Incidental maternal findings on fetal MRI.

AIM: To evaluate the type and frequency of maternal findings incidentally identified during fetal magnetic resonance imaging (MRI). MATERIALS AND METHODS: A retrospective single-centre study was undertaken which included all consecutive fetal MRI studies performed between July 2017 and May 2021 at a tertiary institution. Two fellowship-trained radiologists reviewed the studies independently to determine the type and frequency of incidental maternal findings of both no clinical significance (requiring no further follow-up) and of clinical significance (requiring further follow-up, work-up, and/or management). Differences in acquisition were resolved by two-reader consensus. Non-diagnostic MRI examinations or abdominal MRI examinations indicated for maternal complications were excluded from review. RESULTS: A total of 455 consecutive fetal MRI examinations performed in 429 women were included. Mean age was 30 years (SD 5.5 years). At least one incidental maternal finding was identified in 58% (265/455) of studies. Umbilical hernias (35%), maternal hydronephrosis (19%), and maternal hydro-ureter (15%) were the most common. Only two studies (0.5%) showed clinically significant incidental maternal findings (pancreatic pseudocyst and ovarian cyst). CONCLUSIONS: Incidental maternal findings are common on fetal MRI but rarely require further follow-up, work-up, and/or management.

A dynamic baseline for dissolved methane in English groundwater.

Elevated dissolved methane (CH4) concentrations in groundwater are an environmental concern associated with hydraulic fracturing for shale gas. Therefore, determining dissolved CH4 baselines is important for detecting and understanding any potential environmental impacts. Such baselines should change in time and space to reflect ongoing environmental change and should be able to predict the probability that a change in dissolved CH4 concentration has occurred. We considered four dissolved CH4 concentration datasets of English groundwater using a Bayesian approach: two national datasets and two local datasets from shale gas exploration sites. The most sensitive national dataset (the previously published British Geological Survey CH4 baseline) was used as a strong prior for a larger (2153 measurements compared to 439) but less sensitive (detection limit 1000 times higher) Environment Agency dataset. The use of the strong prior over a weak prior improved the precision of the Environment Agency dataset by 75%. The expected mean dissolved CH4 concentration in English groundwater based on the Bayesian approach is 0.24 mg/l, with a 95% credible interval of 0.11 to 0.45 mg/l, and a Weibull distribution of W(0.35 ± 0.01, 0.34 ± 0.16). This result indicates the amount of CH4 degassing from English groundwater to the atmosphere equates to between 0.7 and 3.1 kt CH4/year, with an expected value of 1.65 kt CH4/year and a greenhouse gas warming potential of 40.3 kt CO2eq/year. The two local monitoring datasets from shale gas exploration sites, in combination with the national datasets, show that dissolved CH4 concentrations in English groundwater are generally low, but locations with concentrations greater than or equal to the widely used risk action level of 10.0 mg/l do exist. Statistical analyses of groundwater redox conditions at these locations suggest that it may be possible to identify other locations with dissolved CH4 concentrations ≥10.0 mg/l using redox parameters such as Fe concentration.

Identifying groundwater compartmentalisation for hydraulic fracturing risk assessments.

An environmental concern with hydraulic fracturing (fracking) is that injected fluids or formation fluids could migrate upwards along high-permeability faults and contaminate shallow groundwater resources. However, numerical modelling has suggested that compartmentalisation by low-permeability faults may be a greater risk factor to shallow aquifers than high-permeability faults because lateral groundwater flow is reduced and upward flow through strata may be encouraged. Therefore, it is important that compartmentalisation can be adequately identified prior to fracking. As a case study we used historical groundwater quality data and two-dimensional seismic reflection data from the Bowland Basin, northwest England, to investigate if compartmentalisation could be adequately identified in a prospective shale basin. Five groundwater properties were spatially autocorrelated and interpolation suggests a regional trend from recent (<10 000 years old) meteoric groundwater in the upland Forest of Bowland to more brackish groundwater across the Fylde plain. Principal components analysis suggests two end-member brackish groundwater types. These end-members along with seismic interpretation suggest that a fault may structurally compartmentalise the northwest Bowland Basin. Furthermore, the Woodsfold fault structurally compartmentalises the southern Fylde and the Blackpool area provides evidence for stratigraphic compartmentalisation in the superficial deposits. However, large areas of the Bowland Basin are not sampled and the influence of known faults on groundwater is therefore difficult to assess. Consequently, the adequate identification of compartmentalisation in prospective basins may require supplementing historic data with dedicated basin-wide groundwater monitoring programmes and the acquisition of new seismic reflection data in areas of poor coverage or quality.

A proposed model for a collaborative approach to dental hygiene research.

As dental hygiene responds to the increased need for quality oral health services, dental hygienists seek quality research findings on which to base their practice decisions. However, the amount of research published by dental hygienists, and addressing dental hygiene interventions, remains limited. There are few dental hygienists in Canada working in positions that have time dedicated to research activities. To increase the amount of dental hygiene research, innovative approaches such as collaborative research must be considered. This paper considers measures that facilitate the conduct of collaborative research, and discusses challenges to the process that should be considered during the design. An example of a group investigation is presented, involving dental hygiene educators who collaborated on a research project implemented within their respective educational institutions. A model for a collaborative approach to future research initiatives is proposed. Lessons learned are shared and recommendations are put forward. It is suggested that innovative collaborations such as this may help to increase the body of knowledge for dental hygiene in Canada.

A pilot study to determine the effectiveness of garlic oil capsules in the treatment of dyspeptic patients with Helicobacter pylori.

BACKGROUND: Resistance of Helicobacter pylori to clarithromycin and metronidazole is now found worldwide. Steam-distilled garlic oil has in vitro activity against H. pylori and may be a useful alternative treatment strategy. MATERIALS AND METHODS: In this pilot study dyspeptic patients with positive serology for H. pylori confirmed by 13C urea breath test (UBT), at 0 and 2 weeks, were enrolled. Treatment consisted of one 4 mg garlic oil capsule with a meal four times per day for 14 days. H. pylori eradication was defined as a negative UBT at both follow-up appointments. Suppression was defined as a 50% fall in 13C excess between baseline and follow-up 1. RESULTS: Five patients completed the study. There was no evidence of either eradication or suppression of H. pylori or symptom improvement whilst taking garlic oil. CONCLUSION: These negative results show that, within the gastric milieu, garlic oil at this dose does not inhibit H. pylori. A higher dose administered for a longer time-period may be effective. Antibiotics are usually combined with a proton-pump inhibitor or bismuth salt, as the only antibiotic with any in vivo activity against H. pylori in monotherapy is clarithromycin. A proton pump inhibitor raises gastric pH and, by increasing bacterial division, may increase the in vivo activity of garlic oil. This may be worth pursuing in a future trial.

Inositol 1,3,4-trisphosphate 5/6-kinase is a protein kinase that phosphorylates the transcription factors c-Jun and ATF-2.

Phosphorylation of inositol 1,3,4-trisphosphate by inositol 1,3,4-trisphosphate 5/6-kinase is the first committed step in the formation of higher phosphorylated forms of inositol. We have shown that the eight proteins called the COP9 signalosome complex copurify with calf brain 5/6-kinase. Because the complex has been shown to phosphorylate c-Jun in vitro, we tested both the complex and 5/6-kinase and found that both are able to phosphorylate c-Jun and ATF-2 on serine/threonine residues. These findings establish a link between two major signal transduction systems: the inositol phosphates and the stress response system.

A multicentre, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blasts in transformation.

The primary objective of this study was to determine the complete remission (CR) rate achieved with the FLAG (fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor) regimen in patients with relapsed or refractory acute myeloid leukaemia (AML) or de novo refractory anaemia with excess of blasts in transformation (RAEB-t). Secondary objectives were to evaluate survival and toxicity. Induction treatment consisted of between one and two courses of FLAG. Patients achieving CR received between one and two courses of consolidation treatment. Eighty-three of the 89 patients entering the study were eligible for assessment. CR rates were: 17 out of 21 (81%) in late relapse AML (Group 1), 13 out of 44 (30%) in early relapse/refractory AML (Group 2), and 10 out of 18 (56%) in de novo RAEB-t (Group 3). Thirty-four of the 40 responders (85%) achieved CR after one induction course. Median survival times were 1.4 years, 3 months and 1.6 years in Groups 1, 2 and 3 respectively. Other than myelosuppression, the FLAG regimen was not generally associated with clinically significant toxicity and was well tolerated by most patients including the elderly. The FLAG regimen offers a very effective alternative treatment for CR induction in poor prognosis adult patients with either relapsed or refractory AML or de novo RAEB-t. FLAG delivers high-dose treatment without increasing overall toxicity, an approach which is of particular value in older patients, who constitute the majority in these diseases. It is therefore an important advance in developing new treatment options for these patients.

The isolation and characterization of a cDNA encoding phospholipid-specific inositol polyphosphate 5-phosphatase.

We report the cDNA cloning and characterization of a novel human inositol polyphosphate 5-phosphatase (5-phosphatase) that has substrate specificity unlike previously described members of this large gene family. All previously described members hydrolyze water soluble inositol phosphates. This enzyme hydrolyzes only lipid substrates, phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 4,5-bisphosphate. The cDNA isolated comprises 3110 base pairs and predicts a protein product of 644 amino acids and M(r) = 70,023. We designate this 5-phosphatase as type IV. It is a highly basic protein (pI = 8.8) and has the greatest affinity toward phosphatidylinositol 3,4,5-trisphosphate of known 5-phosphatases. The K(m) is 0.65 micrometer, 1/10 that of SHIP (5.95 micrometer), another 5-phosphatase that hydrolyzes phosphatidylinositol 3,4,5-trisphosphate. The activity of 5-phosphatase type IV is sensitive to the presence of detergents in the in vitro assay. Thus the enzyme hydrolyzes lipid substrates in the absence of detergents or in the presence of n-octyl beta-glucopyranoside or Triton X-100, but not in the presence of cetyltriethylammonium bromide, the detergent that has been used in other studies of the hydrolysis of phosphatidylinositol 4,5-bisphosphate. Remarkably SHIP, a 5-phosphatase previously characterized as hydrolyzing only substrates with d-3 phosphates, also readily hydrolyzed phosphatidylinositol 4,5-bisphosphate in the presence of n-octyl beta-glucopyranoside but not cetyltriethylammonium bromide. We used antibodies prepared against a peptide predicted by the cDNA to identify the 5-phosphatase type IV enzyme in human tissues and find that it is highly expressed in the brain as determined by Western blotting. We also performed Western blotting of mouse tissues and found high levels of expression in the brain, testes, and heart with lower levels of expression in other tissues. mRNA was detected in many tissues and cell lines as determined by Northern blotting.

The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity.

Phosphatidylinositol-4,5-bisphosphate plays a pivotal role in the regulation of cell proliferation and survival, cytoskeletal reorganization, and membrane trafficking. However, little is known about the temporal and spatial regulation of its synthesis. Higher eukaryotic cells have the potential to use two distinct pathways for the generation of phosphatidylinositol-4,5-bisphosphate. These pathways require two classes of phosphatidylinositol phosphate kinases, termed type I and type II PIP kinases. While highly related by sequence, these kinases localize to different subcellular compartments, phosphorylate distinct substrates, and are functionally nonredundant. Here, we show that a 20- to 25-amino acid loop spanning the catalytic site, termed the activation loop, determines both enzymatic specificity and subcellular targeting of PIP kinases. Therefore, the activation loop controls signaling specificity and PIP kinase function at multiple levels.

Prevalence and predictors of white-coat response in patients with treated hypertension.

BACKGROUND: White-coat response, defined as higher office blood pressure readings than ambulatory readings, is common. Few studies have estimated its prevalence among subjects with treated hypertension, and almost none have defined its determinants. The objective of this study was to estimate the prevalence of white-coat response among subjects with treated hypertension and to determine whether the phenomenon could be predicted using clinical and psychometric data. METHODS: A total of 103 treated patients (55 men and 48 women) with uncontrolled hypertension who attended a hypertension outpatient clinic in Saskatoon between September 1993 and December 1995 were entered into the study. Patients had at least 2 clinic blood pressure readings of 140/90 mm Hg or higher, had no target organ damage or left ventricular hypertrophy, and had been prescribed 2 or more classes of antihypertensive drugs. Patients had blood pressure measured in the supine position in the clinic, were placed on 24-hour ambulatory blood pressure monitoring and then completed questionnaires before returning to the clinic. Patients were classified as exhibiting a white-coat response if their mean daytime ambulatory systolic/diastolic blood pressure was 139/89 mm Hg (both) or less, or if the systolic/diastolic pressure was at least 20/15 mm Hg (both) lower than the clinic reading. RESULTS: Eleven men (20%, 95% confidence interval [CI] 10%-33%) and 26 women (54%, 95% CI 39%-69%) showed white-coat response. Logistic regression modelling showed that determinants such as stress had significantly different effects among men and women. Separate models were therefore created for men and women. For women, perceived level of stress was the most important predictor of white-coat response (odds ratio [OR] per unit 7.0, 95% CI 1.3-36.0), followed by time since diagnosis. For men, depression was a weak predictor, with higher depression scores predicting sustained hypertension (OR per unit 1.2, 95% CI 1.01-1.5). INTERPRETATION: Sex is an important factor in white-coat response. Attempts to predict white-coat response from psychometric variables should take sex differences into account. Clinical variables were not effective as predictors of white-coat response.

Laboratory role in the management of hospital acquired infections.

The microbiology laboratory has many important roles. It must collaborate with the infection control team on the investigations of outbreaks. During outbreaks, it must save relevant samples, look for reservoirs and undertake typing techniques, all of which should be timely. New technology should be available to detect, identify and characterize micro-organisms. Molecular biological techniques have enhanced the speed and sensitivity of detection methods and have allowed the laboratory to identify organisms that do not grow or grow slowly in culture. Molecular techniques also enable the microbiologist to identify antibiotic resistance genes and to 'fingerprint' hospital organisms, thereby facilitating studies of nosocomial transmission.

The campaign to enact New York City's Smoke-Free Air Act.

On January 10, 1995, New York City's mayor signed into law a bill restricting smoking in most public facilities including restaurant dining areas, workplaces, and sports stadiums. This law was the subject of extensive public debate and was considered quite controversial at the time it was enacted. Passage of the smoking law (known as the New York City Smoke-Free Air Act) helped pave the way for other localities in New York to enact similar restrictions on smoking in public facilities. This article documents the process of enacting the New York City Smoke-Free Air Act.

Compliance with the New York City Smoke-Free Air Act.

This study's objective was to determine the level of compliance with the New York City Smoke-Free Air Act. Three data sources were used: (1) a population-based telephone survey of 251 New York City restaurant owners/managers; (2) independent inspections of the 251 surveyed restaurants; and (3) complaint records from the New York City Department of Health from April 1995 to March 1997. Ninety percent of restaurant owners/managers reported their indoor dining area was smoke-free in compliance with the law. Most New York City restaurants were able to comply with the smoke-free law with relative ease and little expense.

Multicenter phase II study of fludarabine phosphate for patients with newly diagnosed lymphoplasmacytoid lymphoma, Waldenström's macroglobulinemia, and mantle-cell lymphoma.

PURPOSE: Fludarabine phosphate (F-AMP) has significant activity in follicular lymphoma and in B-cell chronic lymphatic leukemia, where it has demonstrated high complete response (CR) rates. Lymphoplasmacytoid (LPC) lymphoma, Waldenstrom's macroglobulinemia (WM), and mantle-cell lymphoma (MCL) also present with advanced-stage disease and are incurable with standard alkylator-based chemotherapy. A phase II trial was undertaken to determine the activity of F-AMP in patients newly diagnosed with these diseases. PATIENTS AND METHODS: Between 1992 and 1996, 78 patients (aged 18 to 75 years) received intravenous F-AMP (25 mg/m2/d for 5 days, every 4 weeks) until maximum response, plus two further cycles as consolidation. The primary end point was response rate; secondary end points included time to progression (TTP), duration of response, and overall survival (OS). RESULTS: Forty-four (62%) of 71 assessable patients had a response to F-AMP (LPC lymphoma, 63%; WM, 79%; MCL, 41%); the CR rate was 15%. At a median follow-up of 1.5 years, 19 of 44 responding patients have had progression of lymphoma; the median duration of response was 2.5 years. The median survival has not yet been reached. There was no significant difference in the duration of response or OS between patients with different histologies; TTP was shorter in patients with MCL (P = .015). Myelosuppression was relatively common, and the treatment-related mortality (TRM) was 5%, mostly associated with pancytopenia and infection. CONCLUSION: Single-agent fludarabine phosphate is active in previously untreated LPC lymphoma and WM, with only moderate activity in MCL. However, the CR rate is low, and the TRM is relatively high. Its role in combination chemotherapy remains to be demonstrated.

Bovine spermatozoal head size variation and evaluation of a separation technique based on this size.

The objectives of this study were to determine the variation of head areas of normal spermatozoa attributable to breed, individual bull and ejaculate and to verify separation of X and Y chromosome-bearing spermatozoa and separation effectiveness. Spermatozoa were evaluated using video enhanced contrast microscopy combined with video intensified fluorescent microscopy and the polymerase chain reaction (PCR). In Experiment 1, spermatozoal head areas were measured from 2 ejaculates collected from bulls of 3 beef and 2 dairy breeds. No differences in head areas were found between breeds or between bulls within breeds; variation was observed among ejaculates from individual bulls across breeds. In Experiment 2, spermatozoa from 5 ejaculates were separated on individual SEPDEVICEs (Patented). Head area, fluorescent intensity and PCR of spermatozoa retained in the SEPDEVICEs suggested a separation based on size in 1 of 5 samples. Ejaculate variation in head areas affected separation efficiency.

SopB, a protein required for virulence of Salmonella dublin, is an inositol phosphate phosphatase.

Several proteins secreted by enteric bacteria are thought to contribute to virulence by disturbing the signal transduction of infected cells. Here, we report that SopB, a protein secreted by Salmonella dublin, has sequence homology to mammalian inositol polyphosphate 4-phosphatases and that recombinant SopB has inositol phosphate phosphatase activity in vitro. SopB hydrolyzes phosphatidylinositol 3,4,5-trisphosphate, an inhibitor of Ca2+-dependent chloride secretion. In addition, SopB hydrolyzes inositol 1,3,4,5,6 pentakisphosphate to yield inositol 1,4,5, 6-tetrakisphosphate, a signaling molecule that increases chloride secretion indirectly by antagonizing the inhibition of chloride secretion by phosphatidylinositol 3,4,5-trisphosphate [Eckmann, L., Rudolf, M. T., Ptasznik, A., Schultz, C., Jiang, T., Wolfson, N., Tsien, R., Fierer, J., Shears, S. B., Kagnoff, M. F., et al. (1997) Proc. Natl. Acad. Sci. USA 94, 14456-14460]. Mutation of a conserved cysteine that abolishes phosphatase activity of SopB results in a mutant strain, S. dublin SB c/s, with decreased ability to induce fluid secretion in infected calf intestine loops. Moreover, HeLa cells infected with S. dublin SB c/s do not accumulate high levels of inositol 1,4,5,6-tetrakisphosphate that are characteristic of wild-type S. dublin-infected cells. Therefore, SopB mediates virulence by interdicting inositol phosphate signaling pathways.

Susceptibility testing of Stenotrophomonas maltophilia to carbapenems.

The susceptibility of 20 clinical isolates of Stenotrophomonas maltophilia to the carbapenems imipenem and meropenem was investigated by various methods. S. maltophilia appeared sensitive to meropenem but resistant to imipenem by disc testing in Iso-sensitest agar. Agar dilution MICs were performed using Iso-sensitest agar and with incubation under three sets of atmospheric conditions. MICs of meropenem were considerably lower than those of imipenem; this effect was maximal after incubation in 5% CO2 when the MIC of meropenem was approximately 64 times less than that of imipenem. Induction experiments showed that both carbapenems could induce production of the L1 carbapenemase. However, disc approximation tests showed that imipenem could induced resistance to meropenem. Partially stably derepressed mutants were readily selected in vitro. We conclude that, although S. maltophilia may give large zones of inhibition to meropenem on disc testing, resistant mutants are readily selected and therefore standard sensitivity tests may be poorly predictive of clinical outcome of treatment of S. maltophilia infections with meropenem.