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https://www.readbyqxmd.com/read/29441052/harnessing-the-mtor-pathway-for-tuberculosis-treatment
#1
REVIEW
Pooja Singh, Selvakumar Subbian
Tuberculosis (TB) remains as one of the leading killer infectious diseases of humans. At present, the standard therapeutic regimen to treat TB comprised of multiple antibiotics administered for a minimum of six months. Although these drugs are useful in controlling TB burden globally, they have not eliminated the disease. In addition, the lengthy duration of treatment with multiple drugs contributes to patient non-compliance that can result in the development of drug resistant strains (MDR and XDR) of Mycobacterium tuberculosis (Mtb), the causative agent of TB...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29433128/-the-new-national-immunization-program-2017-2019-and-the-essential-care-levels-what-is-going-to-change
#2
Chiara De Waure, Leuconoe Grazia Sisti, Andrea Poscia, Walter Ricciardi
Italy is witnessing relevant challenges in the field of prevention and control of vaccine-preventable diseases. The worrying and growing phenomenon of "vaccine-hesitancy" has contributed to the reduction of vaccination coverage, undermining goals reached thanks to vaccines introduction. The new Italian National Immunization Plan (NIP) 2017-2019 and the update of the list of Essential Care Levels (LEA), approved in the current year, extend the vaccination offer based on the latest scientific evidence with the introduction of new vaccines and the enlargement of target population...
September 2017: Igiene e Sanità Pubblica
https://www.readbyqxmd.com/read/29422899/sensing-bacterial-induced-dna-damaging-effects-via-natural-killer-group-2-member-d-immune-receptor-from-dysbiosis-to-autoimmunity-and-carcinogenesis
#3
REVIEW
J Luis Espinoza, Mika Minami
The human genome is constantly exposed to exogenous and endogenous DNA damaging factors that frequently cause DNA damages. Unless repaired, damaged DNA can result in deleterious mutations capable of causing malignant transformation. Accordingly, cells have developed an advanced and effective surveillance system, the DNA damage response (DDR) pathway, which maintains genetic integrity. In addition to well-defined outcomes, such as cell cycle arrest, apoptosis, and senescence, another consequence of DDR activation is the induction of natural killer group 2 member D ligands (NKG2D-Ls) on the surface of stressed cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29422065/fresh-insights-into-the-pyrimidine-metabolism-in-the-trypanosomatids
#4
REVIEW
Kartikeya Tiwari, Vikash Kumar Dubey
The trypanosomatid parasites continue their killing spree resulting in significant annual mortality due to the lack of effective treatments and the prominence of these diseases in poorer countries. These dimorphic parasites thrive unchecked in the host system, outsmarting the immune mechanisms. An understanding of biology of these parasitic forms will help in the management and elimination of these fatal diseases. Investigation of various metabolic pathways in these parasites has shed light in the understanding of the unique biology of the trypansomatids...
February 8, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29413815/natural-killer-cell-education-in-human-health-and-disease
#5
REVIEW
Jeanette E Boudreau, Katharine C Hsu
Natural killer (NK) cells maintain immune homeostasis by detecting and eliminating damaged cells. Simultaneous activating and inhibitory input are integrated by NK cells, with the net signal prompting cytotoxicity and cytokine production, or inhibition. Chief among the inhibitory ligands for NK cells are 'self' human leukocyte antigen (HLA) molecules, which are sensed by killer immunoglobulin-like receptors (KIR). Through a process called 'education', the functional capabilities of each NK cell are counterbalanced by their sensitivity for inhibition by co-inherited 'self' HLA...
January 27, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29412713/mortality-disparities-in-racial-ethnic-minority-groups-in-the-veterans-health-administration-an-evidence-review-and-map
#6
Kim Peterson, Johanna Anderson, Erin Boundy, Lauren Ferguson, Ellen McCleery, Kallie Waldrip
BACKGROUND: Continued racial/ethnic health disparities were recently described as "the most serious and shameful health care issue of our time." Although the 2014 US Affordable Care Act-mandated national insurance coverage expansion has led to significant improvements in health care coverage and access, its effects on life expectancy are not yet known. The Veterans Health Administration (VHA), the largest US integrated health care system, has a sustained commitment to health equity that addresses all 3 stages of health disparities research: detection, understanding determinants, and reduction or elimination...
March 2018: American Journal of Public Health
https://www.readbyqxmd.com/read/29407908/rthlvffark-nh2-a-potent-and-selective-modulator-on-cu2-mediated-amyloid-%C3%AE-protein-aggregation-and-cytotoxicity
#7
Jie Meng, Huan Zhang, Xiaoyan Dong, Fufeng Liu, Yan Sun
Dysfunctional accumulation of amyloid-β (Aβ) protein stimulated by Cu2+ is considered as a key process in the pathogenesis of Alzheimer's disease (AD). Thus, bifunctional substances capable of chelating Cu2+ and inhibiting Aβ aggregation are promising therapeutic agents against AD. Herein, a novel bifunctional decapeptide RTHLVFFARK-NH2 (RK10) was developed by integrating a metal chelating tripeptide (RTH) and an Aβ aggregation inhibitor Ac-LVFFARK-NH2 (LK7). The high selectivity of RK10 for Cu2+ over other biologically relevant metal ions was demonstrated by isothermal titration calorimetry...
February 2, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29401670/converging-human-and-malaria-vector-diagnostics-with-data-management-towards-an-integrated-holistic-one-health-approach
#8
REVIEW
Konstantinos Mitsakakis, Sebastian Hin, Pie Müller, Nadja Wipf, Edward Thomsen, Michael Coleman, Roland Zengerle, John Vontas, Konstantinos Mavridis
Monitoring malaria prevalence in humans, as well as vector populations, for the presence of Plasmodium, is an integral component of effective malaria control, and eventually, elimination. In the field of human diagnostics, a major challenge is the ability to define, precisely, the causative agent of fever, thereby differentiating among several candidate (also non-malaria) febrile diseases. This requires genetic-based pathogen identification and multiplexed analysis, which, in combination, are hardly provided by the current gold standard diagnostic tools...
February 3, 2018: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29399396/serine-protease-inhibitor-6-protects-alloreactive-t-cells-from-granzyme-b-mediated-mitochondrial-damage-without-affecting-graft-versus-tumor-effect
#9
Wei Du, Hemn Mohammadpour, Rachel E O'Neill, Sandeep Kumar, Chuan Chen, Michelle Qiu, Lin Mei, Jingxin Qiu, Philip L McCarthy, Kelvin P Lee, Xuefang Cao
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for hematologic malignancies. Donor T cells are able to eliminate residual tumor cells after allo-HCT, producing the beneficial graft-versus-tumor (GVT) effect, but can also cause graft-versus-host disease (GVHD) when attacking host normal tissues. We previously reported that granzyme B (GzmB) is involved in activation-induced cell death (AICD) of donor T cells and exerts differential impacts on GVHD and GVT effect. Serine protease inhibitor 6 (Spi6) is the sole endogenous inhibitor of GzmB that can protect immune and tissue cells against GzmB-mediated damage...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29394096/protein-quality-control-of-the-endoplasmic-reticulum-and-ubiquitin-proteasome-triggered-degradation-of-aberrant-proteins-yeast-pioneers-the-path
#10
Nicole Berner, Karl-Richard Reutter, Dieter H Wolf
Cells must constantly monitor the integrity of their macromolecular constituents. Proteins are the most versatile class of macromolecules but are sensitive to structural alterations. Misfolded or otherwise aberrant protein structures lead to dysfunction and finally aggregation. Their presence is linked to aging and a plethora of severe human diseases. Thus, misfolded proteins have to be rapidly eliminated. Secretory proteins constitute more than one-third of the eukaryotic proteome. They are imported into the endoplasmic reticulum (ER), where they are folded and modified...
February 2, 2018: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/29370069/tauroursodeoxycholic-acid-protects-against-the-effects-of-p-cresol-induced-reactive-oxygen-species-via-the-expression-of-cellular-prion-protein
#11
Seung Pil Yun, Yeo Min Yoon, Jun Hee Lee, Minjee Kook, Yong-Seok Han, Seo Kyung Jung, Sang Hun Lee
Mesenchymal stem cells (MSCs) could be a promising solution in the treatment of various diseases including chronic kidney disease (CKD). However, endoplasmic reticulum (ER) stress induced by ischemia in the area of application limits the integration and survival of MSCs in patients. In our study, we generated ER stress-induced conditions in MSCs using P-cresol. As P-cresol is a toxic compound accumulated in the body of CKD patients and induces apoptosis and inflammation through reactive oxygen species (ROS), we observed ER stress-induced MSC apoptosis activated by oxidative stress, which in turn resulted from ROS generation...
January 25, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29360040/endosomal-rab-cycles-regulate-parkin-mediated-mitophagy
#12
Koji Yamano, Chunxin Wang, Shireen A Sarraf, Christian Münch, Reika Kikuchi, Nobuo N Noda, Yohei Hizukuri, Masato T Kanemaki, Wade Harper, Keiji Tanaka, Noriyuki Matsuda, Richard J Youle
Damaged mitochondria are selectively eliminated by mitophagy. Parkin and PINK1, gene products mutated in familial Parkinson's disease, play essential roles in mitophagy through ubiquitination of mitochondria. Cargo ubiquitination by E3 ubiquitin ligase Parkin is important to trigger selective autophagy. Although autophagy receptors recruit LC3-labeled autophagic membranes onto damaged mitochondria, how other essential autophagy units such as ATG9A-integrated vesicles are recruited remains unclear. Here, using mammalian cultured cells, we demonstrate that RABGEF1, the upstream factor of the endosomal Rab GTPase cascade, is recruited to damaged mitochondria via ubiquitin binding downstream of Parkin...
January 23, 2018: ELife
https://www.readbyqxmd.com/read/29347919/knowledge-attitudes-and-practices-on-schistosomiasis-in-sub-saharan-africa-a-systematic-review
#13
Hlengiwe Sacolo, Moses Chimbari, Chester Kalinda
BACKGROUND: Schistosomiasis remains a global health problem with an estimated 250 million people in 78 countries infected, of whom 85% live in Sub-Saharan Africa. Preventive chemotherapy remains the key public health strategy to combat schistosomiasis worldwide. Recently the WHO emphasized on the use of integrative approaches in the control and elimination of schistosomiasis. However, a detailed understanding of sociocultural factors that may influence the uptake of the intended health activities and services is vital...
January 18, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29344305/a-tumor-activatable-theranostic-nanomedicine-platform-for-nir-fluorescence-guided-surgery-and-combinatorial-phototherapy
#14
Xiaoning Li, Canan Schumann, Hassan A Albarqi, Christopher J Lee, Adam W G Alani, Shay Bracha, Milan Milovancev, Olena Taratula, Oleh Taratula
Fluorescence image-guided surgery combined with intraoperative therapeutic modalities has great potential for intraoperative detection of oncologic targets and eradication of unresectable cancer residues. Therefore, we have developed an activatable theranostic nanoplatform that can be used concurrently for two purposes: (1) tumor delineation with real-time near infrared (NIR) fluorescence signal during surgery, and (2) intraoperative targeted treatment to further eliminate unresected disease sites by non-toxic phototherapy...
2018: Theranostics
https://www.readbyqxmd.com/read/29329553/inhibitors-of-the-integrase-transportin-sr2-interaction-block-hiv-nuclear-import
#15
Jonas Demeulemeester, Jolien Blokken, Stéphanie De Houwer, Lieve Dirix, Hugo Klaassen, Arnaud Marchand, Patrick Chaltin, Frauke Christ, Zeger Debyser
BACKGROUND: Combination antiretroviral therapy efficiently suppresses HIV replication in infected patients, transforming HIV/AIDS into a chronic disease. Viral resistance does develop however, especially under suboptimal treatment conditions such as poor adherence. As a consequence, continued exploration of novel targets is paramount to identify novel antivirals that do not suffer from cross-resistance with existing drugs. One new promising class of targets are HIV protein-cofactor interactions...
January 12, 2018: Retrovirology
https://www.readbyqxmd.com/read/29302179/where-public-health-meets-human-rights-integrating-human-rights-into-the-validation-of-the-elimination-of-mother-to-child-transmission-of-hiv-and-syphilis
#16
Eszter Kismödi, Karusa Kiragu, Olga Sawicki, Sally Smith, Sophie Brion, Aditi Sharma, Lilian Mworeko, Alexandrina Iovita
In 2014, the World Health Organization (WHO) initiated a process for validation of the elimination of mother-to-child transmission (EMTCT) of HIV and syphilis by countries. For the first time in such a process for the validation of disease elimination, WHO introduced norms and approaches that are grounded in human rights, gender equality, and community engagement. This human rights-based validation process can serve as a key opportunity to enhance accountability for human rights protection by evaluating EMTCT programs against human rights norms and standards, including in relation to gender equality and by ensuring the provision of discrimination-free quality services...
December 2017: Health and Human Rights
https://www.readbyqxmd.com/read/29295708/epidemiological-characteristics-and-post-exposure-prophylaxis-of-human-rabies-in-chongqing-china-2007-2016
#17
Li Qi, Kun Su, Tao Shen, Wenge Tang, Bangzhong Xiao, Jiang Long, Han Zhao, Xi Chen, Yu Xia, Yu Xiong, Dayong Xiao, Liangui Feng, Qin Li
BACKGROUND: According to the global framework of eliminating human rabies, China is responding to achieve the target of zero human death from dog-mediated rabies by 2030. Chongqing is the largest municipality directly under central government in China. We described the epidemiological characteristics and post-exposure prophylaxis (PEP) of human rabies in this area, in order to provide a reliable epidemiology basis for further control and prevention of human rabies. METHODS: The most updated epidemiological data for human rabies cases from 2007 to 2016 in Chongqing were collected from the National Disease Reporting Information System...
January 3, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29281691/impaired-pge2-stimulated-cl-and-hco3-secretion-contributes-to-cystic-fibrosis-airway-disease
#18
Zachary M Sellers, Beate Illek, Miriam Frankenthal Figueira, Gopika Hari, Nam Soo Joo, Eric Sibley, Jackson Souza-Menezes, Marcelo M Morales, Horst Fischer, Jeffrey J Wine
BACKGROUND: Airway mucociliary clearance (MCC) is an important defense mechanism against pulmonary infections and is compromised in cystic fibrosis (CF). Cl- and HCO3- epithelial transport are integral to MCC. During pulmonary infections prostaglandin E2 (PGE2) production is abundant. AIM: To determine the effect of PGE2 on airway Cl- and HCO3- secretion and MCC in normal and CF airways. METHODS: We examined PGE2 stimulated MCC, Cl- and HCO3- secretion using ferret trachea, human bronchial epithelial cell cultures (CFBE41o- with wildtype CFTR (CFBE41 WT) or homozygous F508del CFTR (CFBE41 CF) and human normal bronchial submucosal gland cell line (Calu-3) in Ussing chambers with or without pH-stat...
2017: PloS One
https://www.readbyqxmd.com/read/29246882/viral-hepatitis-strategic-information-to-achieve-elimination-by-2030-key-elements-for-hiv-program-managers
#19
Yvan Hutin, Daniel Low-Beer, Isabel Bergeri, Sarah Hess, Jesus Maria Garcia-Calleja, Chika Hayashi, Antons Mozalevskis, Annemarie Rinder Stengaard, Keith Sabin, Hande Harmanci, Marc Bulterys
Evidence documenting the global burden of disease from viral hepatitis was essential for the World Health Assembly to endorse the first Global Health Sector Strategy (GHSS) on viral hepatitis in May 2016. The GHSS on viral hepatitis proposes to eliminate viral hepatitis as a public health threat by 2030. The GHSS on viral hepatitis is in line with targets for HIV infection and tuberculosis as part of the Sustainable Development Goals. As coordination between hepatitis and HIV programs aims to optimize the use of resources, guidance is also needed to align the strategic information components of the 2 programs...
December 15, 2017: JMIR Public Health and Surveillance
https://www.readbyqxmd.com/read/29232385/sustaining-visceral-leishmaniasis-elimination-in-bangladesh-could-a-policy-brief-help
#20
Alyssa Fitzpatrick, Noor Saad M S Al-Kobaisi, Jessica Beitman Maya, Yu Ren Chung, Satyender Duhan, Erdene Elbegdorj, Sushant Jain, Edward Kuhn, Alexandra Nastase, Be-Nazir Ahmed, Piero Olliaro
Bangladesh has made significant progress towards elimination of visceral leishmaniasis, and is on track to achieve its target of less than one case per 10,000 inhabitants in each subdistrict in 2017. As the incidence of disease falls, it is likely that the political capital and financial resources dedicated towards the elimination of visceral leishmaniasis may decrease, raising the prospect of disease resurgence. Policy memos may play a crucial role during the transition of the elimination plan from the 'attack' to the 'consolidation' and 'maintenance' phases, highlighting key stakeholders and areas where ongoing investment is crucial...
December 2017: PLoS Neglected Tropical Diseases
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