Role of Telomere Length in Radiation Response of Hematopoietic Stem & Progenitor Cells in Newborns.

OBJECTIVE: Wide inter-individual variations in ionizing radiation (IR) responses of neonatal hematopoietic system calls for identifying reliable biomarkers to effectively estimate radiation exposure damages in neonates. METHODS: Association between telomere length (TL) at birth and radiation sensitivity of cord blood hematopoietic stem cells (HSC) from 166 healthy newborns were investigated by assessing their clonogenic differentiation. TL was determined as terminal restriction fragment (TRF) by Southern blot method. RESULTS: TL correlated with surviving fractions of total progenitor colony forming cell (CFC) content at 0.75 Gy (p < 0.05), granulo-macrophagic lineage colony forming units (CFU-GM) at 0.75 Gy (p < 0.05) and erythroid burst forming unit (BFU-E) at 0.75 Gy (p < 0.05) & at 3 Gy (p < 0.05) of newborns. CONCLUSION: Our results indicate risks for HSC clonogenic survival in neonates with shorter telomeres after IR exposure. These observations might aid in considering TL at birth as an assessment factor for radiation related hematopoietic challenges in children.

Effect of an extraoral scavenging device on eliminating droplets and aerosols generated in ultrasonic supragingival scaling: A randomised clinical trial.

OBJECTIVES: Ultrasonic scaling is extensively applied as part of the initial therapy for periodontal diseases, which has been restricted since the outbreak of the COVID-19 pandemic due to droplets and aerosols generated by ultrasonic devices. An extraoral scavenging device (EOS) was designed for diminishing droplets and aerosols in dental clinics. The objective of this study is to evaluate the effect of EOS on eliminating droplets and aerosols during ultrasonic supragingival scaling. METHODS: This single-blinded, randomised controlled clinical trial enrolled 45 patients with generalised periodontitis (stage I or II, grade A or B) or plaque-induced gingivitis. The patients were randomly allocated and received ultrasonic supragingival scaling under three different intervention measures: only saliva ejector (SE), SE plus EOS and SE plus high-volume evacuation (HVE). The natural sedimentation method was applied to sample droplets and aerosols before or during supragingival scaling. After aerobic culturing, colony-forming units (CFUs) were counted and analysed. RESULTS: Compared with the level before treatment, more CFUs of samples throughout treatment could be obtained at the operator's chest and the patient's chest and the table surface when using SE alone (p < 0.05). Compared with the SE group, the SE + EOS group and the SE + HVE group obtained decreasing CFUs at the operator's chest and the patient's chest (p < 0.05), while no significant difference was determined between these two groups. CONCLUSIONS: The EOS effectively eliminated splatter contamination from ultrasonic supragingival scaling, which was an alternative precaution for nosocomial contamination in dental clinics.

Differences in the Differentiation Potential and Relative Levels of Gene Expression in the Bone Marrow-Derived Fibroblast Colony-Forming Units in Patients during the Onset of Aplastic Anemia Depending on the Disease Severity.

The differentiation potential of individual clones of fibroblast CFU (CFU-F) was studied and the relative expression level of genes was analyzed in the culture of CFU-F from the bone marrow in patients with non-severe and severe forms of aplastic anemia at the onset of the disease. The differentiation potential of CFU-F clones was determined by the relative expression of marker genes using quantitative PCR. In aplastic anemia, the ratio of CFU-F clones with different differentiation potential changes, but the molecular mechanisms of this phenomenon are different in non-severe and severe aplastic anemia. In the culture of CFU-F in non-severe and severe aplastic anemia, the relative expression level of genes associated with the maintenance of the hematopoietic stem cell in the bone marrow niche changes, but the decrease in the expression of immunoregulatory genes occurs in severe form only, which may reflect differences in the pathogenesis of non-severe and severe aplastic anemia.

Extracellular vesicles from bone marrow mesenchymal stromal cells of severe aplastic anemia patients attenuate hematopoietic functions of CD34+ hematopoietic stem and progenitor cells.

Mesenchymal stromal cells (MSC) regulate hematopoiesis in the bone marrow (BM) niche and extracellular vesicles (EVs) released by BM-MSC are important mediators of the cross-talk between BM-MSC and hematopoietic stem and progenitor cells (HSPC). We have previously demonstrated that BM-MSC of severe aplastic anemia (SAA) patients have an altered expression of hematopoiesis regulatory molecules. In the present study, we observed that CD34+ HSPC when cocultured with BM-MSC EVs from aplastic anemia patients exhibited a significant reduction in colony-forming units (p = .001), cell proliferation (p = .002), and increased apoptosis (p > .001) when compared to coculture with BM-MSC EVs from controls. Collectively, our results highlight that EVs derived from the BM-MSC of SAA patients impair the hematopoiesis supporting function of HSPC.

Gamma-Tocotrienol Modulates Total-Body Irradiation-Induced Hematopoietic Injury in a Nonhuman Primate Model.

Radiation exposure causes acute damage to hematopoietic and immune cells. To date, there are no radioprotectors available to mitigate hematopoietic injury after radiation exposure. Gamma-tocotrienol (GT3) has demonstrated promising radioprotective efficacy in the mouse and nonhuman primate (NHP) models. We determined GT3-mediated hematopoietic recovery in total-body irradiated (TBI) NHPs. Sixteen rhesus macaques divided into two groups received either vehicle or GT3, 24 h prior to TBI. Four animals in each treatment group were exposed to either 4 or 5.8 Gy TBI. Flow cytometry was used to immunophenotype the bone marrow (BM) lymphoid cell populations, while clonogenic ability of hematopoietic stem cells (HSCs) was assessed by colony forming unit (CFU) assays on day 8 prior to irradiation and days 2, 7, 14, and 30 post-irradiation. Both radiation doses showed significant changes in the frequencies of B and T-cell subsets, including the self-renewable capacity of HSCs. Importantly, GT3 accelerated the recovery in CD34+ cells, increased HSC function as shown by improved recovery of CFU-granulocyte macrophages (CFU-GM) and burst-forming units erythroid (B-FUE), and aided the recovery of circulating neutrophils and platelets. These data elucidate the role of GT3 in hematopoietic recovery, which should be explored as a potential medical countermeasure to mitigate radiation-induced injury to the hematopoietic system.

Investigation of indoor and outdoor air quality in a university campus during COVID-19 lock down period.

The pandemic of COVID-19 currently shadows the world; the whole earth has been on an unprecedented lockdown. Social distancing among people interrupted domestic and international air traffic, suspended industrial productions and economic activities, and had various far-reaching and undetermined implications on air quality. Improvement in air quality has been reported in many cities during the lockdown. On March 22, 2020, the Turkish government enforced strict lockdown measures to reduce coronavirus disease transmission. This lockdown had a significant impact on the movement of people within the country, which resulted in a major drop in worldwide commercial activities. During this period, university campuses were emptied due to the transition to distance education. In this study, various air pollutants sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), fine particulate matter (PM2.5), total bacteria, and total fungi were measured in different indoor environments at Eskisehir Technical University Campus in Eskisehir, Turkey during COVID-19 lock down period. Also, to calculate the indoor and outdoor ratios (I/O) of the pollutants, simultaneous outdoor measurements were also carried out. The average indoor SO2, NO2, O3, and PM2.5 concentrations in different indoor environments ranged between 2.10 and 54.58, 1.36-30.89, 12.01-39.05, and 21-94 µg/m3, respectively. The total number of bacteria and fungi ranged between 21.83-514.15 and 13.10-83.36 CFU/m3, respectively. Our study intends to give a glimpse to quantify the impact of a pandemic on air quality in different indoor environments in a university campus in Eskisehir, Turkey and calls for follow-up studies. Indoor concentrations were evaluated together with outdoor concentrations. In general, it can be said that the calculated I/O ratios for SO2, NO2, O3, bacteria, and fungi were less than 1 in most indoor environments.

Comparative analysis of dental pulp stem cells and stem cells from human exfoliated teeth in terms of growth kinetics, immunophenotype, self-renewal and multi lineage differentiation potential for future perspective of calcified tissue regeneration.

Background and Objectives: Owing to high proliferation rate, multipotency and self-renewal capability, dental pulp stem cells (DPSC) and stem cells from human exfoliated teeth (SHED) have become stem cell source of choice for cell based regenerative therapies. We aimed to compare DPSC and SHED as stem cell sources with a future use in regeneration of calcified tissue. Methods: Explant derived human DPSC (n=9) and SHED (n=1) were cryopreserved, thawed and expanded for analysis of population doubling time, colony forming unit assay and efficiency. A growth curve was plotted to determine population doubling time, while colony forming numbers and efficiency was determined at plating cell densities of 5.6, 11.1 and 22.2 / cm2. The isolated cells were characterized for the presence of stem cell markers by immunophenotyping and immunofluorescence staining, and tri-lineage differentiation. Statistical analysis was performed by Pearson correlation, Exponential regression and two way Anova with Tukey test at p<0.05. Results: DPSC and SHED exhibited spindle shaped fibroblast like morphology. SHED was found superior than DPSC in terms of proliferation and colony forming efficiency. Immunophenotypes showed that DPSC contain 62.6±26.3 %, 90.9±14.8% and 19.8±0.1%, while SHED contain 90.5%, 97.7% and 0.1% positive cells for CD90, CD73 and CD105. DPSC were strongly positive for vimentin, CD29, CD73, while reactivity was moderate to weak against CD44 and CD90. SHED expressed vimentin, CD29, CD105, CD90 and CD44. Both were negative for CD45. Upon induction, both cell types differentiated into bone, fat and cartilage like cells. Conclusion: Cultured DPSC and SHED were proliferative and exhibited self-renewal property. Both DPSC and SHED expressed stem cell markers and were able to differentiate into bone, fat and cartilage like cells. Thus, these could be a suitable stem cell sources for cell based regenerative therapies.

16α-Bromoepiandrosterone as a new candidate for experimental diabetes-tuberculosis co-morbidity treatment.

Tuberculosis (TB) is the leading cause of death from a single bacterial infectious agent and is one of the most relevant issues of public health. Another pandemic disease is type II diabetes mellitus (T2D) that is estimated to affect half a billion people in the world. T2D is directly associated with obesity and a sedentary lifestyle and is frequently associated with immunosuppression. Immune dysfunction induced by hyperglycemia increases infection frequency and severity. Thus, in developing countries the T2D/TB co-morbidity is frequent and represents one of the most significant challenges for the health-care systems. Several immunoendocrine abnormalities are occurring during the chronic phase of both diseases, such as high extra-adrenal production of active glucocorticoids (GCs) by the activity of 11-ß-hydroxysteroid dehydrogenase type 1 (11-ßHSD1). 11-ßHSD1 catalyzes the conversion of inactive cortisone to active cortisol or corticosterone in lungs and liver, while 11-ß-hydroxysteroid dehydrogenase type 2 (11-ßHSD2) has the opposite effect. Active GCs have been related to insulin resistance and suppression of Th1 responses, which are deleterious factors in both T2D and TB. The anabolic adrenal hormone dehydroepiandrosterone (DHEA) exerts antagonistic effects on GC signaling in immune cells and metabolic tissues; however, its anabolic effects prohibit its use to treat immunoendocrine diseases. 16α-bromoepiandrosterone (BEA) is a water miscible synthetic sterol related to DHEA that lacks an anabolic effect while amplifying the immune and metabolic properties with important potential therapeutic uses. In this work, we compared the expression of 11-ßHSD1 and the therapeutic efficacy of BEA in diabetic mice infected with tuberculosis (TB) (T2D/TB) with respect to non-diabetic TB-infected mice (TB). T2D was induced by feeding mice with a high-fat diet and administering a single low-dose of streptozotocin. After 4 weeks of T2D establishment, mice were infected intratracheally with a high-dose of Mycobacterium tuberculosis strain H37Rv. Then, mice were treated with BEA three times a week by subcutaneous and intratracheal routes. Infection with TB increased the expression of 11-ßHSD1 and corticosterone in the lungs and liver of both T2D/TB and TB mice; however, T2D/TB mice developed a more severe lung disease than TB mice. In comparison with untreated animals, BEA decreased GC and 11-ßHSD1 expression while increasing 11-ßHSD2 expression. These molecular effects of BEA were associated with a reduction in hyperglycemia and liver steatosis, lower lung bacillary loads and pneumonia. These results uphold BEA as a promising effective therapy for the T2D/TB co-morbidity.

A localized laminar flow device decreases airborne particulates during shoulder arthroplasty: a randomized controlled trial.

BACKGROUND: Although the rate of periprosthetic joint infection following shoulder arthroplasty is low, it is a morbid and costly complication. Airborne particulates have long been recognized as a potential source of wound contamination, and operating room-mounted and smaller localized laminar airflow devices have been developed to minimize airborne particulates. This randomized controlled trial evaluated the effectiveness of a localized laminar flow device in reducing the intrusion of ambient airborne particles and bacteria into the surgery site during shoulder arthroplasty as measured by overall particle counts and colony-forming units (CFUs). METHODS: Patients undergoing primary anatomic or reverse shoulder arthroplasty were eligible for participation. After providing informed consent, patients were randomly assigned to the Air Barrier System (ABS) group or control group. For all patients, the ABS was placed on the surgical field; however, it was only turned on by the technician for those randomized to the ABS. Study participants, surgeons, and surgical staff were blinded to group assignment. Bacterial CFUs were collected from within 5 cm of the surgical wound every 10 minutes, whereas airborne particulates were collected every minute. Poisson regression models were used to determine whether differences existed in CFUs and particulate counts between the ABS and control groups. RESULTS: A total of 43 patients were randomized into the ABS (n = 21) or control (n = 22) group. Surgical time (P = .53) and the average staff count (P = .16) in the operating room did not differ between groups. Poisson regression showed that the ABS group had significantly lower CFUs (ß = -0.583, P < .001) along with surgical time and particulates with a diameter ≥ 5 µm. Staff count and particulates with a diameter < 5 µm were not significant predictors of CFUs. Infection was not a primary outcome; however, no postoperative infections have been reported in either study group with a minimum of 1-year follow-up for all patients. DISCUSSION: This double-blinded, randomized trial demonstrated that a localized laminar flow device dramatically reduced the count of CFUs in the air directly above the wound and beneath the ABS (adjusted for the number of operating room personnel and surgical time). The use of the device was not associated with a longer case duration; however, some additional setup time was required prior to surgical incision to place the device. Further study is required to determine the clinical implications of this finding-specifically, whether such devices result in lower rates of periprosthetic joint infection after shoulder arthroplasty.

Comparison of the Efficacy of Two Novel Antitubercular Agents in Free and Liposome-Encapsulated Formulations.

Tuberculosis is one of the top ten causes of death worldwide, and due to the appearance of drug-resistant strains, the development of new antituberculotic agents is a pressing challenge. Employing an in silico docking method, two coumaran (2,3-dihydrobenzofuran) derivatives-TB501 and TB515-were determined, with promising in vitro antimycobacterial activity. To enhance their effectiveness and reduce their cytotoxicity, we used liposomal drug carrier systems. Two types of small unilamellar vesicles (SUV) were prepared: multicomponent pH-sensitive stealth liposome (SUVmixed) and monocomponent conventional liposome. The long-term stability of our vesicles was obtained by the examination of particle size distribution with dynamic light scattering. Encapsulation efficiency (EE) of the two drugs was determined from absorption spectra before and after size exclusion chromatography. Cellular uptake and cytotoxicity were determined on human MonoMac-6 cells by flow cytometry. The antitubercular effect was characterized by the enumeration of colony-forming units on Mycobacterium tuberculosis H37Rv infected MonoMac-6 cultures. We found that SUVmixed + TB515 has the best long-term stability. TB515 has much higher EE in both types of SUVs. Cellular uptake for native TB501 is extremely low, but if it is encapsulated in SUVmixed it appreciably increases; in the case of TB515, quasi total uptake is accessible. It is concluded that SUVmixed + TB501 seems to be the most efficacious antitubercular formulation given the presented experiments; to find the most promising antituberculotic formulation for therapy further in vivo investigations are needed.

Changes in Bone Marrow Stromal Progenitor Cells in Patients with Hematoblastosis at the Onset of the Disease.

Multipotent mesenchymal stromal cells (MSC) are the key regulators of hematopoiesis. We studied changes in MSC characteristics in patients with myeloid leukemia and patients with lymphoproliferative diseases. MSC were obtained from the bone marrow of patients at the time of diagnostic puncture using a standard technique. Their proliferative potential and expression of genes associated with differentiation and regulation of hematopoiesis were studied. The total cell production of MSC in patients with leukemia at the onset of the disease did not differ from that in the group of healthy donors. The relative expression of the IL6, TGFb1 and TGFb2, PPARG genes was similar in all patients. The relative expression of the JAG1, LIF, IGF1, CSF1, IL1b, and IL1bR1 genes in MSC of patients with leukemia was enhanced and the relative expression of SDF1 was unchanged in comparison with MSC from donors. MSC from patients with leukemia were characterized by enhanced relative expression of PDGFRA and PDGFRB, and reduced expression of SOX9. Changes functions of the stromal microenvironment in patients with hemoblastoses attested to the role of stromal cells in the maintenance and spread of tumor cells.

Colony-forming units optimization and human papillomavirus detection in umbilical cord blood.

INTRODUCTION: Analysis of several parameters is required for adequate quality control in umbilical cord blood units (UCBU) when used for therapeutic purposes. OBJECTIVE: To optimize colony-forming units (CFU) from clonogenic cultures and to detect the human papillomavirus (HPV) genome in UCBU. METHODS: One hundred and forty-one umbilical cord blood (UCB), segment or CFU samples from UCBU clonogenic cultures were included. DNA extraction, quantification and endogenous GAPDH gene PCR amplification were carried out. Subsequently, HPV L1 gene was detected using the MY09/MY11 and GP5/GP6+ oligonucleotides. PCR products were analyzed with electrophoresis in agarose gel. CFU-extracted purified DNA was analyzed by electrophoresis in agarose gel, as well as some DNAs, using the sequence-specific priming technique. RESULTS: CFU-extracted DNA concentration was higher in comparison with that of UCB (p = 0.0041) and that of the segment (p < 0.0001), as well as that of UCB in comparison with that of the segment (p < 0.0001). All samples were positive for GAPDH amplification and negative for MY09/MY/11 and GP5/GP6+. CONCLUSIONS: Cryopreserved UCBUs were HPV-negative. Obtaining CFU DNA from clonogenic cultures with high concentrations and purity is feasible.

INTRODUCCIÓN: Se requiere analizar diversos parámetros para el control de calidad adecuado de las unidades de sangre de cordón umbilical (USCU) cuando se utilizan con fines terapéuticos. OBJETIVO: Optimizar las unidades formadoras de colonias (UFC) de cultivos clonogénicos y detectar el genoma del virus del papiloma humano (VPH) en USCU. MÉTODOS: Se incluyeron 141 muestras de sangre de cordón umbilical (SCU), de segmento y de UFC de cultivos clonogénicos de USCU. Se realizó extracción de ADN, cuantificación y amplificación por PCR del gen endógeno GAPDH. Se detectó el gen L1 del VPH con los oligonucleótidos MY09/MY11 y GP5/GP6+; los productos de PCR se migraron en electroforesis de agarosa. El ADN purificado de las UFC se analizó mediante electroforesis de agarosa y algunos ADN, con la técnica sequence specific priming. RESULTADOS: La concentración de ADN extraído de UFC fue superior comparada con la de SCU (p = 0.0041) y la de segmento (p < 0.0001); así como la de SCU comparada con la de segmento (p < 0.0001). Todas las muestras fueron positivas para la amplificación de GAPDH y negativas para MY09/MY11 y GP5/GP6+. CONCLUSIONES: Las USCU criopreservadas fueron VPH netativas; además, es factible obtener ADN en altas concentraciones y con alta pureza a partir de UFC de los cultivos clonogénicos.

Variations in the C-unit of bedaquiline provides analogues with improved biology and pharmacology.

Analogues of the anti-tuberculosis drug bedaquiline, bearing a 3,5-dimethoxy-4-pyridyl C-unit, retain high anti-bacterial potency yet exert less inhibition of the hERG potassium channel, in vitro, than the parent compound. Two of these analogues (TBAJ-587 and TBAJ-876) are now in preclinical development. The present study further explores structure-activity relationships across a range of related 3,5-disubstituted-4-pyridyl C-unit bedaquiline analogues of greatly varying lipophilicity (clogP from 8.16 to 1.89). This broader class shows similar properties to the 3,5-dimethoxy-4-pyridyl series, being substantially more potent in vitro and equally active in an in vivo (mouse) model than bedaquiline, while retaining a lower cardiovascular risk profile through greatly attenuated hERG inhibition.

Benzoyl peroxide use transiently decreases Cutibacterium acnes load on the shoulder.

BACKGROUND: Cutibacterium acnes is the most common pathogen in shoulder prosthetic joint infections. Short-contact benzoyl peroxide (BPO) solutions effectively reduce C acnes loads on the shoulder preoperatively. It is unknown how long the effect of BPO lasts. We evaluated C acnes counts 1 week after BPO application. We hypothesized that BPO would decrease C acnes burden with a rebound after 1 week. METHODS: Screening of 102 healthy volunteers with no history of shoulder surgery or C acnes infection was performed to establish bacterial counts. Thirty-four participants were selected based on an established threshold. Each was given BPO 5% for 3 consecutive days of application on either the left or right shoulder as indicated by a random number generator. Deep sebaceous gland cultures were obtained with a detergent scrub technique before BPO application, after 3 days of use, and 1 week after BPO treatment commenced. RESULTS: The differences between the logarithmic reduction and the logarithmic rebound at the anterior, lateral, and posterior sites were statistically significant. Anteriorly, the average log reduction was -0.44 and the average log rebound was 0.69 (P = .003). Laterally, reduction was -0.64 and rebound was 0.74 (P = .003). Posteriorly, reduction was -0.63 and rebound was 0.78 (P = .008). At the axilla, reduction was -0.40 and rebound was 0.31 (P = .10). The differences in C acnes burden between pretreatment and 1-week counts at all sites were not statistically significant. CONCLUSION: A significant decrease in C acnes burden occurred after BPO application but was not permanent. Significant rebound occurred just 1 week later.

Comparison of Aerosolized Hydrogen Peroxide Fogging with a Conventional Disinfection Product for a Dental Surgery.

AIM AND OBJECTIVE: The study aimed to determine the efficacy of adding a 12% hydrogen peroxide dry hydrogen peroxide vapor fogger system as an additional layer of infection control in a dental surgery. MATERIALS AND METHODS: A total number of agar plates from the five locations were used during the treatment of the 22 patients (n = 440). During the treatment of each patient, four agar plates (n = 4) were used per location [location 1: X-ray, location 2: the dental arm, location 3: left side desk, location 4: under the foot of the dental chair, location 5: ri ght side desk and (n = 20 for the five locations per patient)]. The control agar plates were incubated after the treatment of the patient was completed period. The test agar plate groups were sprayed with a 70% isopropanol surface disinfectant, or received exposure to an automated 12% hydrogen peroxide fog, or a 70% isopropanol surface disinfectant spray immediately followed by exposure to the automated 12% hydrogen peroxide. RESULTS: One-way ANOVA and Scheffé's method identified significant differences (p < 0.01). Between the control agar plates and the three disinfection methods used a significantly lower colony count was established for colonies recorded in the surgery assessed as a whole, the X-ray unit, and the ri ght side desk. CONCLUSION: The disinfection of dental surgery r equires sufficient time as it not only includes the working surfaces but also various inanimate objects. Surface disinfectant spray followed by hydrogen peroxide decontamination has potential for dental surgery, as the colony-forming units have been r educed further compared to spray alone and even just fog alone for all the various areas of the dental surgery that was assessed. CLINICAL SIGNIFICANCE: The infection control protocols with hydrogen peroxide vapor would ensure the maximum efficacy of the disinfection protocols.

Combined Effects of Irradiation and Hindlimb Suspension on Erythroid Lineage Precursors from Rat Bone Marrow.

Erythroid precursors from the femoral bone marrow of Wistar rats were characterized after 30-day hindlimb suspension, fractionated γ-radiation, and their combination. After hindlimb suspension, the total content of myeloid CFU decreased; activity of erythroid differon also considerably suppressed, which manifested in a decrease in the number of erythroid burst-forming units and area of colonies formed by erythrocyte precursors. After irradiation and combined exposure to these two factors, no significant differences from the control were revealed; optical density of formed colonies slightly increased in all experimental groups. Thus, suppression of the erythroid lineage was most pronounced during hindlimb unloading. The combined effect of radiation and hindlimb suspension produced no appreciable negative effect on erythropoiesis in rat bone marrow.

Microbial contamination and plaque scores of nanogold-coated toothbrush.

OBJECTIVE: The study aimed to evaluate the microbial contamination and plaque scores of nanogold-coated and uncoated toothbrushes. METHODS: This study was designed as a single-centre, parallel, examiner-blinded, randomized, two-group clinical trial. Eighty-four participants were enrolled and randomly assigned to receive either a nanogold or uncoated toothbrush. Basic periodontal therapy was performed for all the recruited subjects, and plaque scores of zero were considered baseline values. All participants were instructed to follow a twice-daily brushing regimen without dentifrice and to refrain from other oral hygiene care during the one-week study period. Plaque levels were assessed after one week using the Turesky modification of the Quigley-Hein Plaque Index (TMQHPI). The bristles were tested for microbial contamination by viable cell counting. The recorded data were statistically analysed, and a P-value of <.05 was accepted as statistically significant. RESULTS: After one week of brushing without using toothpaste, the mean plaque index scores were 0.37 ± 0.07 in the nanogold group and 0.58 ± 0.10 in the uncoated group. A significant difference in the mean plaque scores was observed between the groups (P < .001). The mean colony-forming unit (CFU) was 21 ± 48.8 for the nanogold-coated group and 100 ± 128.4 for the uncoated group. The difference in the mean CFUs observed between the groups was significant (P = .014). CONCLUSION: The use of a nanogold-coated toothbrush demonstrated significantly lower bristle contamination and lower plaque scores after one week compared with uncoated toothbrushes without using dentifrice.

3,5-Dialkoxypyridine analogues of bedaquiline are potent antituberculosis agents with minimal inhibition of the hERG channel.

Bedaquiline is a new drug of the diarylquinoline class that has proven to be clinically effective against drug-resistant tuberculosis, but has a cardiac liability (prolongation of the QT interval) due to its potent inhibition of the cardiac potassium channel protein hERG. Bedaquiline is highly lipophilic and has an extremely long terminal half-life, so has the potential for more-than-desired accumulation in tissues during the relatively long treatment durations required to cure TB. The present work is part of a program that seeks to identify a diarylquinoline that is as potent as bedaquiline against Mycobacterium tuberculosis, with lower lipophilicity, higher clearance, and lower risk for QT prolongation. Previous work led to the identification of compounds with greatly-reduced lipophilicity compounds that retain good anti-tubercular activity in vitro and in mouse models of TB, but has not addressed the hERG blockade. We now present compounds where the C-unit naphthalene is replaced by a 3,5-dialkoxy-4-pyridyl, demonstrate more potent in vitro and in vivo anti-tubercular activity, with greatly attenuated hERG blockade. Two examples of this series are in preclinical development.

Is a 10-minute surgical scrub necessary in urologic prosthetic surgery? A randomized study of the effect of a 5- vs 10-minute surgical scrub on bacterial colony counts in the genital skin.

AIMS: To determine the antiseptic efficacy on bacterial colony counts of a 5- vs 10-minute surgical site scrub in urologic surgery. METHODS: A prospective cohort study was conducted in 101 patients presenting for elective urological procedures. Patients were randomized to a 5- or 10-minute groin scrub with Betadine (povidone-iodine). Skin swabs were taken immediately after skin clipping and following routine painting with Betadine. A third swab was taken after the betadine skin scrub. Bacterial colony counts were reported as a number of colony-forming units (CFUs). The primary outcome measure was a quantitative comparison of CFUs in the two arms. RESULTS: Fifty-three patients were randomized to a 5-minute scrub and 48 to a 10-minute scrub. After Betadine painting, CFUs were present in 38% of patients in the 5-minute group (mean, 33.5 CFU) and in 27% of the 10-minute group (mean, 45.4 CFU). Following the surgical scrub, only 7.5% of the 5-minute group and 8.3% of the 10-minute group had a measurable CFU count of greater than or equal to 1, and colony counts were low in both groups (5- minute group: mean, 1.5 CFU; 10-minute group: mean, 2.0 CFU). There was no significant difference in CFUs following a 5- or 10-minute scrub (P = 0.28). CONCLUSIONS: The addition of a surgical skin scrub leads to a fourfold reduction in the skin CFU count compared with Betadine painting. However, there is no difference between the antibacterial effects of a 5- and 10-minute scrub. A 5-minute scrub may be sufficient in urologic prosthetic surgery.

Assessing the ability of silage lactic acid bacteria to incorporate and transform inorganic selenium within laboratory scale silos.

Selenium (Se) is a non-metallic trace element essential for normal cellular function, which has been linked with reduced risk of cancer, cardiovascular disease, cognitive decline and thyroid disease in humans. Se deficiency in livestock is associated with white muscle disease, retained placenta, ill-thrift and mastitis. Where Se status or bioavailability from the soil for plants is poor, livestock rely on supplemental Se in their diets predominantly as either sodium selenite (inorganic form) or selenised-yeast (organic form). As lactic acid bacteria (LAB) have been shown to incorporate Se as either organic or elemental (Nano-Se) there may be potential to use silage inoculant bacteria to improve the Se status of feed to provide the Se requirements of livestock. We screened twenty-seven LAB in MRS broth in the presence of sodium selenite for growth and uptake of Se as organic (selenocysteine and selenomethionine), inorganic (selenite and selenate) or/and Nano-Se, with the aim to identify potential candidates for a mini-silo study. Sodium selenite addition into the growth medium of LAB reduced growth rates but also resulted in the conversion of the inorganic sodium selenite into predominately Nano-Se and small quantities of organic-Se. Based on a rank analysis of growth and ability to take up (total Se content) and convert inorganic Se (Nano and organic Se content), three LAB were selected for further investigation as silage inoculants: L. brevis DSMZ (A), L. plantarum LF1 (B), and L. plantarum SSL MC15 (C). Each LAB was used as an inoculant within a grass mini-silo trial, either cultured in the presence of sodium selenite before inoculation or sodium selenite added to the inoculum at inoculation versus controls with no Se. The addition of sodium selenite either into the growth media of LAB or applied at inoculation of grass silage did not interfere with the ability of the LAB to act as a silage inoculant with no difference in silage fermentation characteristic between LAB with no Se added. The addition of sodium selenite either to the LAB growth medium or at inoculation resulted in the conversion of sodium selenite into Nano-Se and organic-Se (Nano-Se, ca. 103 higher than organic), as previously shown in the screening trial. There was no difference between the three LAB for incorporation of Se or in silage quality, indicating the potential to develop silage inoculants to increase the bioavailable form of Se (elemental and organic) to livestock through conversion of inorganic forms during ensiling.