Search

Extracellular vesicles (EVs) function as potent mediators of intercellular communication for many in vivo processes, contributing to both health and disease related conditions. Given their biological origins and diverse functionality from correspondingly unique "cargo" compositions, both endogenous and modified EVs are garnering attention as promising therapeutic modalities and vehicles for targeted therapeutic delivery applications. Their diversity in composition, however, has revealed a significant need for more comprehensive analytical-based characterization methods, and manufacturing processes that are consistent and scalable. In this review, we explore the dynamic landscape of EV research and development efforts, ranging from novel isolation approaches, to their analytical assessment through novel characterization techniques, and to their production by industrial-scale manufacturing process considerations. Expanding the horizon of these topics to EVs for in-human applications, we underscore the need for stringent development and adherence to Good Manufacturing Practice (GMP) guidelines. Wherein, the intricate interplay of raw materials, production in bioreactors, and isolation practices, along with analytical assessments compliant with the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines, in conjunction with reference standard materials, collectively pave the way for standardized and consistent GMP production processes. [ABSTRACT FROM AUTHOR]

Interleukin-2 (IL-2) is a multi-faceted cytokine, known for promoting proliferation, survival, and cell death depending on the cell type and state. For example, IL-2 facilitates cell death only in activated T cells when antigen and IL-2 are abundant. The availability of IL-2 clearly impacts this process. Our laboratory recently demonstrated that IL-2 is retained in blood vessels by heparan sulfate, and that biologically active IL-2 is released from vessel tissue by heparanase. We now demonstrate that heparanase digestion also releases a dimeric form of IL-2 that is highly cytotoxic to cells expressing the IL-2 receptor. These cells include "traditional" IL-2 receptor-bearing cells such as lymphocytes, as well as those less well known for IL-2 receptor expression, such as epithelial and smooth muscle cells. The morphologic changes and rapid cell death induced by dimeric IL-2 imply that cell death is mediated by disruption of membrane permeability and subsequent necrosis. These findings suggest that IL-2 has a direct and unexpectedly broad influence on cellular homeostatic mechanisms in both immune and non-immune systems.

Introduction The transport and fate of organic compounds in the saturated zone are generally assumed to be controlled by both physical and chemical parameters of the sorbent, and by the [...]

Interleukin-2 (IL-2) is a multi-faceted cytokine, known for promoting proliferation, survival, and cell death depending on the cell type and state. For example, IL-2 facilitates cell death only in activated T cells when antigen and IL-2 are abundant. The availability of IL-2 clearly impacts this process. Our laboratory recently demonstrated that IL-2 is retained in blood vessels by heparan sulfate, and that biologically active IL-2 is released from vessel tissue by heparanase. We now demonstrate that heparanase digestion also releases a dimeric form of IL-2 that is highly cytotoxic to cells expressing the IL-2 receptor. These cells include “traditional” IL-2 receptor-bearing cells such as lymphocytes, as well as those less well known for IL-2 receptor expression, such as epithelial and smooth muscle cells. The morphologic changes and rapid cell death induced by dimeric IL-2 imply that cell death is mediated by disruption of membrane permeability and subsequent necrosis. These findings suggest that IL-2 has a direct and unexpectedly broad influence on cellular homeostatic mechanisms in both immune and non-immune systems. [ABSTRACT FROM AUTHOR]

Background: Rabies remains endemic in Sri Lanka despite a strong government patronized anti-rabies campaign. Personal, cultural or religious beliefs have been thought to influence health practices that could render rabies prevalent in the country. Methodology: The knowledge, attitudes, and beliefs of 580 household heads/members from Nuwara Eliya District, Sri Lanka, regarding rabies were explored through a structured questionnaire. An improvement/deterioration in their knowledge and practices after the use of information and education campaign (IEC) materials was assessed through a repeat exploration at an interval of four weeks. Results: Respondents showed inclination toward animal birth control (60%) rather than elimination methods (24%). There was disparity between pet owners. enthusiasm to take pets for rabies inoculation (57%) and their ability to show dog vaccination cards (40%). Almost twice more pet owners than non-pet owners believed that it is their responsibility to control the population of roaming pet dogs (aOR=1.78; 95% CI: 1.14 to 2.76). The rabies leaflets were very effective in informing the people on how to deal with rabid animals, the earliest schedule for anti-rabies vaccine (ARV), and repeat vaccination. Conclusions: Awareness and proper attitude toward rabies management and canine population control are adequate among the rural Sinhalese and Buddhist populations of Sri Lanka; however, their current health practices should be improved. The rabies KAP could be further enhanced through the use of IEC materials. [ABSTRACT FROM AUTHOR]

As nurses, we learn that tragedy and miracles sometimes travel together--as my own family discovered after the death of our precious baby. [ABSTRACT FROM AUTHOR]

The article presents the report of the committee of the Institute of Criminal Law and Criminology, on crime and immigration. The Executive Board of the Institute at the last annual meeting referred to this committee the following questions for investigation, and report: First: Do existing treaty provisions directly or by implication and interpretation sufficiently protect the alien's rights and remedies in the U.S.? Second: Do existing legal provisions, either in the statutes or in the treaties, sufficiently protect the U.S. from alien criminals? Third: Is it advisable to settle the status of the immigrant by international agreement?" Owing partly to the fact of the absence of the chairman of the committee in Europe, where he made study of Italian penal institutions, and largely to the impossibility of getting together a group of very busy men geographically scattered in different states, it has been impossible to prepare a committee's report as such, that is, a report which should embody the views of all or of a majority of the committee, whose membership is composed of men and women of very divers callings and of very divided opinions and convictions.

Changes in osseous tissue after injury were studied in monkeys with the use of thermogravimetric analysis (TGA) and mechanical strength measurements. An exponential relationship was found to exist between strength and weight loss for repair tissues 3 to 8 weeks old. The quantitative techniques investigated seem promising for the improved characterization of mineralized tissue. [ABSTRACT FROM AUTHOR]

The article presents research on the variations in the amino acid composition of dentin and enamel. Tooth tissues were separated and decalcified by Battistone's and Burnett's methods. The tissues of powdered teeth were separated by a modified flotation technique or the enamel was separated from the dentin by chipping. The test results are also provided.

The article presents quantitative research of the amino acid composition of dentin decalcified by a chelating agent near neutrality and of a water soluble extract of powdered dentin. The analyzed dentin belonged to caries-free, permanent human teeth from men above the age of 18. A chart is also presented which details the amino acids in human dentinal protein.

In this article the authors used paper chromatography to analyze the amino acid content of enamel protein. Ethylenediamine tetraacetic acid (EDTA) was used to prepare the enamel protein for analysis. The results of the tests were that the amino acids accounted for 99.21 percent of the total nitrogen of enamel.

Background: Human immunodeficiency virus (HIV) prevalence is relatively lower in Sri Lanka than in other Asian countries; however, the number of HIV-infected persons has rapidly increased in recent years. Methodology: A baseline study on HIV, acquired immunodeficiency virus (AIDS), and sexually transmitted infections (STI) knowledge, attitude, and practice was conducted at two construction sites in Sri Lanka from January to February 2007 to design an effective intervention strategy for the construction workers. Results: Among 611 respondents (mostly males, mean age 32.8 years), nearly two-thirds lived away from home. Knowledge was fairly good on AIDS prevention but poorer on STI than on HIV. Some misconceptions were also observed. A high percentage did not consider HIV/AIDS as their own personal issue, and over 50% respondents expressed discriminatory attitudes towards HIV positives. Condom access was limited due to social and cultural norms. Mobility was not significantly associated with practice of prevention of HIV and STI. Conclusion: This study showed that the construction workers were not specially at higher risk of HIV at that time. In order to minimize the potential risk of infection, however, it would be effective to reduce stigma and discrimination among them through the prevention program, working together with community or religious leaders in the areas. More comprehensive assessment among other population groups would also be beneficial to identify their risk of infection. [ABSTRACT FROM AUTHOR]

Background: Malignant pleural mesothelioma is an aggressive tumor that has a poor prognosis and is resistant to unimodal approaches. Multimodal treatment has provided encouraging results., Methods: Phase II, open-label study of the combination of chemotherapy (pemetrexed 500 mg/m²+cisplatin 75 mg/m² IV every 21 days × 3 cycles), followed by surgery (en-bloc extrapleural pneumonectomy, 3-8 weeks after chemotherapy) and hemithoracic radiation (total radiation beam 54 Gy, received 4-8 weeks post-surgery). The primary endpoint was event-free survival, defined as the time from enrollment to time of first observation of disease progression, death due to any cause, or early treatment discontinuation., Results: Fifty-four treatment-naïve patients with T1-3 N0-2 malignant pleural mesothelioma were enrolled, 52 (96.3%) completed chemotherapy, 45 (83.3%) underwent surgery, 22 (40.7%) completed the whole treatment including 90-day post-radiation follow-up. The median event-free survival was 6.9 months (95%CI: 5.0-10.5), median overall survival was 15.5 months (95%CI 11.0-NA) while median time-to-tumor response was 4.8 months (95%CI: 2.5-8.0). Eighteen (33.3%) and 13 (24.1%) patients were still event-free after 1 and 2 years, respectively. The most common treatment-emergent adverse events were nausea (63.0%), anemia (51.9%) and hypertension (42.6%).Following two cardiopulmonary radiation-related deaths the protocol was amended (21 [38.9%] patients were already enrolled in the study): the total radiation beam was reduced from 54 Gy to 50.4 Gy and a more accurate selection of patients was recommended., Conclusions: The combination of pemetrexed plus cisplatin followed by surgery and hemithoracic radiation is feasible and has a manageable toxicity profile in carefully selected patients. It may be worthy of further investigation., Trial Registration: Clinicaltrial.com registrationID #NCT00087698.

One hundred seventy-one patients with clinical suspicion of prostate cancer were initially selected and underwent total and free PSA determination, digital rectal examination and transrectal ultrasonography. Sixty-five had total PSA values between 4 to 20 ng/ml. In these patients in addition to the free to total PSA ratio, the sensitivity, specificity, positive predictive value, true and false negative predictive value were evaluated, comparing these findings with histopathological characterization. Receiver Operating Characteristic Analysis was also performed. No statistically significant differences were evidenced between benign and neoplastic prostates comparing total PSA values, while significant differences were found by comparing both free PSA and the free to total PSA ratio (p < 0.01). Our experience demonstrates that using a 0.20 free to total PSA ratio cut-off, it is possible avoid 44.4% of following clinical tests, and biopsies could be saved in almost 40% of patients with a considerable cost-benefit ratio.