Reversal of typical multidrug resistance by cyclosporin and its non-immunosuppressive analogue SDZ PSC 833 in Chinese hamster ovary cells expressing the mdr1 phenotype

Summary The new non-immunosuppressive cyclosporin derivative SDZ PSC 833 (PSC) is a potent agent used to overcome typical multidrug resistance (MDR) associated with overexpression of themdr1 gene encoding for a P-170 glycoprotein. In the present study, the efficacy of PSC as compared with cyclosporin was determined in Chinese hamster ovary cell lines exhibiting different levels of resistance to colchicine (0, 0.1, 0.2 and 10 μg/ml, respectively). Low concentrations of PSC (8.2nm) increased the cytotoxicity of colchicine in cell lines expressing low levels of drug resistance. The concentration resulting in 50% cell survival (LC50 value) found for colchicine alone or in combination with PSC in the CHO-A3 cell line that was resistant to 100 ng colchicine/ml decreased from >500 to 200 ng/ml at 8.2nm PSC and to 500 ng/ml for colchicine alone to 500 ng/ml for colchicine used in combination with 8.2nm PSC and to <100 ng/ml for colchicine combined with 82 or 820nm PSC. At a concentration of 82nm PSC, the maximal effect in MDR reversal was observed in the cell lines exhibiting moderate resistance. In the highly resistant cell line, PSC (820nm) also reversed colchicine resistance. In drug-accumulation experiments, we obtained a 4-fold increase in intracellular doxorubicin accumulation using 820nm PSC. A comparison of PSC with cyclosporin revealed that a cyclosporin concentration 20-fold that of PSC was required to obtain the same sensitising effect. On the basis of these data, it may be concluded that PSC is a most promising chemosensitiser

The protective value of trait mindfulness for mothers' anxiety during the perinatal period

Objectives:Anxiety is highly prevalent in the perinatal period and can have negative consequences for the mother and the child. Extensive research has been done on risk factors for anxiety during the perinatal period, but less is known about protective factors. The current study aims to determine the relative contribution of trait mindfulness as a protective factor for anxiety.Methods: A longitudinal study design was used, with four measurement points: 12, 22, and 32 weeks of pregnancy (T0, T1, and T2, respectively), and 6 weeks postpartum (T3). General anxiety was measured at T1, T2, and T3, pregnancy-specific distress was measured at T1 and T2, mindfulness facets (acting with awareness, non-reacting, and non-judging) and partner involvement were measured at T1, and other known risk factors for anxiety were measured at T0. Multilevel regression models were used for statistical analyses.Results:Mindfulness facets measured at T1 were negatively associated with anxiety at T1, T2, and T3, and pregnancy-specific distress at T1 and T2. Of the mindfulness facets, non-judging was shown to have the largest protective effect against anxiety and pregnancy-specific distress. Also compared to partner-involvement and known risk factors, non-judging showed the largest effect on anxiety and pregnancy-specific distress.Conclusions:For pregnant women who are at risk for developing or experiencing high levels of anxiety, it may be beneficial to participate in a mindfulness training with special attention for the attitudinal aspects of mindfulness.</p

Draft Whole-Genome Sequences of 11 Bacillus cereus Food Isolates

Bacillus cereus is a foodborne pathogen causing emetic and diarrheal-type syndromes. Here, we report the whole-genome sequences of 11 B. cereus food isolates.</p

High-Level Heat Resistance of Spores of Bacillus amyloliquefaciens and Bacillus licheniformis Results from the Presence of a spoVA Operon in a Tn1546 Transposon

Bacterial endospore formers can produce spores that are resistant to many food processing conditions, including heat. Some spores may survive heating processes aimed at production of commercially sterile foods. Recently, it was shown that a spoVA operon, designated spoVA(2mob), present on a Tn1546 transposon in Bacillus subtilis, leads to profoundly increased wet heat resistance of B. subtilis spores. Such Tn1546 transposon elements including the spoVA(2mob) operon were also found in several strains of Bacillus amyloliquefaciens and Bacillus licheniformis, and these strains were shown to produce spores with significantly higher resistances to wet heat than their counterparts lacking this transposon. In this study, the locations and compositions of Tn1546 transposons encompassing the spoVA(2mob) operons in B. amyloliquefaciens and B. licheniformis were analyzed. Introduction of these spoVA(2mob) operons into B. subtilis 168 (producing spores that are not highly heat resistant) rendered mutant 168 strains that produced high-level heat resistant spores, demonstrating that these elements in B. amyloliquefaciens and B. licheniformis are responsible for high level heat resistance of spores. Assessment of growth of the nine strains of each species between 5.2°C and 57.7°C showed some differences between strains, especially at lower temperatures, but all strains were able to grow at 57.7°C. Strains of B. amyloliquefaciens and B. licheniformis that contain the Tn1546 elements (and produce high-level heat resistant spores) grew at temperatures similar to those of their Tn1546-negative counterparts that produce low-level heat resistant spores. The findings presented in this study allow for detection of B. amyloliquefaciens and B. licheniformis strains that produce highly heat resistant spores in the food chain

Online mindfulness-based intervention for women with pregnancy distress:Design of a randomized controlled trial

Background:  Psychological distress during pregnancy is common: up to 20% of the childbearing women experience symptoms of depression and anxiety. Apart from the adverse effects on the woman herself, pregnancy distress can negatively affect pregnancy outcomes, infant health, postpartum mother-child interaction and child development. Therefore, the development of interventions that reduce pregnancy distress is very important. Mindfulness-based interventions (MBIs) show promising positive effects on pregnancy distress, but there is a need for randomized controlled trials with sufficient power. Trials on online MBIs, which are readily accessible and not expensive, also show positive effects on stress reduction in non-pregnant populations. Moreover, specific working mechanisms of MBIs remain unclear. The aim of the current study is to test the effectiveness of an online MBI in pregnant women with pregnancy distress, as well as exploring potential working mechanisms. Methods:  The current study is a randomized controlled trial with repeated measures. Consenting women with elevated levels of pregnancy distress will be randomized into an intervention group (MBI) or control group (care as usual) around 12 weeks of pregnancy, with an intended sample size of 103 women in each group. The primary outcome, pregnancy distress, will be assessed via questionnaires at baseline, halfway through the intervention and post intervention in both intervention and control group, and after 8 weeks follow-up in the intervention group. Secondary outcomes are mindfulness skills, rumination and self-compassion, which are also seen as potential working mechanisms, and will be assessed via questionnaires before intervention, halfway through the intervention, post intervention and after 8 weeks follow-up in the intervention group. Tertiary outcome variables are obstetric data and will be collected from the obstetric records for both intervention and control group. Analyses will be based on the intention-to-treat principle. Multilevel regression models for repeated measures (mixed models) will be used to evaluate changes in primary and secondary outcome variables. Tertiary outcomes will be compared between groups using independent t-tests and Chi Square analyses. Discussion:  The trial is expected to increase knowledge about the effectiveness of online MBIs during pregnancy in women with pregnancy distress and to evaluate potential working mechanisms.

A three-year study of brain atrophy after autologous hematopoietic stem cell transplantation in rapidly evolving secondary progressive multiple sclerosis

BACKGROUND AND PURPOSE: In multiple sclerosis (MS), autologous hematopoietic stem cell transplantation (AHSCT) induces a profound suppression of clinical activity and MR imaging-detectable inflammation, but it may be associated with a rapid brain volume loss in the months subsequent to treatment. The aim of this study was to assess how AHSCT affects medium-term evolution of brain atrophy in MS. MATERIALS AND METHODS: MR imaging scans of the brain from 14 patients with rapidly evolving secondary-progressive MS obtained 3 months before and every year after AHSCT for 3 years were analyzed. Baseline normalized brain volumes and longitudinal percentage of brain volume changes (PBVCs) were assessed using the Structural Image Evaluation of Normalized Atrophy software. RESULTS: The median decrease of brain volume was 1.92% over the first year after AHSCT and then declined to 1.35% at the second year and to 0.69% at the third year. The number of enhancing lesions seen on the pretreatment scans was significantly correlated with the PBVCs between baseline and month 12 (r = -0.62; P = .02); no correlation was found with the PBVCs measured over the second and third years. CONCLUSIONS: After AHSCT, the rate of brain tissue loss in patients with MS declines dramatically after the first 2 years. The initial rapid development of brain atrophy may be a late consequence of the pretransplant disease activity and/or a transient result of the intense immunoablative conditioning procedure

The COVID-19 outbreak increases maternal stress during pregnancy, but not the incidence of postpartum depression

The COVID-19 pandemic affects society and may especially have an impact on mental health of vulnerable groups, such as perinatal women. This prospective cohort study compared perinatal symptoms of depression and stress during and before the pandemic. Pregnancy-specific stress increased significantly in women during the pandemic. We found no increase in depressive symptoms during pregnancy nor an increase in incidence of postnatal depression during the pandemic. Clinicians should be aware of increased stress in pregnant women and offer adequate care

COVID-19-associated immune thrombocytopenia

Thrombocytopenia is a risk factor for increased morbidity and mortality in patients with the new severe acute respiratory syndrome corona virus, SARS-CoV-2 infection (COVID-19 infection).1 Thrombocytopenia in COVID-19 patients may be caused by disseminated intravascular coagulation (DIC), sepsis or drug-induced. Recently a single case report suggested immune thrombocytopenia (ITP) may be associated with COVID-19 infection.2 ITP is a rare autoimmune disease characterized by a platelet count < 100x109/L, leading to an increased bleeding risk.3 Several risk factors have been described for ITP including environmental (e.g. infection, malignancy and drugs) and genetic predisposition.4 We report here the first case series of three patients with ITP associated with COVID-19 infection

Mindfulness During Pregnancy and Parental Stress in Mothers Raising Toddlers

Objectives: Parental stress has been associated with adverse child outcomes and maternal functioning. Yet, maternal factors during pregnancy that can potentially protect against later parental stress, such as mindfulness, have not been studied. Therefore, we aimed to address the possible associations between prenatal mindfulness and levels of parental stress in mothers raising toddlers. Methods: Women in the current study (n = 165) were prospectively followed from pregnancy until 3 years after childbirth, as part of a longitudinal population based cohort (HAPPY study). At 22 weeks of pregnancy, women completed the Three Facet Mindfulness Questionnaire–Short Form (TFMQ-SF) to assess facets of mindfulness (acting with awareness, non-judging, and non-reacting). Women completed the Parenting Stress Questionnaire (PSQ) 3 years after childbirth, reporting on three components of parental stress: (1) parent-child relationship problems, (2) parenting problems, and (3) role restriction. Results: Results of multiple linear regression analyses showed that the acting with awareness facet of mindfulness during pregnancy was a significant predictor of fewer parent-child relationship problems and parenting problems, even when adjusted for prenatal and maternal distress and child behavior problems. Higher levels of non-reacting during pregnancy were also significantly associated with fewer parenting problems in mothers raising toddlers. Conclusions: The current study emphasizes that mindfulness during pregnancy may be a protective factor for later parental stress. More research is needed to confirm these findings and to evaluate the possible benefit of a mindfulness intervention training during pregnancy on parenting and child outcomes