Untargeted Metabolomics Profiling for Determination of the Time since Deposition of Biofluids in a Forensic Context: A Proof-of-Concept for Urine, Saliva, and Semen in Addition to Blood.

In a criminal trial, the reconstruction of a crime is one of the fundamental steps of the prosecution process. Common questions, such as what happened, where and how it happened, and who made it happen, need to be solved. Biological evidence at crime scenes can be crucial in the determination of these fundamental questions. One of the more challenging riddles to solve is the when? A trace left at a crime scene can prove a person's presence at the crime scene. Knowledge about when it was deposited there, the time since deposition (TsD), would allow linking the person in space and time to the site. This could fortify allegations against a suspect or discharge accusations if proven to be outside of the temporal boundaries where a suspected crime had occurred. Determining the TsD has yet to become routine forensic casework, despite recent research efforts, especially for blood traces. However, next to blood, other biological traces are also commonly encountered in crime scenes. We here present a study to profile the metabolomes of artificially aged dried body fluid spots of blood, semen, saliva, and urine over 4 weeks by liquid chromatography high-resolution mass spectrometry and data-dependent acquisition. All four body fluids (BFs) exhibited diverse time-dependent changes, and a large number of molecular features (MF) were associated with TsD. Still, significant differences between the BFs were observed, limiting universal interpretability independent of the BF and facilitating a need to further study time-dependent changes of different BFs individually toward the goal of TsD estimation.

Determination of the Time since Deposition of Blood Traces Utilizing a Liquid Chromatography-Mass Spectrometry-Based Proteomics Approach.

Knowledge about when a bloodstain was deposited at a crime scene can be of critical value in forensic investigation. A donor of a genetically identified bloodstain could be linked to a suspected time frame and the crime scene itself. Determination of the time since deposition (TsD) has been extensively studied before but has yet to reach maturity. We therefore conducted a proof-of-principle study to study time- and storage-dependent changes of the proteomes of dried blood stains. A bottom-up proteomics approach was employed, and high-resolution liquid-chromatography-mass-spectrometry (HR-LC-MS) and data-independent acquisition (DIA) were used to analyze samples aged over a 2 month period and two different storage conditions. In multivariate analysis, samples showed distinct clustering according to their TsD in both principal component analysis (PCA) and in partial least square discriminant analysis (PLS DA). The storage condition alters sample aging and yields different separation-driving peptides in hierarchical clustering and in TsD marker peptide selection. Certain peptides and amino acid modifications were identified and further assessed for their applicability in assessing passed TsD. A prediction model based on data resampling (Jackknife) was applied, and prediction values for selected peptide ratios were created. Depending on storage conditions and actual sample age, mean prediction performances ranges in between 70 and 130% for the majority of peptides and time points. This places this study as a first in investigating LC-MS based bottom-up proteomics approaches for TsD determination.

Improved 3D Printing and Cell Biology Characterization of Inorganic-Filler Containing Alginate-Based Composites for Bone Regeneration: Particle Shape and Effective Surface Area Are the Dominant Factors for Printing Performance.

The use of organic-inorganic 3D printed composites with enhanced properties in biomedical applications continues to increase. The present study focuses on the development of 3D printed alginate-based composites incorporating inorganic fillers with different shapes (angular and round), for bone regeneration. Reactive fillers (bioactive glass 13-93 and hydroxyapatite) and non-reactive fillers (inert soda-lime glass) were investigated. Rheological studies and the characterization of various extrusion-based parameters, including material throughput, printability, shape fidelity and filament fusion, were carried out to identify the parameters dominating the printing process. It was shown that the effective surface area of the filler particle has the highest impact on the printing behavior, while the filler reactivity presents a side aspect. Composites with angular particle morphologies showed the same high resolution during the printing process, almost independent from their reactivity, while composites with comparable amounts of round filler particles lacked stackability after printing. Further, it could be shown that a higher effective surface area of the particles can circumvent the need for a higher filler content for obtaining convincing printing results. In addition, it was proven that, by changing the particle shape, the critical filler content for the obtained adequate printability can be altered. Preliminary in vitro biocompatibility investigations were carried out with the bioactive glass containing ink. The 3D printed ink, forming an interconnected porous scaffold, was analyzed regarding its biocompatibility in direct or indirect contact with the pre-osteoblast cell line MC3T3-E1. Both kinds of cell tests showed increased viability and a high rate of proliferation, with complete coverage of the 3D scaffolds' surface already after 7 d post cell-seeding.

Correction: Al-Zamel, N., et al. A Dual GLP-1/GIP Receptor Agonist Does Not Antagonize Glucagon at Its Receptor but May Act as a Biased Agonist at the GLP-1 Receptor. Int. J. Mol. Sci. 2019, 20, 3532.

The author wishes to make the following correction to this paper [...].

A Dual GLP-1/GIP Receptor Agonist Does Not Antagonize Glucagon at Its Receptor but May Act as a Biased Agonist at the GLP-1 Receptor.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are important regulators of metabolism, making their receptors (GLP-1R and GIPR) attractive targets in the treatment of type 2 diabetes mellitus (T2DM). GLP-1R agonists are used clinically to treat T2DM but the use of GIPR agonists remains controversial. Recent studies suggest that simultaneous activation of GLP-1R and GIPR with a single peptide provides superior glycemic control with fewer adverse effects than activation of GLP-1R alone. We investigated the signaling properties of a recently reported dual-incretin receptor agonist (P18). GLP-1R, GIPR, and the closely related glucagon receptor (GCGR) were expressed in HEK-293 cells. Activation of adenylate cyclase via Gαs was monitored using a luciferase-linked reporter gene (CRE-Luc) assay. Arrestin recruitment was monitored using a bioluminescence resonance energy transfer (BRET) assay. GLP-1, GIP, and glucagon displayed exquisite selectivity for their receptors in the CRE-Luc assay. P18 activated GLP-1R with similar potency to GLP-1 and GIPR with higher potency than GIP. Interestingly, P18 was less effective than GLP-1 at recruiting arrestin to GLP-1R and was inactive at GCGR. These data suggest that P18 can act as both a dual-incretin receptor agonist, and as a G protein-biased agonist at GLP-1R.

A new metabolomics-based strategy for identification of endogenous markers of urine adulteration attempts exemplified for potassium nitrite.

Urine adulteration to circumvent positive drug testing represents a problem for toxicological laboratories. While creatinine is a suitable marker for dilution, detection of chemicals is often performed by dipstick tests associated with high rates of false positives. Several methods would be necessary to check for all possible adulterants. Untargeted mass spectrometry (MS) methods used in metabolomics should theoretically allow detecting concentration changes of any endogenous urinary metabolite or presence of new biomarkers produced by chemical adulteration. As a proof of concept study, urine samples from 10 volunteers were treated with KNO2 and analyzed by high-resolution MS. For statistical data evaluation, XCMSplus and MetaboAnalyst were used. Compound identification was performed by database searches using an in-house database, Chemspider, METLIN, HMDB, and NIST. Principle component analysis revealed clear separation between treated and untreated urine samples. In detail, 307 features showed significant concentration changes with fold changes greater than 2 (79 decreased; 228 increased). Mainly amino acids (e.g., histidine, methylhistidine, di- and trimethyllysine) and purines (uric acid) were detected in lower amounts. 5-HO-isourate was found to be formed as a new compound from uric acid and, e.g., imidazole lactate concentrations increased due to the breakdown of histidine. This metabolomics-based strategy allowed for a broad identification range of markers of urinary adulteration. More studies will be needed to investigate routine applicability of identified potential markers exploring urinary conditions of their formation and stability. Selected markers might then be integrated into routine MS screening procedures allowing for detection of adulteration within routine MS analysis. Graphical Abstract ᅟ.

AN EVALUATION OF INFRARED THERMOGRAPHY FOR DETECTION OF BUMBLEFOOT (PODODERMATITIS) IN PENGUINS.

The objective of this study was to evaluate infrared thermography as a noninvasive screening tool for detection of pododermatitis during the developing and active stages of disease in three species of penguins: king penguin (Aptenodytes patagonicus) , macaroni penguin (Eudyptes chrysolophus), and rockhopper penguin (Eudyptes chrysocome). In total, 67 penguins were examined every 3 mo over a 15-mo period. At each exam, bumblefoot lesions were characterized and measured, and a timed series of thermal images were collected over a 4-min period. Three different methods were compared for analysis of thermograms. Feet with active lesions that compromise the surface of the foot were compared to feet with inactive lesions and no lesions. The hypothesis was that feet with active lesions would have warmer surface temperatures than the other conditions. Analysis of the data showed that although feet with active bumblefoot lesions are warmer than feet with inactive or no lesions, the variability seen in each individual penguin from one exam day to the next and the overlap seen between temperatures from each condition made thermal imaging an unreliable tool for detection of bumblefoot in the species studied.

Successful five-item triage for the broad spectrum of mental disorders in pregnancy - a validation study.

BACKGROUND: Mental disorders are prevalent during pregnancy, affecting 10% of women worldwide. To improve triage of a broad spectrum of mental disorders, we investigated the decision impact validity of: 1) a short set of currently used psychiatric triage items, 2) this set with the inclusion of some more specific psychiatric items (intermediate set), 3) this new set with the addition of the 10-item Edinburgh Depression Scale (extended set), and 4) the final set with the addition of common psychosocial co-predictors (comprehensive set). METHODS: This was a validation study including 330 urban pregnant women. Women completed a questionnaire including 20 psychiatric and 10 psychosocial items. Psychiatric diagnosis (gold standard) was obtained through Structured Clinical Interviews of DSM-IV axis I and II disorders (SCID-I and II). The outcome measure of our analysis was presence (yes/no) of any current mental disorder. The performance of the short, intermediate, extended, and comprehensive triage models was evaluated by multiple logistic regression analysis, by analysis of the area under the ROC curve (AUC) and through associated performance measures, including, for example, sensitivity, specificity and the number of missed cases. RESULTS: Diagnostic performance of the short triage model (1) was acceptable (Nagelkerke's R(2)=0.276, AUC=0.740, 48 out of 131 cases were missed). The intermediate model (2) performed better (R(2)=0.547, AUC=0.883, 22 cases were missed) including the five items: ever experienced a traumatic event, ever had feelings of a depressed mood, ever had a panic attack, current psychiatric symptoms and current severe depressive or anxious symptoms. Addition of the 10-item Edinburgh Depression Scale or the three psychosocial items unplanned pregnancy, alcohol consumption and sexual/physical abuse (models 3 and 4) further increased R(2) and AUC (>0.900), with 23 cases missed. Missed cases included pregnant women with a current eating disorder, psychotic disorder and the first onset of anxiety disorders. CONCLUSIONS: For a valid detection of the full spectrum of common mental disorders during pregnancy, at least the intermediate set of five psychiatric items should be implemented in routine obstetric care. For a brief yet comprehensive triage, three high impact psychosocial items should be added as independent contributors.

Carriers for hydrophobic drug molecules: lipid-coated hollow mesoporous silica particles, and the influence of shape and size on encapsulation efficiency.

Hydrophobic drugs, while designed to interact with specific receptors or enzymes located in lipid-rich cell membranes, often face challenges of limited bioavailability and insufficient circulation time due to their insolubility in aqueous environments. One plausible pathway to increase their blood circulation time is to load these drugs into biocompatible and hydrophilic carriers to enhance their uptake. In this study, mesoporous silica (mSiO2) nanocarriers of various morphologies (including cubes, capsules, and spheres) were synthesized. These nanocarriers were then surface-functionalized with alkyl chain hydrocarbons, specifically octadecyl-trimethoxysilane, (OCH3)3Si(CH2)17CH3, to render them hydrophobic. The resulting nanocarriers (((OCH3)3Si(CH2)17CH3)@mSiO2) showed up to 80% uptake for hydrophobic drugs. However, a significant drawback was observed as most of the drugs were prone to uncontrollable release within 6 h. This challenge of premature drug release was successfully mitigated by effectively sealing the drug-loaded nanocarriers with a pH-sensitive lipid overlayer. The lipid-coated nanocarriers prolonged drug containment and sustained release up to 72 h, compared to 6 h for uncoated nanocarriers, thereby facilitating longer blood circulation times. Moreover, the shape and size of nanocarriers were found to influence both drug entrapment capacity and release behavior with cubic forms exhibiting superior loading capacity due to higher surface area and porosity. Additionally, it was observed that the molecular weight and chemical structure of the drug molecules played a crucial role in determining their uptake and release profiles. Furthermore, the influence of different morphologies of nanocarriers on cell uptake and cytotoxicity in immune cells was elucidated. These findings underscore the importance of nanocarrier morphology and drug properties to enhance loading capacities and controlled release profiles, for designing drug delivery systems tailored for hydrophobic drugs.

Determination of the Time since Deposition of blood-traces in a forensic context: Application of untargeted LC-HR-MS/MS metabolomics profiling.

Being able to attest when a bloodstain was deposited at a crime scene can be invaluable to a prosecution process, and methods to provide that information have long been desired. Determining the Time since Deposition (TsD) of a trace would allow placing a subject both in space and time to the crime scene-or prove that a trace left by that person was unrelated to it because it was deposited before or after the time the crime had occurred. To this day, no method for TsD determination has made its way into routine forensic casework, mainly because of the numerous challenges that await when trying to understand and account for all the influencing and confounding factors that affect the aging process (such as, e.g., temperature, UV-light exposure, or humidity). Here, we present an untargeted metabolomics-based study using liquid chromatography high-resolution mass spectrometry (LC-HR-MS) and data-dependent acquisition to analyze blood samples aged under two distinctly different storage conditions over 48 weeks. Global differences in age- and storage-dependent changes in blood metabolomes were described, and TsD-classification strategies based on qualitative and quantitative assessment of molecular features (MFs) have been proposed. Based on the selected criteria to best predict the TsD, the dipeptide Phenylalanylalanine (PheAla) can be considered as a promising candidate for TsD prediction. In essence, changes in the blood metabolome dynamics showed a strong association with increasing TsD, but significant differences depending on storage conditioning were observed, facilitating the need to study further the influence of individual influencing factors on TsD determination.

Do dried blood spots have the potential to support result management processes in routine sports drug testing?-Part 3: LC-MS/MS-based peptide analysis for dried blood spot sampling time point estimation.

Along with the recent acknowledgement of the World Anti-Doping Agency to use dried blood spot (DBS) samples for routine doping control purposes, there have been propositions to use DBS as a matrix that allows regular proactive remotely supervised self-sampling, providing potential longitudinal monitoring of an athlete's exposure to doping agents. However, several organizational aspects have to be considered before implementation, such as the verification of the sample collections time point. Based on a previous untargeted proteomics workflow utilizing liquid chromatography-high-resolution mass spectrometry (LC-HRMS) to identify protein/peptide markers to define the time since deposition of a bloodstain, the aim of the current study was to develop a targeted LC-HRMS/MS analytical method for promising peptidic target analytes. A long-term DBS storage experiment was carried out over a 3-month period (sample collection time points: 0, 2, 4, 7, 14, 21, 28, 42, 56, 70, 84 and 91 days) with DBS samples of 10 volunteers for longitudinal investigation of signal abundance changes of targeted peptide sequences at different storage temperatures (room temperature [RT], 4°C and -20°C). Prior to experimental analysis, LC-HRMS/MS method characteristics were successfully assessed, including intraday precision, carryover and sample extract stability. For estimation of DBS sample collection time points, ratios of two peptides that originate from the same protein prior to tryptic digestion were created. Two targeted peptide area ratios were found to significantly increase after being stored at RT for 28 days, representing potential markers for future use in routine doping controls that contribute to advancing complementary avenues in anti-doping.

Histologic chorioamnionitis, fetal involvement, and antenatal steroids: effects on neonatal outcome in preterm infants.

OBJECTIVE: The objective of the study was to study the effects of histologic chorioamnionitis (HC) with or without fetal involvement and antenatal steroid (AS) exposure on neonatal outcome in a prospective cohort of preterm infants. STUDY DESIGN: The clinical characteristics and placental histology were prospectively collected in 301 infants born at a gestational age 32.0 weeks or less in the Erasmus University Medical Center. RESULTS: In univariable analyses, HC without fetal involvement (n=53) was associated with decreased severe respiratory distress syndrome (RDS) (11% vs 28%; P<.05), whereas HC with fetal involvement infants (n=68) had more necrotizing enterocolitis (9% vs 2%; P<.05), intraventricular hemorrhage (IVH) (25% vs 12%; P<.05), and neonatal mortality (19% vs 9%; P<.05). In HC without fetal involvement infants, AS reduced the incidences of RDS (43% vs 85%; P<.05) and IVH (5% vs 39%; P<.01). In multivariable analyses, HC without fetal involvement was associated with decreased severe RDS (odds ratio, 0.22; 95% confidence interval, 0.05-0.93; P<.05) and increased early-onset sepsis (odds ratio, 2.22; 95% confidence interval, 1.02-4.83; P<.05). CONCLUSION: In a prospective cohort of preterm infants, multivariable analyses reveal only a modest association between histologic chorioamnionitis and neonatal outcome.

Natural orifice surgery on thyroid gland: totally transoral video-assisted thyroidectomy (TOVAT): report of first experimental results of a new surgical method.

BACKGROUND: Neck surgery is one of the newest fields of application of minimally invasive surgery. The technique of minimally invasive video-assisted thyroidectomy (MIVAT) developed by Miccoli [1] is the method that has so far become most widespread. Limiting factors of this method include the bothersome 20-mm cervical incision and consequently the specimen size to remove. Several papers describing an access outside the front neck region have been published. Such approaches are via the chest, axillary, a combined axillary bilateral breast, or a bilateral axillary breast approach [2-5]. The development of cervical scarless thyroid surgery is a great step toward better cosmetic outcomes. However, these techniques just moved the scars from the front neck region to the axilla or the chest where they are still visible. And the mentioned minimally invasive accesses as well as the conventional approaches to the thyroid gland do not respect the anatomically given surgical planes. This may result in complaints by the patients, e.g., scar development and swallowing disorders. Furthermore, the extracervical approaches do not comply with the use of the term "minimally invasive," because they are associated with an extensive dissection of the chest and neck region, thus being rather maximally invasive for the patients. The main goal of this project was the introduction of a technique of thyroid resection that fulfills the following criteria: (i. Respecting surgical planes and minimizing surgical trauma in thyroidectomy, ii. The access itself should be close to the thyroid gland to achieve a minimally invasive procedure, iii. Achieving an optimal cosmetic result may only be obtained by performing a scarless operation, iv. This optimal cosmetic result with scarless surgery should be achieved with minimal trauma, v. The minimally invasive character of this approach and the optimal cosmetic result may not be reached at the expense of patient's safety.). The technique that meets all of these criteria is the transoral access because the distance between the sublingual place and the thyroid gland is short, thus avoiding extensive dissection maneuvers. Furthermore, the mouth mucosa can be sutured without difficulties and repairs itself without leaving any visible scars. Feasibility of the transoral access has been recently demonstrated by a member of our group in a porcine model by using a modified axilloscope [6]. However, the described technique is a hybrid one because an additional medial access (3.5-mm incision) 15-mm below the larynx was necessary for the insertion of a fixation forceps through a trocar. The main goal of our project was the investigation and introduction of a technique of totally endoscopic thyroid resection that is minimally invasive and safe for the patient and at the same time cosmetically optimal (scarless). METHODS: For this purpose, a total of five human cadavers were used. In three cadavers, safety and reproducibility to reach and resect the thyroid gland was assessed according to a defined road map. At the end of the procedure, the cadavers were dissected to evaluate all defined anatomical key structures regarding possible injuries and also allow an evaluation of the surgery performed. The TOVAT itself was performed on two more human cadavers with the help of one 5-mm and two 3-mm trocars that were introduced through the mouth floor and the vestibulum of the mouth subplatysmal. A working space was created by insufflating CO(2) at a pressure of 4-6 mmHg ("air dissection"). Surgical dissection of the further working space was realized with 3-mm bipolar scissors. The procedure consists of the following steps: (i. Patient in supine position and nasotracheal intubation, ii. 5-mm small incision between the carunculae sublinguales, iii. Penetration through the mouth floor along the superficial fascia colli with a blunt instrument, iv. Insertion of a 5-mm trocar, v. Blunt dissection subplatysmal by CO(2) insufflation ("air dissection"), vi. CO(2) insufflation (4-6 mmHg) and creation of a working space, vii. Insertion of two 3-mm trocars in the vestibulum oris on the right and left side, viii. Separation of the platysma from the strap muscles approximately at level of the larynx, extending up to the suprasternal notch. Laterally, this dissection can be continued up to the medial border of the sternocleidomastoid muscles, ix. Division of the linea alba coli and exposure of the strap muscles, x. Separation of the strap muscles from the thyroid gland, xi. Isthmus transection and blunt dissection of the thyroid gland from the trachea, xii. Dissection and division of the upper pole arteries and medial thyroid vein closely to the gland, xiii. Division of branches of the inferior thyroid artery closely to the gland, xiv. If necessary, preparation of the retro-thyroidal area, including visualization of the recurrent laryngeal nerve, xv. Thyroid resection from cranial to caudal and transoral removal of the specimen through the 5-mm midline incision. If the gland is too large, the midline incision can be extended longitudinally, xvi. All three incisions are closed with absorbable sutures.) RESULTS: Description of landmarks of surgical steps and dissection of defined anatomic structures could be achieved. The subplatysmal space could be reached without any major problems within a short time. Anatomical dissection showed intact muscles and vascular structures. One-side subtotal thyroid resection could be successfully performed without any additional skin incision in 60 minutes. CONCLUSIONS: The minimally invasive aspect and the scarless character of TOVAT form the rationale for the preclinical investigation of this method in human cadavers. We could succeed in defining objective parameters, which describe the procedure in details and also allow an evaluation of the surgery performed. Access and feasibility of TOVAT could be demonstrated. The next step will be its application in living pigs before it may be applied in humans. To our knowledge of the literature, this is the first report on NOS application in thyroid surgery and also the first totally and scarless performed video-assisted thyroidectomy.

Analytical considerations for (un)-targeted metabolomic studies with special focus on forensic applications.

Over the past few years, the interest in metabolomics has increased in various fields including forensic toxicology. Forensic analysis typically requires a high degree of accuracy, which is often a problem in metabolomics applications. We aimed for a systematic evaluation of different analytical considerations of a metabolomics workflow allowing a targeted approach within an untargeted setup. Samples with 69 metabolites from different chemical classes were qualitatively and quantitatively analyzed on a high resolution quadrupole time of flight mass spectrometer coupled to liquid chromatography (UHPLC-QTOF). Three issues were addressed: (a) Two different approaches on "blind matrix" a simulated body fluid (SBF) and plasma-filtrate, were tested for calibration samples; (b) comparison of two different HPLC columns, reverse-phase (RP) and hydrophilic interaction chromatography (HILIC); and (c) comparison of three different acquisition modes (TOF-MS, information dependent data acquisition (IDA), and sequential window acquisition of all theoretical fragment-ion spectra (SWATH). Samples were measured repeatedly for method comparison based on sensitivity, accuracy, precision, and detection robustness. The blind matrices showed similar accuracy for most analytes, while SBF provided an easier preparation with satisfying results. To cover a wide part of the human metabolome, a combination of RP and HILIC showed the best results. The different scan modes performed equally regarding metabolite quantification while TOF-MS was more sensitive but lacked MS/MS spectra generation. IDA and SWATH files were aligned to various databases where IDA showed good MS/MS spectra matches. SWATH seemed to be beneficial in detection rate but was incompatible with many important software tools in metabolomics.

Group-based multicomponent treatment to reduce depressive symptoms in women with co-morbid psychiatric and psychosocial problems during pregnancy: A randomized controlled trial.

BACKGROUND: Depressive symptoms in pregnant women, which are common and debilitating, are often co-morbid with other mental disorders (e.g. anxiety and personality disorders), and related to low socioeconomic status (SES). This situation may hamper treatment outcome, which has often been neglected in previous studies on the treatment of depression during pregnancy. We developed a new group-based multicomponent treatment (GMT) comprising cognitive behavioral therapy, psycho-education and body-oriented therapy and compared the effect on depressive symptoms with individual counseling (treatment as usual, TAU) in a heterogeneous group of pregnant women with co-morbid mental disorders and/or low SES. METHODS: An outpatient sample from a university hospital of 158 pregnant women who met DSM-IV criteria for mental disorders were included and 99 participants were randomized to GMT or TAU from January 2010 until January 2013. The Edinburgh Depression Scale (EDS) was used at baseline, every 5 weeks during pregnancy and as the primary outcome measure of depressive symptoms at 6 weeks postpartum. Secondary outcome measures included the clinician-reported Hamilton Depression Rating Scale (HDRS), obstetric outcomes and a 'Patient Satisfaction' questionnaire. RESULTS: 155 participants were included the intention-to-treat (ITT)-analysis. GMT was not superior above TAU according to estimated EDS (ß = 0.13, CI = - 0.46-0.71, p = 0.67) and HDRS scores (ß = - 0.39, CI = - 0.82-0.05, p = 0.08) at 6 weeks postpartum. There were no differences in secondary outcomes between the GMT and TAU, nor between the randomized condition and patient-preference condition. LIMITATIONS: The ability to detect an effect of GMT may have been limited by sample size, missing data and the ceiling effect of TAU. CONCLUSIONS: GMT is an acceptable treatment for a heterogeneous group of pregnant women with depressive symptoms and co-morbid mental disorders and/or low SES, but not superior to TAU. Further research should focus on understanding and treating co-morbid disorders and psychosocial problems during pregnancy. CLINICAL TRIALS REGISTRATION: Dutch trial registry, www.trialregister.nl under reference number: NTR3015.

Placental malaria and the relationship to pregnancy outcome at Gushegu District Hospital, Northern Ghana.

One complication of malaria infection during pregnancy is the sequestration of parasites in the placenta. The aim of this study was to determine the association between placental malaria and pregnancy outcome. This study was conducted at the Gushegu District Hospital in Ghana from June to August 2010. Sulfadoxine-pyrimethamine (SP) was used as intermittent preventative treatment (IPT) during pregnancy. All mothers reporting for delivery were enrolled, except in cases of multiple pregnancies. The data was documented using a questionnaire. A placental blood sample was collected and analysed for malaria parasites. There were 56/107(52%) malaria positive samples. In women with placental malaria perinatal mortality was higher, duration of pregnancy shorter and birth weight lower. These results were statistically significant. In primigravidae the negative effects were more obvious. IPT is extensively implemented in Ghana, but this study found no evidence for an association between the number of doses and the outcome of pregnancy.

An innovative screen-and-advice model for psychopathology and psychosocial problems among urban pregnant women: an exploratory study.

BACKGROUND: Increased adverse pregnancy outcomes related to psychiatric and psychosocial problems can be observed for urban areas when compared to national averages. We developed a personal digital assistant (PDA)-based self-report screening model that produces tailored intervention advices. After having adapted the model to local care pathways, we tested the reliability, validity and feasibility of the model in routine antenatal care. METHODS: Observational study among pregnant women in a Dutch urban area included women with a booking visit. Women answered questions posed by the PDA-tool while waiting for their appointment. If the tool suggested specific interventions (screen result), this was discussed during booking visit. A randomly selected subsample of participants completed the questionnaire again at a subsequent pregnancy check (retest). After the study was conducted, prenatal caregivers and assistants were interviewed for feasibility judgments. Psychometric and diagnostic performance of this approach was established. RESULTS: Response rate among invited pregnant women was 94% on weighted average (n=621). Internal reliability ranged 0.88-0.90, test-retest reliability ranged 0.64-1.00. Positive predictive value was 86% and negative predictive value was 97%. No interpractice psychometrical differences were observed. Migrant women more often received an intervention advice than native women (p<0.001). The approach was well accepted among prenatal caregivers for its time efficiency and patient-friendliness. CONCLUSION: Psychometric properties of our screen-and-advice tool were favorable under routine conditions, and the feasibility of this integral approach appeared good. The technical flexibility renders the model suitable for broader application. Local care pathways can easily be incorporated. We suggest implementation of this model in prenatal care in urbanized settings in order to make tailored mental healthcare broadly available.