The Impact of Short-Term,Intensive Antifolate Treatment (with Pyrimethamine and Sulfadoxine) and Antibiotics Followed by Long-Term,Secondary Antifolate Prophylaxis on the Rate of Toxoplasmic Retinochoroiditis Recurrence

PurposeTo assess the impact of intensive antifolate treatment, followed by secondary antifolate prophylaxis (A-SP) on the recurrence rate of toxoplasmic retinochoroiditis (TRC). To investigate whether there are any other factors potentially predisposing for recurrence.ResultsWhen secondary antifolate prophylaxis (A-SP) was instituted immediately after the treatment for TRC, the probability of 3-year recurrence–free survival after the first course of A-SP was 90.9%. A recurrence was most likely approximately 3.5 years after the first treatment. A univariate Cox regression model demonstrated that a risk for recurrence was 2.82 times higher (p = 0.02) in patients with retinal scars. In the multivariate analysis, the risk for recurrence was 2.41 higher (p = 0.06). In patients with haemorrhagic lesions the risk for recurrence was lower, aRR = 0.17 (approaching borderline statistical significance p = 0.08).ConclusionsWith the institution of A-SP of immediately after the intensive treatment for TRC, i.e. when a reactivation was most likely, there was no recurrence during A-SP. Following A-SP the recurrence rates were low and recurrence-free periods tended to be longer. The treatment regimen employed had a beneficial effect on the recurrence interval as it reduced and delayed the highest probability of recurrence.     

Detecting cell lysis using viscosity monitoring in E. coli fermentation to prevent product loss

Monitoring the physical or chemical properties of cell broths to infer cell status is often challenging due to the complex nature of the broth. Key factors indicative of cell status include cell density, cell viability, product leakage, and DNA release to the fermentation broth. The rapid and accurate prediction of cell status for hosts with intracellular protein products can minimise product loss due to leakage at the onset of cell lysis in fermentation. This article reports the rheological examination of an industrially relevant E. coli fermentation producing antibody fragments (Fab'). Viscosity monitoring showed an increase in viscosity during the exponential phase in relation to the cell density increase, a relatively flat profile in the stationary phase, followed by a rapid increase which correlated well with product loss, DNA release and loss of cell viability. This phenomenon was observed over several fermentations that a 25% increase in broth viscosity (using induction‐point viscosity as a reference) indicated 10% product loss. Our results suggest that viscosity can accurately detect cell lysis and product leakage in postinduction cell cultures, and can identify cell lysis earlier than several other common fermentation monitoring techniques. This work demonstrates the utility of rapidly monitoring the physical properties of fermentation broths, and that viscosity monitoring has the potential to be a tool for process development to determine the optimal harvest time and minimise product loss. © 2016 The Authors. Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers, 32:1069–1076, 2016     

Investigating DNA Radiation Damage Using X-Ray Absorption Spectroscopy

The biological influence of radiation on living matter has been studied for years; however, several questions about the detailed mechanism of radiation damage formation remain largely unanswered. Among all biomolecules exposed to radiation, DNA plays an important role because any damage to its molecular structure can affect the whole cell and may lead to chromosomal rearrangements resulting in genomic instability or cell death. To identify and characterize damage induced in the DNA sugar-phosphate backbone, in this work we performed x-ray absorption spectroscopy at the P K-edge on DNA irradiated with either UVA light or protons. By combining the experimental results with theoretical calculations, we were able to establish the types and relative ratio of lesions produced by both UVA and protons around the phosphorus atoms in DNA.     

Adhesion of the genome-sequenced <Emphasis Type="Italic">Lactococcus lactis</Emphasis> subsp. <Emphasis Type="Italic">cremoris</Emphasis> IBB477 strain is mediated by specific molecular determinants

Understanding the nature of mucus-microbe interactions will provide important information that can help to elucidate the mechanisms underlying probiotic adhesion. This study focused on the adhesive properties of the Lactococcus lactis subsp. cremoris IBB477 strain, previously shown to persist in the gastrointestinal tract of germ-free rats. The shear flow-induced detachment of L. lactis cells was investigated under laminar flow conditions. Such a dynamic approach demonstrated increased adhesion to bare and mucin-coated polystyrene for IBB477, compared to that observed for the MG1820 control strain. To identify potential genetic determinants giving adhesive properties to IBB477, the improved high-quality draft genome sequence comprising chromosome and five plasmids was obtained and analysed. The number of putative adhesion proteins was determined on the basis of surface/extracellular localisation and/or the presence of adhesion domains. To identify proteins essential for the IBB477 specific adhesion property, nine deletion mutants in chromosomal genes have been constructed and analysed using adhesion tests on bare polystyrene as well as mucin-, fibronectin- or collagen IV-coated polystyrene plates in comparison to the wild-type strain. These experiments demonstrated that gene AJ89_07570 encoding a protein containing DUF285, MucBP and four Big_3 domains is involved in adhesion to bare and mucin-coated polystyrene. To summarise, in the present work, we characterised the adhesion of IBB477 under laminar flow conditions; identified the putative adherence factors present in IBB477, which is the first L. lactis strain exhibiting adhesive and mucoadhesive properties to be sequenced and demonstrated that one of the proteins containing adhesion domains contributes to adhesion.     

The effectiveness of the peer-delivered Thinking Healthy PLUS (THPP+) Program for maternal depression and child socioemotional development in Pakistan: study protocol for a randomized controlled trial

BackgroundThe negative effects of perinatal depression on the mother and child start early and persist throughout the lifecourse (Lancet 369(9556):145–57, 2007; Am J Psychiatry 159(1):43-7, 2002; Arch Dis Child 77(2):99–101, 1997; J Pak Med Assoc 60(4):329; J Psychosoma Res 49(3):207–16, 2000; Clin Child Fam Psychol Rev 14(1):1–27, 2011). Given that 10–35 % of children worldwide are exposed to perinatal depression in their first year of life (Int Rev Psychiatry 8(1):37–54, 1996), mitigating this intergenerational risk is a global public health priority (Perspect Public Health 129(5):221–7, 2009; Trop Med Int Health 13(4):579–83, 2008; Br Med Bull 101(1):57–79, 2012). However, it is not clear whether intervention with depressed women can have long-term benefits for the mother and/or her child. We describe a study of the effectiveness of a peer-delivered depression intervention delivered through 36 postnatal months, the Thinking Healthy Program Peer-delivered PLUS (THPP+) for women and their children in rural Pakistan.Methods/designThe THPP+ study aims are: (1) to evaluate the effects of an extended 36-month perinatal depression intervention on maternal and index child outcomes using a cluster randomized controlled trial (c-RCT) and (2) to determine whether outcomes among index children of perinatally depressed women in the intervention arm converge with those of index children born to perinatally nondepressed women. The trial is designed to recruit 560 pregnant women who screened positive for perinatal depression (PHQ-9 score ≥10) from 40 village clusters, of which 20 receive the THPP+ intervention. An additional reference group consists of 560 perinatally nondepressed women from the same 40 clusters as the THPP+ trial. The women in the nondepressed group are not targeted to receive the THPP+ intervention; but, by recruiting pregnant women from both intervention and control clusters, we are able to evaluate any carryover effects of the THPP+ intervention on the women and their children. Perinatally depressed women in the THPP+ intervention arm receive bimonthly group-based sessions. Primary outcomes are 3-year maternal depression and 3-year child development indicators. Analyses are intention-to-treat and account for the clustered design.DiscussionThis trial, together with the reference group, has the potential to further our understanding of the early developmental lifecourse of children of both perinatally depressed and perinatally nondepressed women in rural Pakistan and to determine whether intervening with women’s depression in the perinatal period can mitigate the negative effects of maternal depression on 36-month child development.

Trial registration

THPP-P ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02111915","term_id":"NCT02111915"}}NCT02111915 (registered on 9 April 2014).THPP+ ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02658994","term_id":"NCT02658994"}}NCT02658994 (registered on 21 January 2016).Sponsor: Human Development Research Foundation (HDRF).

Electronic supplementary material

The online version of this article (doi:10.1186/s13063-016-1530-y) contains supplementary material, which is available to authorized users.     

The relationship between chronotype and personality among patients with alcohol dependence syndrome: Pilot study

The study investigates the distribution of chronotypes among alcohol-dependent subjects and the relationship between personality and chronotype. Fifty-eight alcohol-dependent patients and 29 age-matched healthy controls were studied using Ogińska’s Chronotype Questionnaire (ChQ), Eysenck’s Personality Questionnaire – Revised (EPQ-R), Selzer’s Michigan Alcoholism Screening Test (MAST) and a sociodemographic status questionnaire designed by the authors. The alcohol-dependent patients tended to be morning type, based on the morningness–eveningness ChQ scale, with a weakly marked rhythm, based on the distinctness ChQ scale. Preference towards morningness was associated with older age, but no relation between chronotype and severity of alcohol dependence was found. A high amplitude of the rhythm was associated with higher neuroticism. Therefore, despite being in the minority, patients with a distinct circadian rhythm (i.e. with a high amplitude) are at greater risk of mood and anxiety disorders and hence should be given special consideration.