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BMC Genomics Jan 2020Spirochetal organisms of the Treponema genus are responsible for causing Treponematoses. Pathogenic treponemes is a Gram-negative, motile, spirochete pathogen that...
BACKGROUND
Spirochetal organisms of the Treponema genus are responsible for causing Treponematoses. Pathogenic treponemes is a Gram-negative, motile, spirochete pathogen that causes syphilis in human. Treponema pallidum subsp. endemicum (TEN) causes endemic syphilis (bejel); T. pallidum subsp. pallidum (TPA) causes venereal syphilis; T. pallidum subsp. pertenue (TPE) causes yaws; and T. pallidum subsp. Ccarateum causes pinta. Out of these four high morbidity diseases, venereal syphilis is mediated by sexual contact; the other three diseases are transmitted by close personal contact. The global distribution of syphilis is alarming and there is an increasing need of proper treatment and preventive measures. Unfortunately, effective measures are limited.
RESULTS
Here, the genome sequences of 53 T. pallidum strains isolated from different parts of the world and a diverse range of hosts were comparatively analysed using pan-genomic strategy. Phylogenomic, pan-genomic, core genomic and singleton analysis disclosed the close connection among all strains of the pathogen T. pallidum, its clonal behaviour and showed increases in the sizes of the pan-genome. Based on the genome plasticity analysis of the subsets containing the subspecies T pallidum subsp. pallidum, T. pallidum subsp. endemicum and T. pallidum subsp. pertenue, we found differences in the presence/absence of pathogenicity islands (PAIs) and genomic islands (GIs) on subsp.-based study.
CONCLUSIONS
In summary, we identified four pathogenicity islands (PAIs), eight genomic islands (GIs) in subsp. pallidum, whereas subsp. endemicum has three PAIs and seven GIs and subsp. pertenue harbours three PAIs and eight GIs. Concerning the presence of genes in PAIs and GIs, we found some genes related to lipid and amino acid biosynthesis that were only present in the subsp. of T. pallidum, compared to T. pallidum subsp. endemicum and T. pallidum subsp. pertenue.
Topics: Genome, Bacterial; Genomic Islands; Humans; Phylogeny; Syphilis; Treponema pallidum
PubMed: 31924165
DOI: 10.1186/s12864-019-6430-6 -
Candida albicans biofilms on different materials for manufacturing implant abutments and prostheses.Medicina Oral, Patologia Oral Y Cirugia... Jan 2020Morphological, physical and chemical properties of both implants and prostheses can determine the biofilm formation on their surface and increase the risk of biological...
BACKGROUND
Morphological, physical and chemical properties of both implants and prostheses can determine the biofilm formation on their surface and increase the risk of biological complications. The aim of this study was to evaluate the capacity of biofilm formation of Candida albicans on different materials used to manufacture abutments and prostheses.
MATERIAL AND METHODS
Biofilm formation was analyzed on cp grade II titanium, cobalt-chromium alloy and zirconia, silicone, acrylic resin (polymethylmethacrylate) and nano-hybrid composite. Some samples were partially covered with lithium disilicate glass ceramic to study specifically the junction areas.C. albicans was incubated in a biofilm reactor at 37 °C with agitation. The biofilm formation was evaluated at 24 and 48 hours. In addition, the morphology of the biofilm was evaluated by scanning electron microscopy.
RESULTS
C. albicans developed biofilms on the surface of all materials tested. Cobalt-chromium alloy showed the lowest density of adhered biofilm, followed by zirconia and titanium. Silicone and resin showed up to 20 times higher density of biofilm. A higher biofilm formation was observed when junctions of materials presented micropores or imperfections.
CONCLUSIONS
The biofilm formed in the three materials used in the manufacture of abutments and prostheses showed no major differences, being far less dense than in the resins. Two clinical recommendations can be made: to avoid the presence of resins in the subgingival area of implant prostheses and to design prostheses placing cobalt-chromium alloy/ceramic or titanium/ceramic junctions as far as possible from implants.
Topics: Biofilms; Candida albicans; Dental Implants; Microscopy, Electron, Scanning; Surface Properties; Titanium
PubMed: 31880295
DOI: 10.4317/medoral.23157 -
Science Translational Medicine Oct 2019Nonalcoholic fatty liver disease (NAFLD) is estimated to affect up to one-third of the general population, and new therapies are urgently required. Our laboratory...
Nonalcoholic fatty liver disease (NAFLD) is estimated to affect up to one-third of the general population, and new therapies are urgently required. Our laboratory previously developed a controlled-release mitochondrial protonophore (CRMP) that is functionally liver-targeted and promotes oxidation of hepatic triglycerides. Although we previously demonstrated that CRMP safely reverses hypertriglyceridemia, fatty liver, hepatic inflammation, and fibrosis in diet-induced rodent models of obesity, there remains a critical need to assess its safety and efficacy in a model highly relevant to humans. Here, we evaluated the impact of longer-term CRMP treatment on hepatic mitochondrial oxidation and on the reversal of hypertriglyceridemia, NAFLD, and insulin resistance in high-fat, fructose-fed cynomolgus macaques ( 6) and spontaneously obese dysmetabolic rhesus macaques ( 12). Using positional isotopomer nuclear magnetic resonance tracer analysis (PINTA), we demonstrated that acute CRMP treatment (single dose, 5 mg/kg) increased rates of hepatic mitochondrial fat oxidation by 40%. Six weeks of CRMP treatment reduced hepatic triglycerides in both nonhuman primate models independently of changes in body weight, food intake, body temperature, or adverse reactions. CRMP treatment was also associated with a 20 to 30% reduction in fasting plasma triglycerides and low-density lipoprotein (LDL)-cholesterol in dysmetabolic nonhuman primates. Oral administration of CRMP reduced endogenous glucose production by 18%, attributable to a 20% reduction in hepatic acetyl-coenzyme A (CoA) content [as assessed by whole-body β-hydroxybutyrate (β-OHB) turnover] and pyruvate carboxylase flux. Collectively, these studies provide proof-of-concept data to support the development of liver-targeted mitochondrial uncouplers for the treatment of metabolic syndrome in humans.
Topics: Animals; Delayed-Action Preparations; Diet, High-Fat; Dyslipidemias; Insulin Resistance; Lipid Metabolism; Macaca mulatta; Male; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress; Proton Ionophores
PubMed: 31578240
DOI: 10.1126/scitranslmed.aay0284 -
The Journal of Clinical Investigation Nov 2019In order to determine whether the glucose-alanine cycle regulates rates of hepatic mitochondrial oxidation in humans, we applied positional isotopomer NMR tracer...
In order to determine whether the glucose-alanine cycle regulates rates of hepatic mitochondrial oxidation in humans, we applied positional isotopomer NMR tracer analysis (PINTA) to assess rates of hepatic mitochondrial oxidation and pyruvate carboxylase flux in healthy volunteers following both an overnight (12 hours) and a 60-hour fast. Following the 60-hour fast, rates of endogenous glucose production and mitochondrial oxidation decreased, whereas rates of hepatic pyruvate carboxylase flux remained unchanged. These reductions were associated with reduced rates of alanine turnover, assessed by [3-13C]alanine, in a subgroup of participants under similar fasting conditions. In order to determine whether this reduction in alanine turnover was responsible for the reduced rates of hepatic mitochondrial oxidation, we infused unlabeled alanine into another subgroup of 60-hour fasted subjects to increase rates of alanine turnover, similar to what was measured after a 12-hour fast, and found that this perturbation increased rates of hepatic mitochondrial oxidation. Taken together, these studies demonstrate that 60 hours of starvation induce marked reductions in rates of hepatic mitochondrial oxidation, which in turn can be attributed to reduced rates of glucose-alanine cycling, and reveal a heretofore undescribed role for glucose-alanine in the regulation of hepatic mitochondrial oxidation in humans.
Topics: Adult; Alanine; Fasting; Glucose; Humans; Male; Mitochondria, Liver; Oxidation-Reduction; Starvation
PubMed: 31545298
DOI: 10.1172/JCI129913 -
Vaccine Oct 2019Herpes zoster (HZ) risk appears to vary by sex and geographic ancestry/ethnicity. (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy of the adjuvanted recombinant zoster vaccine (RZV) by sex, geographic region, and geographic ancestry/ethnicity: A post-hoc analysis of the ZOE-50 and ZOE-70 randomized trials.
BACKGROUND
Herpes zoster (HZ) risk appears to vary by sex and geographic ancestry/ethnicity.
METHODS
In 2 randomized clinical trials, participants received 2 doses of adjuvanted recombinant zoster vaccine (RZV) or placebo intramuscularly, 2 months apart. In this post-hoc analysis, we investigate efficacy of RZV against HZ and postherpetic neuralgia (PHN) by sex, geographic region, and geographic ancestry/ethnicity in ≥50-year-olds (ZOE-50: NCT01165177) and ≥70-year-olds (pooled data from ZOE-50 and ZOE-70: NCT01165229).
RESULTS
Vaccine efficacy against HZ or PHN was similar in women and men. Across geographic regions, efficacy against HZ ranged between 95.7 and 97.2% in ≥50-year-olds, and between 87.3% and 95.1% in ≥70-year-olds; efficacy against PHN ranged between 86.8 and 100% in ≥70-year-olds. Across ancestral/ethnic groups, efficacy ranged between 88.1 and 100% against HZ and between 65.9 and 100% against PHN in ≥70-year-olds.
CONCLUSIONS
While the ZOE-50/70 studies were not powered or pre-designed for these post-hoc analyses, RZV appears efficacious against HZ and PHN irrespective of sex, region, or geographic ancestry/ethnicity.
Topics: Adjuvants, Immunologic; Aged; Aged, 80 and over; Data Interpretation, Statistical; Ethnicity; Female; Geography; Herpes Zoster; Herpes Zoster Vaccine; Herpesvirus 3, Human; Humans; Male; Middle Aged; Neuralgia, Postherpetic; Sex Factors; Vaccine Potency; Vaccines, Subunit; Vaccines, Synthetic
PubMed: 31537443
DOI: 10.1016/j.vaccine.2019.09.028 -
BMJ Open Sep 2019Based on the epidemiological and clinical data, acute appendicitis can present either as uncomplicated or complicated. The aetiology of these different appendicitis...
Prospective multicentre cohort trial on acute appendicitis and microbiota, aetiology and effects of antimicrobial treatment: study protocol for the MAPPAC (Microbiology APPendicitis ACuta) trial.
INTRODUCTION
Based on the epidemiological and clinical data, acute appendicitis can present either as uncomplicated or complicated. The aetiology of these different appendicitis forms remains unknown. Antibiotic therapy has been shown to be safe, efficient and cost-effective for CT-confirmed uncomplicated acute appendicitis. Despite appendicitis being one of the most common surgical emergencies, there are very few reports on appendicitis aetiology and pathophysiology focusing on the differences between uncomplicated and complicated appendicitis. Microbiology APPendicitis ACuta (MAPPAC) trial aims to evaluate these microbiological and immunological aspects including immune response in the aetiology of these different forms also assessing both antibiotics non-responders and appendicitis recurrence. In addition, MAPPAC aims to determine antibiotic and placebo effects on gut microbiota composition and antimicrobial resistance.
METHODS AND ANALYSIS
MAPPAC is a prospective clinical trial with both single-centre and multicentre arm conducted in close synergy with concurrent trials APPendicitis ACuta II (APPAC II) (per oral (p.o.) vs intravenous+p.o. antibiotics, NCT03236961) and APPAC III (double-blind trial placebo vs antibiotics, NCT03234296) randomised clinical trials. Based on the enrolment for these trials, patients with CT-confirmed uncomplicated acute appendicitis are recruited also to the MAPPAC study. In addition to these conservatively treated randomised patients with uncomplicated acute appendicitis, MAPPAC will recruit patients with uncomplicated and complicated appendicitis undergoing appendectomy. Rectal and appendiceal swabs, appendicolith, faecal and serum samples, appendiceal biopsies and clinical data are collected during the hospital stay for microbiological and immunological analyses in both study arms with the longitudinal study arm collecting faecal samples also during follow-up up to 12 months after appendicitis treatment.
ETHICS AND DISSEMINATION
This study has been approved by the Ethics Committee of the Hospital District of Southwest Finland (Turku University Hospital, approval number ATMK:142/1800/2016) and the Finnish Medicines Agency. Results of the trial will be published in peer-reviewed journals.
TRIAL REGISTRATION NUMBER
NCT03257423.
Topics: Acute Disease; Administration, Intravenous; Administration, Oral; Anti-Bacterial Agents; Appendectomy; Appendicitis; Cost-Benefit Analysis; Feces; Finland; Gastrointestinal Microbiome; Humans; Length of Stay; Multicenter Studies as Topic; Prospective Studies; Tomography, X-Ray Computed
PubMed: 31494621
DOI: 10.1136/bmjopen-2019-031137 -
Journal of Market Access & Health Policy 2019: To update the health economic evaluation of pirfenidone in the treatment of idiopathic pulmonary fibrosis (IPF) compared to all available alternatives strategies (Best...
: To update the health economic evaluation of pirfenidone in the treatment of idiopathic pulmonary fibrosis (IPF) compared to all available alternatives strategies (Best supportive care - BSC and nintedanib), based on a cost-utility model previously validated by the CEESP's (French Committee for Economic Evaluation) in 2014. : A standard Markov cohort model, adapted to French methodology guidelines, was used to simulate the therapeutic management and the course of IPF patients (including potential adverse events) using the collective perspective. Cost-effectiveness was evaluated regarding life years (LY); quality-adjusted life-years (QALY); average cumulative costs; the incremental cost-effectiveness ratio (ICER) expressed in cost per QALY gained. Data were retrieved from trials, meta-analysis, literature, health insurance and hospitalisation databases, and national tariffs. : Over 15 years, total costs accumulated in the pirfenidone strategy were estimated at €99,477 per patient, €104,610 in nintedanib, and €14,177 in Best Supportive Care (BSC). The total number of QALYs accumulated equalled 5.20 (6.91 LYs), 4.52 (5.98 LYs), and 3.79 (4.98 LYs), respectively. Pirfenidone was estimated to be dominant over nintedanib with incremental costs of -€5,133 and 0.67 more QALYs accumulated. Incremental cost versus BSC was €85,300 and 1,404 QALY gained. The cost-effectiveness ratio was estimated at 60,738€/QALY when compared to BSC. : Pirfenidone is likely to be a cost-effective strategy compared to BSC and seems more efficient and less costly compared to nintedanib for the treatment of patients with IPF in France.
PubMed: 31275535
DOI: 10.1080/20016689.2019.1626171 -
Surgical Endoscopy Jan 2020Laparoscopic incisional ventral hernia repair (LIVHR) is often followed by seroma formation, bulging and failure to restore abdominal wall function. These outcomes are... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Laparoscopic incisional ventral hernia repair (LIVHR) is often followed by seroma formation, bulging and failure to restore abdominal wall function. These outcomes are risk factors for hernia recurrence, chronic pain and poor quality of life (QoL). We aimed to evaluate whether LIVHR combined with defect closure (hybrid) follows as a diminished seroma formation and thereby has a lower rate of hernia recurrence and chronic pain compared to standard LIVHR.
METHODS
This study is a multicentre randomised controlled clinical trial. From November 2012 to May 2015, 193 patients undergoing LIVHR for primary incisional hernia with fascial defect size from 2 to 7 cm were recruited in 11 Finnish hospitals. Patients were randomised to either a laparoscopic (LG) or a hybrid (HG) repair group. The main outcome measure was hernia recurrence, evaluated clinically and radiologically at a 1-year follow-up visit. At the same time, chronic pain scores and QoL were also measured.
RESULTS
At the 1-year-control visit, we found no difference in hernia recurrence between the study groups. Altogether, 11 recurrent hernias were found in ultrasound examination, producing a recurrence rate of 6.4%. Of these recurrences, 6 (6.7%) were in the LG group and 5 (6.1%) were in the HG group (p > 0.90). The visual analogue scores for pain were low in both groups; the mean visual analogue scale (VAS) was 1.5 in LG and 1.4 in HG (p = 0.50). QoL improved significantly comparing preoperative status to 1 year after operation in both groups since the bodily pain score increased by 7.8 points (p < 0.001) and physical functioning by 4.3 points (p = 0.014).
CONCLUSION
Long-term follow-up is needed to demonstrate the potential advantage of a hybrid operation with fascial defect closure. Both techniques had low hernia recurrence rates 1 year after operation. LIVHR reduces chronic pain and physical impairment and improves QoL.
TRIAL REGISTRY
Clinical trial number NCT02542085.
Topics: Abdominal Wound Closure Techniques; Female; Hernia, Ventral; Herniorrhaphy; Humans; Incisional Hernia; Laparoscopy; Male; Middle Aged; Outcome and Process Assessment, Health Care; Postoperative Complications; Quality of Life; Secondary Prevention; Seroma; Surgical Mesh
PubMed: 30941550
DOI: 10.1007/s00464-019-06735-9 -
Vaccine Apr 2019The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.
METHODS
Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period.
RESULTS
Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race.
CONCLUSIONS
No safety concerns arose, supporting the favorable benefit-risk profile of RZV.
Topics: Adjuvants, Immunologic; Aged; Cohort Studies; Data Interpretation, Statistical; Female; Herpes Zoster; Herpes Zoster Vaccine; Humans; Male; Middle Aged; Vaccines, Synthetic
PubMed: 30935742
DOI: 10.1016/j.vaccine.2019.03.043 -
European Radiology Oct 2019The gold standard of postpartum anal sphincter imaging has been the 3D endoanal ultrasound (EAUS). Development of magnetic resonance imaging (MRI) has allowed anal... (Observational Study)
Observational Study
OBJECTIVES
The gold standard of postpartum anal sphincter imaging has been the 3D endoanal ultrasound (EAUS). Development of magnetic resonance imaging (MRI) has allowed anal sphincter evaluation without the use of endoanal coils. The aim of this study is to compare these two modalities in diagnosing residual sphincter lesions post obstetric anal sphincter injury (OASI).
METHODS
Forty women were followed up after primary repair of OASI with both 3D EAUS and external phased array MRI. Details of the anal sphincter injury and sphincter musculature were gathered and analysed.
RESULTS
There was a moderate interrater reliability (κ = 0.510) between the two imaging modalities in detecting sphincter lesions, with more lesions detected by MRI. There was a moderate intraclass correlation (ICC) between the circumference of the tear (κ = 0.506) and a fair ICC between the external anal sphincter thickness measurements at locations 3 and 9 on the proctologic clock face (κ = 0.320) and (κ = 0.336).
CONCLUSIONS
The results of our study indicate that the use of external phased array MRI is feasible for detecting obstetric anal sphincter lesions postpartum. This allows for imaging of the sphincter defects in centres where EAUS imaging is not available.
KEY POINTS
• A two centre prospective study that showed external phased array MRI to be a valid imaging modality for diagnosing obstetric anal sphincter injuries.
Topics: Adult; Anal Canal; Delivery, Obstetric; Endosonography; Female; Humans; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Pilot Projects; Postpartum Period; Pregnancy; Prospective Studies; Reproducibility of Results; Rupture
PubMed: 30915565
DOI: 10.1007/s00330-019-06125-8