Abstract
Food-grade polymers are largely employed in food industry for a variety of purposes, including food preservation, texture modification and food packaging. They are considered safe for human ...consumption and are approved by regulatory bodies such as the FDA and EFSA. One of the most common uses of food-grade polymers is in food packaging. They are used to create packaging materials that are resistant to moisture, oxygen and to prevent contamination. Food- grade polymers are also used in the formulation of dietary supplements, fortified foods, and modified-release pharmaceuticals. They help improve the stability, shelf life and bioavailability of active ingredients. For example, specific polymers can be tailored to create controlled-release formulations, in which the active ingredient is released gradually over time, resulting in a more consistent and prolonged effect. In addition, food-grade polymers can be used to improve the texture and appearance of dietary supplements and oral pharmaceutical forms, mask unpleasant tastes and odors and making them more palatable to consumers. This paper overviews the application of food-grade polymers in the preparation of modified and targeted delivery systems for drugs and nutraceutical ingredients.
Streams of the pampas region (central Argentina) are characterized by the lack of riparian forests and by low current velocities, and receive a large amount of industrial and domestic effluents. ...Intensive agriculture in the region has greatly increased during the last years; nevertheless, regional studies to determine baseline conditions are not available. Here, we characterized pampean streams considering physico-chemical water features and the composition of macrophyte communities, and we established if the regions proposed by an early hydrological regionalization show differentiated water chemistry and macrophyte assemblages.
Forty-one streams were sampled in autumn, spring and summer. Streams were characterized by alkaline waters, with high conductivities and dissolved oxygen concentrations, and they can be classified as eutrophic. A good discrimination among regions was achieved based on streamwater features in all seasons; variables that most contribute to the discrimination were related to pH, eutrophication, and conservative ions. Regional differences may be due to variations in water availability, parent material, and land use practices.
The aquatic plant communities reflected the eutrophic state of waters, but macrophyte composition was not useful to differentiate among regions because it is not affected by differences in water chemistry. Macrophyte species grouped according to their growth form and assemblage distribution were related to chemical variables (as conductivity and nitrate) and possibly to flow conditions.
MVA-BN-PRO (BN ImmunoTherapeutics) is a candidate immunotherapy product for the treatment of prostate cancer. It encodes 2 tumor-associated antigens, prostate-specific antigen (PSA), and prostatic ...acid phosphatase (PAP), and is derived from the highly attenuated modified vaccinia Ankara (MVA) virus stock known as MVA-BN. Past work has shown that the immunogenicity of antigens can be improved by targeting their localization to exosomes, which are small, 50- to 100-nm diameter vesicles secreted by most cell types. Exosome targeting is achieved by fusing the antigen to the C1C2 domain of the lactadherin protein. To test whether exosome targeting would improve the immunogenicity of PSA and PAP, 2 additional versions of MVA-BN-PRO were produced, targeting either PSA (MVA-BN-PSA-C1C2) or PAP (MVA-BN-PAP-C1C2) to exosomes, while leaving the second transgene untargeted. Treatment of mice with MVA-BN-PAP-C1C2 led to a striking increase in the immune response against PAP. Anti-PAP antibody titers developed more rapidly and reached levels that were 10- to 100-fold higher than those for mice treated with MVA-BN-PRO. Furthermore, treatment with MVA-BN-PAP-C1C2 increased the frequency of PAP-specific T cells 5-fold compared with mice treated with MVA-BN-PRO. These improvements translated into a greater frequency of tumor rejection in a PAP-expressing solid tumor model. Likewise, treatment with MVA-BN-PSA-C1C2 increased the antigenicity of PSA compared with treatment with MVA-BN-PRO and resulted in a trend of improved antitumor efficacy in a PSA-expressing tumor model. These experiments confirm that targeting antigen localization to exosomes is a viable approach for improving the therapeutic potential of MVA-BN-PRO in humans.
We have designed short peptides composed of two functional domains, one a tumor blood vessel 'homing' motif and the other a programmed cell death-inducing sequence, and synthesized them by simple ...peptide chemistry. The 'homing' domain was designed to guide the peptide to targeted cells and allow its internalization. The pro-apoptotic domain was designed to be nontoxic outside cells, but toxic when internalized into targeted cells by the disruption of mitochondrial membranes. Although our prototypes contain only 21 and 26 residues, they were selectively toxic to angiogenic endothelial cells and showed anti-cancer activity in mice. This approach may yield new therapeutic agents.
Transcription of eukaryotic genes within a chromatin environment requires the sequential recruitment of histone modification enzymes and the general transcription factors (GTFs) by activators. ...However, it is unknown how preinitiation complex assembly is coordinated with chromatin modification. Here, we show that the model activator GAL4-VP16 directs the ordered assembly of Mediator, histone acetyltransferases (HATs), and GTFs onto immobilized chromatin and naked DNA templates in vitro. Using purified proteins, we found that the Mediator regulates this assembly process by binding to p300 and TFIID. An acetyl-CoA-dependent catalytic switch causes p300 to acetylate chromatin and then dissociate. Dissociation of p300 enhances TFIID binding and active transcription. The dissociation is caused by an autoacetylation-induced conformational change in the catalytic domain of p300. We conclude that autoacetylation-induced dissociation of p300 acts as a catalytic switch, which allows TFIID binding and subsequent preinitiation complex assembly.
ATPases and histone chaperones facilitate RNA polymerase II (pol II) elongation on chromatin. In vivo, the coordinated action of these enzymes is necessary to permit pol II passage through a ...nucleosome while restoring histone density afterward. We have developed a biochemical system recapitulating this basic process. Transcription through a nucleosome in vitro requires the ATPase remodels structure of chromatin (RSC) and the histone chaperone nucleosome assembly protein 1 (NAP1). In the presence of NAP1, RSC generates a hexasome. Despite the propensity of RSC to evict histories, NAP1 reprograms the reaction such that the hexasome is retained on the template during multiple rounds of transcription. This work has implications toward understanding the mechanism of pol II elongation on chromatin.
Endostatin, a fragment of collagen XVIII, is a potent antagonist of angiogenesis and inhibitor of tumor growth in mouse models. At present, the mechanism of action of endostatin is unknown. We show ...here that recombinantly produced human endostatin interacts with α5- and αv-integrins on the surface of human endothelial cells. We further demonstrate that the endostatin-integrin interaction is of functional significance in vitro, as we found that immobilized endostatin supports endothelial cell survival and migration in an integrin-dependent manner. Soluble endostatin in turn inhibits integrin-dependent endothelial cell functions, such as cell migration. Taken together, these results implicate integrins as potential targets for endostatin function and support the importance of integrins in endothelial cell biology and angiogenesis.
Bladder stones (BS) are still endemic in children in developing nations and account for a high volume of paediatric urology workload in these areas. The aim of this systematic review is to ...comparatively assess the benefits and risks of minimally invasive and open surgical interventions for the treatment of bladder stones in children.
This systematic review was conducted in accordance with Cochrane Guidance. Database searches (January 1970– March 2021) were screened, abstracted, and assessed for risk of bias for comparative randomised controlled trials (RCTs) and non-randomised studies (NRSs) with >10 patients per group. Open cystolithotomy (CL), transurethral cystolithotripsy (TUCL), percutaneous cystolithotripsy (PCCL), extracorporeal shock wave lithotripsy (ESWL) and laparoscopic cystolithotomy (LapCL) were evaluated.
In total, 3040 abstracts were screened, and 8 studies were included. There were 7 retrospective non-randomised studies (NRS's) and 1 quasi-RCT with 1034 eligible patients (CL: n=637, TUCL: n=196, PCCL: n=138, ESWL: n=63, LapCL n=0). Stone free rate (SFR) was given in 7 studies and measured 100%, 86.6%-100%, and 100% for CL, TUCL and PCCL respectively. CL was associated with a longer duration of inpatient stay than PCCL and TUCL (p<0.05). One NRS showed that SFR was significantly lower after 1 session with outpatient ESWL (47.6%) compared to TUCL (93.5%) and CL (100%) (p<0.01 and p<0.01 respectively). One RCT compared TUCL with laser versus TUCL with pneumatic lithotripsy and found that procedure duration was shorter with laser for stones <1.5cm (n=25, p=0.04).
In conclusion, CL, TUCL and PCCL have comparable SFRs but ESWL is less effective for treating stones in paediatric patients. CL has the longest duration of inpatient stay. Information gathered from this systematic review will enable paediatric urologists to comparatively assess the risks and benefits of all urological modalities when considering surgical intervention for bladder stones.
In Nicaragua, cervical cancer is the leading cause of cancer-related death for women ages 15-44, yet access to the HPV vaccine is limited to those with financial resources to pay for it. Cervical ...cytology is provided free of charge in public clinics; however, only 10% of women receive Pap smears at the nationally recommended frequency. Previous studies have not investigated how beliefs regarding cervical cancer screening may differ for urban and rural populations in Nicaragua. Furthermore, no investigation has assessed Nicaraguan women's beliefs about a potential HPV immunization campaign. Given beliefs' influence on health behavior, we investigated the structural, sociocultural, and knowledge-based factors influencing women's beliefs regarding cervical cancer screening among urban and rural women in León, Nicaragua, and assessed acceptance of a potential HPV immunization program.
Our sequential explanatory mixed-methods study consisted of two phases: (1) a close-ended questionnaire, followed by (2) a qualitative, in-depth interview. Our quantitative sample contained 117 urban and 112 rural participants aged 18-49. We assessed beliefs regarding cervical cancer screening using a 22-item scale, with higher scores indicating screening-promoting beliefs in simple linear and multiple linear regressions. Twenty qualitative interviews, exploring the sociocultural dimensions of knowledge and attitudes indicated by our quantitative findings, were conducted with a sample of 13 urban and 7 rural women aged 19-46.
The multiple linear regression indicates that greater knowledge of Pap smears, HPV, and cervical cancer is significantly associated with screening-promoting beliefs after adjusting for other relevant factors. There was no significant difference in screening knowledge and beliefs for urban and rural women. Four recurrent themes representing determinants of knowledge, beliefs, and attitudes regarding cervical cancer screening arose from interviews and built on quantitative findings: (1) women's embarrassment due to the intimate nature of the Pap smear and male gender of exam provider discourages screening; (2) women believe Pap smears and cervical cancer are associated with sexual promiscuity, and this association stigmatizes women with the disease; (3) knowledge of cervical cancer prevention is limited to those who regularly attend health centers; and (4) women find screening inconvenient, believing understaffed clinics increase patient wait time, limit time patients spend with clinicians, and delay Pap results. A fifth theme indicates (5) participants' acceptance of a potential HPV immunization program.
Future interventions should focus on increasing access to information about cervical cancer prevention for women who do not regularly attend health centers. Furthermore, our results suggest that if funding were allocated to make the HPV vaccine accessible in Nicaragua, it would be well received.
Aim of the study was to evaluate efficacy and efficiency of 180-watt Green-Light XPS (GL-XPS) laser photoselective vaporization of the prostate (PVP) in patients under 5-Alpha-Reductase Inhibitors ...(5ARI) treatment.
A consecutive series of patients with lower urinary tract symptoms due to benign prostatic enlargement treated by PVP with the GL-XPS were enrolled. Patients were divided in two groups according to the chronic use (>6 months) of 5ARI. These two groups were compared on lasing density (kilojoules per prostate volume), vaporization efficiency (prostate volume per lasing time), vaporization power (kilojoules per lasing time), Prostate Specific Antigen (PSA) reduction from baseline, symptom score change from baseline and uroflowmetry parameters improvement. Follow-up was performed at 3, 6 and 12 months with International Prostate Symptom Score, Uroflowmetry parameters and PSA.
Overall 193 patients were enrolled. Out of them 87/193 (45%) were on 5ARI treatment. No significant differences were recorded between the two groups at baseline. Median age was 68 years old and median prostate volume was 60 ml. In terms of laser efficiency, no statistically significant differences were recorded in terms of lasing time (25 min vs. 24.5 min; p>0.05); energy used (250 kJ vs. 221 kJ; p>0.05), lasing density (6.8 kJ/ml vs. 6.6 kJ/ml, p>0.05), vaporization efficiency (1.4 ml/min vs. 1.3 ml/min, p>0.05) and vaporization power (9.6 kJ/min vs. 9.4 kJ/min; p>0.05). Finally, no significant differences were also recorded postoperatively in the two groups in terms of PSA reduction, improvement in symptom score and uroflowmetry parameters (p>0.05).
Thirty-seven efficacy and efficiency outcomes were not statistically different between the two groups. 5ARI does not reduce the performance and ability of the 180-watt Green-Light XPS laser system.
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