The Caries Microbiome: Implications for Reversing Dysbiosis.

The oral microbiome plays a critical role in maintaining oral health. Frequent dietary carbohydrate intake can lead to dysbiosis of the microbial community from overproduction of acid with selection for increases in acidogenic, acid-tolerant bacteria. Knowledge of the caries-associated microbiome is key in planning approaches to reverse the dysbiosis to achieve health. For risk assessment and treatment studies, it would be valuable to establish whether microbial monitoring requires assay of multiple species or whether selected key species would suffice. Early investigations of the oral microbiota relied on culture-based methods to determine the major bacteria in health and disease. Microbial monitoring using gene probes facilitated study of larger populations. DNA probe methods confirmed and expanded the importance of transmission of bacteria from mother to infant and association of preselected species, including mutans streptococci and lactobacilli with caries in larger populations. 16S ribosomal RNA (rRNA) probes confirmed the wide diversity of species in oral and caries microbiomes. Open-ended techniques provide tools for discovery of new species, particularly when strain/clone identification includes gene sequence data. Anaerobic culture highlighted the caries association of Actinomyces and related species. Scardovia wiggsiae, in the Actinomyces/Bifidobacterium family, and several Actinomyces species have the cariogenic traits of acid production and acid tolerance. Next-generation sequencing combined with polymerase chain reaction methods revealed a strong association with mutans streptococci in a high caries population with poor oral hygiene and limited access to care. A population with a lower caries experience generally had lower or no Streptococcus mutans detection but harbored other acidogenic taxa in the microbiome. Study of the microbiome suggests a role for the assay of selected putative cariogenic species in more aggressive diseases. For many populations with caries progression, however, assay of multiple species will likely be warranted to determine the caries profile of the population and/or individuals under study.

Distinct forebrain regions define a dichotomous astrocytic profile in multiple system atrophy.

The growing recognition of a dichotomous role of astrocytes in neurodegenerative processes has heightened the need for unraveling distinct astrocytic subtypes in neurological disorders. In multiple system atrophy (MSA), a rare, rapidly progressing atypical Parkinsonian disease characterized by increased astrocyte reactivity. However the specific contribution of astrocyte subtypes to neuropathology remains elusive. Hence, we first set out to profile glial fibrillary acidic protein levels in astrocytes across the human post mortem motor cortex, putamen, and substantia nigra of MSA patients and observed an overall profound astrocytic response. Matching the post mortem human findings, a similar astrocytic phenotype was present in a transgenic MSA mouse model. Notably, MSA mice exhibited a decreased expression of the glutamate transporter 1 and glutamate aspartate transporter in the basal ganglia, but not the motor cortex. We developed an optimized astrocyte isolation protocol based on magnetic-activated cell sorting via ATPase Na+/K+ transporting subunit beta 2 and profiled the transcriptomic landscape of striatal and cortical astrocytes in transgenic MSA mice. The gene expression profile of astrocytes in the motor cortex displayed an anti-inflammatory signature with increased oligodendroglial and pro-myelinogenic expression pattern. In contrast, striatal astrocytes were defined by elevated pro-inflammatory transcripts accompanied by dysregulated genes involved in homeostatic functions for lipid and calcium metabolism. These findings provide new insights into a region-dependent, dichotomous astrocytic response-potentially beneficial in the cortex and harmful in the striatum-in MSA suggesting a differential role of astrocytes in MSA-related neurodegenerative processes.

Sub-nanosecond time-resolved radiation measurement using x-ray focusing crystal spectrometers.

In this paper, we describe a technique using a crystal spectrometer, a silicon-diode detector, and a filtered photoconductive detector to monitor photon energies in the L-shell (0.9-1 keV) and K-shell regimes for nickel and copper hybrid X-pinch x-ray sources. The detectors, system cabling, and an 8 GHz digital oscilloscope in combination enable time resolution better than 200 ps for photoconductive detectors and 700 ps for silicon-diode detectors of the K- and L-shell radiation signals, respectively. We substantially improve the relative timing of signals obtained using the oscilloscope by using an x-ray streak camera with a crystal spectrometer to monitor the L-shell line spectra and, separately, the K-shell line spectra relative to the continuum burst to better than 17 ps time resolution. This combination of instruments enabled and validated a new method by which plasma conditions in nickel and copper X-pinches can be assessed immediately before and after the ∼30 ps continuum x-ray burst produced by 370 kA hybrid X-pinches. In general, the method described here can be applied to observe otherwise highly filter-absorbed radiation in the presence of a broad spectrum of higher energy radiation by combining x-ray crystals and detectors.

Cultivable anaerobic microbiota of severe early childhood caries.

Severe early childhood caries (ECC), while strongly associated with Streptococcus mutans using selective detection (culture, PCR), has also been associated with a widely diverse microbiota using molecular cloning approaches. The aim of this study was to evaluate the microbiota of severe ECC using anaerobic culture. The microbial composition of dental plaque from 42 severe ECC children was compared with that of 40 caries-free children. Bacterial samples were cultured anaerobically on blood and acid (pH 5) agars. Isolates were purified, and partial sequences for the 16S rRNA gene were obtained from 5,608 isolates. Sequence-based analysis of the 16S rRNA isolate libraries from blood and acid agars of severe ECC and caries-free children had >90% population coverage, with greater diversity occurring in the blood isolate library. Isolate sequences were compared with taxon sequences in the Human Oral Microbiome Database (HOMD), and 198 HOMD taxa were identified, including 45 previously uncultivated taxa, 29 extended HOMD taxa, and 45 potential novel groups. The major species associated with severe ECC included Streptococcus mutans, Scardovia wiggsiae, Veillonella parvula, Streptococcus cristatus, and Actinomyces gerensceriae. S. wiggsiae was significantly associated with severe ECC children in the presence and absence of S. mutans detection. We conclude that anaerobic culture detected as wide a diversity of species in ECC as that observed using cloning approaches. Culture coupled with 16S rRNA identification identified over 74 isolates for human oral taxa without previously cultivated representatives. The major caries-associated species were S. mutans and S. wiggsiae, the latter of which is a candidate as a newly recognized caries pathogen.

Complications following pancreatic transplantations: imaging features.

Whole organ vascularized pancreatic transplant is a recognized treatment for diabetes and is increasingly being performed worldwide. The procedure itself is complex and is associated with significant mortality and morbidity. Despite improvements in surgical techniques, postoperative complications of pancreatic transplantation are still common and include graft rejection, pancreatitis, peripancreatic fluid collections, exocrine leaks, vascular thrombosis, and hemorrhage. In this pictorial essay, we review clinical presentation and imaging features of these complications. We also briefly discuss technique and complications of islet cell transplants.

Clonal analysis of the microbiota of severe early childhood caries.

BACKGROUND/AIMS: Severe early childhood caries is a microbial infection that severely compromises the dentition of young children. The aim of this study was to characterize the microbiota of severe early childhood caries. METHODS: Dental plaque samples from 2- to 6-year-old children were analyzed using 16S rRNA gene cloning and sequencing, and by specific PCR amplification for Streptococcus mutans and Bifidobacteriaceae species. RESULTS: Children with severe caries (n = 39) had more dental plaque and gingival inflammation than caries-free children (n = 41). Analysis of phylotypes from operational taxonomic unit analysis of 16S rRNA clonal metalibraries from severe caries and caries-free children indicated that while libraries differed significantly (p < 0.0001), there was increased diversity than detected in this clonal analysis. Using the Human Oral Microbiome Database, 139 different taxa were identified. Within the limits of this study, caries-associated taxa included Granulicatella elegans (p < 0.01) and Veillonella sp. HOT-780 (p < 0.01). The species associated with caries-free children included Capnocytophaga gingivalis (p < 0.01), Abiotrophia defectiva (p < 0.01), Lachnospiraceae sp. HOT-100 (p < 0.05), Streptococcus sanguinis (p < 0.05) and Streptococcus cristatus (p < 0.05). By specific PCR, S. mutans (p < 0.005) and Bifidobacteriaceae spp. (p < 0.0001) were significantly associated with severe caries. CONCLUSION: Clonal analysis of 80 children identified a diverse microbiota that differed between severe caries and caries-free children, but the association of S. mutans with caries was from specific PCR analysis, not from clonal analysis, of samples.

The UK nephrostomy audit. Can a voluntary registry produce robust performance data?

AIM: To investigate the effectiveness of the Royal College of Radiologists Audit Sub-Committee's national prospective registry of percutaneous nephrostomy, which enables participants to audit their practice and compare performance with predetermined standards. METHODS: Following a limited retrospective audit, which permitted setting of achievable targets, a dataset was developed and all UK NHS acute hospitals were invited to participate in web-based prospective data collection. RESULTS: Eighty-five out of 285 (29.8%) hospitals contributed 3262 cases over a 29 month period. A satisfactory level of performance was achieved with an overall technical success rate of 98% and a complication rate of 6.3%. Significant risk factors for complications included rigors, anaemia, and impaired renal function. Low frequency operators were shown to have a lower technical success rate and a higher complication rate than high frequency operators; however, target thresholds were exceeded in all groups. Sepsis was identified as a risk factor in the majority of serious complications and all deaths. Some anomalous results were found due to unusual interpretation of the data entry form in two centres, but no evidence of under-performance was identified at any centre. CONCLUSIONS: Some weaknesses of the registry are discussed. In view of the low response rate, the possibility of significant bias cannot be excluded. In addition, there is no objective verification of the data; therefore, the results have limited credibility. However, individual centres that accurately completed a representative sample of cases can have confidence that their performance achieves an acceptable standard.

Physics-based virtual environment for training core skills in vascular interventional radiological procedures.

Recent years have seen a significant increase in the use of Interventional Radiology (IR) as an alternative to open surgery. A large number of IR procedures commences with needle puncture of a vessel to insert guidewires and catheters: these clinical skills are acquired by all radiologists during training on patients, associated with some discomfort and occasionally, complications. While some visual skills can be acquired using models such as the ones used in surgery, these have limitations for IR which relies heavily on a sense of touch. Both patients and trainees would benefit from a virtual environment (VE) conveying touch sensation to realistically mimic procedures. The authors are developing a high fidelity VE providing a validated alternative to the traditional apprenticeship model used for teaching the core skills. The current version of the CRaIVE simulator combines home made software, haptic devices and commercial equipments.

Hypercementosis Associated with ENPP1 Mutations and GACI.

Mineralization of bones and teeth is tightly regulated by levels of extracellular inorganic phosphate (Pi) and pyrophosphate (PPi). Three regulators that control pericellular concentrations of Pi and PPi include tissue-nonspecific alkaline phosphatase (TNAP), progressive ankylosis protein (ANK), and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). Inactivation of these factors results in mineralization disorders affecting teeth and their supporting structures. This study for the first time analyzed the effect of decreased PPi on dental development in individuals with generalized arterial calcification of infancy (GACI) due to loss-of-function mutations in the ENPP1 gene. Four of the 5 subjects reported a history of infraocclusion, overretained primary teeth, ankylosis, and/or slow orthodontic tooth movement, suggesting altered mineral metabolism contributing to disrupted tooth movement and exfoliation. All subjects had radiographic evidence of unusually protruding cervical root morphology in primary and/or secondary dentitions. High-resolution micro-computed tomography (micro-CT) analyses of extracted primary teeth from 3 GACI subjects revealed 4-fold increased cervical cementum thickness ( P = 0.00007) and a 23% increase in cementum density ( P = 0.009) compared to age-matched healthy control teeth. There were no differences in enamel and dentin densities between GACI and control teeth. Histology revealed dramatically expanded cervical cementum in GACI teeth, including cementocyte-like cells and unusual patterns of cementum resorption and repair. Micro-CT analysis of Enpp1 mutant mouse molars revealed 4-fold increased acellular cementum thickness ( P = 0.002) and 5-fold increased cementum volume ( P = 0.002), with no changes in enamel or dentin. Immunohistochemistry identified elevated ENPP1 expression in cementoblasts of human and mouse control teeth. Collectively, these findings reveal a novel dental phenotype in GACI and identify ENPP1 genetic mutations associated with hypercementosis. The sensitivity of cementum to reduced PPi levels in both human and mouse teeth establishes this as a well-conserved and fundamental biological process directing cementogenesis across species (ClinicalTrials.gov NCT00369421).

Peripheral arterial disease in diabetic and nondiabetic patients: a comparison of severity and outcome.

OBJECTIVE: The aim of this study was to quantify the distribution of peripheral arterial disease in the diabetic and nondiabetic population attending for angiography and to compare severity and outcome between both groups of patients. RESEARCH DESIGN AND METHODS: Randomly selected lower-extremity angiograms were examined according to the Bollinger system. Patient demographics and medical history were recorded and case notes were examined to determine which patients later underwent a revascularization procedure or amputation and which patients had died. RESULTS: A total of 136 arteriograms obtained between 1992 and 1996 were analyzed. The age (mean +/- SD) of the patients was 64.7 +/- 10.8 years. Diabetic patients (43%) and nondiabetic patients were of similar age (63.9 +/- 10.4 vs. 65.3 +/- 11.1 years, P = 0.43), with a similar history of smoking (81.0 vs. 76.9%, P = 0.26), ischemic heart disease (41.4 vs. 37.2%, P = 0.54), and hypercholesterolemia (24.4 vs. 30.8%, P = 0.48). However, there were a greater proportion of hypertensive patients in the diabetic group (63.8 vs. 39.7%, P = 0.006). Diabetic patients had greater severity of arterial disease in the profunda femoris and all arterial segments below the knee (P = 0.02). A greater number of amputations occurred in the diabetic group: diabetic patients were five times more likely to have an amputation (41.4 vs. 11.5%, odds ratio [OR] 5.4, P < 0.0001). Mortality was higher in the diabetic group (51.7 vs. 25.6%, OR 3.1, P = 0.002), and diabetic patients who died were younger at presentation than nondiabetic patients (64.7 +/- 11.4 vs. 71.1 +/- 8.7 years, P = 0.04). CONCLUSIONS: In patients with peripheral arterial disease, diabetic patients have worse arterial disease and a poorer outcome than nondiabetic patients.

Comparison of iodixanol and iohexol in renal impairment.

Iodixanol (Visipaque, Nycomed, Oslo, Norway) is an iodinated contrast medium in the form of a non-ionic dimer which is iso-osmolar with plasma at all iodine concentrations. There is little evidence regarding its renal tolerance in renal impairment. We therefore undertook a prospective randomized comparison of iodixanol and the non-ionic monomer iohexol (Omnipaque, Nycomed, Oslo, Norway). The serum creatinine was measured pre- and post-angiography in a series of in-patients to establish whether there was any clinically detectable evidence of superiority of iodixanol over iohexol in this high risk group. 8/54 (15%) patients in the iodixanol group had a rise in creatinine of > 10% in the week following angiography compared with 15/48 (31%) in the iohexol group (p < 0.05). The creatinine rise was positively correlated with the dose of both contrast media. These results suggest that iodixanol may be slightly less nephrotoxic than iohexol.

Supradiaphragmatic middle aorta syndrome--MR and angiographic imaging.

We describe the case of an asymptomatic 24-year-old man with hypertension who was investigated for aortic coarctation but found on MR scanning to have narrowing of the distal thoracic aorta. Stenosis of the thoracolumbar aorta--the Middle Aorta Syndrome--is rare and is usually found below the diaphragm. The MRI and angiographic findings are presented.

Radiation risk estimation in varicocele embolization.

Varicocele embolization is performed in healthy young men with normal life expectancy. Therefore, it is essential that the radiation risks associated with the procedure are minimized. The radiation risks associated with varicocele embolization have been estimated retrospectively from dose-area product records in a series of 41 cases and compared with a prospective series of 10 cases. Lithium fluoride dosemeters were used to measure gonad dose in the prospective series. Estimated lifetime fatal cancer risk was of the order of 0.1% in the retrospective series. A seven-fold reduction in median radiation dose was observed in the prospective series. The results indicate that with meticulous attention to technique, substantial reductions in radiation exposure can be achieved.

Outpatient angiography: a prospective study of 3 French catheters in unselected patients.

Financial constraints and bed shortages led to a re-evaluation of the policy of routine hospital admission for angiography. All patients referred for peripheral and renal angiography over an 8 month period had the procedure performed as an outpatient with a 3 F catheter. Patients were kept supine for 1 h and discharged 2 h after the angiogram. No significant complications resulted from the early mobilization of 219 patients who had outpatient 3 F angiography. It was a safe, well tolerated procedure, resulting in images of consistently adequate quality.

Case report: inferior vena caval thrombosis following severe liver trauma and perihepatic packing--early detection by intraoperative ultrasonography enabling treatment by percutaneous mechanical thrombectomy.

Patients with severe liver trauma present a major challenge in management. We report the successful treatment of a patient presenting with a severe liver injury. The detection of major inferior vena caval thrombosis by intraoperative ultrasonography enabled the use of a percutaneous thrombectomy device to facilitate dissolution of the thrombus.

Case report: infected false aneurysm at the site of an iliac stent.

False aneurysm formation at the site of iliac artery stent placement is an uncommon but serious complication of the procedure. We report a case of infected false aneurysm at the site of an iliac stent, complicated by renal failure.

Percutaneous varicocele embolization in the treatment of infertility.

Clinical and sub-clinical varicoceles are associated with infertility and abnormal sperm parameters. Percutaneous embolization is a minimally invasive, safe, outpatient method of treatment which is cost effective in comparison to surgery. This study is a retrospective review of embolization of the spermatic vein using stainless steel occluding spring coils, performed in 116 males from two infertility clinics. Follow-up results were complete in 87 patients of which 79 (91%) were successful both technically and clinically and all had sperm analysis performed both before and within 2 years after embolization. There was a highly significant increase in motility (mean 35% before, mean 46% after, p < 0.001). Sperm density showed a trend towards improvement, but only p < 0.10, and there was no significant change in semen volume or morphology. The partners of 29 men (33%) became pregnant in a total of 241 years of follow-up.

The use of TIPS to control bleeding caput medusae.

Two patients with cirrhosis and portal hypertension had persistent bleeding from caput medusae and ascites. Transjugular intrahepatic portosystemic shunt (TIPS) resulted in regression of the caput medusae and ascites in both cases.

Quantifying the disease impact of alcohol with ARDI software.

Alcohol-Related Disease Impact (ARDI) Software has been developed for the Centers for Disease Control (CDC) to allow States to calculate mortality, years of potential life lost (YPLL), direct health-care costs, indirect morbidity and mortality costs, and nonhealth-sector costs associated with alcohol use and misuse. The mortality related measures--mortality, YPLL, and indirect mortality costs--are computed for 35 diagnoses related to alcohol use and misuse. A review of clinical research studies and injury surveillance studies was conducted to produce estimates of the alcohol-attributable fraction (AAF) for each diagnosis. For these measures, age-specific and age-adjusted rates are also calculated. Health care costs, morbidity costs, and nonhealth-sector costs are prorated from national studies to the State or locality. This multiple-measure approach to quantifying a health problem is termed "disease impact estimation." National estimates of the disease impact of alcohol use and misuse have been produced using ARDI software and State-specific estimates are in preparation. Designed to CDC specifications, ARDI is completely menu-driven and operates within Lotus 1-2-3 software as a set of linked spreadsheets. ARDI adapts national epidemiologic and health economics methods for use by State and local health agencies. ARDI produces data on the health consequences of alcohol use and misuse for use by locally based policymakers, public health professionals, and researchers, while permitting comparison and compilation of these data across jurisdictions.

Epidemiologic field investigations by the Centers for Disease control and Epidemic Intelligence Service, 1946-87.

The epidemiologic field investigation is an important tool used by the Centers for Disease Control (CDC) to provide assistance to State, local, and international public health agencies. The Epidemic Intelligence Service (EIS) of the CDC is an ongoing program that gives physicians and other health professionals opportunities to learn and practice epidemiology. In the period 1946-87, EIS Officers and other professional staff based at CDC headquarters participated in 2,900 epidemiologic field investigations requested by State, local, and international public health agencies. Nearly two-thirds of the investigations involved infectious disease problems, while 13 percent involved noninfectious conditions; for 21.1 percent, the etiology of the problem was unknown when the investigation was initiated. Among the specific subcategories, bacterial causes were the most common, accounting for 864 (29.8 percent) of all investigations. During this 41-year period, an increasing proportion of the field epidemiologic investigations involved public health problems of noninfectious etiology. Trends in the types of investigations done probably represent the influence of such factors as CDC's priorities, organizational structure, and budget; the size of the EIS Program; national health initiatives; and the States' needs and programs.