An evaluation of symptom domains in the 2 years before pregnancy as predictors of relapse in the perinatal period in women with severe mental illness

BackgroundSymptoms may be more useful prognostic markers for mental illness than diagnoses. We sought to investigate symptom domains in women with pre-existing severe mental illness (SMI; psychotic and bipolar disorder) as predictors of relapse risk during the perinatal period.MethodsData were obtained from electronic health records of 399 pregnant women with SMI diagnoses from a large south London mental healthcare provider. Symptoms within six domains characteristically associated with SMI (positive, negative, disorganization, mania, depression, and catatonia) recorded in clinical notes 2 years before pregnancy were identified with natural language processing algorithms to extract data from text, and associations investigated with hospitalization during pregnancy and 3 months postpartum.ResultsSeventy-six women (19%) relapsed during pregnancy and 107 (27%) relapsed postpartum. After adjusting for covariates, disorganization symptoms showed a positive association at borderline significance with relapse during pregnancy (adjusted odds ratio [aOR] = 1.36; 95% confidence interval [CI] = 0.99–1.87 per unit increase in number of symptoms) and depressive symptoms negatively with relapse postpartum (0.78; 0.62–0.98). Restricting the sample to women with at least one recorded symptom in any given domain, higher disorganization (1.84; 1.22–2.76), positive (1.50; 1.07–2.11), and manic (1.48; 1.03–2.11) symptoms were associated with relapse during pregnancy, and disorganization (1.54; 1.08–2.20) symptom domains were associated with relapse postpartum.ConclusionsPositive, disorganization, and manic symptoms recorded in the 2 years before pregnancy were associated with increased risk of relapse during pregnancy and postpartum. The characterization of routine health records from text fields is relatively transferrable and could help inform predictive risk modelling.     

Structural vulnerabilities and breastfeeding among female sex workers in Mumbai

Breastfeeding has numerous health, environmental, and economic benefits, and the promotion and support of breastfeeding has been at the centre of efforts from many global organizations such as WHO and UNICEF to promote maternal and child health. Interventions developed from such policies tend to be inaccessible to those who are economically marginalized, however, and thus may further inequities. Understanding the lived experiences of women occupying this segment of society, such as sex workers, illuminates the social and structural determinants of breastfeeding and how they constitute structural vulnerability that renders breastfeeding difficult. This qualitative study explores breastfeeding practices and decisions among sex workers in Mumbai and the factors shaping their experiences. We look at proximal factors—those that women directly indicate as influencing their breastfeeding decision‐making or behaviour, and distal factors—macrolevel forces identified by the women, as indication of their structural vulnerability, particularly in relationship to the decision to initiate and sustain breastfeeding. We conclude with discussing the need to promote appropriate infant feeding practices through culturally responsive interventions and mechanisms, taking both proximal and distal factors into account, to work towards equity in health outcomes.     

Systemic hormonal modulation induces sperm nucleosomal imbalance in rat spermatozoa

Sperm chromatin packaging is a very complex and highly regulated phenomenon. While most of the sperm chromatin is replaced by protamines, some are retained in nucleosomes. It is recently being recognised that these nucleosomes are intentionally retained and could be contributing to the expression of genes in the very early stages of embryogenesis. Endocrine disruption has been previously shown to affect reproductive outcome and sperm DNA methylation. This study aims to decipher the possibility of changes in nucleosome occupancy in sperm chromatin, induced by tamoxifen (selective oestrogen receptor modulator) and cyproterone acetate (androgen antagonist). We used next‐generation sequencing approach (MNase‐Seq) to identify changes in the nucleosome landscape of the spermatozoa. We demonstrated that endocrine disruption affects nucleosome occupancy at critical regions of the genome and many of them harbour genes relevant for embryogenesis. This study emphasises that environmental factors could affect embryo development by way of modulating male epigenetic factors.     

“We want to offer you peace of mind”: Marketing of transnational commercial surrogacy services to intended parents

ABSTRACT

The purpose of this research study was to conduct a content analysis of commercial surrogacy websites to explore how surrogacy is marketed to intended parents. The researchers developed a template to code website data, and a total of 345 website pages were reviewed. Websites depicted surrogacy as a solution to a problem, privileged genetic parenthood, ignored the potential for exploitation, dismissed surrogates’ capacity to bond with the fetuses they carry, emphasized that surrogacy arrangements are mutually beneficial, ignored structural inequalities, and depicted surrogates as conforming to strict gender roles. These framings introduce vulnerabilities to both intended parents and surrogate mothers.     

Predicting Pulmonary Pharmacokinetics from <Emphasis Type="Italic">In Vitro</Emphasis> Properties of Dry Powder Inhalers

Purpose

The ability of two semi-mechanistic simulation approaches to predict the systemic pharmacokinetics (PK) of inhaled corticosteroids (ICSs) delivered via dry powder inhalers (DPIs) was assessed for mometasone furoate, budesonide and fluticasone propionate.

Methods

Both approaches derived the total lung doses and the central to peripheral lung deposition ratios from clinically relevant cascade impactor studies, but differed in the way the pulmonary absorption rate was derived. In approach 1, the rate of in vivo drug dissolution/absorption was predicted for the included ICSs from in vitro aerodynamic particle size distribution and in vitro drug solubility estimates measured in an in vivo predictive dissolution medium. Approach 2 derived a first order absorption rate from the mean dissolution time (MDT), determined for the test formulations in an in vitro Transwell^® based dissolution system.

Results

Approach 1 suggested PK profiles which agreed well with the published pharmacokinetic profiles. Similarly, within approach 2, input parameters for the pulmonary absorption rate constant derived from dissolution rate experiments were able to reasonably predict the pharmacokinetic profiles published in literature.

Conclusion

Approach 1 utilizes more complex strategies for predicting the dissolution/absorption process without providing a significant advantage over approach 2 with regard to accuracy of in vivo predictions.

     

Participation of central imidazoline binding sites in antinociceptive effect of ethanol and nicotine in rats

Despite synergistic morbidity and mortality, concomitant consumption of alcohol and tobacco is increasing, and their antinociceptive effect has been linked with co‐abuse. Present study was designed to investigate the role of imidazoline binding sites in the antinociceptive effect of nicotine, ethanol, and their combination. Separate group of male Sprague–Dawley rats (200–250 g) were treated with different doses of alcohol (0.50–2 g/kg, i.p.) or nicotine (0.25–1 mg/kg, i.p.), and their combination evaluated in tail flick test. Influence of endogenous imidazoline binding site ligands, agonist, and antagonists were determined by their prior treatment with effective or subeffective doses of either ethanol or nicotine. Ethanol, nicotine, or their subeffective dose combination exhibited significant antinociceptive effects in dose‐dependent manner. Antinociceptive effect of ethanol and nicotine was significantly augmented by intracerebroventricular (i.c.v.) administration of endogenous imidazoline receptor ligands, harmane (25 μg/rat, i.c.v.) and agmatine (10 μg/rat, i.c.v.), as well as imidazoline I₁/α₂ adrenergic receptor agonist, clonidine (2 μg/rat, i.c.v.), I₁ agonist moxonidine (25 μg/rat, i.c.v.), and imidazoline I₂ agonist, 2‐BFI (10 μg/rat, i.c.v.). Conversely, antinociception elicited by ethanol or nicotine or their subeffective dose combination was antagonized by pretreatment with imidazoline I₁ antagonist, efaroxan (10 μg/rat, i.c.v.), and I₂ antagonist, idazoxan (4 μg/rat, i.c.v.), at their per se ineffective doses. These findings project imidazoline binding ligands as important therapeutic molecules for central antinociceptive activity as well as may reduce the co‐abuse potential of alcohol and nicotine.     

Case report: Paenibacillus thiaminolyticus: a new cause of human infection, inducing bacteremia in a patient on hemodialysis

Paenibacilli are gram-positive, aerobic bacteria that are related to Bacilli but differ in the DNA encoding their 16S rRNA. Until recently, these organisms were not known to cause human disease. There are now several reports of human infection caused by a few members of this genus, most commonly by P. alvei. We report a human infection in a patient with a permacath for chronic hemodialysis who was found to have bacteremia caused by P. thiaminolyticus, which is an environmental bacterium that has never been found to cause human disease. We identified this bacterium by biochemical tests, cloning, sequencing the genomic DNA encoding its 16S rRNA, growth characteristics, and electron microscopic studies. This constitutes the first report of a human infection caused by this organism.