Redefining the effect of salt on thermophilic starter cell viability, culturability and metabolic activity in cheese.

This study investigated the differential effect of salt concentration in the outside and inside layers of brine salted cheeses on viability, culturability and enzyme activity of starter bacteria. The high-salt environment of the outside layer caused a sharp decrease in L. helveticus viability as measured by traditional plate counts. Remarkably, this was associated with lower release of intracellular enzymes (LDH), reduced levels of proteolysis and larger membrane integrity as measured by flow cytometry (FC) following classical Live/Dead staining. FC analysis of light scattering properties highlighted a significant reduction in size and granularity of the microbiota located in the cheese surface, suggestive of cell shrinkage and condensation of internal macromolecules probably due to hyperosmotic stress. The microbiota of the cheese surface were found to experience greater oxidative stress, as measured by FC analysis of the total levels of reactive oxygen species, compared to that of the interior layer. These results lead us to postulate that the physiology and health status of the microbiota were significantly different in the outer and inner layers of the cheese. The hyperosmotic environment of the outer layer resulted in reduced cell lysis, as measurable by assays based upon membrane integrity, but rather triggered cell death via mechanisms involving cell shrinkage and ROS-mediated damage of vital intracellular components. This study challenges the current thinking on how salt controls microbial activity in ripening cheese, especially in cheeses which are brine salted as local variations in biochemical ripening indices can differ significantly from the outside to the inside of a ripening cheese.

Equivalence of cell survival data for radiation dose and thermal dose in ablative treatments: analysis applied to essential tremor thalamotomy by focused ultrasound and gamma knife.

Thermal dose and absorbed radiation dose have historically been difficult to compare because different biological mechanisms are at work. Thermal dose denatures proteins and the radiation dose causes DNA damage in order to achieve ablation. The purpose of this paper is to use the proportion of cell survival as a potential common unit by which to measure the biological effect of each procedure. Survival curves for both thermal and radiation doses have been extracted from previously published data for three different cell types. Fits of these curves were used to convert both thermal and radiation dose into the same quantified biological effect: fraction of surviving cells. They have also been used to generate and compare survival profiles from the only indication for which clinical data are available for both focused ultrasound (FUS) thermal ablation and radiation ablation: essential tremor thalamotomy. All cell types could be fitted with coefficients of determination greater than 0.992. As an illustration, survival profiles of clinical thalamotomies performed by radiosurgery and FUS are plotted on a same graph for the same metric: fraction of surviving cells. FUS and Gamma Knife have the potential to be used in combination to deliver a more effective treatment (for example, FUS may be used to debulk the main tumour mass, and radiation to treat the surrounding tumour bed). In this case, a model which compares thermal and radiation treatments is valuable in order to adjust the dose between the two.

Treatment intensification for patients with type 2 diabetes and poor glycaemic control.

AIMS: To identify the time to and patient characteristics associated with treatment intensification in patients with type 2 diabetes (T2D) and poor glycaemic control. METHODS: Using a large US insurance claims database, we conducted a retrospective cohort study among adult patients with T2D and glycated haemoglobin (HbA1c) ≥8% (index date) after ≥3 months of therapy including metformin. Patients were required to have continuous enrolment for at least 12 months before (baseline) and after index date, and no injectable antidiabetes medications. We defined treatment intensification as prescription fill for injectable or additional oral antidiabetic drugs (OADs). Cox modelling was performed to identify factors associated with time to treatment intensification. RESULTS: For the 11 525 patients meeting the inclusion criteria, the mean age at index date was 57 years, 40% were female and the mean index HbA1c was 9.1%. Overall, 37% of patients had their treatment intensified <6 months after, 11% had their treatment intensified 6-12 months after, and 52% did not have their treatment intensified <12 months after the index date. A higher index HbA1c was associated with early intensification [hazard ratio (HR) 1.18 for HbA1c ≥9 to <10% and HR 1.41 for HbA1c ≥10% compared with HbA1c ≥8 to <9%; p < 0.0001), and later line of therapy was associated with late intensification (HR 0.78 for metformin with one OAD and HR 0.68 for metformin with ≥2 OADs compared with metformin monotherapy; p < 0.0001). CONCLUSIONS: Fewer than half of patients with T2D and treatment failure received intensification within 12 months in a real-world US population. Factors associated with treatment inertia can be used to target clinical care for these patients.

Reduced-fat Cheddar and Swiss-type cheeses harboring exopolysaccharide-producing probiotic Lactobacillus mucosae DPC 6426.

Exopolysaccharide-producing Lactobacillus mucosae DPC 6426 was previously shown to have promising hypocholesterolemic activity in the atherosclerosis-prone apolipoprotein-E-deficient (apoE(-/-)) murine model. The aim of this study was to investigate the suitability of reduced-fat Cheddar and Swiss-type cheeses as functional (carrier) foods for delivery of this probiotic strain. All cheeses were manufactured at pilot-scale (500-L vats) in triplicate, with standard commercially available starters: for Cheddar, Lactococcus lactis; and for Swiss-type cheese, Streptococcus thermophilus, Lactobacillus helveticus, and Propionibacterium freudenreichii. Lactobacillus mucosae DPC 6426 was used as an adjunct culture during cheese manufacture, at a level of ~10(6) cfu·mL(-1) cheese milk (subsequently present in the cheese curd at>10(7) cfu·g(-1)). The adjunct strain remained viable at >5×10(7) cfu·g(-1) in both Swiss-type and Cheddar cheeses following ripening for 6 mo. Sensory analysis revealed that the presence of the adjunct culture imparted a more appealing appearance in Swiss-type cheese, but had no significant effect on the sensory characteristics of Cheddar cheeses. Moreover, the adjunct culture had no significant effect on cheese composition, proteolysis, pH, or instrumentally quantified textural characteristics of Cheddar cheeses. These data indicate that low-fat Swiss-type and Cheddar cheeses represent suitable food matrices for the delivery of the hypocholesterolemic Lactobacillus mucosae DPC 6426 in an industrial setting.

Response and remission rates with adjunctive aripiprazole in patients with major depressive disorder who exhibit minimal or no improvement on antidepressant monotherapy.

BACKGROUND: The efficacy of adjunctive aripiprazole in patients with major depressive disorder (MDD) with no improvement after 8 weeks of prior antidepressant monotherapy has not been evaluated. METHODS: A post hoc analysis of three similarly designed, randomised, double-blind, placebo-controlled, phase III studies was conducted investigating the efficacy and safety of aripiprazole adjunctive to standard antidepressant treatment (ADT) in MDD patients with a prior inadequate response to one to three ADTs. Minimal improvement to antidepressant monotherapy was defined as a Clinical Global Impressions - Improvement (CGI-I) score of 3 and non-improvement as a CGI-I of 4 at weeks 6 and 8 of antidepressant monotherapy. RESULTS: The end-point response rate for ADT minimal improvers receiving adjunctive aripiprazole was 38.8% vs. 26.6% for adjunctive placebo (p < 0.05; number needed to treat [NNT] = 9 [95% confidence interval: 4.8-27.7]), and for ADT non-improvers receiving adjunctive aripiprazole was 24.0% vs. 10.3% for adjunctive placebo (p < 0.05; NNT = 8 [95% confidence interval: 4.4-21.5]). ADT minimal improvers and non-improvers demonstrated significant improvements in response vs. ADT alone as early as after 1 and 2 weeks of adjunctive treatment, respectively. The end-point remission rate for ADT minimal improvers receiving adjunctive aripiprazole was 34.2% vs. 21.0% for adjunctive placebo (p < 0.05; NNT = 8), and for ADT non-improvers receiving adjunctive aripiprazole was 16.0% vs. 5.9% for adjunctive placebo (p < 0.05; NNT = 10). The most common adverse events for ADT minimal improvers and non-improvers receiving adjunctive aripiprazole were akathisia, restlessness and insomnia. CONCLUSION: Patients with minimal or no improvement after 8 weeks of antidepressant monotherapy significantly benefited from adjunctive aripiprazole treatment, supporting the efficacy of this treatment for MDD patients with all levels of response to ADT.

Kinetic theory of plasma sheaths surrounding electron-emitting surfaces.

A one-dimensional kinetic theory of sheaths surrounding planar, electron-emitting surfaces is presented which accounts for plasma electrons lost to the surface and the temperature of the emitted electrons. It is shown that ratio of plasma electron temperature to emitted electron temperature significantly affects the sheath potential when the plasma electron temperature is within an order of magnitude of the emitted electron temperature. The sheath potential goes to zero as the plasma electron temperature equals the emitted electron temperature, which can occur in the afterglow of an rf plasma and some low-temperature plasma sources. These results were validated by particle in cell simulations. The theory was tested by making measurements of the sheath surrounding a thermionically emitting cathode in the afterglow of an rf plasma. The measured sheath potential shrunk to zero as the plasma electron temperature cooled to the emitted electron temperature, as predicted by the theory.

Three cases of impulse control disorder in Parkinson's disease patients receiving dopamine replacement therapy.

Impulse control disorders (ICDs) are a known side effect of dopamine replacement therapy in patients with Parkinson's disease (PD). They can have devastating consequences for patients and their families.

Suicidal ideation and depressive symptoms in an urban post-partum maternity setting: a retrospective cohort study.

BACKGROUND: Fifteen percent of women worldwide experience depression in the perinatal period. Suicide is now one of the leading causes of maternal mortality in developed countries. Internationally, many healthcare systems screen post-natal women for depressive symptoms and suicidal ideation to facilitate early assessment and intervention. To our knowledge, no Irish data exists on the prevalence of suicidal ideation in this cohort. AIMS: To evaluate the prevalence of suicidal ideation and depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS) in post-natal women attending a large Dublin maternity hospital. METHODS: A retrospective cohort study was conducted. Women were randomly selected by delivery date over a 6 month period. Demographic and medical information was collected from their booking visit and discharge summary data. EPDS results at discharge post-partum were examined. RESULTS: Data was collected on 643 women. Post-partum, 19 women (3.4%) had experienced suicidal ideation in the previous 7 days. Just over half of these women also had high EPDS scores (>12). Overall, 29 women (5.2%) screened positive for depression (EPDS score > 12). CONCLUSIONS: The rate of suicidal ideation is in line with the published international data and emphasises the need for all clinicians to inquire about such thoughts. Training of midwifery and obstetric staff is required. Maternity units should have a policy on the management of suicidal ideation and risk. The prevalence of depressive symptoms post-partum was comparatively low in our study. This could suggest that antenatal screening and early intervention, which are integral parts of the perinatal mental health service, are effective. However, due to limitations of the study, it could also reflect an under-representation of depressive symptom burden in this cohort.

Gamma knife capsulotomy for intractable OCD: Neuroimage analysis of lesion size, location, and clinical response.

Obsessive-compulsive disorder (OCD) affects 2-3% of the population. One-third of patients are poorly responsive to conventional therapies, and for a subgroup, gamma knife capsulotomy (GKC) is an option. We examined lesion characteristics in patients previously treated with GKC through well-established programs in Providence, RI (Butler Hospital/Rhode Island Hospital/Alpert Medical School of Brown University) and São Paulo, Brazil (University of São Paolo). Lesions were traced on T1 images from 26 patients who had received GKC targeting the ventral half of the anterior limb of the internal capsule (ALIC), and the masks were transformed into MNI space. Voxel-wise lesion-symptom mapping was performed to assess the influence of lesion location on Y-BOCS ratings. General linear models were built to compare the relationship between lesion size/location along different axes of the ALIC and above or below-average change in Y-BOCS ratings. Sixty-nine percent of this sample were full responders (≥35% improvement in OCD). Lesion occurrence anywhere within the targeted region was associated with clinical improvement, but modeling results demonstrated that lesions occurring posteriorly (closer to the anterior commissure) and dorsally (closer to the mid-ALIC) were associated with the greatest Y-BOCS reduction. No association was found between Y-BOCS reduction and overall lesion volume. GKC remains an effective treatment for refractory OCD. Our data suggest that continuing to target the bottom half of the ALIC in the coronal plane is likely to provide the dorsal-ventral height required to achieve optimal outcomes, as it will cover the white matter pathways relevant to change. Further analysis of individual variability will be essential for improving targeting and clinical outcomes, and potentially further reducing the lesion size necessary for beneficial outcomes.

Grieving after early pregnancy loss--a common reality.

A miscarriage can be very traumatic for a couple and their immediate family. The aim of this study was to assess, using the Perinatal Grief Scale (PGS), whether the type of early pregnancy loss influences the severity of grief and whether the presence of living children influences the severity of grief. Over a period of 6 months in 2008, seventy five patients were recruited for the study, of which 7 (9.3%) had molar pregnancies, 20 (26.7%) had ectopic pregnancies, 43 (573%) had a miscarriage and 5 (6.7%) had recurrent miscarriages. In this study there was no significant difference in severity of grief, between women that had a miscarriage and ectopic pregnancy (p = 0.14) or, between women that had a miscarriage and a molar pregnancy (p = 0.85). Women who had experienced a ectopic pregnancy did not have a higher grief intensity than the women that had a molar pregnancy (p = 0.75). However, for women with a child, the grief intensity significantly increases with the number of miscarriages (p = 0.015). Women with no children with an ectopic pregnancy grieve significantly more than those with a child (p = 0.019). An appointment for the 'Miscarriage Clinic' should be offered to all of these women but special attention should be paid to those in the categories most at risk

Membrane transport by murine lymphocytes. I. A rapid sampling technique as applied to the adenosine and thymidine systems.

We have developed a rapid sampling technique for animal cells in suspension for the purpose of measuring membrane transport in lymphocytes. The method involves rapid centrifugation of cells through a layer of silicone oil into perchloric acid after incubation periods as short as 4 s. Using this method we have described the uptake of thymidine and the uptake and transport systems of adenosine by murine bulk nonadherent spleen cells. The two uptake systems are markedly different. Adenosine was shown to be taken up by classical carrier-mediated diffusion, while thymidine was not. In addition we have explored the metabolism of the two nucleosides under the conditions we employed for measuring transport or uptake; Both nucleosides are phosphorylated extensively. We also investigated the uptake and metabolism of thymidine over a 2-h interval the standard time used to measure DNA synthesis in lymphocytes. Unless cells were separated from medium by centrifugation through oil before TCA addition, the TCA precipitable counts exceeded the total radioactive uptake. Hence the standard method for measuring thymidine utilization yields estimates under these conditions which can be as much as 100% too high.

The Saccharomyces SUN gene, UTH1, is involved in cell wall biogenesis.

Deletion of the Saccharomyces gene, UTH1, a founding member of the SUN family of fungal genes, has pleiotropic effects. Several phenotypes of Deltauth1 cells including their decreased levels of mitochondrial proteins, their impaired autophagic degradation of mitochondria, and their increased viability in the presence of mammalian BAX, a proapoptotic regulator localized to the mitochondria, have prompted others to propose that the Uth1p functions primarily at the mitochondria. In this report, we show that cells lacking UTH1 have more robust cell walls with higher levels of beta-d-glucan that allows them to grow in the presence of calcofluor white or sodium dodecyl sulfate, two reagents known to perturb the yeast cell wall. Moreover, these Deltauth1 cells are also significantly more resistant to spheroplast formation induced by zymolyase treatment than their wild-type counterparts. Surprisingly, our data suggest that several of the enhanced growth phenotypes of Deltauth1 cells, including their resistance to BAX-mediated toxicity, arise from a strengthened cell wall. Therefore, we propose that Uth1p's role at the cell wall and not at the mitochondria may better explain many of its effects on yeast physiology and programmed cell death.

Munchausen's syndrome--more common than we realize?

Munchausen's syndrome is a condition whereby a patient deliberately simulates symptoms of an illness in order to gain admission to hospital and gain the sick role. It is an uncommon condition and is possibly underdiagnosed. This case-series examines the cases of three patients with Munchausen's syndrome who presented to a Dublin hospital within a four-month period. Two of the presentations involved the feigning of psychiatric symptoms. It is important that clinicians not only in psychiatry, but in all medical specialities have an awareness of this disorder, so that unnecessary procedures and treatments may be avoided.

The general populations' understanding of first trimester miscarriage: a cross sectional survey.

OBJECTIVES: Miscarriage is a common, yet for many, devastating adverse pregnancy outcome. However, despite this the level of public knowledge on the topic is sub-optimal. We aimed to examine the general public's knowledge of miscarriage as well as their health information seeking behaviours associated with this topic. STUDY DESIGN: We commissioned a national cross-sectional telephone survey of adults in the Republic of Ireland. 967 members of the general public consented to participate to this anonymised telephone survey. Sampling procedures ensured proportionality as per national standards. We examined respondents' definitions of miscarriage, its incidence and clinical findings, as well as the information seeking behaviours of the general population surrounding miscarriage. RESULTS: 699 (72%) of respondents provided an estimate of miscarriage frequency, with 28% of respondents correctly estimating that miscarriage occurs in 21-30% of pregnancies, with 61% under-estimating the incidence. Men were three times more likely than women to under-estimate (aOR3.5; 95% CI 2.4-4.9), as were those without children (aOR 1.7; 95% CI 1.2-2.6), or those living in urban areas (aOR 1.6; 95%CI 1.0-2.4. One third of respondents (33%) believed that the risk of miscarriage was higher following only one miscarriage. While 83% of respondents knew someone who had experienced a miscarriage, just over one third had discussed the topic of miscarriage with a family member/friend. CONCLUSIONS: The general populations' knowledge of miscarriage, its incidence and associated factors is concerning, as are their health information seeking behaviours. Improving the level of knowledge of the general public could be achieved by adopting the topic into existing public health and education strategies. This will allow those experiencing miscarriage to frame their experience and expectations.

Hyaluronates: relation between molecular conformations.

The discovery that both potassium and sodium salts of hyaluronic acid can exist in a double-strand helical conformation that will convert to the already known single-strand helical structures illustrates the remarkable conformational versatility of this biopolymer. X-ray diffraction was used to monitor variations in molecular conformation as a function of several independent, controllable variables, such as relative humidity, temperature, and applied tension. A scheme is presented for the interrelation of a range of hyaluronate conformations.

Water-soluble derivatives of 1 -tetrahydrocannabinol.

Delta1-Tetrahydrocannabinol, which is resinous and insoluble in water and therefore difficult to study pharmacologically, can be converted to a watersoluble derivative without loss of its biological activity. This has been achieved by preparing esters bearing a nitrogen moiety with the use of carbodiimide as the condensing agent. The availability of such water-soluble derivatives will allow the evaluation of Delta1-tetrahydrocannabinol in self-administration studies in monkeys for its addiction liability potential in man. This technique of water solubilization is also applicable to other compounds of chemical and biological significance.

Blocks of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21.

Global patterns of human DNA sequence variation (haplotypes) defined by common single nucleotide polymorphisms (SNPs) have important implications for identifying disease associations and human traits. We have used high-density oligonucleotide arrays, in combination with somatic cell genetics, to identify a large fraction of all common human chromosome 21 SNPs and to directly observe the haplotype structure defined by these SNPs. This structure reveals blocks of limited haplotype diversity in which more than 80% of a global human sample can typically be characterized by only three common haplotypes.