Deep remission improves the quality of life of patients with Crohn's disease and anoperineal fistula treated with darvadstrocel: results of a French pilot study.

BACKGROUND: The injection of allogeneic adipose tissue-derived mesenchymal stem cells (MSC) into anal fistulas in patients with Crohn's disease has never been evaluated in "real-life" conditions in France. METHODS: We prospectively studied the first patients receiving MSC injections at our center and undergoing 12 months of follow-up. The primary endpoint was the clinical and radiological response rate. The secondary endpoints were symptomatic efficacy, safety, anal continence, quality of life (Crohn's anal fistula-quality of life scale, CAF-QoL), and predictive factors of success. RESULTS: We included 27 consecutive patients. The complete clinical and radiological response rates at M12 were 51.9% and 50%, respectively. The combined complete clinical-radiological response (deep remission) rate was 34.6%. No major adverse effects or changes in anal continence were reported. The perianal disease activity index decreased from 6.4 to 1.6 (p < 0.001) for all patients. The CAF-QoL score also decreased from 54.0 to 25.5 (p < 0.001). At the end of the study, M12, the CAF-QoL score was significantly lower only in patients with a complete combined clinical-radiological response relative to those without a complete clinical-radiological response (15.0 versus 32.8, p = 0.01). Having a multibranching fistula and infliximab treatment were associated with a combined complete clinical-radiological response. CONCLUSIONS: This study confirms reported efficacy data for the injection of MSC for complex anal fistulas in Crohn's disease. It also shows a positive impact on the quality of life of patients, particularly those for whom a combined clinical-radiological response was achieved.

Patient safety in radiology: Our experience.

Background: Present-day radiology departments have very high footfall of patients and are prone to patient safety errors. This study analyses such errors in our hospital. Methods: Observational cross-sectional analysis of errors over the last 30 months was performed. These were classified using the Eindhoven classification model into technical, organizational, and human errors. Technical errors focused on equipment safety. Organizational errors related to policies. Human errors were subclassified as per the skill rule knowledge model. Root cause analysis was performed wherever necessary, and possible mitigation strategies for ensuring safety were suggested. Errors peculiar to the Armed Forces environment were specifically addressed. Results: Seventy-seven errors were analyzed. Two were equipment based including faulty pressure injector syringes and radiation leakage from the computed tomography gantry. Of 44 skill-based errors, 09 involved dispatch of wrong reports to dependents owing to identifying patients with serving personnel's name. Four were due to scanning wrong sites. Eleven involved reporting abnormality on the wrong side. Six involved underreporting due to not viewing specific images. The rest were due to failure to omit conflicting elements in the report. Rule-based errors included wrong protocol selection (9 errors), omitting a particular sequence due to individual preference (6 errors), and so on. Knowledge-based errors were due to misinterpretation of findings (4 errors), reporting an abnormality as normal (3 errors), and selection of wrong modality (3 errors). Conclusion: The findings of this study highlights the importance of voluntary reporting, diligent recording, and in-depth analysis of errors for understanding the causes and formulating possible mitigation strategies.

Dominant clade-featured SARS-CoV-2 co-occurring mutations reveal plausible epistasis: An in silico based hypothetical model.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into eight fundamental clades with four of these clades (G, GH, GR, and GV) globally prevalent in 2020. To explain plausible epistatic effects of the signature co-occurring mutations of these circulating clades on viral replication and transmission fitness, we proposed a hypothetical model using in silico approach. Molecular docking and dynamics analyses showed the higher infectiousness of a spike mutant through more favorable binding of G614 with the elastase-2. RdRp mutation p.P323L significantly increased genome-wide mutations (p < 0.0001), allowing for more flexible RdRp (mutated)-NSP8 interaction that may accelerate replication. Superior RNA stability and structural variation at NSP3:C241T might impact protein, RNA interactions, or both. Another silent 5'-UTR:C241T mutation might affect translational efficiency and viral packaging. These four G-clade-featured co-occurring mutations might increase viral replication. Sentinel GH-clade ORF3a:p.Q57H variants constricted the ion-channel through intertransmembrane-domain interaction of cysteine(C81)-histidine(H57). The GR-clade N:p.RG203-204KR would stabilize RNA interaction by a more flexible and hypo-phosphorylated SR-rich region. GV-clade viruses seemingly gained the evolutionary advantage of the confounding factors; nevertheless, N:p.A220V might modulate RNA binding with no phenotypic effect. Our hypothetical model needs further retrospective and prospective studies to understand detailed molecular events and their relationship to the fitness of SARS-CoV-2.

Unique mutations in SARS-CoV-2 Omicron subvariants' non-spike proteins: Potential impacts on viral pathogenesis and host immune evasion.

SARS-CoV-2 is the causative agent behind the ongoing COVID-19 pandemic. This virus is a cumulative outcome of mutations, leading to frequent emergence of new variants and their subvariants. Some of them are a matter of high concern, while others are variants of interest for studying the mutational effect. The major five variants of concern (VOCs) are Alpha (B.1.1.7), Beta (B.1.315), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529.*/BA.*). Omicron itself has >100 subvariants at present, among which BA.1 (21K), BA.2 (21L), BA.4 (22A), BA.5 (22B), and BA.2.12.1 (22C) are the dominant ones. Undoubtedly, these variants and sometimes their progeny subvariants have significant differences in their spike region that impart them the unique properties they harbor. But alongside, the mutations in their non-spike regions could also be responsible elements behind their characteristics, such as replication time, virulence, survival, host immune evasion, and such. There exists a probability that these mutations of non-spike proteins may also impart epistatic effects that are yet to be brought to light. The focus of this review encompasses the non-spike mutations of Omicron, especially in its widely circulating subvariants (BA.1, BA.2, BA.4, BA.5, and BA.2.12.1). The mutations such as in NSP3, NSP6, NSP13, M protein, ORF7b, and ORF9b are mentioned few of all, which might have led to the varying properties, including growth advantages, higher transmission rate, lower infectivity, and most importantly better host immune evasion through natural killer cell inactivation, autophagosome-lysosome fusion prevention, host protein synthesis disruption, and so on. This aspect of Omicron subvariants has not yet been explored. Further study of alteration of expression or interaction profile of these non-spike mutations bearing proteins, if present, can add a great deal of knowledge to the current understanding of the viral properties and thus effective prevention strategies.

Extensive suppuration and being overweight are factors associated with the failure of laser treatment for pilonidal disease: lessons from the first French retrospective cohort.

BACKGROUND: The aim of our study was to assess the efficacy of sinus laser therapy (SiLaT) for the treatment of pilonidal disease. METHODS: All adult patients treated with SiLaT in our department between June 1, 2018, and August 23, 2019, were included in the study. Success was defined as the closure of cutaneous orifices and the absence of discharge or abscesses. RESULTS: We included 29 consecutive patients (22 males) with a median age of 32.5 ± 10.5 years. Eight patients had already undergone prior surgery for pilonidal disease. The procedure was performed under spinal (55%) or general (45%) anesthesia. The mean follow-up was 370.3 days (± 165.8 days). We observed 2 primary failures (6.9%) and 7 recurrences (24.1%). Ultimately, 20 patients were considered to have been cured (69%). The mean time to healing was 25 days (± 8.1 days). No serious complications were reported. Usual activities were resumed within a mean of 4.9 days (± 7.2), and 86% of patients reported being "very satisfied" with the treatment. The body mass index was lower for patients who were cured (24.0 ± 3.6) than for those who experienced treatment failure (27.6 ± 3.4; p = 0.018). The cured patients were less likely to have one or more secondary openings (35.0 versus 88.9%, p = 0.014). CONCLUSIONS: Almost 70% of our patients were cured by SiLaT. Complications were rare and mild. The technique appeared to be less effective for overweight patients and those with one or more secondary openings associated with pilonidal pits.

Understanding the possible origin and genotyping of the first Bangladeshi SARS-CoV-2 strain.

The novel coronavirus, SARS-CoV-2, has caused the most unfathomable pandemic in the history of humankind. Bangladesh is also a victim of this critical situation. To investigate the genomic features of the pathogen from Bangladesh, the first complete genome of the virus has very recently been published. Therefore, long-awaited questions regarding the possible origin and typing of the strain(s) can now be answered. Here, we endeavor to mainly discuss the published reports or online-accessed data (results) regarding those issues and present a comprehensive picture of the typing of the virus alongside the probable origin of the subclade containing the Bangladeshi strain. Our observation suggested that this strain might have originated from the United Kingdom or the other European countries epidemiologically linked to the United Kingdom. According to different genotyping classification schemes, this strain belongs to the A2a clade under the G major clade, is of B and/or L type, and is a SARS-CoV-2a substrain. In the future, randomized genomic data will certainly increase in Bangladesh, however because of globalization and immigrant movement, we urgently need a mass regional sequencing approach targeting the partial or complete genome that can link the epidemiological data and may help in further clinical intervention.

Evolutionary dynamics of SARS-CoV-2 nucleocapsid protein and its consequences.

The emerged novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a global health crisis that warrants an accurate and detailed characterization of the rapidly evolving viral genome for understanding its epidemiology, pathogenesis, and containment. Here, we explored 61,485 sequences of the nucleocapsid (N) protein, a potent diagnostic and prophylactic target, for identifying the mutations to review their roles in real-time polymerase chain reaction based diagnosis and observe consequent impacts. Compared to the Wuhan reference strain, a total of 1034 unique nucleotide mutations were identified in the mutant strains (49.15%, n = 30,221) globally. Of these mutations, 367 occupy primer binding sites including the 3'-end mismatch to the primer-pair of 11 well-characterized primer sets. Noteworthily, CDC (USA) recommended the N2 primer set contained a lower mismatch than the other primer sets. Moreover, 684 amino acid (aa) substitutions were located across 317 (75.66% of total aa) unique positions including 82, 21, and 83 of those in the RNA binding N-terminal domain (NTD), SR-rich region, and C-terminal dimerization domain, respectively. Moreover, 11 in-frame deletions, mostly (n = 10) within the highly flexible linker region, were revealed, and the rest was within the NTD region. Furthermore, we predicted the possible consequence of high-frequency mutations (≥20) and deletions on the tertiary structure of the N protein. Remarkably, we observed that a high frequency (67.94% of mutated sequences) co-occuring mutations (R203K and G204R) destabilized and decreased overall structural flexibility. The N protein of SARS-CoV-2 comprises an average of 1.2 mutations per strain compared to 4.4 and 0.4 in Middle East respiratory syndrome-related coronavirus and SARS-CoV, respectively. Despite being proposed as the alternative target to spike protein for vaccine and therapeutics, the ongoing evolution of the N protein may challenge these endeavors, thus needing further immunoinformatics analyses. Therefore, continuous monitoring is required for tracing the ongoing evolution of the SARS-CoV-2 N protein in prophylactic and diagnostic interventions.

Dietary Intake as Determinant Nongenetic Factors to Colorectal Cancer Incidence and Staging Progression: A Study in South Sulawesi Population, Indonesia.

Reports from various population-based studies indicate that the incidence of colorectal cancer may be strongly affected by dietary patterns of the respective populations. The nature of dietary patterns of specific Indonesia population on the risk of colorectal cancer might differ from previously published data with the global population. Therefore, we conducted a study where the dietary pattern in colorectal cancer patient cohorts was compared to age- and population-matched control. We documented 89 colorectal cancer cases and among 173 individuals from the South Sulawesi population. A series of logistic regression and Fisher's exact tests were utilized to test associations of dietary intakes and colorectal cancer risk as well as colorectal cancer staging. Our data demonstrate that vegetable (p-value = 8.70 × 10-26, OR = 0.49) and fruit (p-value = 7.59x10-5, OR = 0.70) intakes are associated with the reduced risk of colorectal cancer incidence. Conversely, acidic food, reheated food, meat, spicy food, and alcohol are associated with the increment case of cancer. Moreover, meat intake (p-value < 0.01) shows a significant association with cancer staging progression. Common dietary pattern is a determinant aspect to the colorectal cancer incidence as well as its staging progression.

Hemorrhoidal surgery in patients with IBD: caution is the parent of safety.

BACKGROUND: The aim of this study was to evaluate the outcome of hemorrhoidal surgery in patients with inflammatory bowel disease (IBD) undergoing surgery at our center. METHODS: All adult patients with IBD undergoing hemorrhoidal surgery in our department between November 1, 2013 and July 7, 2020 were included in the study. At the time of surgery, the patients' IBD was in clinical, biological and endoscopic remission, and none of the patients had specific primary anoperineal lesions. RESULTS: We included 25 patients (48% female) with a mean age 48 years (± 13.1 years). There were 13 cases of CD (52%) and 12 of ulcerative colitis (UC). Pharmacological and instrumental hemorrhoidal treatment had failed in all patients. The CD lesions were exclusively ileal (77%) or ileocolic (23%). The surgical procedures performed for CD were mono-hemorrhoidectomy in three patients (21.4%), tripedicular hemorrhoidectomy in six patients (42.9%), and artery ligations with mucopexy in five patients (35.7%). UC was rectal (16.7%), rectosigmoid (66.7%), or pancolic (16.6%). The surgical procedures performed for UC were a tripedicular hemorrhoidectomy in ten patients (83.3%) and artery ligations with mucopexy in two patients (16.7%). The mean duration of postoperative follow-up was 15.1 months. None of the patients was lost to follow-up. The mean time to wound healing after resection was 71.1 days (± 21 days) for patients with CD and 56.9 days (± 6.7 days) for patients with UC (p = 0.05). Postoperative complications were reported for four patients with CD (28.8%) and two patients with UC (16.7%). There was no suppuration, stenosis, or anal incontinence sequelae. CONCLUSIONS: Hemorrhoidal surgery resulted in a non-negligible frequency of complications in our series of IBD patients, especially in those with CD. Caution is, therefore, still necessary in this patient population.

Identification and qualitative characterization of new therapeutic targets in Stenotrophomonas maltophilia through in silico proteome exploration.

Stenotrophomonas maltophilia is an emerging opportunistic pathogen, and immunocompromised patients are at a higher risk of getting infected with this nosocomial bacterium. The biggest concern is its inherent resistance to most of the commonly used antibiotics, leaving a few options for treatment. Moreover, recent studies have reported the emergence of its resistance to trimethoprim/sulfamethoxazole (TMP/SMX), the drugs of choice against this pathogen. In this study, we employed a subtractive proteome analysis approach to identify new drug targets against Stenotrophomonas maltophilia K279a. We identified 56 proteins to be essential for the survival of this pathogen, 33 of which are exclusively involved in its metabolism. We identified their subcellular locations and performed broad-spectrum analysis, interactome analysis, and functional analysis. Drug targeting properties and docking energy showed that 29 out of 33 proteins have the potential to serve as potential new therapeutic targets, and four proteins (dCTP deaminase, NAD(P)H:quinone oxidoreductase, dihydroneopterin aldolase, and α, α-trehalose-phosphate synthase) bind with high affinity to already approved or experimental drugs. Based on the broad-spectrum analysis and interactome analysis, we identified NAD(P)H:quinone oxidoreductase, dCTP deaminase, Phosphotransferase, and ATP-dependent Clp protease adapter (ClpS) as the most potential therapeutic targets. Notably, phosphotransferase and ClpS are new targets, i.e., they do not interact with any experimental or approved drugs. Overall, our study will guide the development of new and effective drugs for the treatment of Stenotrophomonas maltophilia infection.

Complete genome sequence of a potential foot-and-mouth disease virus serotype O vaccine strain from Bangladesh.

One of the six sublineages of the dominant O/ME-SA/Ind2001 lineage of foot-and-mouth disease virus (FMDV), Ind2001BD1 has already spread throughout 14 countries, including Bangladesh. Here, we report the complete genome sequence of the potential serotype O vaccine strain BAN/TA/Dh-301/2016, which has been shown to provide protection against all the circulating serotype O viruses in Bangladesh. The viral genome is 8,211 nucleotide (nt) long with an open reading frame (ORF) of 6999 nt. The ORF is flanked by a 1098-nt-long 5'-UTR and a 114-nt-long 3'-UTR. Compared to the Indian FMDV serotype O vaccine strain O/India/R2/75 (AF204276), ten mutations were identified in the major antigenic sites of BAN/TA/Dh-301/2016 (MK088170.1).

Characterization and evaluation of lactic acid bacteria from indigenous raw milk for potential probiotic properties.

Raw milk contains wide microbial diversity, composed mainly of lactic acid bacteria (LAB), which are used as probiotics in both human and animal husbandry. We isolated, characterized, and evaluated LAB from indigenous Bangladeshi raw milk to assess probiotic potential, including antagonistic activity (against Escherichia coli O157: H7, Enterococcus faecalis, Salmonella Typhimurium, Salmonella Enteritidis, and Listeria monocytogenes), survivability in simulated gastric juice, tolerance to phenol and bile salts, adhesion to ileum epithelial cells, auto- and co-aggregation, hydrophobicity, α-glucosidase inhibitory activity, and antibiotic susceptibility tests. The 4 most promising LAB strains showed probiotic potential and were identified as Lactobacillus casei, Lactobacillus plantarum (which produced plantaricin EF), Lactobacillus fermentum, and Lactobacillus paracasei. These strains inhibited all pathogens tested at various degrees, and competitively excluded pathogens with viable counts of 3.0 to 6.0 log cfu/mL. Bacteriocin, organic acids, and low-molecular-weight substances were mainly responsible for antimicrobial activity by the LAB strains. All 4 LAB strains were resistant to oxacillin and 3 were resistant to vancomycin and streptomycin, with multiple antibiotic resistance indices >0.2. After further in vivo evaluation, these LAB strains could be considered probiotic candidates with application in the food industry.

FiLaC® and Crohn's disease perianal fistulas: a pilot study of 20 consecutive patients.

BACKGROUND: The aim of our study was to evaluate the efficacy of FiLaC®  (Fistula Laser Closure) in the treatment of perianal fistulas in patients with Crohn's disease. METHODS: All adult patients treated in our department between March 3rd 2016 and November 16th 2018 were included in the study. The fistula was considered healed when the internal and external openings were closed and the patient experienced no pain or leakage (spontaneously or under pressure). RESULTS: We included 20 consecutive patients (10 women) with a mean age of 32 years ± 9.61. The main fistula tracks were intersphincteric (n = 1, 5%), low (n = 3, 15%) or high (n = 14, 70%) transsphincteric, suprasphincteric (n = 1, 5%), or extrasphincteric (n = 1, 5%). Secondary extension (intramural, supralevator, or horseshoe) was found in 6 cases (30%). The average number of previous surgeries was 2.45 ± 1.47. Crohn's disease extension was ileal in 2 patients (10%), ileocolonic in 8 patients (40%), and colonic in 10 patients (50%). Two patients were lost to follow up and were considered as failures. After a median follow-up period of 7.1 months (range 2-22.5 months), fistula healing was observed in 11 patients (55%). On univariate analysis, only the disease-modifying therapy for Crohn's disease was a predictive factor of a response to FiLaC® (p = 0.05). The specific analysis of this subgroup showed that FiLaC® was less effective when patients were treated with anti-tumor necrosis factor (TNF) alone with an OR of 13.06 [1.28; 236.66] (p = 0.02). For combination therapy, the results seemed better (5 of 6 healed versus 2 of 9 healed with anti-TNF alone), but the difference was not significant. CONCLUSIONS: This pilot study suggests that FiLaC® may play an important role in the management of perianal fistulas in patients with Crohn's disease.

Diversity of carbapenemases in clinical isolates: The emergence of blaVIM-5 in Bangladesh.

Global emergence and dissemination of carbapenemases are clinically threatening, notably in countries with endemic blaNDM. To analyze the extent of carbapenemases in Bangladesh, 71 isolates were collected from 7 different clinical sources: wound swab (n = 38), pus (n = 13), urine (n = 9), blood (n = 4), tracheal aspirate (n = 3), pleural fluid (n = 1) and vaginal swab (n = 3) from Dhaka Medical College Hospital, Bangladesh. Among the isolates, 25 were resistant to at least one of the three carbapenems (imipenem, meropenem and doripenem), including 15 being resistant to all. These resistant isolates were identified as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, P. hibiscicola, Proteus mirabilis, Providencia stuartii and Citrobacter sedlakii. Carbapenemase detection among these 25 isolates varied in individual phenotypic assays (83% in Modified Hodge Test, 50% in Combined Disk Test for Metallo-ß-lactamase prediction) as compared with the genotypes observed (96% prevalence of various carbapenemases including blaOXA-1,48, blaNDM-1,5, blaVIM-2,5). blaOXA-48 was the most prevalent gene (84%) followed by blaNDM (72%). Coexistence of multiple gene combination such as blaNDM+blaOXA-48+blaOXA-1 was prevalent (48%). Harborage of blaVIM-5 (n = 1) was characterized for the first time, while blaNDM-5 (n = 5) was reported contemporarily with a recent study in Bangladesh. Presence of plasmids (64%) and integron class 1 (100%) signifies the transferable potential of resistant traits. The emergence of such new variants along with the presence of the mobile genetic elements demands strict surveillance and combating strategies.

The GBA p.Trp378Gly mutation is a probable French-Canadian founder mutation causing Gaucher disease and synucleinopathies.

Biallelic GBA mutations cause Gaucher disease (GD), and heterozygous carriers are at risk for synucleinopathies. No founder GBA mutations in French-Canadians are known. GBA was fully sequenced using targeted next generation and Sanger sequencing in French-Canadian Parkinson disease (PD) patients (n = 436), rapid eye movement (REM)-sleep behavior disorder (RBD) patients (n = 189) and controls (n = 891). Haplotype, identity-by-descent (IBD) and principal component analyses (PCA) were performed using single nucleotide polymorphism-chip data. Data on GD patients from Toronto and Montreal were collected from patients' files. A GBA p.Trp378Gly mutation was identified in two RBD and four PD patients (1% of all patients combined), and not in controls. The two RBD patients had converted to DLB within 3 years of their diagnosis. Haplotype, IBD and PCA analysis demonstrated that this mutation is from a single founder. Out of 167 GD patients screened, 15 (9.0%) carried the p.Trp378Gly mutation, all in trans with p.Asn370Ser. Three (20%) of the GD patients with the p.Trp378Gly mutation had developed Parkinsonism, and 11 patients had family history of PD. The p.Trp378Gly mutation is the first French-Canadian founder GBA mutation to be described, which leads to synucleinopathies and to GD type 1 when in compound heterozygosity with p.Asn370Ser.

Comparison of metal/polymer back reflectors with half-sphere, blazed, and pyramid gratings for light trapping in III-V solar cells.

We report on the fabrication of diffraction gratings for application as back contact reflectors. The gratings are designed for thin-film solar cells incorporating absorbers with bandgap slightly lower than GaAs, i.e. InAs quantum dot or GaInNAs solar cells. Light trapping in the solar cells enables the increase of the absorption leading to higher short circuit current densities and higher efficiencies. We study metal/polymer back reflectors with half-sphere, blazed, and pyramid gratings, which were fabricated either by photolithography or by nanoimprint lithography. The gratings are compared in terms of the total and the specular reflectance, which determine their diffraction capabilities, i.e. the feature responsible for increasing the absorption. The pyramid grating showed the highest diffuse reflection of light compared to the half-sphere structure and the blazed grating. The diffraction efficiency measurements were in agreement with the numerical simulations. The validated model enables designing such metal/polymer back reflectors for other type of solar cells by refining the optimal dimensions of the gratings for different wavelength ranges.

Isolation and genome analysis of a lytic Pasteurella multocida Bacteriophage PMP-GAD-IND.

Currently used alum precipitated and oil adjuvant vaccines against HS caused by Pasteurella multocida B:2, have side effects and short-lived immunity, leading to regular catastrophic outbreaks in bovines in Asian subcontinent. The need for the development of an improved vaccine with longer immunity and the ability to differentiate between vaccinated and infected is essential. Pasteurella phage isolated in present study belongs to family Siphoviridae. PMP-GAD-IND phage exhibited lytic activity against vaccine strain (P52) as well as several field strains of P. multocida (B:2), and fowl cholera agent (P. multocida A:1).The phage has a double stranded DNA (dsDNA) with a genome of 46 335 bp. The complete genome sequence of the Pasteurella multocida phage has been deposited in Gen Bank with accession no: KY203335. PMP-GAD-IND being a lytic phage with broad activity range has a potential to be used in therapy against multidrug resistant P. multocida infections. SIGNIFICANCE AND IMPACT OF THE STUDY: The present work is a part of research for the development of an improved phage lysate marker vaccine and a companion DIVA assay against haemorhagic septicaemia. This study describes the isolation and genome analysis of PMP-GAD-IND a lytic Pasteurella multocida bacteriophage.

In vitro antioxidant and cholinesterase inhibitory activities of Elatostema papillosum leaves and correlation with their phytochemical profiles: a study relevant to the treatment of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD), one of the major causes of dementia, is an overwhelming neurodegenerative disease that particularly affects the brain, leading to memory loss and impairment of language and judgment capacity. The aim of the present study was to investigate the antioxidant and anticholinesterase properties of the leaves of Elatostema papillosum (EPL) and correlate with their phytochemical profiles, which are relevant to the treatment of AD. METHODS: The dried coarse powder of EPL was extracted with 80% methanol (EPL-M80) by cold extraction method. The resultant EPL-M80 was assessed for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity by the Ellman method. The antioxidant activity was determined by DPPH (1, 1-diphenyl-2-picrylhydrazyl) and hydroxyl radical scavenging assays. Quantitative phytochemical (phenolic and flavonoid contents) analysis of endogenous substances in EPL-M80 was performed by standard spectrophotometric methods. RESULTS: EPL-M80 significantly (p < 0.05) inhibited AChE and BChE activity with IC50 of 165.40 ± 4.01 and 213.81 ± 3.57 µg/mL, respectively in a dose-dependent manner. Additionally, EPL-M80 exhibited strong radical scavenging activity against DPPH (IC50 = 32.35 ± 0.68 µg/mL) and hydroxyl radical (IC50 = 19.67 ± 1.42 µg/mL) when compared to that of standards. EPL-M80 was found to be rich in phenolic (23.74 mg gallic acid equivalent/g of dry extract) and flavonoid (31.18 mg quercetin equivalent/g of dry extract) content. Furthermore, a positive correlation (p < 0.001) was observed between the total phenolics and antioxidant as well as the anticholinesterase potential. CONCLUSIONS: The marked inhibition of AChE and BChE, and potent antioxidant activity of the leaves of Elatostema papillosum highlight its potential to provide an effective treatment for AD.

Phenotypic and genotypic study of biofilm formation in Enterococci isolated from urinary tract infections.

BACKGROUND: Urinary tract infection (UTI) is one of the most frequent types of nosocomial and community acquired infections in humans. Management of multidrug-resistant Enterococci UTI due to the limited therapeutic options is a great challenge for physicians and clinical microbiologists. The role of bacterial biofilms in recurrent urinary tract infections and antimicrobial resistance has great importance for public health. The aim of this study was to investigate the antibiotic susceptibility pattern as well as the phenotypic and genotypic biofilm formation ability of Enterococci isolates from patients with UTI. METHODS: A total of 57 isolates of Enterococci were collected from patients with UTI. Enterococcus species were identified using conventional microbiological methods. The antibiotic susceptibility patterns of the isolates were determined by the Kirby-Bauer disk-diffusion. The Modified Congo red agar (MCRA) and Microtiter plate methods used to assess the ability of biofilm formation. All enterococcal isolates were examined for determination of biofilm-related genes, esp, asa1 and ebpR using PCR method. RESULTS: Of 57 enterococcal isolates, 85.9% were recognized as E. faecalis and 14.1% of them were E. faecium. According to our results, linezolid, chloramphenicol and nitrofurantoin were the most effective agents against Enterococcus species. Overall, 26.5% of E. faecalis and 75% of E. faecium isolates were biofilm producers, respectively. Resistance to some antibiotics including penicillin G, ampicillin, vancomycin, nitrofurantoin and chloramphenicol, and ciprofloxacin was significantly higher among biofilm producers than non-biofilm producers Enterococci. The esp, asa1 and ebpR genes were present in 84.2%, 91.2% and 100% isolates. In this study, there was not a significant relationship between presence of these genes and biofilm formation. CONCLUSION: Our findings reinforce the role of biofilm formation in resistance to antimicrobial agents. Quinupristin/dalfopristin, tetracycline and rifampin may be used as an effective treatment for UTI caused by biofilm producers Enterococci. Our results suggest that biofilm formation is complex and depends on various factors but not just esp, asa1 and ebpR genes in Enterococcus strains.