series. Following a three-week assessment baseline (A: 21 days), treatment was delivered via outpatient sessions (B: 147 days), with the follow-up period lasting 63 days. Results show that cruising and pornography usage extinguished. The total sexual outlet score no longer met caseness, and the primary nomothetic hypersexuality outcome measure met recovery criteria. Reduced pornography consumption was mediated by reduced obsessionality and greater interpersonal connectivity. The utility of the CAT model for intimacy problems shows promise. Directions for future HD outcome research are also provided.

Feasibility and Effectiveness of Parent-Child Interaction Therapy with Victims of Domestic Violence: A Pilot Study.

PubMed

Herschell, Amy D; Scudder, Ashley B; Schaffner, Kristen F; Slagel, Leslie A

2017-01-01

Parent-Child Interaction Therapy (PCIT) is an evidence-based treatment for young children (aged 2.5 to 7 years) with externalizing behavior problems. Since its development, PCIT has been applied to a wide array of childhood problems and has a significant evidence base for families with histories of child physical abuse. The current study extended the existing literature by testing the effectiveness and feasibility of PCIT in an urban domestic violence shelter with community-based clinicians delivering the treatment. Seven clinicians implemented PCIT with parent-child dyads which included 21 preschool ( M = 4.57 years; SD = 1.50) children. Families completed assessments at baseline, mid-treatment, and post-treatment. Nine families completed PCIT (43%). Completion of PCIT was associated with improved child behavior, parenting practices, and mental health symptoms. Considerations for treatment delivery and future directions are discussed.

Psychosocial treatments for schizophrenia.

PubMed

Mueser, Kim T; Deavers, Frances; Penn, David L; Cassisi, Jeffrey E

2013-01-01

The current state of the literature regarding psychosocial treatments for schizophrenia is reviewed within the frameworks of the recovery model of mental health and the expanded stress-vulnerability model. Interventions targeting specific domains of functioning, age groups, stages of illness, and human service system gaps are classified as evidence-based practices or promising practices according to the extent to which their efficacy is currently supported by meta-analyses and individual randomized controlled trials (RCTs). Evidence-based practices include assertive community treatment (ACT), cognitive behavior therapy (CBT) for psychosis, cognitive remediation, family psychoeducation, illness self-management training, social skills training, and supported employment. Promising practices include cognitive adaptive therapy, CBT for posttraumatic stress disorder, first-episode psychosis intervention, healthy lifestyle interventions, integrated treatment for co-occurring disorders, interventions targeting older individuals, peer support services, physical disease management, prodromal stage intervention, social cognition training, supported education, and supported housing. Implications and future directions are discussed.

Recombinant Mycobacterium bovis BCG for immunotherapy in nonmuscle invasive bladder cancer.

PubMed

Begnini, K R; Buss, J H; Collares, T; Seixas, F K

2015-05-01

In the past three decades, intravesical instillation of Mycobacterium bovis bacille Calmette-Guérin (BCG) has been used for treating bladder cancer and it still remains at the forefront of immunotherapy for cancer patients. Although BCG-based therapy is the most effective intravesical therapy for this kind of tumor and represents the only agent known to reduce progression into muscle invasive bladder cancer, BCG is ineffective in approximately 30-40 % of cases and disease recurs in up to 50 % of patients. Since that BCG is considered an effective vehicle for delivery of antigens due to its unique characteristics, the genetic manipulation of these mycobacteria has been appealing in the search for less toxic and more potent therapeutic agents for bladder cancer immunotherapy. Herein, we discuss current advances in recombinant BCG construction, research, concerns, and future directions to promote the development of this promising immunotherapeutic approach for bladder cancer.

Potential of eye movement desensitization and reprocessing therapy in the treatment of post-traumatic stress disorder.

PubMed

McGuire, Tracy M; Lee, Christopher W; Drummond, Peter D

2014-01-01

Post-traumatic stress disorder (PTSD) continues to attract both empirical and clinical interest due to its complex symptom profile and the underlying processes involved. Recently, research attention has been focused on the types of memory processes involved in PTSD and hypothesized neurobiological processes. Complicating this exploration, and the treatment of PTSD, are underlying comorbid disorders, such as depression, anxiety, and substance use disorders. Treatment of PTSD has undergone further reviews with the introduction of eye movement desensitization and reprocessing (EMDR). EMDR has been empirically demonstrated to be as efficacious as other specific PTSD treatments, such as trauma-focused cognitive behavioral therapy. There is emerging evidence that there are different processes underlying these two types of trauma treatment and some evidence that EMDR might have an efficiency advantage. Current research and understanding regarding the processes of EMDR and the future direction of EMDR is presented.

Perspectives on stem cell therapy for cardiac regeneration. Advances and challenges.

PubMed

Choi, Sung Hyun; Jung, Seok Yun; Kwon, Sang-Mo; Baek, Sang Hong

2012-01-01

Ischemic heart disease (IHD) accelerates cardiomyocyte loss, but the developing stem cell research could be useful for regenerating a variety of tissue cells, including cardiomyocytes. Diverse sources of stem cells for IHD have been reported, including embryonic stem cells, induced pluripotent stem cells, skeletal myoblasts, bone marrow-derived stem cells, mesenchymal stem cells, and cardiac stem cells. However, stem cells have unique advantages and disadvantages for cardiac tissue regeneration, which are important considerations in determining the specific cells for improving cell survival and long-term engraftment after transplantation. Additionally, the dosage and administration method of stem cells need to be standardized to increase stability and efficacy for clinical applications. Accordingly, this review presents a summary of the stem cell therapies that have been studied for cardiac regeneration thus far, and discusses the direction of future cardiac regeneration research for stem cells.

Advances in pulmonary therapy and drug development: Lung tissue engineering to lung-on-a-chip.

PubMed

Doryab, Ali; Amoabediny, Ghassem; Salehi-Najafabadi, Amir

2016-01-01

Lung disease is one of the major causes of death, and the rate of pulmonary diseases has been increasing for decades. Although lung transplantation is the only treatment for majority of patients, this method has been limited due to lack of donors. Therefore, recently, attentions have increased to some new strategies with the aid of tissue engineering and microfluidics techniques not only for the functional analysis, but also for drug screening. In fact, in tissue engineering, the engineered tissue is able to grow by using the patient's own cells without intervention in the immune system. On the other hand, microfluidics devices are applied in order to evaluate drug screenings, function analysis and toxicity. This article reviews new advances in lung tissue engineering and lung-on-a-chip. Furthermore, future directions, difficulties and drawbacks of pulmonary therapy in these areas are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Vitamin D/VDR, probiotics, and gastrointestinal diseases

PubMed Central

Shang, Mei; Sun, Jun

2016-01-01

Vitamin D is an important factor in regulating inflammation, immune responses, and carcinoma inhibition via action of its receptor, vitamin D receptor (VDR). Recent studies have demonstrated the role of vitamin D/VDR in regulating host-bacterial interactions. Probiotics are beneficial bacteria with the power of supporting or favoring life on the host. In the current review, we will discuss the recent progress on the roles of vitamin D/VDR in gut microbiome and inflammation. We will summarize evidence of probiotics in modulating vitamin D/VDR and balancing gut microbiota in health and gastrointestinal diseases. Moreover, we will review the clinical application of probiotics in prevention and therapy of IBD or colon cancer. Despite of the gains, there remain several barriers to advocate broad use of probiotics in clinical therapy. We will also discuss the limits and future direction in scientific understanding of probiotics, vitamin D/VDR, and host responses. PMID:27915988

Biomedical Applications of Functionalized Hollow Mesoporous Silica Nanoparticles: Focusing on Molecular Imaging

PubMed Central

Shi, Sixiang; Chen, Feng; Cai, Weibo

2013-01-01

Hollow mesoporous silica nanoparticles (HMSNs), with a large cavity inside each original mesoporous silica nanoparticle (MSN), have recently gained increasing interest due to their tremendous potential for cancer imaging and therapy. The last several years have witnessed a rapid development in engineering of functionalized HMSNs (i.e. f-HMSNs) with various types of inorganic functional nanocrystals integrated into the system for imaging and therapeutic applications. In this review article, we summarize the recent progress in the design and biological applications of f-HMSNs, with a special emphasis on molecular imaging. Commonly used synthetic strategies for the generation of high quality HMSNs will be discussed in detail, followed by a systematic review of engineered f-HMSNs for optical, positron emission tomography, magnetic resonance, and ultrasound imaging in preclinical studies. Lastly, we also discuss the challenges and future research directions regarding the use of f-HMSNs for cancer imaging and therapy. PMID:24279491

The recognition of facial emotion expressions in Parkinson's disease.

PubMed

Assogna, Francesca; Pontieri, Francesco E; Caltagirone, Carlo; Spalletta, Gianfranco

2008-11-01

A limited number of studies in Parkinson's Disease (PD) suggest a disturbance of recognition of facial emotion expressions. In particular, disgust recognition impairment has been reported in unmedicated and medicated PD patients. However, the results are rather inconclusive in the definition of the degree and the selectivity of emotion recognition impairment, and an associated impairment of almost all basic facial emotions in PD is also described. Few studies have investigated the relationship with neuropsychiatric and neuropsychological symptoms with mainly negative results. This inconsistency may be due to many different problems, such as emotion assessment, perception deficit, cognitive impairment, behavioral symptoms, illness severity and antiparkinsonian therapy. Here we review the clinical characteristics and neural structures involved in the recognition of specific facial emotion expressions, and the plausible role of dopamine transmission and dopamine replacement therapy in these processes. It is clear that future studies should be directed to clarify all these issues.

Biomimetic strategies for the glioblastoma microenvironment

NASA Astrophysics Data System (ADS)

Cha, Junghwa; Kim, Pilnam

2017-12-01

Glioblastoma multiforme (GBM) is a devastating type of tumor with high mortality, caused by extensive infiltration into adjacent tissue and rapid recurrence. Most therapies for GBM have focused on the cytotoxicity, and have not targeted GBM spread. However, there have been numerous attempts to improve therapy by addressing GBM invasion, through understanding and mimicking its behavior using three-dimensional (3D) experimental models. Compared with two-dimensional models and in vivo animal models, 3D GBM models can capture the invasive motility of glioma cells within a 3D environment comprising many cellular and non-cellular components. Based on tissue engineering techniques, GBM invasion has been investigated within a biologically relevant environment, from biophysical and biochemical perspectives, to clarify the pro-invasive factors of GBM. This review discusses the recent progress in techniques for modeling the microenvironments of GBM tissue and suggests future directions with respect to recreating the GBM microenvironment and preclinical applications.

Virtual Reality-Enhanced Extinction of Phobias and Post-Traumatic Stress.

PubMed

Maples-Keller, Jessica L; Yasinski, Carly; Manjin, Nicole; Rothbaum, Barbara Olasov

2017-07-01

Virtual reality (VR) refers to an advanced technological communication interface in which the user is actively participating in a computer-generated 3-dimensional virtual world that includes computer sensory input devices used to simulate real-world interactive experiences. VR has been used within psychiatric treatment for anxiety disorders, particularly specific phobias and post-traumatic stress disorder, given several advantages that VR provides for use within treatment for these disorders. Exposure therapy for anxiety disorder is grounded in fear-conditioning models, in which extinction learning involves the process through which conditioned fear responses decrease or are inhibited. The present review will provide an overview of extinction training and anxiety disorder treatment, advantages for using VR within extinction training, a review of the literature regarding the effectiveness of VR within exposure therapy for specific phobias and post-traumatic stress disorder, and limitations and future directions of the extant empirical literature.

Comparative Effectiveness and Implementation Research: Directions for Neurology

PubMed Central

Vickrey, Barbara G.; Hirtz, Deborah; Waddy, Salina; Cheng, Eric M.; Johnston, S. Claiborne

2013-01-01

There is an enormous unmet need for knowledge about how new insights from discovery and translational research can yield measurable, population-level improvements in health and reduction in mortality among those having or at risk for neurological disease. Once several, well-conducted randomized controlled trials establish the efficacy of a given therapy, implementation research can generate new knowledge about barriers to uptake of the therapy into widespread clinical care, and what strategies are effective in overcoming those barriers and in addressing health disparities. Comparative effectiveness research aims to elucidate the relative value (including clinical benefit, clinical harms, and/or costs) of alternative efficacious management approaches to a neurological disorder, generally through direct comparisons, and may include comparisons of methodologies for implementation. Congress has recently appropriated resources and established an institute to prioritize funding for such research. Neurologists and neuroscientists should understand the scope and objectives of comparative effectiveness and implementation research, their range of methodological approaches (formal literature syntheses, randomized trials, observational studies, modeling), and existing research resources (centers for literature synthesis, registries, practice networks) relevant to research for neurological conditions, in order to close the well-documented “evidence-to-practice gap.” Future directions include building this research resource capacity, producing scientists trained to conduct rigorous comparative effectiveness and implementation research, and embracing innovative strategies to set research priorities in these areas. PMID:22718542

Therapeutic journery of nitrogen mustard as alkylating anticancer agents: Historic to future perspectives.

PubMed

Singh, Rajesh K; Kumar, Sahil; Prasad, D N; Bhardwaj, T R

2018-05-10

Cancer is considered as one of the most serious health problems today. The discovery of nitrogen mustard as an alkylating agent in 1942, opened a new era in the cancer chemotherapy. This valuable class of alkylating agent exerts its biological activity by binding to DNA, cross linking two strands, preventing DNA replication and ultimate cell death. At the molecular level, nitrogen lone pairs of nitrogen mustard generate a strained intermediate "aziridinium ion" which is very reactive towards DNA of tumor cell as well as normal cell resulting in various adverse side effects alogwith therapeutic implications. Over the last 75 years, due to its high reactivity and peripheral cytotoxicity, numerous modifications have been made in the area of nitrogen mustard to improve its efficacy as well as enhancing drug delivery specifically to tumor cells. This review mainly discusses the medicinal chemistry aspects in the development of various classes of nitrogen mustards (mechlorethamine, chlorambucil, melphalan, cyclophosphamide and steroidal based nitrogen mustards). The literature collection includes the historical and the latest developments in these areas. This comprehensive review also attempted to showcase the recent progress in the targeted delivery of nitrogen mustards that includes DNA directed nitrogen mustards, antibody directed enzyme prodrug therapy (ADEPT), gene directed enzyme prodrug therapy (GDEPT), nitrogen mustard activated by glutathione transferase, peptide based nitrogen mustards and CNS targeted nitrogen mustards. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Dihydroartemisinin selectively inhibits PDGFRα-positive ovarian cancer growth and metastasis through inducing degradation of PDGFRα protein

PubMed Central

Li, Xiaoguang; Ba, Qian; Liu, Yanling; Yue, Qingxi; Chen, Peizhan; Li, Jingquan; Zhang, Haibing; Ying, Hao; Ding, Qiurong; Song, Haiyun; Liu, Hong; Zhang, Ruiwen; Wang, Hui

2017-01-01

To develop traditional medicines as modern pharmacotherapies, understanding their molecular mechanisms of action can be very helpful. We have recently reported that Artemisinin and its derivatives, which are clinically used anti-malarial drugs, have significant effects against ovarian cancer, but the direct molecular targets and related combination therapy have been unclear. Herein, we report that dihydroartemisinin, one of the most active derivatives of Artemisinin, directly targets platelet-derived growth factor receptor-alpha (PDGFRα) to inhibit ovarian cancer cell growth and metastasis. Dihydroartemisinin directly binds to the intercellular domain of PDGFRα, reducing its protein stability by accelerating its ubiquitin-mediated degradation, which further inactivates downstream phosphoinositide 3-Kinase and mitogen-activated protein kinase pathways and subsequently represses epithelial–mesenchymal transition, inhibiting cell growth and metastasis of PDGFRα-positive ovarian cancer in vitro and in vivo. A combinational treatment reveals that dihydroartemisinin sensitizes ovarian cancer cells to PDGFR inhibitors. Our clinical study also finds that PDGFRα is overexpressed and positively correlated with high grade and metastasis in human ovarian cancer. Considering that Artemisinin compounds are currently clinically used drugs with favorable safety profiles, the results from this study will potentiate their use in combination with clinically used PDGFRα inhibitors, leading to maximal therapeutic efficacy with minimal adverse effects in PDGFRα-positive cancer patients. These findings also shed high light on future development of novel Artemisinin-based targeted therapy. PMID:29387451

Dihydroartemisinin selectively inhibits PDGFRα-positive ovarian cancer growth and metastasis through inducing degradation of PDGFRα protein.

PubMed

Li, Xiaoguang; Ba, Qian; Liu, Yanling; Yue, Qingxi; Chen, Peizhan; Li, Jingquan; Zhang, Haibing; Ying, Hao; Ding, Qiurong; Song, Haiyun; Liu, Hong; Zhang, Ruiwen; Wang, Hui

2017-01-01

To develop traditional medicines as modern pharmacotherapies, understanding their molecular mechanisms of action can be very helpful. We have recently reported that Artemisinin and its derivatives, which are clinically used anti-malarial drugs, have significant effects against ovarian cancer, but the direct molecular targets and related combination therapy have been unclear. Herein, we report that dihydroartemisinin, one of the most active derivatives of Artemisinin, directly targets platelet-derived growth factor receptor-alpha (PDGFRα) to inhibit ovarian cancer cell growth and metastasis. Dihydroartemisinin directly binds to the intercellular domain of PDGFRα, reducing its protein stability by accelerating its ubiquitin-mediated degradation, which further inactivates downstream phosphoinositide 3-Kinase and mitogen-activated protein kinase pathways and subsequently represses epithelial-mesenchymal transition, inhibiting cell growth and metastasis of PDGFRα-positive ovarian cancer in vitro and in vivo . A combinational treatment reveals that dihydroartemisinin sensitizes ovarian cancer cells to PDGFR inhibitors. Our clinical study also finds that PDGFRα is overexpressed and positively correlated with high grade and metastasis in human ovarian cancer. Considering that Artemisinin compounds are currently clinically used drugs with favorable safety profiles, the results from this study will potentiate their use in combination with clinically used PDGFRα inhibitors, leading to maximal therapeutic efficacy with minimal adverse effects in PDGFRα-positive cancer patients. These findings also shed high light on future development of novel Artemisinin-based targeted therapy.

The clinical development of p53-reactivating drugs in sarcomas - charting future therapeutic approaches and understanding the clinical molecular toxicology of Nutlins.

PubMed

Biswas, Swethajit; Killick, Emma; Jochemsen, Aart G; Lunec, John

2014-05-01

The majority of human sarcomas, particularly soft tissue sarcomas, are relatively resistant to traditional cytotoxic therapies. The proof-of-concept study by Ray-Coquard et al., using the Nutlin human double minute (HDM)2-binding antagonist RG7112, has recently opened a new chapter in the molecular targeting of human sarcomas. In this review, the authors discuss the challenges and prospective remedies for minimizing the significant haematological toxicities of the cis-imidazole Nutlin HDM2-binding antagonists. Furthermore, they also chart the future direction of the development of p53-reactivating (p53-RA) drugs in 12q13-15 amplicon sarcomas and as potential chemopreventative therapies against sarcomagenesis in germ line mutated TP53 carriers. Drawing lessons from the therapeutic use of Imatinib in gastrointestinal tumours, the authors predict the potential pitfalls, which may lie in ahead for the future clinical development of p53-RA agents, as well as discussing potential non-invasive methods to identify the development of drug resistance. Medicinal chemistry strategies, based on structure-based drug design, are required to re-engineer cis-imidazoline Nutlin HDM2-binding antagonists into less haematologically toxic drugs. In silico modelling is also required to predict toxicities of other p53-RA drugs at a much earlier stage in drug development. Whether p53-RA drugs will be therapeutically effective as a monotherapy remains to be determined.

Immunotherapy in Merkel cell carcinoma: role of Avelumab.

PubMed

Palla, Amruth R; Doll, Donald

2018-01-01

Merkel cell carcinoma (MCC), a rare skin cancer, is associated with high mortality, especially in a metastatic setting. Though conventional chemotherapy with platinum and etoposide has had high response rates, many of the patients have had early relapse without any effective therapy thereafter. Recently, immune check point inhibitors have shown very good durable responses, leading to the approval of a programmed death-ligand 1 inhibitor Avelumab for these patients. We briefly review the epidemiology and immune basis of the pathogenesis of MCC, which therefore explains the excellent response to check point inhibitors, and throw light on future directions of immunotherapy for this cancer.

History of Glial Cell Line-Derived Neurotrophic Factor (GDNF) and Its Use for Spinal Cord Injury Repair.

PubMed

Walker, Melissa J; Xu, Xiao-Ming

2018-06-13

Following an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axonal regeneration. This review focuses on the glial cell line-derived neurotrophic factor (GDNF) and its application, in combination with other factors and cell transplantations, for repairing the injured spinal cord. As studies of recent decades strongly suggest that combinational treatment approaches hold the greatest therapeutic potential for the central nervous system (CNS) trauma, future directions of combinational therapies will also be discussed.

Neurofeedback for autistic spectrum disorder: a review of the literature.

PubMed

Coben, Robert; Linden, Michael; Myers, Thomas E

2010-03-01

There is a need for effective interventions to address the core symptoms and problems associated with autistic spectrum disorder (ASD). Behavior therapy improves communication and behavioral functioning. Additional treatment options include psychopharmacological and biomedical interventions. Although these approaches help children with autistic problems, they may be associated with side effects, risks or require ongoing or long-term treatment. Neurofeedback is a noninvasive approach shown to enhance neuroregulation and metabolic function in ASD. We present a review of the literature on the application of Neurofeedback to the multiple problems associated with ASD. Directions for future research are discussed.

Diagnosis and treatment of polycystic ovary syndrome (PCOS): an interview with Richard Legro.

PubMed

Legro, Richard

2015-03-27

In this podcast, we talk to Professor Richard Legro about the recommendations for the diagnosis and treatment of polycystic ovary syndrome (PCOS) based on clinical practice guidelines and discuss the challenges of diagnosis PCOS at specific age groups. The controversies associated with treatment of PCOS, including therapies for infertility as this is a problem commonly observed in PCOS subjects, are highlighted together with future directions on the topic. The podcast for this interview is available at. http://www.biomedcentral.com/content/supplementary/s12916-015-0299-2-s1.mp3.

Juvenile Firesetting.

PubMed

Peters, Brittany; Freeman, Bradley

2016-01-01

Juvenile firesetting is a significant cause of morbidity and mortality in the United States. Male gender, substance use, history of maltreatment, interest in fire, and psychiatric illness are commonly reported risk factors. Interventions that have been shown to be effective in juveniles who set fires include cognitive behavior therapy and educational interventions, whereas satiation has not been shown to be an effective intervention. Forensic assessments can assist the legal community in adjudicating youth with effective interventions. Future studies should focus on consistent assessment and outcome measures to create more evidence for directing evaluation and treatment of juvenile firesetters. Copyright © 2016 Elsevier Inc. All rights reserved.

Thioredoxin: a key regulator of cardiovascular homeostasis.

PubMed

Yamawaki, Hideyuki; Haendeler, Judith; Berk, Bradford C

2003-11-28

The thioredoxin (TRX) system (TRX, TRX reductase, and NADPH) is a ubiquitous thiol oxidoreductase system that regulates cellular reduction/oxidation (redox) status. The oxidation mechanism for disease pathogenesis states that an imbalance in cell redox state alters function of multiple cell pathways. In this study, we review the essential role for TRX to limit oxidative stress directly via antioxidant effects and indirectly by protein-protein interaction with key signaling molecules, such as apoptosis signal-regulating kinase 1. We propose that TRX and its endogenous regulators are important future targets to develop clinical therapies for cardiovascular disorders associated with oxidative stress.

Drugs and Targets in Fibrosis

PubMed Central

Li, Xiaoyi; Zhu, Lixin; Wang, Beibei; Yuan, Meifei; Zhu, Ruixin

2017-01-01

Fibrosis contributes to the development of many diseases and many target molecules are involved in fibrosis. Currently, the majority of fibrosis treatment strategies are limited to specific diseases or organs. However, accumulating evidence demonstrates great similarities among fibroproliferative diseases, and more and more drugs are proved to be effective anti-fibrotic therapies across different diseases and organs. Here we comprehensively review the current knowledge on the pathological mechanisms of fibrosis, and divide factors mediating fibrosis progression into extracellular and intracellular groups. Furthermore, we systematically summarize both single and multiple component drugs that target fibrosis. Future directions of fibrosis drug discovery are also proposed. PMID:29218009

Play Therapy with Emotionally Damaged Adolescents.

ERIC Educational Resources Information Center

Wilson, Kate; Ryan, Virginia

2002-01-01

This article argues that non-directive play therapy offers an approach that is well suited to addressing adolescent concerns. The argument is illustrated by two accounts of therapy that show how a more traditional non-directive counseling approach was combined with play therapy by the adolescents themselves, allowing exploration of emotional…

Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on Functional Recovery after Spinal Cord Injury

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-12-1-0587 TITLE: Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on Functional Recovery after Spinal Cord...3. DATES COVERED (From - To) 30Sep2014 - 29Sep2015 4. TITLE AND SUBTITLE Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on...ABSTRACT Essentially all spinal cord injured patients receive stretching therapies beginning within the first few weeks post-injury. Despite this fact

Is art therapy a reliable tool for rehabilitating people suffering from brain/mental diseases?

PubMed

Mirabella, Giovanni

2015-04-01

Whether art therapy can be an effective rehabilitative treatment for people with brain or mental diseases (e.g., dementia, Alzheimer's disease, Parkinson's disease, autism, schizophrenia) is a long-standing and highly debated issue. On the one hand, several observational studies and anecdotal evidence enthusiastically support the effectiveness of arts-based therapy. On the other hand, few rigorous clinical investigations have been performed, and there is too little empirical evidence to allow a full assessment of the risks and benefits of this intervention. Nevertheless, there is a progressively increasing demand for the development of appropriate complementary therapies to improve the personal and social lives of patients with neurodegenerative diseases. This is because conventional medical treatments are aimed at alleviating symptoms but cannot arrest or reverse the degenerative process. Thus, as disease progresses and adverse effects emerge, patients' quality of life dramatically decreases; when this occurs patients seek different forms of intervention. Art therapy is a potentially appealing treatment because of its more holistic approach to healthcare. However, as with any medicine, its effects must be tested by using standard, rigorous scientific approaches. This report describes the current state of research into art therapy and outlines many key factors that future research should consider, all of which are directly or indirectly related to the neural mechanism underlying behavioral changes: brain plasticity. Artistic performance could promote some form of brain plasticity that, to some extent, might compensate for the brain damage caused by the disease.

The Impact of ESR1 Mutations on the Treatment of Metastatic Breast Cancer.

PubMed

Pejerrey, Sasha M; Dustin, Derek; Kim, Jin-Ah; Gu, Guowei; Rechoum, Yassine; Fuqua, Suzanne A W

2018-05-07

After nearly 20 years of research, it is now established that mutations within the estrogen receptor (ER) gene, ESR1, frequently occur in metastatic breast cancer and influence response to hormone therapy. Though early studies presented differing results, sensitive sequencing techniques now show that ESR1 mutations occur at a frequency between 20 and 40% depending on the assay method. Recent studies have focused on several "hot spot mutations," a cluster of mutations found in the hormone-binding domain of the ESR1 gene. Throughout the course of treatment, tumor evolution can occur, and ESR1 mutations emerge and become enriched in the metastatic setting. Sensitive techniques to continually monitor mutant burden in vivo are needed to effectively treat patients with mutant ESR1. The full impact of these mutations on tumor response to different therapies remains to be determined. However, recent studies indicate that mutant-bearing tumors may be less responsive to specific hormonal therapies, and suggest that aromatase inhibitor (AI) therapy may select for the emergence of ESR1 mutations. Additionally, different mutations may respond discretely to targeted therapies. The need for more preclinical mechanistic studies on ESR1 mutations and the development of better agents to target these mutations are urgently needed. In the future, sequential monitoring of ESR1 mutational status will likely direct personalized therapeutic regimens appropriate to each tumor's unique mutational landscape.

Industrializing Autologous Adoptive Immunotherapies: Manufacturing Advances and Challenges

PubMed Central

Iyer, Rohin K.; Bowles, Paul A.; Kim, Howard; Dulgar-Tulloch, Aaron

2018-01-01

Cell therapy has proven to be a burgeoning field of investigation, evidenced by hundreds of clinical trials being conducted worldwide across a variety of cell types and indications. Many cell therapies have been shown to be efficacious in humans, such as modified T-cells and natural killer (NK) cells. Adoptive immunotherapy has shown the most promise in recent years, with particular emphasis on autologous cell sources. Chimeric Antigen Receptor (CAR)-based T-cell therapy targeting CD19-expressing B-cell leukemias has shown remarkable efficacy and reproducibility in numerous clinical trials. Recent marketing approval of Novartis' Kymriah™ (tisagenlecleucel) and Gilead/Kite's Yescarta™ (axicabtagene ciloleucel) by the FDA further underscores both the promise and legwork to be done if manufacturing processes are to become widely accessible. Further work is needed to standardize, automate, close, and scale production to bring down costs and democratize these and other cell therapies. Given the multiple processing steps involved, commercial-scale manufacturing of these therapies necessitates tighter control over process parameters. This focused review highlights some of the most recent advances used in the manufacturing of therapeutic immune cells, with a focus on T-cells. We summarize key unit operations and pain points around current manufacturing solutions. We also review emerging technologies, approaches and reagents used in cell isolation, activation, transduction, expansion, in-process analytics, harvest, cryopreservation and thaw, and conclude with a forward-look at future directions in the manufacture of adoptive immunotherapies.

A review of “music and movement” therapies for children with autism: embodied interventions for multisystem development

PubMed Central

Srinivasan, Sudha M.; Bhat, Anjana N.

2013-01-01

The rising incidence of Autism Spectrum Disorders (ASDs) has led to a surge in the number of children needing autism interventions. This paper is a call to clinicians to diversify autism interventions and to promote the use of embodied music-based approaches to facilitate multisystem development. Approximately 12% of all autism interventions and 45% of all alternative treatment strategies in schools involve music-based activities. Musical training impacts various forms of development including communication, social-emotional, and motor development in children with ASDs and other developmental disorders as well as typically developing children. In this review, we will highlight the multisystem impairments of ASDs, explain why music and movement therapies are a powerful clinical tool, as well as describe mechanisms and offer evidence in support of music therapies for children with ASDs. We will support our claims by reviewing results from brain imaging studies reporting on music therapy effects in children with autism. We will also discuss the critical elements and the different types of music therapy approaches commonly used in pediatric neurological populations including autism. We provide strong arguments for the use of music and movement interventions as a multisystem treatment tool for children with ASDs. Finally, we also make recommendations for assessment and treatment of children with ASDs, and provide directions for future research. PMID:23576962

Industrializing Autologous Adoptive Immunotherapies: Manufacturing Advances and Challenges.

PubMed

Iyer, Rohin K; Bowles, Paul A; Kim, Howard; Dulgar-Tulloch, Aaron

2018-01-01

Cell therapy has proven to be a burgeoning field of investigation, evidenced by hundreds of clinical trials being conducted worldwide across a variety of cell types and indications. Many cell therapies have been shown to be efficacious in humans, such as modified T-cells and natural killer (NK) cells. Adoptive immunotherapy has shown the most promise in recent years, with particular emphasis on autologous cell sources. Chimeric Antigen Receptor (CAR)-based T-cell therapy targeting CD19-expressing B-cell leukemias has shown remarkable efficacy and reproducibility in numerous clinical trials. Recent marketing approval of Novartis' Kymriah™ (tisagenlecleucel) and Gilead/Kite's Yescarta™ (axicabtagene ciloleucel) by the FDA further underscores both the promise and legwork to be done if manufacturing processes are to become widely accessible. Further work is needed to standardize, automate, close, and scale production to bring down costs and democratize these and other cell therapies. Given the multiple processing steps involved, commercial-scale manufacturing of these therapies necessitates tighter control over process parameters. This focused review highlights some of the most recent advances used in the manufacturing of therapeutic immune cells, with a focus on T-cells. We summarize key unit operations and pain points around current manufacturing solutions. We also review emerging technologies, approaches and reagents used in cell isolation, activation, transduction, expansion, in-process analytics, harvest, cryopreservation and thaw, and conclude with a forward-look at future directions in the manufacture of adoptive immunotherapies.

Update on the Genetic Polymorphisms of Drug-Metabolizing Enzymes in Antiepileptic Drug Therapy

PubMed Central

Saruwatari, Junji; Ishitsu, Takateru; Nakagawa, Kazuko

2010-01-01

Genetic polymorphisms in the genes that encode drug-metabolizing enzymes are implicated in the inter-individual variability in the pharmacokinetics and pharmaco-dynamics of antiepileptic drugs (AEDs). However, the clinical impact of these polymorphisms on AED therapy still remains controversial. The defective alleles of cytochrome P450 (CYP) 2C9 and/or CYP2C19 could affect not only the pharmacokinetics, but also the pharmacodynamics of phenytoin therapy. CYP2C19 deficient genotypes were associated with the higher serum concentration of an active metabolite of clobazam, N-desmethylclobazam, and with the higher clinical efficacy of clobazam therapy than the other CYP2C19 genotypes. The defective alleles of CYP2C9 and/or CYP2C19 were also found to have clinically significant effects on the inter-individual variabilities in the population pharmacokinetics of phenobarbital, valproic acid and zonisamide. EPHX1 polymorphisms may be associated with the pharmacokinetics of carbamazepine and the risk of phenytoin-induced congenital malformations. Similarly, the UDP-glucuronosyltransferase 2B7 genotype may affect the pharmacokinetics of lamotrigine. Gluthatione S-transferase null genotypes are implicated in an increased risk of hepatotoxicity caused by carbamazepine and valproic acid. This article summarizes the state of research on the effects of mutations of drug-metabolizing enzymes on the pharmacokinetics and pharmacodynamics of AED therapies. Future directions for the dose-adjustment of AED are discussed. PMID:27713373

Gold Nanostructures as a Platform for Combinational Therapy in Future Cancer Therapeutics

PubMed Central

Jelveh, Salomeh; Chithrani, Devika B.

2011-01-01

The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of spherical gold NPs (GNPs), gold nanorods (GNRs), gold nanoshells (GNSs) and gold nanocages (GNCs) in cancer therapeutics. In treating cancer, radiation therapy and chemotherapy remain the most widely used treatment options and recent developments in cancer research show that the incorporation of gold nanostructures into these protocols has enhanced tumor cell killing. These nanostructures further provide strategies for better loading, targeting, and controlling the release of drugs to minimize the side effects of highly toxic anticancer drugs used in chemotherapy and photodynamic therapy. In addition, the heat generation capability of gold nanostructures upon exposure to UV or near infrared light is being used to damage tumor cells locally in photothermal therapy. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research. PMID:24212654

Protons -- The Future of Radiation Therapy?

NASA Astrophysics Data System (ADS)

Avery, Steven

2007-03-01

Cancer is the 2^nd highest cause of death in the United States. The challenges of controlling this disease remain more difficult as the population lives longer. Proton therapy offers another choice in the management of cancer care. Proton therapy has existed since the late 1950s and the first hospital based center in the United States opened in 1990. Since that time four hospital based proton centers are treating patients with other centers either under construction or under consideration. This talk will focus on an introduction to proton therapy: it's medical advantages over current treatment modalities, accelerators and beam delivery systems, applications to clinical radiation oncology and the future outlook for proton therapy.

Developing New Treatments for Heart Failure: Focus on the Heart.

PubMed

Gheorghiade, Mihai; Larson, Christopher J; Shah, Sanjiv J; Greene, Stephen J; Cleland, John G F; Colucci, Wilson S; Dunnmon, Preston; Epstein, Stephen E; Kim, Raymond J; Parsey, Ramin V; Stockbridge, Norman; Carr, James; Dinh, Wilfried; Krahn, Thomas; Kramer, Frank; Wahlander, Karin; Deckelbaum, Lawrence I; Crandall, David; Okada, Shunichiro; Senni, Michele; Sikora, Sergey; Sabbah, Hani N; Butler, Javed

2016-05-01

Compared with heart failure (HF) care 20 to 30 years ago, there has been tremendous advancement in therapy for ambulatory HF with reduced ejection fraction with the use of agents that block maladaptive neurohormonal pathways. However, during the past decade, with few notable exceptions, the frequency of successful drug development programs has fallen as most novel therapies have failed to offer incremental benefit or raised safety concerns (ie, hypotension). Moreover, no therapy has been approved specifically for HF with preserved ejection fraction or for worsening chronic HF (including acutely decompensated HF). Across the spectrum of HF, preliminary results from many phase II trials have been promising but are frequently followed by unsuccessful phase III studies, highlighting a disconnect in the translational process between basic science discovery, early drug development, and definitive clinical testing in pivotal trials. A major unmet need in HF drug development is the ability to identify homogeneous subsets of patients whose underlying disease is driven by a specific mechanism that can be targeted using a new therapeutic agent. Drug development strategies should increasingly consider therapies that facilitate reverse remodeling by directly targeting the heart itself rather than strictly focusing on agents that unload the heart or target systemic neurohormones. Advancements in cardiac imaging may allow for more focused and direct assessment of drug effects on the heart early in the drug development process. To better understand and address the array of challenges facing current HF drug development, so that future efforts may have a better chance for success, the Food and Drug Administration facilitated a meeting on February 17, 2015, which was attended by clinicians, researchers, regulators, and industry representatives. The following discussion summarizes the key takeaway dialogue from this meeting. © 2016 American Heart Association, Inc.

Does Parent-Child Interaction Therapy Reduce Future Physical Abuse? A Meta-Analysis

ERIC Educational Resources Information Center

Kennedy, Stephanie C.; Kim, Johnny S.; Tripodi, Stephen J.; Brown, Samantha M.; Gowdy, Grace

2016-01-01

Objective: To use meta-analytic techniques to evaluating the effectiveness of parent-child interaction therapy (PCIT) at reducing future physical abuse among physically abusive families. Methods: A systematic search identified six eligible studies. Outcomes of interest were physical abuse recurrence, child abuse potential, and parenting stress.…

Neuroimaging and neuropsychological follow-up study in a pediatric brain tumor patient treated with surgery and radiation.

PubMed

Schmidt, Adam T; Martin, Rebecca B; Ozturk, Arzu; Kates, Wendy R; Wharam, Moody D; Mahone, E Mark; Horska, Alena

2010-02-01

Intracranial tumors are the most common neoplasms of childhood, accounting for approximately 20% of all pediatric malignancies. Radiation therapy has led directly to significant increases in survival of children with certain types of intracranial tumors; however, given the aggressive nature of this therapy, children are at risk for exhibiting changes in brain structure, neuronal biochemistry, and neurocognitive functioning. In this case report, we present neuropsychological, magnetic resonance imaging, proton magnetic resonance spectroscopic imaging, and diffusion tensor imaging data for two adolescents (one patient with ependymal spinal cord tumor with intracranial metastases, and one healthy, typically developing control) from three time points as defined by the patient's radiation schedule (baseline before the patient's radiation therapy, 6 months following completion of the patient's radiation, and 27 months following the patient's radiation). In the patient, there were progressive decreases in gray and white matter volumes as well as early decreases in mean N-acetyl aspartate/choline (NAA/Cho) ratios and fractional anisotropy (FA) in regions with normal appearance on conventional MRI. At the last follow-up, NAA/Cho and FA tended to change in the direction to normal values in selected regions. At the same time, the patient had initial reduction in language and motor skills, followed by return to baseline, but later onset delay in visuospatial and visual perceptual skills. Results are discussed in terms of sensitivity of the four techniques to early and late effects of treatment, and avenues for future investigations.

Impact of SAMMPRIS on the future of intracranial atherosclerotic disease management: polling results from the ICAD symposium at the International Stroke Conference.

PubMed

Zaidat, Osama O; Castonguay, Alicia C; Nguyen, Thanh N; Becker, Kyra J; Derdeyn, Colin P; Nelson, Peter K; Amarenco, Pierre; Brott, Thomas G

2014-04-01

There are few data regarding the effect of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial results on the management of intracranial atherosclerotic disease (ICAD). We sought to understand the impact of the SAMMPRIS trial on current ICAD clinical practices and future trial design. During the ICAD symposium at the 2012 International Stroke Conference, electronic data were collected regarding attendees' clinical management of ICAD and opinions on the feasibility of future trials post-SAMMPRIS. 217 attendees from different specialties, including neurologists (57%), neurointerventionalists (9%) and neurosurgeons (5%), participated in the session. The majority of respondents (77%) indicated that the results of SAMMPRIS have impacted their consideration for intracranial stenting. Post-SAMMPRIS, 84% selected 'SAMMPRIS-style' medical management for the treatment of ICAD. For patients with ICAD who failed aggressive medical therapy, 82% would consider an alternative approach to continuing medical therapy (30% considered clinical trial enrollment, 28% suggested angioplasty and stenting and 24% angioplasty). The majority of participants (85%) were willing to randomize patients with symptomatic ICAD in future trials. For the next ICAD trial, 29% indicated that angioplasty alone should be compared with aggressive medical therapy. Our polling results suggest that the SAMMPRIS trial has had an impact on the current treatment of ICAD. Treatment of patients who failed medical therapy varied widely from aggressive medical therapy to balloon angioplasty, stenting or enrollment in future clinical trials. The willingness to continue clinical trials and randomize patients supports the need for future ICAD studies.

Biomarkers in Pediatric ARDS: Future Directions.

PubMed

Orwoll, Benjamin E; Sapru, Anil

2016-01-01

Acute respiratory distress syndrome (ARDS) is common among mechanically ventilated children and accompanies up to 30% of all pediatric intensive care unit deaths. Though ARDS diagnosis is based on clinical criteria, biological markers of acute lung damage have been extensively studied in adults and children. Biomarkers of inflammation, alveolar epithelial and capillary endothelial disruption, disordered coagulation, and associated derangements measured in the circulation and other body fluids, such as bronchoalveolar lavage, have improved our understanding of pathobiology of ARDS. The biochemical signature of ARDS has been increasingly well described in adult populations, and this has led to the identification of molecular phenotypes to augment clinical classifications. However, there is a paucity of data from pediatric ARDS (pARDS) patients. Biomarkers and molecular phenotypes have the potential to identify patients at high risk of poor outcomes, and perhaps inform the development of targeted therapies for specific groups of patients. Additionally, because of the lower incidence of and mortality from ARDS in pediatric patients relative to adults and lack of robust clinical predictors of outcome, there is an ongoing interest in biological markers as surrogate outcome measures. The recent definition of pARDS provides additional impetus for the measurement of established and novel biomarkers in future pediatric studies in order to further characterize this disease process. This chapter will review the currently available literature and discuss potential future directions for investigation into biomarkers in ARDS among children.

Biomarkers in Pediatric ARDS: Future Directions

PubMed Central

Orwoll, Benjamin E.; Sapru, Anil

2016-01-01

Acute respiratory distress syndrome (ARDS) is common among mechanically ventilated children and accompanies up to 30% of all pediatric intensive care unit deaths. Though ARDS diagnosis is based on clinical criteria, biological markers of acute lung damage have been extensively studied in adults and children. Biomarkers of inflammation, alveolar epithelial and capillary endothelial disruption, disordered coagulation, and associated derangements measured in the circulation and other body fluids, such as bronchoalveolar lavage, have improved our understanding of pathobiology of ARDS. The biochemical signature of ARDS has been increasingly well described in adult populations, and this has led to the identification of molecular phenotypes to augment clinical classifications. However, there is a paucity of data from pediatric ARDS (pARDS) patients. Biomarkers and molecular phenotypes have the potential to identify patients at high risk of poor outcomes, and perhaps inform the development of targeted therapies for specific groups of patients. Additionally, because of the lower incidence of and mortality from ARDS in pediatric patients relative to adults and lack of robust clinical predictors of outcome, there is an ongoing interest in biological markers as surrogate outcome measures. The recent definition of pARDS provides additional impetus for the measurement of established and novel biomarkers in future pediatric studies in order to further characterize this disease process. This chapter will review the currently available literature and discuss potential future directions for investigation into biomarkers in ARDS among children. PMID:27313995

Towards host-directed therapies for tuberculosis.

PubMed

Zumla, Alimuddin; Maeurer, Markus; Chakaya, Jeremiah; Hoelscher, Michael; Ntoumi, Francine; Rustomjee, Roxana; Vilaplana, Cristina; Yeboah-Manu, Dorothy; Rasolof, Voahangy; Munderi, Paula; Singh, Nalini; Aklillu, Eleni; Padayatchi, Nesri; Macete, Eusebio; Kapata, Nathan; Mulenga, Modest; Kibiki, Gibson; Mfinanga, Sayoki; Nyirenda, Thomas; Maboko, Leonard; Garcia-Basteiro, Alberto; Rakotosamimanana, Niaina; Bates, Matthew; Mwaba, Peter; Reither, Klaus; Gagneux, Sebastien; Edwards, Sarah; Mfinanga, Elirehema; Abdulla, Salim; Cardona, Pere-Joan; Russell, James B W; Gant, Vanya; Noursadeghi, Mahdad; Elkington, Paul; Bonnet, Maryline; Menendez, Clara; Dieye, Tandakha N; Diarra, Bassirou; Maiga, Almoustapha; Aseffa, Abraham; Parida, Shreemanta; Wejse, Christian; Petersen, Eskild; Kaleebu, Pontiano; Oliver, Matt; Craig, Gill; Corrah, Tumena; Tientcheu, Leopold; Antonio, Martin; Rao, Martin; McHugh, Timothy D; Sheikh, Aziz; Ippolito, Giuseppe; Ramjee, Gita; Kaufmann, Stefan H E; Churchyard, Gavin; Steyn, Andrie; Grobusch, Martin; Sanne, Ian; Martinson, Neil; Madansein, Rajhmun; Wilkinson, Robert J; Mayosi, Bongani; Schito, Marco; Wallis, Robert S

2015-08-01

The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies.

Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies.

PubMed

Alelign, Tilahun; Ahmed, Momina M; Bobosha, Kidist; Tadesse, Yewondwossen; Howe, Rawleigh; Petros, Beyene

2018-01-01

Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA) is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy.

Review of the treatment of psoriatic arthritis with biological agents: choice of drug for initial therapy and switch therapy for non-responders.

PubMed

D'Angelo, Salvatore; Tramontano, Giuseppina; Gilio, Michele; Leccese, Pietro; Olivieri, Ignazio

2017-01-01

Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease with a broad clinical spectrum and variable course. It can involve musculoskeletal structures as well as skin, nails, eyes, and gut. The management of PsA has changed tremendously in the last decade, thanks to an earlier diagnosis, an advancement in pharmacological therapies, and a wider application of a multidisciplinary approach. The commercialization of tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) as well as interleukin (IL)-12/23 (ustekinumab) and IL-17 (secukinumab) inhibitors is representative of a revolution in the treatment of PsA. No evidence-based strategies are currently available for guiding the rheumatologist to prescribe biological drugs. Several international and national recommendation sets are currently available with the aim to help rheumatologists in everyday clinical practice management of PsA patients treated with biological therapy. Since no specific biological agent has been demonstrated to be more effective than others, the drug choice should be made according to the available safety data, the presence of extra-articular manifestations, the patient's preferences (e.g., administration route), and the drug price. However, future studies directly comparing different biological drugs and assessing the efficacy of treatment strategies specific for PsA are urgently needed.

The clinical applications of genome editing in HIV.

PubMed

Wang, Cathy X; Cannon, Paula M

2016-05-26

HIV/AIDS has long been at the forefront of the development of gene- and cell-based therapies. Although conventional gene therapy approaches typically involve the addition of anti-HIV genes to cells using semirandomly integrating viral vectors, newer genome editing technologies based on engineered nucleases are now allowing more precise genetic manipulations. The possible outcomes of genome editing include gene disruption, which has been most notably applied to the CCR5 coreceptor gene, or the introduction of small mutations or larger whole gene cassette insertions at a targeted locus. Disruption of CCR5 using zinc finger nucleases was the first-in-human application of genome editing and remains the most clinically advanced platform, with 7 completed or ongoing clinical trials in T cells and hematopoietic stem/progenitor cells (HSPCs). Here we review the laboratory and clinical findings of CCR5 editing in T cells and HSPCs for HIV therapy and summarize other promising genome editing approaches for future clinical development. In particular, recent advances in the delivery of genome editing reagents and the demonstration of highly efficient homology-directed editing in both T cells and HSPCs are expected to spur the development of even more sophisticated applications of this technology for HIV therapy. © 2016 by The American Society of Hematology.

Advances and Future Directions in the Treatment of Hepatocellular Carcinoma

PubMed Central

Gosalia, Ashil J.; Martin, Paul

2017-01-01

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Liver transplant is considered the gold standard for curative therapy for HCC when patients are not candidates for surgical resection or ablation. Because a subset of patients with HCC have a survival rate with liver transplantation that is comparable to that of cirrhotic patients without tumors, the organ allocation system allows for increased priority for transplant in potential recipients within the Milan criteria. With the recent change in the Model for End-Stage Liver Disease exception point allocation, patients with HCC will now need to wait at least 6 months before being awarded extra points. This extension leads to increased time on the transplant waiting list and underscores the importance of locoregional therapy to contain the tumor burden. Fortunately, there has been significant progress in therapy for HCC in the past few decades, namely due to advances in interventional radiology, radiotherapy, and expanded surgical and transplant criteria. Recent advances in immunotherapy also provide promising options for patients who are not candidates for other therapies. This article highlights the major therapeutic options for HCC, including surgical resection, liver transplant, thermal and nonthermal ablation, chemoembolization, radiotherapy, and systemic chemotherapy, as well as discusses the evidence supporting these approaches. PMID:28867968

Permanent Leadless Cardiac Pacemaker Therapy: A Comprehensive Review.

PubMed

Tjong, Fleur V Y; Reddy, Vivek Y

2017-04-11

A new technology, leadless pacemaker therapy, was recently introduced clinically to address lead- and pocket-related complications in conventional transvenous pacemaker therapy. These leadless devices are self-contained right ventricular single-chamber pacemakers implanted by using a femoral percutaneous approach. In this review of available clinical data on leadless pacemakers, early results with leadless devices are compared with historical results with conventional single-chamber pacing. Both presently manufactured leadless pacemakers show similar complications, which are mostly related to the implant procedure: cardiac perforation, device dislocation, and femoral vascular access site complications. In comparison with conventional transvenous single-chamber pacemakers, slightly higher short-term complication rates have been observed: 4.8% for leadless pacemakers versus 4.1% for conventional pacemakers. The complication rate of the leadless pacemakers is influenced by the implanter learning curve for this new procedure. No long-term outcome data are yet available for the leadless pacemakers. Larger leadless pacing trials, with long-term follow-up and direct randomized comparison with conventional pacing systems, will be required to define the proper clinical role of these leadless systems. Although current leadless pacemakers are limited to right ventricular pacing, future advanced, communicating, multicomponent systems are expected to expand the potential benefits of leadless therapy to a larger patient population. © 2017 American Heart Association, Inc.

Genetic engineered molecular imaging probes for applications in cell therapy: emphasis on MRI approach

PubMed Central

Cho, In K; Wang, Silun; Mao, Hui; Chan, Anthony WS

2016-01-01

Recent advances in stem cell-based regenerative medicine, cell replacement therapy, and genome editing technologies (i.e. CRISPR-Cas 9) have sparked great interest in in vivo cell monitoring. Molecular imaging promises a unique approach to noninvasively monitor cellular and molecular phenomena, including cell survival, migration, proliferation, and even differentiation at the whole organismal level. Several imaging modalities and strategies have been explored for monitoring cell grafts in vivo. We begin this review with an introduction describing the progress in stem cell technology, with a perspective toward cell replacement therapy. The importance of molecular imaging in reporting and assessing the status of cell grafts and their relation to the local microenvironment is highlighted since the current knowledge gap is one of the major obstacles in clinical translation of stem cell therapy. Based on currently available imaging techniques, we provide a brief discussion on the pros and cons of each imaging modality used for monitoring cell grafts with particular emphasis on magnetic resonance imaging (MRI) and the reporter gene approach. Finally, we conclude with a comprehensive discussion of future directions of applying molecular imaging in regenerative medicine to emphasize further the importance of correlating cell graft conditions and clinical outcomes to advance regenerative medicine. PMID:27766183

Purines: forgotten mediators in traumatic brain injury.

PubMed

Jackson, Edwin K; Boison, Detlev; Schwarzschild, Michael A; Kochanek, Patrick M

2016-04-01

Recently, the topic of traumatic brain injury has gained attention in both the scientific community and lay press. Similarly, there have been exciting developments on multiple fronts in the area of neurochemistry specifically related to purine biology that are relevant to both neuroprotection and neurodegeneration. At the 2105 meeting of the National Neurotrauma Society, a session sponsored by the International Society for Neurochemistry featured three experts in the field of purine biology who discussed new developments that are germane to both the pathomechanisms of secondary injury and development of therapies for traumatic brain injury. This included presentations by Drs. Edwin Jackson on the novel 2',3'-cAMP pathway in neuroprotection, Detlev Boison on adenosine in post-traumatic seizures and epilepsy, and Michael Schwarzschild on the potential of urate to treat central nervous system injury. This mini review summarizes the important findings in these three areas and outlines future directions for the development of new purine-related therapies for traumatic brain injury and other forms of central nervous system injury. In this review, novel therapies based on three emerging areas of adenosine-related pathobiology in traumatic brain injury (TBI) were proposed, namely, therapies targeting 1) the 2',3'-cyclic adenosine monophosphate (cAMP) pathway, 2) adenosine deficiency after TBI, and 3) augmentation of urate after TBI. © 2016 International Society for Neurochemistry.

Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

PubMed Central

Ahmed, Momina M.; Bobosha, Kidist; Tadesse, Yewondwossen; Howe, Rawleigh; Petros, Beyene

2018-01-01

Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA) is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy. PMID:29693023

Opioid pharmaceuticals and addiction: the issues, and research directions seeking solutions.

PubMed

Walwyn, Wendy M; Miotto, Karen A; Evans, Christopher J

2010-05-01

There are few pharmaceuticals superior to opiates for the treatment of pain. However, with concerns of addiction, withdrawal and questionable efficacy for all types of pain, these compounds are far from a magical panacea for pain-relief. As it is unlikely that other classes of compounds will supersede the opioids in the very near future, it is important to both optimize current opioid therapies and curb the astounding diversion of opioids from their intended analgesic use to non-medical abuse. In optimizing opioid therapeutics it is necessary to enhance the clinical awareness of the benefits of treating pain and combine this with aggressive strategies to reduce diversion for non-medical use. At the heart of the issue of opioid misuse is the role of opioid systems in the reward circuitry, and the adaptive processes associated with repetitive opioid use that manifest during withdrawal. Emerging pharmacological insights of opioid receptors will be reviewed that provide future hope for developing opioid-based analgesics with reduced addictive properties and perhaps, reduced opponent processes. In addition, with the increased understanding of nociceptive circuitry and the molecules involved in transmitting pain, new therapeutic targets have become evident that may result in effective analgesics either alone or in combination with current opioid therapies.

Digital Technologies in the Treatment of Anxiety: Recent Innovations and Future Directions.

PubMed

Firth, Joseph; Torous, John; Carney, Rebekah; Newby, Jill; Cosco, Theodore D; Christensen, Helen; Sarris, Jerome

2018-05-19

This review aims to provide a comprehensive overview of the efficacy, limitations, and future of e-health treatments for anxiety. Within this, we provide detail on "first-generation" e-health approaches, such as computerized therapies. Additionally, we assess the emergence and early efficacy of newer methods of treatment delivery, including smartphone apps and virtual reality interventions, discussing the potential and pitfalls for each. There is now substantial clinical research demonstrating the efficacy of internet-delivered cognitive behavioral therapy in the treatment of anxiety. However, the ability of these interventions for engaging patients in "real-world" settings is unclear. Recently, smartphone apps for anxiety have presented a more popular and ubiquitous method of intervention delivery, although the evidence base supporting these newer approaches drastically falls behind the extensive marketing and commercialization efforts currently driving their development. Meanwhile, the increasing availability of novel technologies, such as "virtual reality" (VR), introduces further potential of e-health treatments for generalized anxiety and anxiety-related disorders such as phobias and obsessive compulsive disorder, while also creating additional challenges for research. Although still in its infancy, e-health research is already presenting several promising avenues for delivering effective and scalable treatments for anxiety. Nonetheless, several important steps must be taken in order for academic research to keep pace with continued technological advances.

Adherence to cognitive behavioral therapy for insomnia: a systematic review.

PubMed

Matthews, Ellyn E; Arnedt, J Todd; McCarthy, Michaela S; Cuddihy, Leisha J; Aloia, Mark S

2013-12-01

Chronic insomnia is a significant public health problem worldwide, and insomnia has considerable personal and social costs associated with serious health conditions, greater healthcare utilization, work absenteeism, and motor-vehicle accidents. Cognitive behavioral therapy for insomnia (CBTI) is an efficacious treatment, yet attrition and suboptimal adherence may diminish its impact. Despite the increasing use of CBTI, surprisingly little attention has been devoted to understanding the role of adherence. This review describes a comprehensive literature search of adherence to CBTI. The search revealed 15 studies that evaluated adherence to CBTI in adults using valid and reliable measures of sleep, and measure of adherence other than study withdrawals. The primary purposes of this review were to 1) synthesize current study characteristics, methodology, adherence rates, contributing factors, and impact on outcomes, 2) discuss measurement issues, and 3) identify future practice and research directions that may lead to improved outcomes. Strong patterns and inconsistencies were identified among the studies, which complicate an evaluation of the role of adherence as a factor and outcome of CBTI success. The importance of standardized adherence and outcome measures is discussed. In light of the importance of adherence to behavior change, this systematic review may better inform future intervention efforts. Copyright © 2013 Elsevier Ltd. All rights reserved.

Opioid pharmaceuticals and addiction: The issues, and research directions seeking solutions

PubMed Central

Walwyn, Wendy M.; Miotto, Karen A.; Evans, Christopher J.

2011-01-01

There are few pharmaceuticals superior to opiates for the treatment of pain. However, with concerns of addiction, withdrawal and questionable efficacy for all types of pain, these compounds are far from a magical panacea for pain-relief. As it is unlikely that other classes of compounds will supersede the opioids in the very near future, it is important to both optimize current opioid therapies and curb the astounding diversion of opioids from their intended analgesic use to non-medical abuse. In optimizing opioid therapeutics it is necessary to enhance the clinical awareness of the benefits of treating pain and combine this with aggressive strategies to reduce diversion for non-medical use. At the heart of the issue of opioid misuse is the role of opioid systems in the reward circuitry, and the adaptive processes associated with repetitive opioid use that manifest during withdrawal. Emerging pharmacological insights of opioid receptors will be reviewed that provide future hope for developing opioid-based analgesics with reduced addictive properties and perhaps, reduced opponent processes. In addition, with the increased understanding of nociceptive circuitry and the molecules involved in transmitting pain, new therapeutic targets have become evident that may result in effective analgesics either alone or in combination with current opioid therapies. PMID:20188495