Abstract Promising results are emerging in clinical trials focused on stem cell therapy for cardiology applications. However, the low homing and engraftment of the injected cells to target tissue ...continues to be a problem. Cellular glycoengineering can address this limitation by enabling the targeting of stem cells to sites of vascular injury/inflammation. Two such glycoengineering methods are presented here: i. The non-covalent incorporation of a P-selectin glycoprotein ligand-1 (PSGL-1) mimetic 19FcFUT7+ via lipid-protein G fusion intermediates that intercalate onto the cell surface, and ii. Over-expression of the α(1,3)fucosyltransferse FUT7 in cells. Results demonstrate the efficient coupling of 19FcFUT7+ onto both cardiosphere-derived cells (CDCs) and mesenchymal stem cells (MSCs), with coupling being more efficient when using protein G fused to single-tailed palmitic acid rather than double-tailed DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine). This non-covalent cellular modification was mild since cell proliferation and stem-cell marker expression was unaltered. Whereas coupling using 19FcFUT7+ enhanced cell capture on recombinant P-selectin or CHO-P cell surfaces, α(1,3)fucosylation was necessary for robust binding to E-selectin and inflamed endothelial cells under shear. Pilot studies confirm the safety and homing efficacy of the modified stem cells to sites of ischemia-reperfusion in the porcine heart. Overall, glycoengineering with physiological selectin-ligands may enhance stem cell engraftment.
A novel dual-band printed loop antenna very promising for application in mobile phones as an internal antenna is presented. The antenna comprises an outer loop strip and an inner inverted-L strip ...connected to and enclosed by the outer loop strip. The antenna occupies a compact area of 15 times 50 mm 2 only, yet generating three resonant modes to form two wide bands at about 900 and 1800 MHz for the Global System for Mobile Communication/Digital Communication System operation. Detailed design considerations of the three excited modes are described in the paper. When a shielding metal case is placed close to the antenna, small effects on the antenna's impedance matching are seen, allowing compact integration of the antenna with nearby conducting elements or electronic components. The antenna is also found to result in small excited surface current distributions on the system ground plane of the mobile phone. This behavior is expected to lead to reduced user's hand effects on the radiation efficiency of the antenna
Acquired therapeutic resistance is the major drawback to effective systemic therapies for cancers. Aggressive triple-negative breast cancers (TNBC) develop resistance to chemotherapies rapidly, ...whereas the underlying mechanisms are not completely understood. Here we show that genotoxic treatments significantly increased the expression of miR-181a in TNBC cells, which enhanced TNBC cell survival and metastasis upon Doxorubicin treatment. Consistently, high miR-181a level associated with poor disease free survival and overall survival after treatments in breast cancer patients. The upregulation of miR-181a was orchestrated by transcription factor STAT3 whose activation depended on NF-κB-mediated IL-6 induction in TNBC cells upon genotoxic treatment. Intriguingly, activated STAT3 not only directly bound to MIR181A1 promoter to drive transcription but also facilitated the recruitment of MSK1 to the same region where MSK1 promoted a local active chromatin state by phosphorylating histone H3. We further identified BAX as a direct functional target of miR-181a, whose suppression decreased apoptosis and increased invasion of TNBC cells upon Dox treatment. These results were further confirmed by evidence that suppression of miR-181a significantly enhanced therapeutic response and reduced lung metastasis in a TNBC orthotopic model. Collectively, our data suggested that miR-181a induction had a critical role in promoting therapeutic resistance and aggressive behavior of TNBC cells upon genotoxic treatment. Antagonizing miR-181a may serve as a promising strategy to sensitize TNBC cells to chemotherapy and mitigate metastasis.
Over the past decade, the global response to HIV has led to a reduction in the number of new infections, and a decrease in associated mortality. Yet, the number of people living with HIV (PLHIV) is ...high, with an estimated 38 million infected worldwide. As HIV shifts from being an acute terminal illness to a chronic condition, evaluating programmatic responses to HIV with sole reliance on biological markers (such as viral load or CD4 cell count) as proxies for patient health may no longer be suitable. HIV affects the lives of those infected in myriad ways which should be reflected in programme evaluations by measuring health-related quality of life, in addition to biomarkers.
In this commentary we argue that there is a pressing need to review how a "good" health outcome is defined and measured in light of care systems moving towards value-based frameworks that measure value in terms of the actual health outcomes achieved (rather than processes of care), global response shifting to providing long-term care for PLHIV in the community, and integrating HIV as part of universal health coverage plans. Efforts should be directed towards validating generic and disease specific patient-reported measures of PLHIV, to identify the most suitable tools. Such efforts will ensure that patient experience is appropriately captured, especially to be used in programme or economic evaluations.
It is only by recognising and measuring the full range of health, mental and social outcomes related to the disease that the health status of PLHIV can be fully understood.
High‐efficiency white polymer light‐emitting diodes are demonstrated by using a hole‐injection/transport bilayer. The excellent solvent resistance of the fully crosslinked hole‐injection layer ...ensures the subsequent solution processing of the light‐emitting layer. High power efficiency can be achieved. The device also emits quite stable white light. The figure shows a schematic of the device and the chemical structure of the VB‐TCTA layer.
Humans and higher primates are unique in that they lack uricase, the enzyme capable of oxidizing uric acid. As a consequence of this enzyme deficiency, humans have high serum uric acid levels. In ...some people, uric acid levels rise above the solubility limit resulting in crystallization in joints, acute inflammation in response to those crystals causes severe pain; a condition known as gout. Treatment for severe gout includes injection of non-human uricase to reduce serum uric acid levels. Krystexxa® is a hyper-PEGylated pig-baboon chimeric uricase indicated for chronic refractory gout that induces an immunogenic response in 91% of treated patients, including infusion reactions (26%) and anaphylaxis (6.5%). These properties limit its use and effectiveness. An innovative approach has been used to develop a therapeutic uricase with improved properties such as: soluble expression, neutral pH solubility, high E. coli expression level, thermal stability, and excellent activity. More than 200 diverse uricase sequences were aligned to guide protein engineering and reduce putative sequence liabilities. A single uricase lead candidate was identified, which showed low potential for immunogenicity in >200 human donor samples selected to represent diverse HLA haplotypes. Cysteines were engineered into the lead sequence for site specific PEGylation and studies demonstrated >95% PEGylation efficiency. PEGylated uricase retains enzymatic activity in vitro at neutral pH, in human serum and in vivo (rats and canines) and has an extended half-life. In canines, an 85% reduction in serum uric acid levels was observed with a single subcutaneous injection. This PEGylated, non-immunogenic uricase has the potential to provide meaningful benefits to patients with gout.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The pyrolysis of polyvinyl chloride (PVC) was qualitatively analyzed by TG-FTIR, and HCl removal efficiency of Ca-based additives were semi-quantitatively studied also by means of TG-FTIR. ...Additionally, the thermodynamic equilibrium modeling was also carried out to understand the formation of HCl from PVC and from mixtures of PVC with different additives. Experimental results showed that the pyrolysis of PVC took place in two steps accompanied by the release of HCl and hydrocarbon, respectively. Almost all Cl transformed to HCl, and hardly any other kinds of Cl compounds were detected. The addition of Ca-based additives extended the second weight loss step of PVC, but they did not affect the release time when the maximum HCl concentration appeared. The maximum HCl concentration decreased according to the increase of additive amount, that is to say, the HCl removal efficiency increased as the Ca/Cl molar ratio increased, however when the Ca/Cl ratio increased to a certain value, the increase of HCl removal efficiency was not proportional to the increase of additive amount. For different additives, different Ca/Cl ratios should be chosen based on the cost, HCl removal efficiency and utilization efficiency of additive.
BackgroundCountries are recommended to progressively work towards universal health coverage (UHC), and to make explicit choices regarding the expansion of priority services. However, there is little ...guidance on how to manage the inclusion of vertical programmes, funded by external partners, in health benefits packages (HBP) in low and middle-income countries (LMICs).ObjectiveWe conducted a scoping review to map the inclusion of six vertical programmes (HIV, tuberculosis, malaria, maternal and child health, contraceptives, immunisation) in 26 LMICs.MethodsWe identified 26 LMICs with an HBP that was not aspirational (eg, with evidence of implementation or funding). For each HBP, we collected information on the corresponding UHC scheme, health financing at the time of establishment, revisions since inception and entitlements. For each vertical programme, we developed a list of tracer interventions based on the Disease Control Priorities 3 and the 100 Core Health Indicators List. We then used this list of tracer interventions to map the coverage of the six vertical programmes.ResultsThe review shows that there is no common starting point for countries embarking into UHC. Some HBPs were almost three decades old. Whole package revisions are rare. The inclusion of vertical programme does not follow a given pattern based on health financing indicators or country’s income group. Maternal child health services are the most often included and family planning the least. Six countries in our sample covered all vertical programmes, while one covered only one of six.ConclusionsThis review has shown that there has been a long history of countries facing this question and we have provided the first mapping of inclusion of vertical programmes in UHC. The results of the mapping can inform decisions in countries embarking in UHC.
Real-time monitoring of mainstream and social media can inform public health practitioners and policy makers about vaccine sentiment and hesitancy. We describe a publicly available platform for ...monitoring vaccination-related content, called the Vaccine Sentimeter. With automated data collection from 100,000 mainstream media sources and Twitter, natural-language processing for automated filtering, and manual curation to ensure accuracy, the Vaccine Sentimeter offers a global real-time view of vaccination conversations online. To assess the system's utility, we followed two events: polio vaccination in Pakistan after a news story about a Central Intelligence Agency vaccination ruse and subsequent attacks on health care workers, and a controversial episode in a television program about adverse events following human papillomavirus vaccination. For both events, increased online activity was detected and characterized. For the first event, Twitter response to the attacks on health care workers decreased drastically after the first attack, in contrast to mainstream media coverage. For the second event, the mainstream and social media response was largely positive about the HPV vaccine, but antivaccine conversations persisted longer than the provaccine reaction. Using the Vaccine Sentimeter could enable public health professionals to detect increased online activity or sudden shifts in sentiment that could affect vaccination uptake.
In May 2022, cases of monkeypox were reported in non-monkeypox endemic countries such as Europe and the United States. As of 26 May, a cumulative total of 257 laboratory-confirmed cases and ...approximately 120 suspected cases had been reported to WHO from non-monkeypox endemic countries. This event immediately caused great concern and alarm to the WHO and national virologists. This paper aims to summarize the epidemiological and clinical features of previous monkeypox virus infections and the current local outbreaks in non-monkeypox endemic countries and propose countermeasures to control the current localized infections in non-monkeypox endemic areas as soon as possible. We reviewed the literature and websites related to monkeypox. We searched Google Scholar, PubMed, Web of Science, Embase, and African Journals Online using the medical subject terms "monkeypox", "monkeypox virus", "monkeypox outbreak", "non-monkeypox endemic areas", "clinical features", "epidemiology", "transmission", and "infection". We found that monkeypox is a zoonotic disease of forest animals that has occurred mainly in West and Central Africa since the first case was reported in the Congo in 1970, with occasional cases spreading to countries such as the United States and Europe. It is common among students, housekeepers, hunters, farmers and housewives. It is more common in males than females, occurs below middle age, and is more common in children under 10. The incubation period is 5 to 21 days, and the rash usually appears within 1 to 3 days after the onset of fever. Clinical manifestations include fever, rash, swollen lymph nodes, headache, muscle pain and unusual weakness. Most patients have mild symptoms that last from 2 to 4 weeks. The source of the sudden outbreak in Europe and the United States is currently unknown and occurs mostly in homosexuals who have sex with men (MSM). Outbreaks of monkeypox virus infection in non-monkeypox endemic areas have received widespread attention and focus. We believe that a scientific response to the transmission route of monkeypox virus and, where necessary, vaccination of high-risk groups against the monkeypox smallpox will control infection in non-monkeypox endemic areas.
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