scholarly journals A Toxicity Screening Approach to Identify Bacteriophage-Encoded Anti-Microbial Proteins

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1057 ◽  
Author(s):  
Ushanandini Mohanraj ◽  
Xing Wan ◽  
Cindy M. Spruit ◽  
Mikael Skurnik ◽  
Maria I. Pajunen
Keyword(s):  
Pathogenic Bacteria ◽  
Plasmid Vector ◽  
Toxicity Screening ◽  
Screening Assay ◽  
Screening Approach ◽  
Significant Difference ◽  
Phage Genomics ◽  
Toxic Gene ◽  
Rapid Emergence

The rapid emergence of antibiotic resistance among many pathogenic bacteria has created a profound need to discover new alternatives to antibiotics. Bacteriophages, the viruses of microbes, express special proteins to overtake the metabolism of the bacterial host they infect, the best known of which are involved in bacterial lysis. However, the functions of majority of bacteriophage encoded gene products are not known, i.e., they represent the hypothetical proteins of unknown function (HPUFs). In the current study we present a phage genomics-based screening approach to identify phage HPUFs with antibacterial activity with a long-term goal to use them as leads to find unknown targets to develop novel antibacterial compounds. The screening assay is based on the inhibition of bacterial growth when a toxic gene is expression-cloned into a plasmid vector. It utilizes an optimized plating assay producing a significant difference in the number of transformants after ligation of the toxic and non-toxic genes into a cloning vector. The screening assay was first tested and optimized using several known toxic and non-toxic genes. Then, it was applied to screen 94 HPUFs of bacteriophage φR1-RT, and identified four HPUFs that were toxic to Escherichia coli. This optimized assay is in principle useful in the search for bactericidal proteins of any phage, and also opens new possibilities to understanding the strategies bacteriophages use to overtake bacterial hosts.

Improvement Of Curvilinear Diagrams Of Concrete Deformation

2019 ◽  
pp. 99-104
Keyword(s):  
Reinforced Concrete ◽  
Peak Load ◽  
Experimental Studies ◽  
Concrete Structures ◽  
Deformation Model ◽  
Reinforced Concrete Structures ◽  
Significant Difference ◽  
Deformation Diagrams

Problems when calculating reinforced concrete structures based on the concrete deformation under compression diagram, which is presented both in Russian and foreign regulatory documents on the design of concrete and reinforced concrete structures are considered. The correctness of their compliance for all classes of concrete remains very approximate, especially a significant difference occurs when using Euronorm due to the different shape and sizes of the samples. At present, there are no methodical recommendations for determining the ultimate relative deformations of concrete under axial compression and the construction of curvilinear deformation diagrams, which leads to limited experimental data and, as a result, does not make it possible to enter more detailed ultimate strain values into domestic standards. The results of experimental studies to determine the ultimate relative deformations of concrete under compression for different classes of concrete, which allowed to make analytical dependences for the evaluation of the ultimate relative deformations and description of curvilinear deformation diagrams, are presented. The article discusses various options for using the deformation model to assess the stress-strain state of the structure, it is concluded that it is necessary to use not only the finite values of the ultimate deformations, but also their intermediate values. This requires reliable diagrams "s–e” for all classes of concrete. The difficulties of measuring deformations in concrete subjected to peak load, corresponding to the prismatic strength, as well as main cracks that appeared under conditions of long-term step loading are highlighted. Variants of more accurate measurements are proposed. Development and implementation of the new standard GOST "Concretes. Methods for determination of complete diagrams" on the basis of the developed method for obtaining complete diagrams of concrete deformation under compression for the evaluation of ultimate deformability of concrete under compression are necessary.

Percutaneous glycerol rhizotomy for trigeminal neuralgia in patients with multiple sclerosis: a long-term retrospective cohort study

2020 ◽  
Vol 132 (5) ◽  
pp. 1405-1413 ◽  
Author(s):  
Michael D. Staudt ◽  
Holger Joswig ◽  
Gwynedd E. Pickett ◽  
Keith W. MacDougall ◽  
Andrew G. Parrent
Keyword(s):  
Multiple Sclerosis ◽  
Pain Relief ◽  
Trigeminal Neuralgia ◽  
Retrospective Chart Review ◽  
Medication Usage ◽  
Free Response ◽  
Free Survival ◽  
Time To Recurrence ◽  
Significant Difference

OBJECTIVEThe prevalence of trigeminal neuralgia (TN) in patients with multiple sclerosis (MS-TN) is higher than in the general population (idiopathic TN [ITN]). Glycerol rhizotomy (GR) is a percutaneous lesioning surgery commonly performed for the treatment of medically refractory TN. While treatment for acute pain relief is excellent, long-term pain relief is poorer. The object of this study was to assess the efficacy of percutaneous retrogasserian GR for the treatment of MS-TN versus ITN.METHODSA retrospective chart review was performed, identifying 219 patients who had undergone 401 GR procedures from 1983 to 2018 at a single academic institution. All patients were diagnosed with medically refractory MS-TN (182 procedures) or ITN (219 procedures). The primary outcome measures of interest were immediate pain relief and time to pain recurrence following initial and repeat GR procedures. Secondary outcomes included medication usage and presence of periprocedural hypesthesia.RESULTSThe initial pain-free response rate was similar between groups (p = 0.726): MS-TN initial GR 89.6%; MS-TN repeat GR 91.9%; ITN initial GR 89.6%; ITN repeat GR 87.0%. The median time to recurrence after initial GR was similar between MS-TN (2.7 ± 1.3 years) and ITN (2.1 ± 0.6 years) patients (p = 0.87). However, there was a statistically significant difference in the time to recurrence after repeat GR between MS-TN (2.3 ± 0.5 years) and ITN patients (1.2 ± 0.2 years; p < 0.05). The presence of periprocedural hypesthesia was highly predictive of pain-free survival (p < 0.01).CONCLUSIONSPatients with MS-TN achieve meaningful pain relief following GR, with an efficacy comparable to that following GR in patients with ITN. Initial and subsequent GR procedures are equally efficacious.

Distribution of Enteric Viruses and Microorganisms in Long-Term Sewage-Treated Soil

1983 ◽  
Vol 15 (5) ◽  
pp. 129-135 ◽  
Author(s):  
Z Filip ◽  
K Seidel ◽  
H Dizer
Keyword(s):  
Soil Bacteria ◽  
Pathogenic Bacteria ◽  
Sewage Treatment ◽  
Anaerobic Bacteria ◽  
Enteric Viruses ◽  
Sewage Irrigation ◽  
Groundwater Samples ◽  
West Berlin ◽  
Aerobic Soil

To determine whether long-term sewage treatment can take place without a pollution risk for soil and groundwater, samples from sewage irrigation fields in West Berlin which have been in use since about 1890 were analyzed for enteric viruses and microorganisms. Enteric viruses were detected in only seven samples from a total number of eighty seven taken from different soil depths. With only one exception, no viruses were found below 60 cm. No viruses were detected in groundwater samples. Long-term sewage irrigation did not result in significant changes in the colony courts of aerobic soil bacteria, but the counts of anaerobic bacteria and actinomycetes were slightly elevated and those of microscopic fungi slightly decreased. Potentially pathogenic bacteria were not detected in soil below 90 cm.

scholarly journals A206 EVOLUTION OF PEDIATRIC AUTOIMMUNE CHOLANGITIS AND PRIMARY SCLEROSING CHOLANGITIS INTO ADULTHOOD

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 234-236
Author(s):  
P Willems ◽  
J Hercun ◽  
C Vincent ◽  
F Alvarez
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Response To Treatment ◽  
Similar Proportion ◽  
Autoimmune Cholangitis ◽  
Significant Difference ◽  
One Year ◽  
Liver Tests

Abstract Background The natural history of primary sclerosing cholangitis (PSC) in children seems to differ from PSC in adults. However, studies on this matter have been limited by short follow-up periods and inconsistent classification of patients with autoimmune cholangitis (AIC) (or overlap syndrome). Consequently, it remains unclear if long-term outcomes are affected by the clinical phenotype. Aims The aims of this is study are to describe the long-term evolution of PSC and AIC in a pediatric cohort with extension of follow-up into adulthood and to evaluate the influence of phenotype on clinical outcomes. Methods This is a retrospective study of patients with AIC or PSC followed at CHU-Sainte-Justine, a pediatric referral center in Montreal. All charts between January 1998 and December 2019 were reviewed. Patients were classified as either AIC (duct disease on cholangiography with histological features of autoimmune hepatitis) or PSC (large or small duct disease on cholangiography and/or histology). Extension of follow-up after the age of 18 was done for patients followed at the Centre hospitalier de l’Université de Montréal. Clinical features at diagnosis, response to treatment at one year and liver-related outcomes were compared. Results 40 patients (27 PSC and 13 AIC) were followed for a median time of 71 months (range 2 to 347), with 52.5% followed into adulthood. 70% (28/40) had associated inflammatory bowel disease (IBD) (78% PSC vs 54% AIC; p=0.15). A similar proportion of patients had biopsy-proven significant fibrosis at diagnosis (45% PSC vs 67% AIC; p=0.23). Baseline liver tests were similar in both groups. At diagnosis, all patients were treated with ursodeoxycholic acid. Significantly more patients with AIC (77% AIC vs 30 % PSC; p=0.005) were initially treated with immunosuppressive drugs, without a significant difference in the use of Anti-TNF agents (0% AIC vs 15% PSC; p= 0.12). At one year, 55% (15/27) of patients in the PSC group had normal liver tests versus only 15% (2/13) in the AIC group (p=0.02). During follow-up, more liver-related events (cholangitis, liver transplant and cirrhosis) were reported in the AIC group (HR=3.7 (95% CI: 1.4–10), p=0.01). Abnormal liver tests at one year were a strong predictor of liver-related events during follow-up (HR=8.9(95% CI: 1.2–67.4), p=0.03), while having IBD was not (HR=0.48 (95% CI: 0.15–1.5), p=0.22). 5 patients required liver transplantation with no difference between both groups (8% CAI vs 15% CSP; p=0.53). Conclusions Pediatric patients with AIC and PSC show, at onset, similar stage of liver disease with comparable clinical and biochemical characteristics. However, patients with AIC receive more often immunosuppressive therapy and treatment response is less frequent. AIC is associated with more liver-related events and abnormal liver tests at one year are predictor of bad outcomes. Funding Agencies None

scholarly journals 1005 Antibiotic-Impregnated Calcium Sulfate Beads Are Not Effective in the Primary Prevention of Infection in Open Femur and Tibia Fractures

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
A Fung ◽  
A Ward ◽  
K Patel ◽  
M Krkovic
Keyword(s):  
Primary Prevention ◽  
Infection Rate ◽  
Calcium Sulfate ◽  
Acute Infection ◽  
Open Fractures ◽  
Prevention Of Infection ◽  
Significant Difference ◽  
Tibia Fractures ◽  
Systemic Antibiotics

Abstract Introduction Infection is a major complication of open fractures. Antibiotic-impregnated calcium sulfate (AICS) beads are widely used as an adjuvant to systemic antibiotics. Whilst their efficacy in the secondary prevention of infection is established, we present the first retrospective study evaluating AICS beads in the primary prevention of infection in open fractures. Method 214 open femur and tibia fractures in 207 patients were reviewed over a seven-year period. 148 fractures received only systemic antibiotic prophylaxis. 66 fractures also received AICS beads. The occurrence of acute infection (wound infection and acute osteomyelitis) was recorded, as well as that of long-term complications (chronic osteomyelitis, non-union and death). Results Fractures that received AICS with systemic antibiotics had an overall acute infection rate of 42% (28/66), compared to 43% (63/148) in fractures that received only systemic antibiotics (p &gt; 0.05). There was no significant difference in infection rate even when fractures were stratified by Gustilo-Anderson grade. There was also no significant difference in the rate of long-term complications. Conclusions Our results indicate that the adjuvant use of AICS beads is not effective for the primary prevention of acute infection or long-term complications in open leg fractures. Further research is needed to elucidate the factors influencing the outcomes of AICS use.

scholarly journals Long-Term Mortality after Histoplasma Infection in People with HIV

2021 ◽  
Vol 7 (5) ◽  
pp. 369
Author(s):  
Joseph Cherabie ◽  
Patrick Mazi ◽  
Adriana M. Rauseo ◽  
Chapelle Ayres ◽  
Lindsey Larson ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Modern Art ◽  
Private Insurance ◽  
Early Mortality ◽  
Late Mortality ◽  
Significant Difference ◽  
Common Opportunistic Infection ◽  
Long Term Survivors ◽  
Long Term Mortality

Histoplasmosis is a common opportunistic infection in people with HIV (PWH); however, no study has looked at factors associated with the long-term mortality of histoplasmosis in PWH. We conducted a single-center retrospective study on the long-term mortality of PWH diagnosed with histoplasmosis between 2002 and 2017. Patients were categorized into three groups based on length of survival after diagnosis: early mortality (death < 90 days), late mortality (death ≥ 90 days), and long-term survivors. Patients diagnosed during or after 2008 were considered part of the modern antiretroviral therapy (ART) era. Insurance type (private vs. public) was a surrogate indicator of socioeconomic status. Out of 54 PWH infected with histoplasmosis, overall mortality was 37%; 14.8% early mortality and 22.2% late mortality. There was no statistically significant difference in survival based on the availability of modern ART (p = 0.60). Insurance status reached statistical significance with 38% of survivors having private insurance versus only 8% having private insurance in the late mortality group (p = 0.05). High mortality persists despite the advent of modern ART, implicating a contribution from social determinants of health, such as private insurance. Larger studies are needed to elucidate the role of these factors in the mortality of PWH.

scholarly journals Is It Definitely Clear That Long-Term Survival after Breast Cancer Surgery Is Not Affected by Anaesthetics?

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3390
Author(s):  
Mats Enlund
Keyword(s):  
Breast Cancer ◽  
Survival Data ◽  
Retrospective Studies ◽  
Breast Cancer Surgery ◽  
Breast Cancer Patients ◽  
Term Survival ◽  
Long Term Survival ◽  
Significant Difference ◽  
One Year

Retrospective studies indicate that cancer survival may be affected by the anaesthetic technique. Propofol seems to be a better choice than volatile anaesthetics, such as sevoflurane. The first two retrospective studies suggested better long-term survival with propofol, but not for breast cancer. Subsequent retrospective studies from Asia indicated the same. When data from seven Swedish hospitals were analysed, including 6305 breast cancer patients, different analyses gave different results, from a non-significant difference in survival to a remarkably large difference in favour of propofol, an illustration of the innate weakness in the retrospective design. The largest randomised clinical trial, registered on clinicaltrial.gov, with survival as an outcome is the Cancer and Anesthesia study. Patients are here randomised to propofol or sevoflurane. The inclusion of patients with breast cancer was completed in autumn 2017. Delayed by the pandemic, one-year survival data for the cohort were presented in November 2020. Due to the extremely good short-term survival for breast cancer, one-year survival is of less interest for this disease. As the inclusions took almost five years, there was also a trend to observe. Unsurprisingly, no difference was found in one-year survival between the two groups, and the trend indicated no difference either.

scholarly journals Intracameral Bevacizumab Versus Sub-Tenon’s Mitomycin C as Adjuncts to Trabeculectomy: 3-Year Results of a Prospective Randomized Study

2021 ◽  
Vol 10 (10) ◽  
pp. 2054
Author(s):  
Gerasimos Kopsinis ◽  
Dimitrios Tsoukanas ◽  
Dimitra Kopsini ◽  
Theodoros Filippopoulos
Keyword(s):  
Mitomycin C ◽  
Primary Outcome ◽  
Randomized Study ◽  
Primary Outcome Measure ◽  
Complication Rates ◽  
Filtration Surgery ◽  
Significant Difference ◽  
Exfoliative Glaucoma

Conjunctival wound healing determines success after filtration surgery and the quest for better antifibrotic agents remains active. This study compares intracameral bevacizumab to sub-Tenon’s mitomycin C (MMC) in trabeculectomy. Primary open-angle or exfoliative glaucoma patients were randomized to either bevacizumab (n = 50 eyes) or MMC (n = 50 eyes). The primary outcome measure was complete success, defined as Intraocular Pressure (IOP) > 5 mmHg and ≤ 21 mmHg with a minimum 20% reduction from baseline without medications. Average IOP and glaucoma medications decreased significantly in both groups at all follow-up points compared to baseline (p < 0.001), without significant difference between groups at 3 years (IOP: bevacizumab group from 29 ± 9.4 to 15 ± 3.4 mmHg, MMC group from 28.3 ± 8.7 to 15.4 ± 3.8 mmHg, p = 0.60; Medications: bevacizumab group from 3.5 ± 0.9 to 0.5 ± 1, MMC group from 3.6 ± 0.7 to 0.6 ± 1.1, p = 0.70). Complete success, although similar between groups at 3 years (66% vs. 64%), was significantly higher for bevacizumab at months 6 and 12 (96% vs. 82%, p = 0.03; 88% vs. 72%, p = 0.04, respectively) with fewer patients requiring medications at months 6, 9 and 12 (4% vs. 18%, p = 0.03; 6% vs. 20%, p = 0.04; 8% vs. 24%, p = 0.03, respectively). Complication rates were similar between groups. In conclusion, intracameral bevacizumab appears to provide similar long-term efficacy and safety results as sub-Tenon’s MMC after trabeculectomy.

scholarly journals The Long-Term Follow-Up of Patients with Cystine Stones: A Single-Center Experience for 13 Years

2021 ◽  
Vol 10 (7) ◽  
pp. 1336
Author(s):  
Toshifumi Takahashi ◽  
Shinya Somiya ◽  
Katsuhiro Ito ◽  
Toru Kanno ◽  
Yoshihito Higashi ◽  
...  
Keyword(s):  
Surgical Intervention ◽  
Median Number ◽  
Small Sample ◽  
Age At Diagnosis ◽  
Surgical Interventions ◽  
Significant Difference ◽  
Long Term Follow Up ◽  
Cystine Stones

Introduction: Cystine stone development is relatively uncommon among patients with urolithiasis, and most studies have reported only on small sample sizes and short follow-up periods. We evaluated clinical courses and treatment outcomes of patients with cystine stones with long-term follow-up at our center. Methods: We retrospectively analyzed 22 patients diagnosed with cystine stones between January 1989 and May 2019. Results: The median follow-up was 160 (range 6–340) months, and the median patient age at diagnosis was 46 (range 12–82) years. All patients underwent surgical interventions at the first visit (4 extracorporeal shockwave lithotripsy, 5 ureteroscopy, and 13 percutaneous nephrolithotripsy). The median number of stone events and surgical interventions per year was 0.45 (range 0–2.6) and 0.19 (range 0–1.3) after initial surgical intervention. The median time to stone events and surgical intervention was 2 years and 3.25 years, respectively. There was a significant difference in time to stone events and second surgical intervention when patients were divided at 50 years of age at diagnosis (p = 0.02, 0.04, respectively). Conclusions: Only age at a diagnosis under 50 was significantly associated with recurrent stone events and intervention. Adequate follow-up and treatment are needed to manage patients with cystine stones safely.

scholarly journals A millifluidic chip for cultivation of fish embryos and toxicity testing fabricated by 3D printing technology

RSC Advances ◽  
2021 ◽  
Vol 11 (33) ◽  
pp. 20507-20518
Author(s):  
Petr Panuška ◽  
Zuzana Nejedlá ◽  
Jiří Smejkal ◽  
Petr Aubrecht ◽  
Michaela Liegertová ◽  
...  
Keyword(s):  
3D Printing ◽  
Toxicity Testing ◽  
Toxicity Screening ◽  
Printing Technology ◽  
3D Printing Technology ◽  
Fish Embryos ◽  
3D Printed ◽  
Novel Design

A novel design of 3D printed zebrafish millifluidic system for embryonic long-term cultivation and toxicity screening has been developed. The chip unit provides 24 cultivation chambers and a selective individual embryo removal functionality.

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