[The relationship between oral microbiota and taste]. / De relatie tussen mondmicrobiota en smaak.

Disruption of the perception of taste can have severe consequences on general health. Although evidence suggests that the oral microbiota plays a role in taste perception, little is known about this possible influence. In this scoping review, the influence of oral microbiota on taste perception was studied. Current scientific literature is heterogeneous in study methods and study populations, which impedes comparison of results. Although the findings of this review provide insufficient evidence to confirm the influence of oral microbiota on taste perception, some results show a relationship between taste perception and specific microorganisms. Several factors play a role in taste perception, including tongue coating, use of medication, advanced age, and decreased salivary flow rate, and when these factors are present, it is important to be alert to possible changes in taste. Large-scale studies, in which the multifactorial etiology of taste perception is addressed, are needed to clarify the role of the oral microbiota on taste perception.

Oral Microbiome Transmission and Infant Feeding Habits.

Transmission of oral microbiota from mother to infant is a highly relevant and, so far, understudied topic due to lack of mainstream high-throughput methods for the assessment of bacterial diversity at a strain level. In their recent article in mBio, S. Kageyama, M. Furuta, T. Takeshita, J. Ma, et al. (mBio 13:e03452-21, 2021, https://doi.org/10.1128/mbio.03452-21) evaluated oral microbial transmission from mothers to their infants by using full-length analysis of the 16S rRNA gene and demonstrated the applicability of this method for assessment of transmission of oral bacteria at the single-nucleotide-difference level. By analyzing different metadata of the mother-infant pairs, they discovered that the presence of maternal oral bacteria was higher in formula-fed infants compared to infants who were breastfed or received mixed feeding. This interesting finding suggests that breastfeeding may prevent early maturation of infant's oral microbiome. The physiological role of this phenomenon still needs to be elucidated.

The evidence for placental microbiome and its composition in healthy pregnancies: A systematic review.

OBJECTIVE: To assess the available scientific evidence regarding the placental microbial composition of a healthy pregnancy, the quality of this evidence, and the potential relation between placental and oral microbiome. MATERIALS AND METHODS: Data sources: MEDLINE and EMBASE up to August 1, 2019. STUDY ELIGIBILITY CRITERIA: Human subjects; healthy women; term deliveries; healthy normal birth weight; assessment of microorganisms (bacteria) in placental tissue; full research papers in English. The quality of the included studies was assessed by a modified Joanna Briggs Institute checklist for analytical cross-sectional studies. RESULTS: 57 studies passed the inclusion criteria. Of these, 33 had a high risk of quality bias (e.g., insufficient infection control, lack of negative controls, poor description of the healthy cases). The remaining 24 studies had a low (N = 12) to moderate (N = 12) risk of bias and were selected for in-depth analysis. Of these 24 studies, 22 reported microorganisms in placental tissues, where Lactobacillus (11 studies), Ureaplasma (7), Fusobacterium (7), Staphylococcus (7), Prevotella (6) and Streptococcus (6) were among the most frequently identified genera. Methylobacterium (4), Propionibacterium (3), Pseudomonas (3) and Escherichia (2), among others, although frequently reported in placental samples, were often reported as contaminants in studies that used negative controls. CONCLUSIONS: The results support the existence of a low biomass placental microbiota in healthy pregnancies. Some of the microbial taxa found in the placenta might have an oral origin. The high risk of quality bias for the majority of the included studies indicates that the results of individual papers should be interpreted with caution.

Acquisition and establishment of the oral microbiota.

Acquisition and establishment of the oral microbiota occur in a dynamic process over various stages and involve close and continuous interactions with the host and its environment. In the present review, we discuss the stages of this process in chronological order. We start with the prenatal period and address the following questions: 'Is the fetus exposed to maternal microbiota during pregnancy?' and 'If so, what is the potential role of this exposure?' We comment on recent reports of finding bacterial DNA in placenta during pregnancies, and provide current views on the potential functions of prenatal microbial encounters. Next, we discuss the physiological adaptations that take place in the newborn during the birth process and the effect of this phase of life on the acquisition of the oral microbiota. Is it really just exposure to maternal vaginal microbes that results in the difference between vaginally and Cesarian section-born infants? Then, we review the postnatal phase, in which we focus on transmission of microbes, the intraoral niche specificity, the effects of the host behavior and environment, as well as the role of genetic background of the host on shaping the oral microbial ecosystem. We discuss the changes in oral microbiota during the transition from deciduous to permanent dentition and during puberty. We also address the finite knowledge on colonization of the oral cavity by microbes other than the bacterial component. Finally, we identify the main outstanding questions that limit our understanding of the acquisition and establishment of a healthy microbiome at an individual level.

Home sampling is a feasible method for oral microbiota analysis for infants and mothers.

OBJECTIVES: Large longitudinal cohort studies in infants are needed to understand oral microbiome maturation in relation to general health. The logistics of such studies are complex and costs involved high. Methods like home sampling by caretakers might be a solution to these issues. This study aimed to evaluate feasibility of home sampling by caretakers and to assess which oral niche provides the most reliable sample. METHODS: In this cross-sectional study 30 mothers and their infants aged 2-15 months participated. Swabs of the tongue, buccal mucosa, saliva, and dental plaque of the mother and the infant were collected by the mother after watching an instruction video. Thereafter, the trained researcher repeated the sample collection. Variations on the sampling protocol were listed. Bacterial DNA was quantified and microbial composition was assessed using 16S rDNA amplicon sequencing. RESULTS: None of the sampled niches appeared to be unfeasible based on interviews and observed variations on protocol. No significant differences in bacterial DNA concentration between operators (mother and researcher) were found. In infant's saliva, Shannon diversity of samples collected by the researcher was significantly higher than those collected by mothers (p = 0.0009) and the bacterial composition was influenced by variations on sampling protocol (p = 0.01). CONCLUSIONS: Home sampling by caretakers is a feasible method for oral sample collection in infants and mothers. Oral samples collected by mothers resemble samples collected by a trained researcher, with the tongue sample being the most similar and saliva the least. CLINICAL SIGNIFICANCE: Home sampling can simplify longitudinal oral microbiota collection.

Timing of the first endomyocardial biopsy in heart transplantation after induction immunosuppressive therapy--experience from Canadian Heart Transplant Centre.

BACKGROUND: The exact time point at which the first endomyocardial biopsy could be safely performed after the heart transplantation has not been systematically studied. In an attempt to determine this time point in our population, the number and severity of acute rejection episodes in the first eight weeks after the heart transplantation were assessed in 91 patients who underwent the procedure at St Paul's Hospital, Vancouver between September 1996 and December 2002. METHODS AND RESULTS: For the purpose of our analysis, acute rejection was defined as the grade > or =2 according the International Society for Heart and Lung Transplantation (ISHLT). Three hundred and sixty two endomyocardial biopsies were performed in 87 patients surviving to the first biopsy from one to eight weeks after the heart transplantation. In 85 patients who received induction immunosuppressive therapy, 13 episodes of acute rejection were identified. In two patients who did not receive the induction therapy, three episodes of acute rejection occurred. Acute rejection grade ISHLT 3 was found in 2 patients who did not receive induction therapy and in three patients who did. ISHLT grade 4 rejection occurred at weeks 5 and 7 in two patients who received induction therapy. Only one patient who received induction therapy had acute rejection within the first three weeks after the heart transplantation. CONCLUSIONS: Our analysis reveals that the frequency of acute rejection within the first eight weeks after the heart transplantation using induction therapy is low in this cohort, suggesting that the first routine endomyocardial biopsy could be delayed until the week four post-transplant.

Improvement in quality of life outcomes 2 weeks after left ventricular assist device implantation.

BACKGROUND: The successful use of left ventricular assist devices (LVADs) as a bridge to heart transplantation has prompted our examination of quality of life (QOL) outcomes. The purposes of this study are to describe QOL in patients 1 to 2 weeks after LVAD implantation and to compare QOL in a smaller cohort of patients from before to 1 to 2 weeks after surgery. METHODS: Data were collected from a convenience sample of 81 patients who completed booklets of questionnaires that measure domains of QOL 1 to 2 weeks after LVAD insertion and from 30 of 81 patients who completed booklets at both the pre-implantation and post-implantation periods. Patients completed booklets of 6 to 8 self-reporting instruments, with acceptable reliability and validity. Data were analyzed using descriptive and comparative statistics (chi-square, Mann-Whitney U and Wilcoxon signed ranks tests) with p = 0.01 considered statistically significant. RESULTS: One to 2 weeks after LVAD implantation, patients were quite satisfied with their lives, experienced moderately low amounts of stress, coped well, and perceived themselves as having good health and QOL, low symptom distress, and moderately low functional disability. Patients reported significantly better QOL, more satisfaction with health and functioning, and were significantly less distressed by symptoms from immediately pre-operatively to post-operatively. However, patients reported significantly more self-care disability and more dissatisfaction with socioeconomic areas of life from before to immediately after surgery. Psychological distress was low and did not change with time. CONCLUSION: Given that QOL improved from before to after LVAD implantation, our findings provide a springboard for investigation of the impact of LVADs on long-term QOL outcomes.

Pharmacokinetics of cyclosporine in heart transplant recipients receiving metabolic inhibitors.

BACKGROUND: Inhibitors of cyclosporine metabolism are commonly co-administered with cyclosporine in transplant recipients. The aim of this study was to compare cyclosporine pharmacokinetics using the conventional formulation (Sandimmune) and after switching to the microemulsion (Neoral) formulation, in stable heart transplant recipients receiving various cyclosporine metabolic inhibitors. METHODS: Steady-state blood concentration-time profiles of Sandimmune were studied in 47 transplant recipients receiving either cyclosporine alone (Group A, n = 11) or in combination with diltiazem (120 mg/day, Group B, n = 11), ketoconazole (200 mg/day, Group C, n = 13), or both ketoconazole and diltiazem (200 and 120 mg/day, respectively, Group D, n = 12), and restudied 1 week after switching to Neoral. RESULTS: Neoral resulted in more rapid cyclosporine absorption as judged by the shorter absorption half-lives in all groups (p < 0.05). The mean percentage increase in the values of area-under-the-concentration-time curve was 42% and 37.5% higher for Neoral compared with Sandimmune for Groups A and B, respectively, but only 5.4% higher for Group C and 9.5% higher for Group D. The mean morning trough concentration of cyclosporine was not significantly different after administration of Neoral compared with Sandimmune in any of the groups studied (179 vs. 167 microg/liter for Group A; 171 vs. 147 microg/liter for Group B; 189 vs. 194 microg/liter for Group C; and 181 vs 201 microg/liter for Group D). Neoral did not alter serum concentrations of sodium, potassium, creatinine, and urea in any of the study groups. CONCLUSIONS: The faster absorption and improved bioavailability of cyclosporine (around 40%) with Neoral compared with Sandimmune was not seen in patients receiving ketoconazole, where in fact cyclosporine bioavailability was already maximal. Mean morning trough levels of cyclosporine did not reflect the improvement in bioavailability seen in patients switching from Sandimmune to Neoral. Cyclosporine dose adjustment may be needed when switching from Sandimmune to Neoral for patients not receiving sparing agents or who receive diltiazem, but trough levels cannot necessarily be relied upon to determine the degree of adjustment needed. For patientson ketoconazole, the absorption profile is already optimized and no dosage alteration seems necessary.

Development of a nurse practitioner role in heart failure management: an Australian experience.

This paper describes the history of nurse practitioners and outlines the Australian experience in developing and implementing such a role. The legislative process and changes in introducing a nurse practitioner role are noted, and a trial to develop a framework for the nurse practitioner role in acute care in South Australia is highlighted.

The Mad1-Sin3B interaction involves a novel helical fold.

Sin3A or Sin3B are components of a corepressor complex that mediates repression by transcription factors such as the helix-loop-helix proteins Mad and Mxi. Members of the Mad/Mxi family of repressors play important roles in the transition between proliferation and differentiation by down-regulating the expression of genes that are activated by the proto-oncogene product Myc. Here, we report the solution structure of the second paired amphipathic helix (PAH) domain (PAH2) of Sin3B in complex with a peptide comprising the N-terminal region of Mad1. This complex exhibits a novel interaction fold for which we propose the name 'wedged helical bundle'. Four alpha-helices of PAH2 form a hydrophobic cleft that accommodates an amphipathic Mad1 alpha-helix. Our data further show that, upon binding Mad1, secondary structure elements of PAH2 are stabilized. The PAH2-Mad1 structure provides the basis for determining the principles of protein interaction and selectivity involving PAH domains.

Efficacy and safety of pravastatin vs simvastatin after cardiac transplantation.

Prior studies of cardiac transplant recipients have shown that pravastatin reduces 12-month rejection and mortality after cardiac transplantation and simvastatin reduces 4-year mortality, low-density lipoprotein (LDL) cholesterol levels, and intimal thickening. In a 12-month observational study, cardiac transplant recipients received open-label pravastatin 40 mg (n = 42) or simvastatin 20 mg daily (n = 45) on an alternating basis from the time of transplantation. Lipid levels, safety, and post-transplant outcomes were compared. We found no significant differences in total LDL or high-density lipoprotein cholesterol, triglycerides, linearized infection or rejection rates, liver function tests, or immunosuppressant dosages between groups at 1, 3, 6, or 12 months. Rhabdomyolysis or myositis occurred only in patients on simvastatin (n = 6, 13.3%) with no episodes for patients on pravastatin (p = 0. 032). Survival at 12 months on an actual treatment basis was 97.6% for patients on pravastatin and 83.7% for those on simvastatin (p = 0.078). Immunosuppression-related deaths occurred in only 2.4% (1 patient) on pravastatin vs 15.6% (n = 7) on simvastatin (p = 0.06). Pravastatin and simvastatin resulted in comparable lipid profiles. Pravastatin use was however free from the high rates of rhabdomyolysis and myositis seen with simvastatin use. Pravastatin was additionally associated with a trend toward superior survival, attributable to fewer immunosuppression-related deaths. For safety and pharmacokinetic reasons, pravastatin should be considered the statin of choice after heart transplantation.

Cord blood IgE: its determinants and prediction of development of asthma and other allergic disorders at 12 months.

BACKGROUND: The value of cord blood IgE in predicting the development of asthma and other IgE-mediated allergic diseases is unclear. OBJECTIVE: The purpose of this study is twofold: (1) to determine factors affecting cord blood IgE level and (2) to determine whether cord blood IgE predicts the development of asthma and other IgE-mediated allergic diseases in high risk (defined as those with at least one first degree relative with asthma or 2 first degree relatives with other IgE-mediated allergic diseases) infants at 12 months. METHODS: The study utilized cord blood obtained from a group of high risk infants who took part in a randomized controlled trial to assess the effectiveness of an intervention program in the primary prevention of asthma and other IgE-mediated allergic diseases. Total IgE and cotinine in the cord blood were measured. Assessment of the infants was done at 12 months for these diseases. RESULTS: Sixty-four (17.8%) infants had detectable total IgE in cord blood >0.5 kU/L. The proportion of infants with elevated cord blood IgE was significantly higher among nonwhites, birth during winter months, and those with a maternal history of asthma. There was no correlation between cord blood IgE and cord blood cotinine level. Cord blood IgE was found to be a significant predictor for the development of urticaria due to food allergy but not for other outcomes. CONCLUSION: Both genetic and environmental risk factors play a role in determining the level of IgE in cord blood. Cord blood IgE was a significant risk factor for the development of urticaria due to food allergy at 12 months of life. As urticaria due to food allergy is a prodrome for anaphylaxis, measurement of IgE in cord blood may be indicated in infants at high risk for developing allergic diseases so that preventive measures can be applied.

Isolation and functional characterization of two distinct sexual-stage-specific promoters of the human malaria parasite Plasmodium falciparum.

Transmission of malaria depends on the successful development of the sexual stages of the parasite within the midgut of the mosquito vector. The differentiation process leading to the production of the sexual stages is delineated by several developmental switches. Arresting the progression through this sexual differentiation pathway would effectively block the spread of the disease. The successful development of such transmission-blocking agents is hampered by the lack of a detailed understanding of the program of gene expression that governs sexual differentiation of the parasite. Here we describe the isolation and functional characterization of the Plasmodium falciparum pfs16 and pfs25 promoters, whose activation marks the developmental switches executed during the sexual differentiation process. We have studied the differential activation of the pfs16 and pfs25 promoters during intraerythrocytic development by transfection of P. falciparum and during gametogenesis and early sporogonic development by transfection of the related malarial parasite P. gallinaceum. Our data indicate that the promoter of the pfs16 gene is activated at the onset of gametocytogenesis, while the activity of the pfs25 promoter is induced following the transition to the mosquito vector. Both promoters have unusual DNA compositions and are extremely A/T rich. We have identified the regions in the pfs16 and pfs25 promoters that are essential for high transcriptional activity. Furthermore, we have identified a DNA-binding protein, termed PAF-1, which activates pfs25 transcription in the mosquito midgut. The data presented here shed the first light on the details of processes of gene regulation in the important human pathogen P. falciparum.

Immunological properties of recombinant proteins of the transmission blocking vaccine candidate, Pfs48/45, of the human malaria parasite Plasmodium falciparum produced in Escherichia coli.

A precondition for the development of a transmission blocking vaccine based on the sexual stage-specific surface antigen Pfs48/45 of Plasmodium falciparum is its heterologous synthesis in a native state. Here we describe the production of recombinant Pfs48/45 in Escherichia coli. Two recombinant proteins, of which one is a glutathione-S-transferase fusion protein, were produced. Enzyme-linked immunosorbent assays showed that at least a subfraction of the recombinant proteins had a conformation capable of binding transmission blocking monoclonal antibodies. However, despite the fact that both proteins were very immunogenic, they did not induce transmission blocking immunity in mice or rabbits. Immunological studies with congenic mouse strains demonstrated that immune responses could be boosted with gametocyte extracts and were not restricted to a particular class II major histocompatibility complex haplotype.

Adjunctive use of inhaled nitric oxide during implantation of a left ventricular assist device.

BACKGROUND: The aim of this study was to evaluate the efficacy of inhaled nitric oxide in the prevention and reversal of pulmonary hypertension during and after left ventricular assist device implantation. METHODS: Inhaled nitric oxide (20 ppm) was administered to seven consecutive patients undergoing implantation of a left ventricular assist device at the time of implantation and for the first 24 hours after operation. RESULTS: Withdrawal of inhaled nitric oxide at 24 hours after operation was associated with a significant rise in both the transpulmonary gradient (from 8+/-1 to 14+/-2 mm Hg, p < 0.01) and in pulmonary vascular resistance (from 110+/-19 to 196+/-32 dynes x sec x cm[-5], p < 0.01). In two patients, the rise in pulmonary vascular resistance resulted in a critical fall in left ventricular assist device flow and hemodynamic deterioration, necessitating urgent reinstitution of inhaled nitric oxide. CONCLUSION: The administration of inhaled nitric oxide at the time of left ventricular assist device implantation prevents rises in pulmonary vascular resistance that in some patients result in critical reductions in left ventricular assist device flow. We suggest that inhaled nitric oxide is a useful adjunctive treatment that should be routinely available at the time of left ventricular assist device implantation.

Continuous home ambulatory intravenous inotropic drug therapy in severe heart failure: safety and cost efficacy.

Some patients with dilated cardiomyopathy who are inotrope dependent but remain well by undergoing infusions can be managed by ambulatory infusions at home. We report our results in 20 patients awaiting heart transplantation, unable to be weaned from intravenous inotropic therapy on 2 or more occasions, but who were well while receiving inotropes and received home ambulatory infusions. The patients were treated with ACE inhibitors, digoxin, diuretics, vasodilators, close electrolyte management, and low-dose amiodarone for those with more than four-beat ventricular tachycardia. Infusions were delivered by a tunneled subclavian catheter and syringe driver. Thirteen patients received dopamine, four received dobutamine, and three received both. Mean duration of inotropic therapy was 5 months with 70% of the time spent as an outpatient. Eleven patients received transplants, two remain on the waiting list, and seven died after being removed from the list because of general deterioration or renal dysfunction. There were no sudden deaths. Actuarial survival was 71% at 3 months, which is not less than that expected for an inotrope-dependent population. All patients with idiopathic dilated cardiomyopathy survived to transplantation. In contrast, all three with right heart failure caused by pulmonary vascular disease and four of seven with ischemic cardiomyopathy died. Inpatient days were reduced by 70%, leading to considerable cost savings. Home ambulatory inotropic therapy is safe, cost-effective, best suited to those with idiopathic dilated cardiomyopathy, and dramatically reduces inpatient hospital duration.

Conventional and saturation-transfer EPR of spin-labeled mutant bacteriophage M13 coat protein in phospholipid bilayers.

A mutant of bacteriophage M13 was prepared in which a cysteine residue was introduced at position 25 of the major coat protein. The mutant coat protein was spin-labeled with a nitroxide derivative of maleimide and incorporated at different lipid-to-protein (L/P) ratios in DOPC or DOPG. The rotational dynamics of the reconstituted mutant coat protein was studied using EPR and saturation transfer (ST) EPR techniques. The spectra are indicative for an anisotropic motion of the maleimide spin label with a high order parameter (S = 0.94). This is interpreted as a wobbling motion of the spin label with a correlation time of about 10(-6) to 10(-5) s within a cone, and a rotation of the spin label about its long molecular axis with a correlation time of about l0(-7) s. The wobbling motion is found to correspond generally to the overall rotational motion of a coat protein monomer about the normal to the bilayer. This motion is found to be sensitive to the temperature and L/P ratio. The high value of the order parameter implies that the spin label experiences a strong squeezing effect by its local environment, that reduces the amplitude of the wobbling motion. This squeezing effect is suggested to arise from a turn structure in the coat protein from Gly23 to Glu20.