Good Tolerance
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2021 ◽  
Vol 20 (1) ◽  
Jiliang Deng ◽  
Yanling Wu ◽  
Zhaohui Zheng ◽  
Nanzhu Chen ◽  
Xiaozhou Luo ◽  

Abstract Background Saccharomyces cerevisiae is an important synthetic biology chassis for microbial production of valuable molecules. Promoter engineering has been frequently applied to generate more synthetic promoters with a variety of defined characteristics in order to achieve a well-regulated genetic network for high production efficiency. Galactose-inducible (GAL) expression systems, composed of GAL promoters and multiple GAL regulators, have been widely used for protein overexpression and pathway construction in S. cerevisiae. However, the function of each element in synthetic promoters and how they interact with GAL regulators are not well known. Results Here, a library of synthetic GAL promoters demonstrate that upstream activating sequences (UASs) and core promoters have a synergistic relationship that determines the performance of each promoter under different carbon sources. We found that the strengths of synthetic GAL promoters could be fine-tuned by manipulating the sequence, number, and substitution of UASs. Core promoter replacement generated synthetic promoters with a twofold strength improvement compared with the GAL1 promoter under multiple different carbon sources in a strain with GAL1 and GAL80 engineering. These results represent an expansion of the classic GAL expression system with an increased dynamic range and a good tolerance of different carbon sources. Conclusions In this study, the effect of each element on synthetic GAL promoters has been evaluated and a series of well-controlled synthetic promoters are constructed. By studying the interaction of synthetic promoters and GAL regulators, synthetic promoters with an increased dynamic range under different carbon sources are created.

2021 ◽  
Vol 13 (3) ◽  
pp. 92-100
N. V. Sizova ◽  
E. S. Obizhaeva ◽  
S. O. Mayorova

Purpose of the study. Evaluation of the efficacy, safety and tolerability of raltegravir regimens in HIV-infected patients with concomitant pathology in real clinical practice.Materials and methods. A retrospective analysis was carried out of 277 outpatient records of HIV-infected patients who received raltegravir (RAL) as a third component both in patients without previous experience of antiretroviral therapy (ART) and in patients with experience of treatment with various somatic pathologies. The main criterion for the effectiveness of the scheme was the proportion of patients with undetectable viral load at the start of the analysis. Additional criteria for evaluating the efficacy and safety of the regimen were the dynamics of the number of CD4-lymphocytes, the frequency and nature of undesirable side reactions.Results. On average, patients with no experience of treatment and with experience of treatment received regimens with raltegravir for about 5 years. At the time of the study in 2020, 69.8% of patients on ART for the first time continued to take a regimen containing raltegravir. In this group, the proportion of patients with virological suppression (PCR of HIV RNA less than 50 kopecks / ml) was 97.7%. 75.2% of patients in the second group in 2020 continued to take the RAL regimen. The proportion of patients with virological suppression (VL less than 50 kopecks / ml) in this group was 97.5%. During the treatment, there was no discontinuation of the regimen in both groups due to undesirable side reactions to raltegravir.Conclusion. The results of this study confirm that RAL-based regimens provide a high level of efficacy with a good tolerance and safety profile in routine clinical practice for both naive and experienced patients with various somatic pathologies.

2021 ◽  
Vol 12 (1) ◽  
Xinwen Yan ◽  
Miao Xiong ◽  
Xin-Yu Deng ◽  
Kai-Kai Liu ◽  
Jia-Tong Li ◽  

AbstractDoping has been widely used to control the charge carrier concentration in organic semiconductors. However, in conjugated polymers, n-doping is often limited by the tradeoff between doping efficiency and charge carrier mobilities, since dopants often randomly distribute within polymers, leading to significant structural and energetic disorder. Here, we screen a large number of polymer building block combinations and explore the possibility of designing n-type conjugated polymers with good tolerance to dopant-induced disorder. We show that a carefully designed conjugated polymer with a single dominant planar backbone conformation, high torsional barrier at each dihedral angle, and zigzag backbone curvature is highly dopable and can tolerate dopant-induced disorder. With these features, the designed diketopyrrolopyrrole (DPP)-based polymer can be efficiently n-doped and exhibit high n-type electrical conductivities over 120 S cm−1, much higher than the reference polymers with similar chemical structures. This work provides a polymer design concept for highly dopable and highly conductive polymeric semiconductors.

2021 ◽  
Akil LOMANI ◽  
Dennis S Nielsen ◽  
Larbi Ahmed Amine ◽  
Tahri Ahmed ◽  
Mediani Ahmed

Abstract Milk and indigenous fermented, milk based products are a rich source of lactic acid bacteria (LAB) and may serve as a source of potential probiotics. In the present study LAB were isolated from raw cows’ milk sampled at five different Algerian farms. A total of 24 Gram positive, catalase negative isolates where identified to species level using a combination of (GTG) 5-based rep-PCR fingerprinting and 16S rRNA gene sequencing. All isolates were identified as Enterococcus faecium and all isolates had highly similar rep-PCR profiles. Four representative isolates were screened for acid tolerance, bile salts tolerance, antimicrobial susceptibility, antibacterial activity and haemolysis. The four selected strains all exhibited good tolerance to low pH (2, 3, and 4), and to bile salts (concentrations of 0.5%, 1%, and 2%) and were sensitive to chloramphenicol, vancomycin, tetracycline, gentamicine and peniciline G, but were resistant to oxaciline. Cell-free supernatants of the four tested strains all inhibited Staphylococcus aureus, Escherichia coli and Listeria monocytogenes but not Salmonella Typhi. No haemolytic activity was observed.

Horticulturae ◽  
2021 ◽  
Vol 7 (10) ◽  
pp. 341
Valentina Ljubej ◽  
Erna Karalija ◽  
Branka Salopek-Sondi ◽  
Dunja Šamec

Kale (Brassica oleracea var acephala) is known as a vegetable with good tolerance of environmental stress and numerous beneficial properties for human health, which are attributed to different phytochemicals. In the present study, investigation of how low temperatures affect proline, pigments and specialized metabolites content was performed using 8-weeks old kale plants subjected to chilling (at 8 °C, for 24 h) followed by short freezing (at −8 °C, for 1 h after previous acclimation at 8 °C, for 23 h). Plants growing at 21 °C served as a control. In both groups of plants (exposed to low temperatures and exposed to short freezing) a significant increase in proline content (14% and 49%, respectively) was recorded. Low temperatures (8 °C) induced an increase of pigments (total chlorophylls 7%) and phytochemicals (phenolic acids 3%; flavonoids 5%; carotenoids 15%; glucosinolates 21%) content, while exposure to freezing showed a different trend dependent upon observed parameter. After freezing, the content of chlorophylls, carotenoids, and total phenolic acids retained similar levels as in control plants and amounted to 14.65 ± 0.36 mg dw g−1, 2.58 ± 0.05 mg dw g−1 and 13.75 ± 0.07 mg dw CEA g−1, respectively. At the freezing temperature, total polyphenol content increased 13% and total flavonoids and glucosinolates content decreased 21% and 54%, respectively. Our results suggest that acclimatization (23 h at 8 °C) of kale plants can be beneficial for the accumulation of pigments and phytochemicals, while freezing temperatures affect differently specialized metabolite synthesis. The study suggests that growing temperature during kale cultivation must be considered as an important parameter for producers that are orientated towards production of crops with an increasing content of health-related compounds.

Tchamba Mbiada Mervie Noël ◽  
Bouba Adji Mohammadou ◽  
Nodem Shanang Francky Steve ◽  
Léopold Ngoune Tatsadjieu ◽  
Mbarga Manga Joseph Arsene ◽  

Background and Aim: Lactic acid bacteria (LAB) became a field of interest by scientists in recent years due to their technological and probiotic properties. The aim of this work was to study the technological and probiotic properties of LAB isolated from the bottle gourds (calabashes)of milk fermentation, in Mbéré, Cameroun. Methods: Five different bottle gourds from milk fermentation were collected and used for LAB isolation. These LABs were characterized using conventional cultural method, the technological (such as proteolytic, lipolytic activities) and probiotic properties (including acid and bile salt tolerance, cholesterol assimilation and antioxidant activities) were assessed. Results: From these samples, 30 LABs were isolated and among them, 21 exhibited great lipolytic and proteolytic activities with the maximum values of 18 and 29 mm respectively. In addition, 10 LAB isolates showed interesting antimicrobial activity against pathogens germs tested and good tolerance ability under acid and bile salt stress after 24h of incubation. Cholesterol assimilation and antioxidant tests revealed that isolated BC4 and BC3 have the greatest activity (35 and 39 mm respectively) while, BC4 and BL4 have the greatest antioxidant activity (IC50 = 0,15 and 0,13 respectively). Conclusion: LAB isolated from the bottle gourds (calabashes) of milk fermentation, in Mbéré, Cameroon can be used to develop dairy industry and manage the cardiovascular diseases.

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3268
Chia-Chun Tang ◽  
Tai-Chung Huang ◽  
Feng-Ming Tien ◽  
Jing-Meei Lin ◽  
Yi-Chen Yeh ◽  

Short-term calorie reduction (SCR) requires individuals to reduce their calorie intake to less than 50% of normal requirements and has shown good tolerance and potential benefits in prior studies addressing gynecological cancer patients. More studies are needed to further confirm its safety, feasibility, and effects in patients with different cancers, including hematological malignancies. This pilot cohort study with a matched-pair comparison group was registered at [201810112RIND]. Adult patients diagnosed with advanced-stage diffuse large-B cell lymphoma were recruited (SCR group) and matched with one comparison patient (comparison group), each in a manner blinded to their outcomes. The SCR group undertook at least two cycles of 48 h water fast along with their chemotherapy R-CHOP. Descriptive analysis and generalized estimating equations were used to analyze the data. Six participants completed multiple cycles of SCR and were compared to their six counterparts in the comparison group. The results showed that SCR is safe and feasible in terms of a high compliance rate and stable nutritional status. The SCR was associated with benefits in post-chemotherapy hematological parameters (i.e., erythrocyte [p < 0.001] and lymphocyte counts [p < 0.001]). More randomized controlled trials are needed to validate the effects of SCR on different types of cancer populations.

2021 ◽  
Vol 21 (1) ◽  
Frédérick Gaultier ◽  
Anne-laure Ejeil ◽  
Sébastien Jungo ◽  
Saskia Ingen-Housz-Oro ◽  
François Le Pelletier de Clatigny ◽  

Abstract Background Chronic erosive gingivitis, also called desquamative gingivitis, defines a clinical picture that can be generated by several inflammatory and immune diseases. Pathology is therefore essential for the differential diagnosis. However, when the gingival lesion is initial, exclusive or predominant, selecting the biopsy site and protocol may be problematic due to tissue fragility. Especially since there are few studies on the subject, the aim of our study was to assess the protocol, diagnostic relevance and tolerance of an original protocol using interdental papilla biopsy. Methods We conducted a retrospective bicentric study, from October 2011 to July 2019, including all patients with a chronic erosive gingivitis who had received, for diagnostic purposes, a interdental papilla biopsy. Results The contribution levels for the two hospital departments were 94.7% and 97.1%, respectively. No postoperative complication was recorded in the short or long term. Conclusion The interdental papilla biopsy protocol is perfectly adapted to the anatomopathological examinations required to establish differential diagnosis of chronic erosive gingivitis. This surgical protocol is simple to perform, non iatrogenic with a very good tolerance and and accessible to all clinicians. It is highly efficient with an excellent contribution level. ClinicalTrials NCT04293718 (March 3, 2020). Health Data Hub N° F20201109083211 (November 9, 2020).

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4657
Tim Schneider ◽  
Annalisa Patriarca ◽  
Alberto Degiovanni ◽  
Manuel Gallas ◽  
Yolanda Prezado

(1) Background: Proton minibeam radiation therapy (pMBRT) is a novel therapeutic approach with the potential to significantly increase normal tissue sparing while providing tumour control equivalent or superior to standard proton therapy. For reasons of efficiency, flexibility and minibeam quality, the optimal implementation of pMBRT should use magnetically focussed minibeams which, however, could not yet be generated in a clinical environment. In this study, we evaluated our recently proposed minibeam nozzle together with a new clinical proton linac as a potential implementation. (2) Methods: Monte Carlo simulations were performed to determine under which conditions minibeams can be generated and to evaluate the robustness against focussing magnet errors. Moreover, an example of conventional pencil beam scanning irradiation was simulated. (3) Results: Excellent minibeam sizes between 0.6 and 0.9 mm full width at half maximum could be obtained and a good tolerance to errors was observed. Furthermore, the delivery of a 10 cm × 10 cm field with pencil beams was demonstrated. (4) Conclusion: The combination of the new proton linac and minibeam nozzle could represent an optimal implementation of pMBRT by allowing the generation of magnetically focussed minibeams with clinically relevant parameters. It could furthermore be used for conventional pencil beam scanning.

2021 ◽  
pp. 43-46
Uma Jain ◽  
Jayshree chimrani ◽  
Kajal Krishna

INTRODUCTION- Polycystic ovarian syndrome (PCOS) is a common, heterogeneous disorder affecting 5-15% of women of reproducing age group and characterized by hyperandrogenic skin symptoms, (acne, Hirsutism and female pattern alopecia,) irregular menstrual bleeding, obesity, dysmenorrhea infertility, and increased risk of metabolic syndrome and endometrial cancer. MATERIAL AND METHOD-The present study was conducted in a private gynecological Clinic Shivpuri, (M.P.). After taking Consent women suffering from PCOS (Fullled the clinical and USG criteria of PCOS(Rotterdam criteria )) along with androgenic symptoms like acne, hirsutism and androgenetic alopecia with or without other symptoms like menstrual irregularities and dysmenorrhea were included in the study.. All patients then received a combination of ethenyl Estradiol (0.035mg) + Cyproterone acetate (2mg). The Patients were followed in the third month, Sixth month, and at about 1 year for improvement in various complaints RESULT- According to presenting symptoms the most common presenting symptom was acne 72.72%, followed by menstrual irregularities 68.18%, hirsutism 50%, alopecia 27.27%, and dysmenorrhea in 27.27%. In acne patients, 37.5% of patients showed improvement after 3 cycles of CPA/EE, 75% showed at 6 months and in 93.75%, improvement was seen at 12 months. In the case of alopecia (83.33%) patient showed improvement after >6 cycles. Patients with hirsutism showed no improvement after 3 months of therapy but 54.54% of the patients showed a change in texture after 6 months of therapy and 72.72% after 9-12 months of therapy. Patients with dysmenorrhea reported a decrease in pain after therapy. The acceptance of the treatment was very good. In 86.36% of patients, good tolerance of drug was seen and in only 3 patients adverse effects (headache and nausea) of the drug were there. All the patients were having good to moderate satisfaction with the therapy. CONCLUSION- Since androgen excess is the prime defect in polycystic ovarian disease, its reduction is the main therapeutic target for most women. Our study found that combined hormonal contraceptives containing ethenyl Estradiol (0.035mg) + Cyproterone acetate (2mg) in a 21/7 regimen had a positive effect in the treatment of acne, hirsutism, menstrual irregularity, and dysmenorrhea in PCOS patients.

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