Morphological and molecular characterization of Ptychodiscus noctiluca revealed the polyphyletic nature of the order Ptychodiscales (Dinophyceae).

The planktonic dinoflagellate Ptychodiscus noctiluca combined distinctive morphological features such as a disk-shaped anteroposteriorly compressed cell body and an apical carina, together with a flexible and tough cell covering, suggesting intermediate characteristics between thecate and naked dinoflagellates. Ptychodiscus noctiluca was examined by light, epifluorescence, and scanning electron microscopy from specimens collected in the Mediterranean Sea and the North and South Atlantic Ocean. Ptychodiscus noctiluca showed a straight apical groove that bisected the carina, a cell covering with a polygonal surface reticulum, nucleus without capsule, sulcal intrusion in the episome, sulcal ventral flange, and yellowish-green chloroplasts that are shared characters with Brachidinium/Karenia. The cell division was the typical binary fission of gymnodinioid dinoflagellates, although exceptionally in an oblique transversal axis. We examined the intraspecific variability during incubation experiments. In the fattened cells, termed as Ptychodiscus carinatus, chloroplasts transformed into dark granules, and the cell acquired the swollen and smaller stage, termed as P. inflatus. Ptychodiscus carinatus, P. inflatus, and Diplocystis antarctica are synonyms of P. noctiluca. Molecular phylogeny based on the SSU rDNA sequence revealed that Ptychodiscus branched within the short-branching dinokaryotic dinoflagellates as an independent lineage with affinity to Brachidinium/Karenia and Karlodinium/Takayama in a generally poorly resolved clade. Our results indicated that the order Ptychodiscales, established for unarmored dinoflagellates with a strongly developed pellicle, has artificially grouped thecate dinoflagellates (Kolkwitziella, Herdmania), naked dinoflagellates with thick cell covering (Balechina, Cucumeridinium) and other insufficiently known unarmored genera with typical cell coverings (Brachidinium, Ceratoperidinium).

Disparities in Cervical Cancer Characteristics and Survival Between White Hispanics and White Non-Hispanic Women.

BACKGROUND: Cervical cancer is the second most common cancer among women resulting in nearly 500,000 cases annually. Screening leads to better treatment and survival time. However, human papillomavirus (HPV) exposure, screening, and treatment vary among races and ethnicities in the United States. The purpose of this study is to examine disparities in characteristics of cervical cancer and survival of cases between White Hispanic (WH) and White non-Hispanic (WNH) women in the United States. METHODS: We used a stratified random sampling method to select cervical cancer patient records from nine states; a simple random sampling method to extract the demographic and disease characteristics data within states from the Surveillance Epidemiology and End Results (SEER) database. We used statistical probability distribution methods for discrete and continuous data. The chi-square test and independent samples t-test were used to evaluate statistically significant differences. Furthermore, the Cox Proportional Regression and the Kaplan-Meier survival estimators were used to compare WH and WNH population survival times in the United States. RESULTS: The samples of WNH and WH women included 4,000 cervical cancer cases from 1973-2009. There were statistically significant differences between ethnicities: marital status (p < 0.001); primary site of cancer (p < 0.001); lymph node involvement (p < 0.001); grading and differentiation (p < 0.0001); and tumor behavior (p < 0.001). The mean age of diagnosis for both groups showed no statistical differences. However, the mean survival time for WNH was 221.7 (standard deviation [SD] = 118.1) months and for WH was 190.3 (SD = 120.3), which differed significantly (p < 0.001). CONCLUSIONS: Clear disparities exist in risk factors, cervical cancer characteristics, and survival time between WH and WNH women.

A millennial view of cystic fibrosis.

Although only identified as a distinct disease in the 1930s, it was soon apparent that Cystic Fibrosis (CF) had been present, but unrecognised, in European populations for many years - perhaps even centuries [1] . Within a decade of the early descriptions, the autosomal recessive nature of this genetic disease had been clarified, and its clinical features had been expanded. Secondary nutritional deficiencies complicated the underlying condition: the first clear description of CF as "a new disease", which included a speculation about its genetic basis (because there were 2 pairs of sibs in the case series) was published as Vitamin A deficiency in children [2]. The diagnosis was most often made at autopsy. When it was suspected in life, the diagnostic tests used included duodenal intubation to obtain fluid which would show impaired tryptic digestion of the coating of X-Ray film in CF children, and measurement of vitamin A in the blood. Some nutritional improvement could be expected with simple, rather inefficient pancreatic enzyme preparations, but it was not until mid-century that antibiotics began to treat pulmonary infections effectively. As a young doctor in the 1950s I soon became aware that the median age at death for affected children was about one year, and most died before reaching school age. .

MCJ/DnaJC15, an endogenous mitochondrial repressor of the respiratory chain that controls metabolic alterations.

Mitochondria are the main engine that generates ATP through oxidative phosphorylation within the respiratory chain. Mitochondrial respiration is regulated according to the metabolic needs of cells and can be modulated in response to metabolic changes. Little is known about the mechanisms that regulate this process. Here, we identify MCJ/DnaJC15 as a distinct cochaperone that localizes at the mitochondrial inner membrane, where it interacts preferentially with complex I of the electron transfer chain. We show that MCJ impairs the formation of supercomplexes and functions as a negative regulator of the respiratory chain. The loss of MCJ leads to increased complex I activity, mitochondrial membrane potential, and ATP production. Although MCJ is dispensable for mitochondrial function under normal physiological conditions, MCJ deficiency affects the pathophysiology resulting from metabolic alterations. Thus, enhanced mitochondrial respiration in the absence of MCJ prevents the pathological accumulation of lipids in the liver in response to both fasting and a high-cholesterol diet. Impaired expression or loss of MCJ expression may therefore result in a "rapid" metabolism that mitigates the consequences of metabolic disorders.

Draft consensus guidelines for diagnosis and treatment of Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by pancreatic exocrine insufficiency and bone marrow failure, often associated with neurodevelopmental and skeletal abnormalities. Mutations in the SBDS gene have been shown to cause SDS. The purpose of this document is to provide draft guidelines for diagnosis, evaluation of organ and system abnormalities, and treatment of hematologic, pancreatic, dietary, dental, skeletal, and neurodevelopmental complications. New recommendations regarding diagnosis and management are presented, reflecting advances in understanding the genetic basis and clinical manifestations of the disease based on the consensus of experienced clinicians from Canada, Europe, and the United States. Whenever possible, evidence-based conclusions are made, but as with other rare diseases, the data on SDS are often anecdotal. The authors welcome comments from readers.

Simultaneous composition and thickness measurement of paper using terahertz time-domain spectroscopy.

We present a noncontact method for quantitative composition and thickness monitoring of flat sheet products using terahertz time-domain spectroscopy. We apply the method to obtain simultaneous measurement of thickness and moisture content of paper sheets. The paper is modeled as an effective medium of water mixed with fibers, and model parameters are estimated from fits to the measured transmission amplitude. We demonstrate the method on two different paper samples and obtain uncertainties that are comparable with existing sensor technology. Monte Carlo simulations indicate that these uncertainties can be reduced further by at least an order of magnitude.

An international/multicentre report on patients with cystic fibrosis (CF) over the age of 40 years.

BACKGROUND: The lifespan of patients with cystic fibrosis (CF) is increasing significantly. The objective of this international pilot study was to study the characteristics of these long-term survivors. METHODS: Four centres with large CF clinics from London (UK), Minneapolis (USA), Toronto (Canada) and Verona (Italy) identified 366 patients who had survived 40 years and longer. RESULTS: At all centres males survived longer than females. There were more pancreatic sufficient patients in Verona (60%) and Toronto (40%) than in London (16%) and Minneapolis (21%). The percentage of DeltaF508 homozygous patients varied between 47% in London and 45% in Minneapolis to only 26% in Toronto and 9% in Verona. Average FEV(1) and BMI values of the surviving population appeared to stabilise after 40 years of age. FEV(1) was on average 12% higher in patients who were pancreatic sufficient (p > 0.0001). There was no difference in survival between the centres. The overall median survival after the age of 40 was 13 years. The estimated annual death rate was approximately 3.4% from the age of 40-60 years. CONCLUSIONS: Significant numbers of patients are now surviving to 40 years or more, and it is hoped that an in-depth study of these patients may identify the factors contributing to longer survival.

Genetic testing and disability insurance: an alternative opinion.

As members of the Working Group on Genetic Testing in Disability Insurance, the authors of this alternative opinion describe their areas of disagreement with some of the conclusions in the paper written by Susan M. Wolf and Jeffrey P. Kahn.

Predictive medical information and underwriting.

Medical underwriting involves the application of actuarial science by analyzing medical information to predict the future risk of a claim. The objective is that individuals with like risk are treated in a like manner so that the premium paid is proportional to the risk of future claim.

Accumulation of NFAT mediates IL-2 expression in memory, but not naïve, CD4+ T cells.

In contrast to naïve CD4+ T cells, memory CD4+ T cells rapidly express high levels of effector cytokines in response to antigen stimulation. The molecular mechanism for this specific behavior is not well understood. The nuclear factor of activated T cells (NFAT) family of transcription factors plays an important role in the transcription of many cytokine genes. Here we show that memory CD4+ T cells rapidly induce NFAT-mediated transcription upon T cell receptor ligation whereas NFAT activation in naïve CD4+ T cells requires longer periods of stimulation. The difference in kinetics correlates with the low levels of NFATc1 and NFATc2 proteins present in naïve CD4+ T cells and their high levels in memory CD4+ T cells. Accordingly, IL-2 expression requires NFAT activation only in memory CD4+ T cells whereas it is NFAT-independent in naïve CD4+ T cells. Thus, the accumulation of NFATc1 and NFATc2 in memory CD4+ T cells represents a previously uncharacterized regulatory mechanism for the induction of early gene expression after antigen stimulation.

Cystic fibrosis: nutritional consequences and management.

Life expectancy for patients with Cystic Fibrosis (CF) has steadily improved during the last three decades, and death in childhood is now uncommon. Nutrition is a critical component of the management of CF, and nutritional status is directly associated with both pulmonary status and survival. Expert dietetic care is necessary, and attention must be given to ensuring an adequate energy intake in the face of demands which may be increased by inadequately controlled malabsorption, chronic broncho-pulmonary colonisation by bacteria and fungi, exacerbations of acute lung infection, impaired lung function, and the need for rehabilitation, repair and growth. Pancreatic enzyme replacement therapy (PERT) is needed by up to 90% of CF patients in Northern Europe, where the 'severe' mutation deltaF508 predominates, but a smaller proportion in Mediterranean countries and elsewhere, because pancreatic insufficiency is one of few features of CF which correlate with genotype. Complications of CF including liver disease and CF-related diabetes pose further challenges. In addition, deficiency of specific nutrients including fat soluble vitamins (particularly A, E and K) essential fatty acids and occasionally minerals occur for a variety of reasons. Osteopenia is common and poorly understood. Liver disease increases the likelihood of vitamin D deficiency. Glucose intolerance and diabetes affect at least 25% of CF adults, and the diabetes differs from both types 1 and 2 diabetes mellitus, but it inversely correlates with prognosis. Management consists of anticipating problems and addressing them vigorously as soon as they appear. Supplements of vitamins are routinely given. Energy supplements can be oral, enteral or, rarely, parenteral. All supplements, including PERT, are adjusted to individual needs.