Exploring ex vivo biofilm dynamics: consequences of low ampicillin concentrations on the human oral microbiome.

Prolonged exposure to antibiotics at low concentration can promote processes associated with bacterial biofilm formation, virulence and antibiotic resistance. This can be of high relevance in microbial communities like the oral microbiome, where commensals and pathogens share a common habitat and where the total abundance of antibiotic resistance genes surpasses the abundance in the gut. Here, we used an ex vivo model of human oral biofilms to investigate the impact of ampicillin on biofilm viability. The ecological impact on the microbiome and resistome was investigated using shotgun metagenomics. The results showed that low concentrations promoted significant shifts in microbial taxonomic profile and could enhance biofilm viability by up to 1 to 2-log. For the resistome, low concentrations had no significant impact on antibiotic resistance gene (ARG) diversity, while ARG abundance decreased by up to 84%. A positive correlation was observed between reduced microbial diversity and reduced ARG abundance. The WHO priority pathogens Streptococcus pneumoniae and Staphylococcus aureus were identified in some of the samples, but their abundance was not significantly altered by ampicillin. Most of the antibiotic resistance genes that increased in abundance in the ampicillin group were associated with streptococci, including Streptococcus mitis, a well-known potential donor of ARGs to S. pneumoniae. Overall, the results highlight the potential of using the model to further our understanding of ecological and evolutionary forces driving antimicrobial resistance in oral microbiomes.

Thorough design and pre-trial quality assurance (QA) decrease dosimetric impact of delineation and dose planning variability in the STRICTLUNG and STARLUNG trials for stereotactic body radiotherapy (SBRT) of central and ultra-central lung tumours.

INTRODUCTION: SBRT of central lung tumours implies significant risk of toxicity. We are initiating two phase II trials prescribing 56 Gy/eight fractions to PTV, allowing for dose escalation of GTV. We prioritize organs at risk (OAR) constraints over target coverage, making the treatment plans very sensitive to OAR delineation variations. The aim of this study is to quantify the dosimetric impact of contouring variations and to provide a thorough description of pre-trial quality assurance to be used in upcoming trials to provide consistent clinical care. MATERIALS AND METHODS: Delineation: Seven physicians delineated OAR in three rounds, with evaluations in-between. For each patient case, seven treatment plans, repeatedly using each of the OAR structure sets from the seven physicians, were made and compared to evaluate the dosimetric effect of delineation variability. Treatment planning: Treatment plans for seven cases were made at six departments in two rounds, with discussion in-between. RESULTS: OAR delineation variation between centres resulted in high variabilities in OAR dose for simulated plans and led to potential overdosage of the lobar bronchus (constraint: D0.03cc < 45 Gy), with maximum doses ranging between 58 Gy (first round), and 50 Gy (third round). For mediastinal tissue, the constraint (D0.03cc < 45 Gy) was violated for the majority of the delineations in all three rounds, with maximum doses of 84 Gy (first round), and 72 Gy (third round).For the treatment planning study, the range of the standard deviation for GTV mean dose was 12.8-18.5 Gy (first round) and 2.8-3.5 Gy (second round). CONCLUSIONS: Even small variations in OAR delineation led to high OAR overdosage. The study demonstrates the importance of having extensive QA procedures in place before initiating clinical trials on dose escalation in SBRT.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is associated with IRF7, BANK1 and TBX21 polymorphisms in two populations.

BACKGROUND AND PURPOSE: Autoantibodies targeting the GluN1(NR1) subunit of the anti-N-methyl-D-aspartate receptor (NMDAR) cause encephalitis. Although it has been shown that anti-NMDAR encephalitis is associated with human leukocyte antigen (HLA) loci, susceptibility genes for the disease outside the HLA loci remain unidentified. In this study, we aimed to explore the association of anti-NMDAR encephalitis with non-HLA genes. METHODS: Two Chinese anti-NMDAR encephalitis cohorts from Han populations were recruited for this study. The North Chinese case-control set consisted of 98 patients and 460 controls, while the South Chinese case-control set included 78 patients and 541 controls. All participants were genotyped for 28 single nucleotide polymorphisms that are associated with autoimmune disorders or infectious diseases. RESULTS: In two independent case-control sets, we identified significant associations of anti-NMDAR encephalitis with IRF7 rs1131665 (odds ratio [OR] 3.34, 95% confidence interval [CI] 1.99-5.63; P < 0.000001, Padjusted  = 0.00004), BANK1 rs4522865 (OR 1.44, 95% CI 1.15-1.82; P = 0.0017, Padjusted  = 0.0149), and TBX21 rs17244587 (OR 2.03, 95% CI 1.35-3.05; P = 0.00051, Padjusted  = 0.0066). Furthermore, analysis of the three polymorphisms with clinical features of the disease revealed that the IRF7 rs1131665 was associated with tumor status. CONCLUSION: The present study has for the first time identified non-HLA susceptibility genes for anti-NMDAR encephalitis. The association of IRF7, BANK1 and TBX21 with anti-NMDAR encephalitis suggests that B-cell activation, Th1 responses, virus infection and the type I interferon signaling pathway are involved in the pathogenesis of the disease.

Complete Genome Sequence of Streptococcus pneumoniae Serotype 19F Strain EF3030.

We report the complete genome sequence of Streptococcus pneumoniae EF3030, a serotype 19F isolate that colonizes the nasopharynx of mice while being mostly noninvasive. Such attributes make this strain highly attractive in pneumococcal carriage studies. The availability of its complete genomic sequence is likely to advance studies in the field.

Characterization of a Signaling System in Streptococcus mitis That Mediates Interspecies Communication with Streptococcus pneumoniae.

Streptococcus mitis is found in the oral cavity and nasopharynx and forms a significant portion of the human microbiome. In this study, in silico analyses indicated the presence of an Rgg regulator and short hydrophobic peptide (Rgg/SHP) cell-to-cell communication system in S. mitis Although Rgg presented greater similarity to a repressor in Streptococcus pyogenes, autoinducing assays and genetic mutation analysis revealed that in S. mitis Rgg acts as an activator. Transcriptome analysis showed that in addition to shp, the system regulates two other downstream genes, comprising a segment of a putative lantibiotic gene cluster that is in a conjugative element locus in different members of the mitis group. Close comparison to a similar lantibiotic gene cluster in Streptococcus pneumoniae indicated that S. mitis lacked the full set of genes. Despite the potential of SHP to trigger a futile cycle of autoinduction, growth was not significantly affected for the rgg mutant under normal or antibiotic stress conditions. The S. mitis SHP was, however, fully functional in promoting cross-species communication and increasing S. pneumoniae surface polysaccharide production, which in this species is regulated by Rgg/SHP. The activity of SHPs produced by both species was detected in cocultures using a S. mitis reporter strain. In competitive assays, a slight advantage was observed for the rgg mutants. We conclude that the Rgg/SHP system in S. mitis regulates the expression of its own shp and activates an Rgg/SHP system in S. pneumoniae that regulates surface polysaccharide synthesis. Fundamentally, cross-communication of such systems may have a role during multispecies interactions.IMPORTANCE Bacteria secrete signal molecules into the environment which are sensed by other cells when the density reaches a certain threshold. In this study, we describe a communication system in Streptococcus mitis, a commensal species from the oral cavity, which we also found in several species and strains of streptococci from the mitis group. Further, we show that this system can promote cross-communication with S. pneumoniae, a closely related major human pathogen. Importantly, we show that this cross-communication can take place during coculture. While the genes regulated in S. mitis are likely part of a futile cycle of activation, the target genes in S. pneumoniae are potentially involved in virulence. The understanding of such complex communication networks can provide important insights into the dynamics of bacterial communities.

Antibiotics alter the window of competence for natural transformation in streptococci.

Streptococcus pneumoniae transformation occurs within a short competence window, during which the alternative sigma factor X (SigX) is activated to orchestrate the expression of genes allowing extracellular DNA uptake and recombination. Importantly, antibiotic stress promotes transcriptional changes that may affect more than 20% of the S. pneumoniae genome, including competence genes. These can be activated or repressed, depending on the antibiotic agent. For most antibiotics, however, it remains unknown whether transcriptional effects on competence translate into altered transformability. Here we investigate the effect of antibiotic subinhibitory concentrations on sigX expression using a luciferase reporter, and correlate for the first time with transformation kinetics. Induction of sigX expression by ciprofloxacin and novobiocin correlated with increased and prolonged transformability in S. pneumoniae. The prolonged effect of ciprofloxacin on competence and transformation was also observed in the streptococcal relatives Streptococcus mitis and Streptococcus mutans. In contrast, tetracycline and erythromycin, which induced S. pneumoniae sigX expression, had either an inhibitory or a nonsignificant effect on transformation, whereas streptomycin and the ß-lactam ampicillin, inhibited both sigX expression and transformation. Thus, the results show that antibiotics may vary in their effects on competence, ranging from inhibitory to stimulatory effects, and that responses affecting transcription of sigX do not always correlate with the transformation outcomes. Antibiotics that increase or decrease transformation are of particular clinical relevance, as they may alter the ability of S. pneumoniae to escape vaccines and antibiotics.

High-resolution profiles of the Streptococcus mitis CSP signaling pathway reveal core and strain-specific regulated genes.

BACKGROUND: In streptococci of the mitis group, competence for natural transformation is a transient physiological state triggered by competence stimulating peptides (CSPs). Although low transformation yields and the absence of a widespread functional competence system have been reported for Streptococcus mitis, recent studies revealed that, at least for some strains, high efficiencies can be achieved following optimization protocols. To gain a deeper insight into competence in this species, we used RNA-seq, to map the global CSP response of two transformable strains: the type strain NCTC12261T and SK321. RESULTS: All known genes induced by ComE in Streptococcus pneumoniae, including sigX, were upregulated in the two strains. Likewise, all sets of streptococcal SigX core genes involved in extracellular DNA uptake, recombination, and fratricide were upregulated. No significant differences in the set of induced genes were observed when the type strain was grown in rich or semi-defined media. Five upregulated operons unique to S. mitis with a SigX-box in the promoter region were identified, including two specific to SK321, and one specific to NCTC12261T. Two of the strain-specific operons coded for different bacteriocins. Deletion of the unique S. mitis sigX regulated genes had no effect on transformation. CONCLUSIONS: Overall, comparison of the global transcriptome in response to CSP shows the conservation of the ComE and SigX-core regulons in competent S. mitis isolates, as well as species and strain-specific genes. Although some S. mitis exhibit truncations in key competence genes, this study shows that in transformable strains, competence seems to depend on the same core genes previously identified in S. pneumoniae.

The Regulatory Role of the Oral Commensal Streptococcus mitis on Human Monocytes.

Streptococcus mitis colonizes all niches of the human oral cavity from early infancy and throughout life. Monocytes patrol blood vessels, lymphoid and non-lymphoid tissues and migrate into infected tissue where they participate in the inflammatory cascade and immune regulation. Here, we studied the effect of S. mitis on monocytes. Transcriptome analysis of monocytes exposed to S. mitis (SmMo) revealed increased transcription of chemotactic factors (CCL2, CCL3, CCL20, CXCL1, CXCL2) and cytokines (IL1A, IL1B, IL6, IL23, IL36G, TNF), indicating that S. mitis may trigger recruitment of leucocytes and initiate inflammation. Increased transcription in SmMo of IL1B, IL6 and IL23 indicated that S. mitis may participate in the induction of Th17 responses and agreed with our earlier findings of S. mitis-mediated memory Th17 reactivity. Furthermore, S. mitis inhibited tetanus toxoid-specific CD4 T cell proliferation. This can be due to the increased secretion of IL-10 and expression of PD-L1 that was observed in SmMo. PGE2 can modulate IL-10 and PD-L1 expression, concomitant with that of CCR7, IL-12 and IL-23 that also were changed. This, along with increased SmMo transcription of PTGS2 (COX2) and PTGER4 (EP4), pointed to a role of PGE2. Measurement of PGE2 secretion by SmMo showed indeed a marked increase, and chemical inhibition of PGE2 production lowered the PD-L1 expression on SmMo. In conclusion, our findings show that S. mitis may trigger immune modulation by recruiting immune cells to the site of infection, while at the same time dampening the severity of the response through expression of IL-10, PGE2 and PD-L1.

Interstitial lung disease increases mortality in systemic sclerosis patients with pulmonary arterial hypertension without affecting hemodynamics and exercise capacity.

Published data suggest that coexisting interstitial lung disease (ILD) has an impact on mortality in patients with systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH), but there is scarce knowledge if this is reflected by hemodynamics, exercise capacity, autoantibody profile, or pulmonary function. In this partially retrospective study, 27 SSc-PAH patients were compared to 24 SSc-PAH patients with coexisting ILD respecting to survival, pulmonary function, hemodynamics, exercise capacity, and laboratory parameters. Survival was significantly worse in SSc-PAH-ILD patients than in SSc patients with isolated PAH (1, 5, and 10-year survival rates 86, 54, and 54% versus 96, 92, and 82%, p = 0.013). Compared to isolated SSc-PAH patients, patients with SSc-PAH-ILD revealed lower forced expiratory volume after 1 s (FEV1) values at the time of PAH diagnosis as well as 1 and 2 years later (p = 0.002) without significant decrease in the PAH course in both groups. At PAH diagnosis, diffusion capacity for carbon monoxide (DLCO) values were lower in the ILD-PAH group. Coexisting ILD was not associated with lower exercise capacity, different FEV1/forced vital capacity (FVC) ratio, higher WHO functional class, or reduced hemodynamics. Higher levels of antibodies against angiotensin and endothelin receptors predict mortality in all SSc-PAH patients but could not differentiate between PAH patients with and without ILD. Our study confirmed an impact of ILD on mortality in SSc-PAH patients. Pulmonary function parameters can be used to distinguish PAH from PAH-ILD. The higher mortality rate cannot be explained by differences in hemodynamics, exercise capacity, or autoantibody levels. Mechanisms of mortality remain to be studied.

Comprehensive Transcriptome Profiles of Streptococcus mutans UA159 Map Core Streptococcal Competence Genes.

In Streptococcus mutans, an oral colonizer associated with dental caries, development of competence for natural genetic transformation is triggered by either of two types of peptide pheromones, competence-stimulating peptides (CSPs) (18 amino acids [aa]) or SigX-inducing peptides (XIPs) (7 aa). Competence induced by CSP is a late response to the pheromone that requires the response regulator ComE and the XIP-encoding gene comS. XIP binds to ComR to allow expression of the alternative sigma factor SigX and the effector genes it controls. While these regulatory links are established, the precise set of effectors controlled by each regulator is poorly defined. To improve the definition of all three regulons, we used a high-resolution tiling array to map global changes in gene expression in the early and late phases of the CSP response. The early phase of the CSP response was limited to increased gene expression at four loci associated with bacteriocin production and immunity. In the late phase, upregulated regions expanded to a total of 29 loci, including comS and genes required for DNA uptake and recombination. The results indicate that the entire late response to CSP depends on the expression of comS and that the immediate transcriptional response to CSP, mediated by ComE, is restricted to just four bacteriocin-related loci. Comparison of the new data with published transcriptome data permitted the identification of all of the operons in each regulon: 4 for ComE, 2 for ComR, and 21 for SigX. Finally, a core set of 27 panstreptococcal competence genes was identified within the SigX regulon by comparison of transcriptome data from diverse streptococcal species. IMPORTANCES. mutans has the hard surfaces of the oral cavity as its natural habitat, where it depends on its ability to form biofilms in order to survive. The comprehensive identification of S. mutans regulons activated in response to peptide pheromones provides an important basis for understanding how S. mutans can transition from individual to social behavior. Our study placed 27 of the 29 transcripts activated during competence within three major regulons and revealed a core set of 27 panstreptococcal competence-activated genes within the SigX regulon.

Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation.

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (>80%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation.

Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients.

Recurrent Clostridium difficile infection (CDI) is a consequence of intestinal dysbiosis and is particularly common following hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) is an effective method of treating CDI by correcting intestinal dysbiosis by passive transfer of healthy donor microflora. FMT has not been widely used in immunocompromised patients, including HSCT recipients, owing to concern for donor-derived infection. Here, we describe initial results of an FMT program for CDI at a US HSCT center. Seven HSCT recipients underwent FMT between February 2015 and February 2016. Mean time post HSCT was 635 days (25-75 interquartile range [IQR] 38-791). Five of the patients (71.4%) were on immunosuppressive therapy at FMT; 4 had required long-term suppressive oral vancomycin therapy because of immediate recurrence after antibiotic cessation. Stool donors underwent comprehensive health and behavioral screening and laboratory testing of serum and stool for 32 potential pathogens. FMT was administered via the naso-jejunal route in 6 of the 7 patients. Mean follow-up was 265 days (IQR 51-288). Minor post-FMT adverse effects included self-limited bloating and urgency. One patient was suspected of having post-FMT small intestinal bacterial overgrowth. No serious adverse events were noted and all-cause mortality was 0%. Six of 7 (85.7%) patients had no recurrence; 1 patient recurred at day 156 post FMT after taking an oral antibiotic and required repeat FMT, after which no recurrence has occurred. Diarrhea was improved in all patients and 1 patient with gastrointestinal graft-versus-host disease was able to taper off systemic immunosuppression after FMT. With careful donor selection and laboratory screening, FMT appears to be a safe and effective therapy for CDI in HSCT patients and may confer additional benefits. Larger studies are necessary to confirm safety and efficacy and explore other possible effects.

Capsule expression in Streptococcus mitis modulates interaction with oral keratinocytes and alters susceptibility to human antimicrobial peptides.

Streptococcus mitis is a colonizer of the oral cavity and the nasopharynx, and is closely related to Streptococcus pneumoniae. Both species occur in encapsulated and unencapsulated forms, but in S. mitis the role of the capsule in host interactions is mostly unknown. Therefore, the aim of this study was to examine how capsule expression in S. mitis can modulate interactions with the host with relevance for colonization. The S. mitis type strain, as well as two mutants of the type strain, an isogenic capsule deletion mutant, and a capsule switch mutant expressing the serotype 4 capsule of S. pneumoniae TIGR4, were used. Wild-type and capsule deletion strains of S. pneumoniae TIGR4 were included for comparison. We found that capsule production in S. mitis reduced adhesion to oral and lung epithelial cells. Further, exposure of oral epithelial cells to encapsulated S. mitis resulted in higher interleukin-6 and CXCL-8 transcription levels relative to the unencapsulated mutant. Capsule expression in S. mitis increased the sensitivity to human neutrophil peptide 1-3 but reduced the sensitivity to human ß-defensin-3 and cathelicidin. This was in contrast with S. pneumoniae in which capsule expression has been generally associated with increased sensitivity to human antimicrobial peptides (AMPs). Collectively, these findings indicate that capsule expression in S. mitis is important in modulating interactions with epithelial cells, and is associated with increased or reduced susceptibility to AMPs depending on the nature of the AMP.

Genome editing by natural genetic transformation in Streptococcus mutans.

Classical mutagenesis strategies using selective markers linked to designed mutations are powerful and widely applicable tools for targeted mutagenesis via natural genetic transformation in bacteria and archaea. However, the markers that confer power are also potentially problematic as they can be cumbersome, risk phenotypic effects of the inserted genes, and accumulate as unwanted genes during successive mutagenesis cycles. Alternative mutagenesis strategies use temporary plasmid or cassette insertions and can in principle achieve equally flexible mutation designs, but design of suitable counter-selected markers can be complex. All these drawbacks are eased by use of direct genome editing. Here we describe a strategy for directly editing the genome of S. mutans, which is applied to the widely studied reference strain UA159 (ATCC 700610) and has the advantage of extreme simplicity, requiring construction of only one synthetic donor amplicon and a single transformation step, followed by a simple PCR screen among a few dozen clones to identify the desired mutant. The donor amplicon carries the mutant sequence and extensive flanking segments of homology, which ensure efficient and precise integration by the recombination machinery specific to competent cells. The recipients are highly competent cells, in a state achieved by treatment with a synthetic competence pheromone.

Bowel Ultrasonography in Inflammatory Bowel Disease.

BACKGROUND: The diagnosis of inflammatory bowel disease (IBD) is based on a combination of endoscopic, clinical and biochemical investigations as well as cross-sectional imaging. The applications of cross-sectional imaging in IBD are manifold. Ultrasonography has emerged as an important imaging modality in the diagnosis of Crohn's disease (CD) as well as for monitoring disease progression and in the therapeutic response to CD and ulcerative colitis (UC). Key Messages: Ultrasonography is non-invasive, radiation free, cheap, easy to use and well tolerated and accepted by patients. Bowel ultrasonography can be used for the primary diagnosis of CD as it has a similar sensitivity and specificity like that of MRI and CT, particularly in the case of CD. Ultrasonography can also be used to monitor treatment response to therapy and to detect disease recurrence of CD as well as UC. In CD, ultrasonography can also be used to detect complications such as strictures as well as extramural complications, including abscesses and fistulas. Contrast-enhanced ultrasonography is a useful tool that might be helpful to detect certain indications in CD, in particular the differentiation between abscesses and inflammation. CONCLUSION: A variety of advantages of bowel ultrasonography over other imaging modalities suggest the more frequent use of this method to manage IBD patients in daily practice. Bowel ultrasonography should be a standard tool in IBD centers.

The clinical impact of vancomycin-resistant Enterococcus colonization and bloodstream infection in patients undergoing autologous transplantation.

BACKGROUND: Although several studies have documented adverse outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, data are inadequate for patients undergoing autologous (auto-)HSCT. METHODS: We conducted a retrospective cohort study of 300 consecutive patients receiving an auto-HSCT between 2006 and 2014. Patients had stool cultures for VRE on admission and weekly during hospitalization. RESULTS: Thirty-six percent of patients had VRE gastrointestinal (GI) colonization and 3% developed a VRE bloodstream infection (BSI), all of whom were colonized. VRE strain typing of BSI isolates showed that some patients shared identical patterns. Rates of colonization and BSI in colonized patients were similar to simultaneous patients undergoing allo-HSCT, except that the latter had a higher rate of colonization at admission. A diagnosis of lymphoma was associated with an increased risk of colonization. VRE BSI was associated with longer lengths of stay and possibly higher costs, but no decrease in overall survival, and colonized patients had no VRE infections during the year following discharge. Repeat stool cultures in patients subsequently undergoing allo-HSCT suggested that most, if not all, VRE-positive auto-HSCT patients lose their detectable GI colonization within a few months of discharge. CONCLUSION: VRE colonization is frequent but carries a low risk for infection in patients undergoing auto-HSCT. However, these patients can serve as reservoirs for transmission to higher risk patients. Moreover, patients may remain colonized if proceeding to an allo-HSCT shortly after auto-HSCT, potentially increasing the risk of the allogeneic procedure.

Sinusoidal obstruction syndrome/veno-occlusive disease: current situation and perspectives-a position statement from the European Society for Blood and Marrow Transplantation (EBMT).

Sinusoidal obstruction syndrome or veno-occlusive disease (SOS/VOD) is a potentially life-threatening complication of hematopoietic SCT (HSCT). This review aims to highlight, on behalf of the European Society for Blood and Marrow Transplantation, the current knowledge on SOS/VOD pathophysiology, risk factors, diagnosis and treatments. Our perspectives on SOS/VOD are (i) to accurately identify its risk factors; (ii) to define new criteria for its diagnosis; (iii) to search for SOS/VOD biomarkers and (iv) to propose prospective studies evaluating SOS/VOD prevention and treatment in adults and children.

The prevalence and severity of dental caries in Chad: a pilot study.

OBJECTIVE: This study was undertaken to determine the prevalence and severity of dental caries among a cross section of a sample from different locations in Chad as part of a general assessment of their oral health status. METHODS: A cross-sectional descriptive survey of a nationwide sample included volunteers, 10 years or older, for a total of 1,011 participants. The survey consisted of a brief interview followed by a 1-2 minute oral examination of each subject. RESULTS: The mean age of the participants was 29.61 ±12.59 years and the total mean value for Decayed/Missing/Filled Teeth (DMFT)=1.96 ±1.78. Females had a higher mean DMFT (2.72 ±1.88); decayed (2.82 ±1.07); missing teeth (1.81 ±1.14) than males (1.61 ±1.60): decayed (2.11 ±1.09); missing (1.45 ±0.89, respectively; all p<0.001). The older group (>30 years) had higher DMFT (2.79 ±1.93) than the younger group (d"30 years; p<0.001). Urban area showed lower DMFT (1.81 ±1.68) than rural areas (2.31 ±1.95). CONCLUSION: In this study, the prevalence of dental caries is very low which is similar to the most of the African Saharan and sub-Saharan countries. However, there is need to establish caries control programs to prevent tooth decay in the future and help people maintain lifelong dental health.

The oral health status and the treatment needs in Chad: a pilot study.

AIMS AND OBJECTIVES: This study was designed to evaluate dental conditions, factors contributing to these conditions, and treatment needs among a population from different places in Chad, as part of a general assessment of their oral health. PATIENTS AND METHODS: A cross-sectional nationwide survey was conducted with 1,011 participants. The survey consisted of a brief health interview (conducted by dental students and public health specialists) followed by a 1-2 minutes oral examination (conducted by dental students and dentists). RESULTS: Sixty four per cent of the subjects had experienced dental pain, 66.7% had decayed teeth, and 56.6% had gum diseases. Dental pain was found to be distributed according to age, gender and locations (p<0.001). Only 25% of the participants had ever visited a dentist. Males were show to engage in more tobacco use than females (19.2% vs. 0.3%), while females were more likely to have visited a dentist than males (30.8% vs. 22.8%). Brushing of teeth occurred more often in urban than in rural locations (p<0.001), while date, sugar cane and cola nut intake were statistically significant in the older generation compared to the younger subjects (p<0.001). CONCLUSION: There was a significant need for dental treatment and care in the sample population. In addition, the availability of sugar, combined with poor knowledge, utilisation of preventive and restorative oral health care services have been contributed to have several dental conditions.

Double umbilical cord blood transplantation in patients with hematologic malignancies using a reduced-intensity preparative regimen without antithymocyte globulin.

Reduced-intensity conditioning (RIC) regimens in cord blood transplant (CBT) are increasingly utilized for older patients and those with comorbidities. However, the optimal conditioning regimen has not yet been established and remains a significant challenge of this therapeutic approach. Antithymocyte globulin (ATG) has been incorporated into conditioning regimens in order to decrease the risk of graft failure; however, use of ATG is often associated with infusion reactions and risk of post-transplant complications. We report the results of a non-ATG-containing RIC regimen, where patients received 2 Gy TBI unless they were considered to be at higher risk of graft failure, in which case they received 3 Gy of TBI. Thirty patients underwent CBT using this protocol for high-risk hematological malignancies. There was only one case of secondary and no cases of primary graft failure. At 1 year, estimates of non-relapse mortality, OS and PFS were 29%, 53% and 45%, respectively. The cumulative incidences of grade III-IV acute and chronic GVHD were 14% and 18%, respectively. In summary, the results of this study demonstrate that this non-ATG-containing conditioning regimen provides a low incidence of graft failure without increasing regimen-related toxicity.