Encephalocele-radial, cardiac, gastrointestinal, anal/renal anomalies: novel evidence for a new condition?

The association between encephalocele and radial defects is considered uncommon. These features have been occasionally described separately in certain recurrent conditions such as VACTERL association, oculo-auriculo-vertebral spectrum and Edwards syndrome (trisomy 18). DK-phocomelia is a rare syndrome characterized by both findings. However, Froster-Iskenius and Meinecke [1992, Clin Dysmorphol 1: 37-41] and Kunze et al. [1992, Eur J Pediatr 151: 467-468] reported patients presenting similar malformations. We proposed, through the description of an additional case, that these last patients present the same condition and thus represent a new syndrome. The fetus presented a cranial vault deformity associated with an exuberant herniation of brain content, compatible with occipital encephalocele. Other uncommon features were also identified: microtia of the left ear with atresia of the external auditory canal; radial defect with aplasia of left radius and thumb; findings suggestive of a congenital heart defect and esophageal atresia; hypoplastic lungs and adrenals; thoracolumbar scoliosis; atrophic right kidney; and single umbilical artery. Thus, based on our review, we believe that these patients represent a new condition characterized by encephalocele and radial defects associated with multiple malformations. We propose, that the name "Encephalocele-radial, cardiac, gastrointestinal, anal/renal anomalies," as suggested by the London Medical Database, or even the name, "Froster-Iskenius and Meinecke syndrome" should be used to indicate these cases. © 2014 Wiley Periodicals, Inc.

Biologically derived epicardial patch induces macrophage mediated pathophysiologic repair in chronically infarcted swine hearts.

There are nearly 65 million people with chronic heart failure (CHF) globally, with no treatment directed at the pathologic cause of the disease, the loss of functioning cardiomyocytes. We have an allogeneic cardiac patch comprised of cardiomyocytes and human fibroblasts on a bioresorbable matrix. This patch increases blood flow to the damaged heart and improves left ventricular (LV) function in an immune competent rat model of ischemic CHF. After 6 months of treatment in an immune competent Yucatan mini swine ischemic CHF model, this patch restores LV contractility without constrictive physiology, partially reversing maladaptive LV and right ventricular remodeling, increases exercise tolerance, without inducing any cardiac arrhythmias or a change in myocardial oxygen consumption. Digital spatial profiling in mice with patch placement 3 weeks after a myocardial infarction shows that the patch induces a CD45pos immune cell response that results in an infiltration of dendritic cells and macrophages with high expression of macrophages polarization to the anti-inflammatory reparative M2 phenotype. Leveraging the host native immune system allows for the potential use of immunomodulatory therapies for treatment of chronic inflammatory diseases not limited to ischemic CHF.

Timing and causes of forest fire at the K-Pg boundary.

We report K-Pg-age deposits in Baja California, Mexico, consisting of terrestrial and shallow-marine materials re-sedimented onto the continental slope, including corals, gastropods, bivalves, shocked quartz grains, an andesitic tuff with a SHRIMP U-Pb age (66.12 ± 0.65 Ma) indistinguishable from that of the K-Pg boundary, and charred tree trunks. The overlying mudstones show an iridium anomaly and fungal and fern spores spikes. We interpret these heterogeneous deposits as a direct result of the Chicxulub impact and a mega-tsunami in response to seismically-induced landsliding. The tsunami backwash carried the megaflora offshore in high-density flows, remobilizing shallow-marine fauna and sediment en route. Charring of the trees at temperatures up to > 1000 °C took place in the interval between impact and arrival of the tsunami, which on the basis of seismic velocities and historic analogues amounted to only tens of minutes at most. This constrains the timing and causes of fires and the minimum distance from the impact site over which fires may be ignited.

Isolated coronary artery bypass grafting in obese individuals: a propensity matched analysis of outcomes.

BACKGROUND: There is conflicting data regarding the impact of obesity on morbidity and mortality in patients undergoing isolated coronary artery bypass grafting (CABG). METHODS AND RESULTS: Retrospective cohort analysis of patients who underwent CABG from January 1, 1995, through July 31, 2010 was performed. Patients were classified as obese or non-obese (body mass index ≥ 30.0 kg/m(2) and <30.0 kg/m(2), respectively). The primary outcome was in-hospital mortality. Secondary outcomes included postoperative respiratory failure, postoperative stroke, postoperative myocardial infarction, sternal and leg wound infections, postoperative atrial fibrillation, postoperative ventricular tachycardia, postoperative renal failure and length of hospital stay. Propensity-matched stepwise multivariable logistic regression was performed. Of 13,115 patients, 4,619 (35.2%) were obese. In the propensity-matched logistic regression models (n = 8,442), obesity was not associated with postoperative mortality (odds ratio = 1.13, 95% confidence interval 0.86-1.48). However, obesity was associated with postoperative respiratory failure, postoperative renal insufficiency, sternal wound infection, and leg wound infection. Obesity was also associated with a decreased risk of postoperative bleeding and re-operation from bleeding. CONCLUSIONS: Obesity was associated with an increased risk of postoperative respiratory failure, postoperative renal failure, and surgical site infections. However, obesity was not associated with in-hospital mortality in patients undergoing CABG.

The only constant in radiography is change: A discussion and primer on change in medical imaging to achieve evidence-based practice.

Medical imaging is an ever changing field with significant advancements in techniques and technologies over the years. Despite being constantly challenged by change, it can be difficult to introduce changes into healthcare settings. In this article we introduce the principles of change management to achieve an evidence-based practice in radiography.

Evidence-based healthcare, knowledge translation, implementation science and radiography: What does it all mean?

Evidence-based healthcare is an approach to practice whereby decision making and service delivery considers the best available evidence, patient choice, local resources and clinical expertise. Although sound in theory, compliance with evidence-based practice is often far from optimal. To address this, related fields such as knowledge translation and implementation science have emerged, which largely focus on methods and techniques to facilitate the transfer of evidence into practice. This introductory article explains the key concepts of evidence-based healthcare by using the JBI Model as a framework to highlight the lifecycle of evidence-based information. Throughout the article we refer to exemplars from medical radiation to highlight these concepts.

Transcriptome analysis of Schistosoma mansoni larval development using serial analysis of gene expression (SAGE).

SUMMARY: Infection of the snail, Biomphalaria glabrata, by the free-swimming miracidial stage of the human blood fluke, Schistosoma mansoni, and its subsequent development to the parasitic sporocyst stage is critical to establishment of viable infections and continued human transmission. We performed a genome-wide expression analysis of the S. mansoni miracidia and developing sporocyst using Long Serial Analysis of Gene Expression (LongSAGE). Five cDNA libraries were constructed from miracidia and in vitro cultured 6- and 20-day-old sporocysts maintained in sporocyst medium (SM) or in SM conditioned by previous cultivation with cells of the B. glabrata embryonic (Bge) cell line. We generated 21 440 SAGE tags and mapped 13 381 to the S. mansoni gene predictions (v4.0e) either by estimating theoretical 3' UTR lengths or using existing 3' EST sequence data. Overall, 432 transcripts were found to be differentially expressed amongst all 5 libraries. In total, 172 tags were differentially expressed between miracidia and 6-day conditioned sporocysts and 152 were differentially expressed between miracidia and 6-day unconditioned sporocysts. In addition, 53 and 45 tags, respectively, were differentially expressed in 6-day and 20-day cultured sporocysts, due to the effects of exposure to Bge cell-conditioned medium.

Developments in immunization planning in Cambodia--rethinking the culture and organization of national program planning.

INTRODUCTION: As part of its health system reconstruction following decades of civil war, Cambodia undertook a program of health sector reform in 1996 to expand coverage of essential health services to the population of 14 million, 80% of whom are resident in over 13 000 rural villages. During this reform period, one of the major national health programs, the National Immunization Program (NIP), adapted its planning system to accommodate changes in social and health sector structure. AIMS: The aims of this article are to review changes made in the approach to national immunization planning and to illustrate how these adaptations can help identify future challenges and opportunities for further improving immunization coverage in Cambodia. Sources of information for the study include immunization plans and data from international and national sources, as well as data from the national health information system. Findings of review: Management and service delivery reforms undertaken by the NIP include (1) strengthening links between immunization, health sector and international health planning; (2) development of immunization program multiyear and financial sustainability plans; (3) strengthening of national program decision making structures and processes; (4) widening of decentralized stakeholder participation in health planning; and (5) implementation of service level micro-planning. OUTCOMES: These management reforms have been associated with significant improvement in public health program performance and outcomes during this period (2003-2006). There has been an increase in vaccination coverage for children under the age of one year, over a five-year period (increase of 29% for fully immunized child at one year of age), with no significant differences in vaccination rates between urban and rural areas, and a sharp decrease in the incidence of vaccine preventable diseases. CONCLUSION: The NIP is now well positioned to take on additional challenges in coming years associated with expanding international partnerships, the continued development of civil society, further health system decentralization, and the requirement to further improve coverage in support of global and regional disease elimination goals. However, as costs continue to rise, planners in the future will need to emphasize the economic and public health benefits of immunization programs in order to sustain increasing levels of national and international investment.

The organization of the suprachiasmatic circadian pacemaker of the rat and its regulation by neurotransmitters and modulators.

The long-term goal of our research is to understand how cells of the suprachiasmatic nucleus (SCN) are organized to form a 24-hr biological clock, and what roles specific neurotransmitters and modulators play in timekeeping and resetting processes. We have been addressing these questions by assessing the pattern of spontaneous neuronal activity, using extracellular and whole-cell patch recording techniques in long-lived SCN brain slices from rats. We have observed that a robust pacemaker persists in the ventrolateral region of microdissected SCN, and have begun to define the electrophysiological properties of neurons in this region. Furthermore, we are investigating changing sensitivities of the SCN to resetting by exogenous neurotransmitters, such as glutamate, serotonin, and neuropeptide Y, across the circadian cycle. Our findings emphasize the complexity of organization and control of mammalian circadian timing.

Melatonin action and signal transduction in the rat suprachiasmatic circadian clock: activation of protein kinase C at dusk and dawn.

Nocturnal synthesis of the pineal hormone melatonin (MEL) is regulated by the circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus. We examined the hypothesis that MEL can feed back to regulate the SCN using a brain slice preparation from rat. We monitored the SCN ensemble firing rate and found that MEL advanced the time of peak firing rate by more than 3 h at restricted circadian times (CTs) near subjective dusk [CT 10-14 (10-14 h after lights on)] and dawn (CT 23-0) on days 2 and 3 after treatment. The effect of MEL at CT 10 was blocked by pertussis toxin. The protein kinase C (PKC) activator, 12-O-tetradecanoylphorbol 13-acetate, reset the SCN firing rate rhythm with a profile of temporal sensitivity congruent with that of MEL. Two specific PKC inhibitors, calphostin C and chelerythrine chloride, independently blocked MEL-induced phase advances at each sensitive period. Furthermore, MEL administration increased PKC phosphotransferase activity transiently to 200% at CT 10 and CT 23, but not at CT 6. These data demonstrate that 1) MEL can directly modulate the circadian timing of the SCN within two windows of sensitivity corresponding to dusk and dawn; and 2) MEL alters SCN cellular function via a pertussis toxin-sensitive G protein pathway that activates PKC.

Non-24-hour sleep-wake syndrome in a sighted man: circadian rhythm studies and efficacy of melatonin treatment.

The case of a 41-year-old sighted man with non-24-hour sleep-wake syndrome is presented. A 7-week baseline assessment confirmed that the patient expressed endogenous melatonin and sleep-wake rhythms with a period of 25.1 hours. We sought to investigate the underlying pathology and to entrain the patient to a normal sleep-wake schedule. No deficiency in melatonin synthesis was found. Furthermore, normal coupling between the melatonin and sleep propensity rhythms was documented using an "ultrashort" sleep-wake protocol. Environmental light exposure was monitored for 41 days, and the circadian timing was calculated. Sensitivity to photic input was determined with light-induced melatonin-suppression tests. Three intensities (500, 1,000, and 2,500 lux) were examined during three separate trials. The 2,500-lux trial resulted in 78% suppression, but the lesser intensity exposures were without substantial effect. Thus, the patient appeared to be subsensitive to bright light. A 4-week trial of daily melatonin administration (0.5 mg at 2100 hours) stabilized the endogenous melatonin and sleep rhythms to a period of 24.1 hours, albeit at a somewhat delayed phase. A 14-month follow-up interview revealed that the patient continued to take melatonin daily, and his sleep-wake schedule was stable to a near 24-hour schedule.

Cardiac autonomic dysfunction in survivors of acute lymphoblastic leukemia in childhood.

The purpose of this study was to investigate autonomic regulation of neurocardiac function in survivors of acute lymphoblastic leukemia (ALL) in childhood, through power spectral and time domain analyses of the heart rate variability signal. Studies were conducted on 34 unselected patients and 34 age matched controls. Patients were in remission, off therapy for at least 20 months and from high risk (HR, n=21) and standard risk (SR, n=13) groups as described by Dana-Farber Cancer Institute protocols 87-01 and 91-01. Twenty-nine patients had received cranial irradiation, 7 on a hyperfractionated schedule. Power spectral analysis of the heart rate (PS/HRV) was performed on 30 min heart rate time series and time domain statistics were computed from 24 h Holter recordings. Left ventricular function was assessed by measuring ejection and shortening fractions on echocardiography. All such measures were normal. Analysis of PS/HRV revealed that the supine low frequency: high frequency (LF:HF) area ratio was elevated in patients compared to controls. Changes in the LF and HF power on standing were attenuated in the patients compared to controls. Circadian analysis revealed a depressed diurnal rhythm of heart rate in the patients. Those from the SR group showed greater reduction of the LF power response to orthostatic stress and a reduced circadian rhythm of the heart rate compared to those with HR ALL. Patients from the HR group showed reductions in both HF and LF power responses to orthostasis compared to controls. Elevated supine LF power and depressed circadian variation in the HF power band were evident only in female subjects. Patients who received standard cranial irradiation had higher LF:HF area ratio and diminished LF and HF power responses to orthostatic stress than did subjects in the hyperfractionated group. These findings suggest that the autonomic nervous regulation of the heart is compromised in patients treated for ALL in childhood even when resting echocardiographic measures provide no evidence of cardiac decompensation. The extent of neurocardiac dysfunction is influenced by risk status, gender and schedule of cranial irradiation.

Expression of mt(1) melatonin receptor subtype mRNA in the entrained rat suprachiasmatic nucleus: a quantitative RT-PCR study across the diurnal cycle.

Melatonin acts on specific receptors in the suprachiasmatic nuclei (SCN) to phase-dependently regulate the phase of the circadian clock. How the gating of melatonin's effect is restricted to particular times of day is not known, but may be related to temporal differences in receptor availability. In the present study, we used a competitive reverse transcription-polymerase chain reaction (RT-PCR) method to determine if the expression of mt(1) melatonin receptor subtype mRNA in rat SCN varied across the 12:12 light-dark (LD) cycle. Measurement of core body temperature using radiotelemetry confirmed that the male Wistar rats used exhibited a robust diurnal rhythm. mt(1) receptor mRNA was readily detected in reduced SCN slices at all times of day. However, there was no significant variation in the amount of mt(1) mRNA with time of day. Expression of MT(2) melatonin receptor subtype mRNA in reduced SCN slices was confirmed by nested PCR. These results indicate that changes in the level of mt(1) mRNA do not underlie the diurnal and/or circadian variation in the response of the SCN circadian clock to the phase-resetting effects of melatonin.

The Giardia genome project database.

The Giardia genome project database provides an online resource for Giardia lamblia (WB strain, clone C6) genome sequence information. The database includes edited single-pass reads, the results of BLASTX searches, and details of progress towards sequencing the entire 12 million-bp Giardia genome. Pre-sorted BLASTX results can be retrieved based on keyword searches and BLAST searches of the high throughput Giardia data can be initiated from the web site or through NCBI. Descriptions of the genomic DNA libraries, project protocols and summary statistics are also available. Although the Giardia genome project is ongoing, new sequences are made available on a bi-monthly basis to ensure that researchers have access to information that may assist them in the search for genes and their biological function. The current URL of the Giardia genome project database is www.mbl.edu/Giardia.

Circadian actions of melatonin at the suprachiasmatic nucleus.

The biological clock in the suprachiasmatic nucleus (SCN) of the hypothalamus plays a well-defined role in regulating melatonin production by the pineal. Emerging evidence indicates that melatonin itself can feed back upon the SCN and thereby influence circadian functions. Melatonin administration has been shown to entrain activity rhythms in rodents and humans. Melatonin binds specifically within the SCN and alters SCN physiology by both acute and clock-resetting mechanisms. The circadian clock in the SCN appears to temporally restrict its own sensitivity to melatonin, such that physiological sensitivity is greatest in the subjective dusk period.

Melatonin directly resets the rat suprachiasmatic circadian clock in vitro.

The environmental photoperiod regulates the synthesis of melatonin by the pineal gland, which in turn induces daily and seasonal adjustments in behavioral and physiological state. The mechanisms by which melatonin mediates these effects are not known, but accumulating data suggest that melatonin modulates a circadian biological clock, either directly or indirectly via neural inputs. The hypothesis that melatonin acts directly at the level of the suprachiasmatic nucleus (SCN), a central mammalian circadian pacemaker, was tested in a rat brain slice preparation maintained in vitro for 2-3 days. Exposure of the SCN to melatonin for 1 h late in the subjective day or early subjective night induced a significant advance in the SCN electrical activity rhythm; at other times melatonin was without apparent effect. These results demonstrate that melatonin can directly reset this circadian clock during the period surrounding the day-night transition.

Resistance of uropathogens in symptomatic urinary tract infections in León, Nicaragua.

Management of urinary tract infections (UTI) in Central America and especially Nicaragua, is complicated by the lack of knowledge about the antibiotic resistance of uropathogens. We conducted a prevalence study to gain more insight into the aetiology, bacterial resistance and risk factors for symptomatic UTI in the region of León, Nicaragua. In 2002, all consecutive patients with UTI symptoms and pyuria >/=10 WBC/hpf were admitted to the study. Positive cultures from midstream urine specimens were defined as >/=10(5) cfu/ml of a single uropathogen. Susceptibility tests were performed with disc diffusion tests using the Kirby-Bauer method and broth microdilution using National Committee for Clinical Laboratory Standards criteria both in León and a reference laboratory in Utrecht. A positive culture was present in 62 of 208 study subjects (30%). Escherichia coli (56%), Klebsiella spp. (18%) and Enterobacter spp. (11%) were the most frequent pathogens isolated. Presence of cystocele, incontinence and increasing age were risk factors for bacterial UTI. E. coli was least resistant to ceftriaxone, amikacin and nitrofurantoin (>90% susceptible). We observed high resistance rates in E. coli to amoxicillin (82%, MIC(90) 128 mg/l), trimethoprim-sulphamethoxazole (TMP-SMX) (64%, MIC(90) 32 mg/l), cephalothin (58%, MIC(90), 32 mg/l), ciprofloxacin (30%; MIC(90), 32 mg/l), amoxicillin/clavulanate (21%, MIC(90) 8 mg/l) and gentamicin (12%, MIC(90) 2 mg/l). Our results suggests that community acquired uropathogens in Nicaragua are highly resistant to many antimicrobial agents. The use of amoxicillin, trimethoprim-sulphamethoxazole and cephalothin against uropathogens needs to be reconsidered. High quinolone resistance rates among E. coli in Nicaragua gives cause for great concern.

Human micronucleus counts are correlated with age, smoking, and cesium-137 dose in the Goiânia (Brazil) radiological accident.

A random sample of 276 people representing control, direct exposure, and probable indirect exposure in the Goiânia, Brazil radiological accident was examined using micronuclei as indicators of cytogenetic damage. The Goiânia subjects were analyzed for interactions of age, lifestyle, and ionizing radiation dose. Increases in micronucleus frequencies were most strongly correlated with the dose of ionizing radiation, but age, alcohol consumption, and smoking habits also affected micronucleus frequencies. Despite these additional influences, micronucleus frequencies can be useful as biological dosimeters.

Reliability assessment of soluble c-erbB-2 concentrations in the saliva of healthy women and men.

BACKGROUND: The protein c-erb B-2, also known as Her2/neu, is a prognostic breast cancer marker assayed in tissue biopsy specimens from women diagnosed with malignant tumors. Current studies suggest that soluble fragments of the c-erb B-2 oncogene may be released from the cell surface and become detectable in patients with a carcinoma of the breast. Consequently, the purpose of this study is to assay soluble c-erb B-2 protein in the saliva of healthy men and women to determine the reliability of the assay. METHODS: To determine the diagnostic utility of this oncogene, we assayed the soluble form of the c-erb B-2 protein in the saliva with an enzyme-linked immunosorbent assay. The study population consisted of 10 healthy women and 9 healthy men who were serially sampled for saliva 3 times a day for a 5-day period. Saliva was collected from each subject at 9 AM, 4 PM, and 9 PM during the 5-day period. RESULTS: We found the presence of c-erb B-2 protein in the saliva of both groups of subjects. The salivary levels of c-erb B-2 were not significantly different when compared for gender differences. Likewise, the results suggest that sampling during various times of the day for salivary c-erb B-2 levels has no effect on marker concentration. Reliability analyses showed that supervised salivary collections were more reliable than unsupervised collections. CONCLUSIONS: The results of this pilot study suggest that the assay for salivary c-erb B-2 protein is reliable and might have potential use in the initial detection and follow-up screening for the recurrence of breast cancer in both men and women.

Thermoregulation in sick foals aged less than one week.

Metabolic rate, rectal temperature Tr and respiratory quotient (RQ) were determined in 16 sick foals, aged 0-182 h. The foals were categorized into three groups: premature, dysmature or those suffering from neonatal maladjustment syndrome. The mean metabolic rate of the premature foals was 71 watts per unit area of body surface (W m(-2)), significantly lower than that of the other two groups. The overall mean metabolic rate for the sick foals was 82 W m(-2), about 25% below that of healthy foals of similar age. Air temperature (Ta) was 9.5-26.3 degrees C, and several foals shivered despite the provision of additional 'warmth' and insulation. Values of Tr were below 38 degrees C until after 4 h postpartum. Thereafter, Tr averaged 38.1 degrees C but fluctuated widely. The RQ (mean value 0.83) was not correlated with Ta. The lower critical temperature for the sick foals was estimated at 24 degrees C, on average. Methods to prevent excessive heat loss from sick foals are suggested.