Preparation for fatherhood: A role for olfactory communication during human pregnancy?

There is evidence across a range of bi-parental species that physiological changes may occur in partnered males prior to the birth of an infant. It has been hypothesised that these hormonal changes might facilitate care-giving behaviours, which could augment infant survival. The mechanism that induces these changes has not been identified, but evidence from several species suggests that odour may play a role. The current study investigated this in humans by recording testosterone and psychological measures related to infant interest and care in men (n = 91) both before and after exposure to odours from either pregnant women or non-pregnant control women. We found no evidence for an effect of odour cues of pregnancy on psychological measures including self-reported sociosexual orientation and social dominance scores, ratings of infant or adult faces, or testosterone levels. However, we found that brief exposure to post-partum odours significantly increased the reward value of infant faces. Our study is the first to show that the odour of peri-partum women may lead to upregulation of men's interest in infants.

Self-collected dried blood spots as a tool for measuring ovarian reserve in young female cancer survivors.

STUDY QUESTION: Are female young cancer survivors (YCS) able to self-collect high-quality dried blood spots (DBSs) at home to provide biospecimens for studying ovarian reserve? SUMMARY ANSWER: YCS can self-collect high-quality DBS specimens in non-clinical settings, and anti-Mullerian hormone (AMH) levels can be assayed in such specimens. WHAT IS KNOWN ALREADY: Large-scale biosample collection is a barrier to studying ovarian reserve in YCS. DBS collected by research personnel has high acceptability. AMH levels measured in DBS are highly correlated with those measured by serum-based methods. STUDY DESIGN, SIZE, DURATION: In a prospective cohort study, YCS were recruited to self-collect DBS samples. AMH levels were assayed in 112 samples. PARTICIPANTS/MATERIALS, SETTING, METHODS: YCS participants, ages 18-44, were recruited from a nationwide longitudinal cohort and DBS collection materials were posted to them. AMH levels were assayed by the Ansh DBS AMH ELISA and compared according to participant characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Among 163 potential participants, 123 (75%) were enrolled. Of those enrolled, 112 (91%) were able to complete DBS self-collection and submit mailed samples adequate for measuring AMH. Participants (mean age 31.6 [SD 5.5]) were 85% white, 87% college graduates and 46% reported higher income. Common cancer types were lymphoma and leukemia (34%), breast cancer (30%) and thyroid or skin cancer (8%). The geometric mean (95% confidence interval) AMH level in DBS samples was 0.24 ng/ml (0.16-0.36). In adjusted analysis, AMH levels for survivors of breast cancer (0.02 ng/ml [0.01-0.07]) or leukemia/lymphoma (0.03 ng/ml [0.01-0.08]) were lower than the levels in thyroid or skin cancer survivors (0.12 ng/ml [0.03-0.44]). Pelvic radiation remained associated with lower AMH levels (0.20 ng/ml [0.10-0.40] in unexposed versus 0.02 ng/ml [0.01-0.06] in exposed). Amenorrheic survivors had AMH levels (0.02 ng/ml [0.01-0.06]) that were lower than those of YCS with 7-9 (0.09 ng/ml [0.03-0.32]) or ≥10 (0.17 ng/ml [0.08-0.37]) menstrual periods in the past year. LIMITATIONS, REASONS FOR CAUTION: The results are generalizable to a population of highly educated, higher income YCS. It is unclear how generalizable the results are to other populations. WIDER IMPLICATIONS OF THE FINDINGS: Self-collected DBS is a patient-friendly and minimally invasive tool for studying ovarian reserve in geographically diverse populations. STUDY FUNDING/COMPETING INTERESTS: Research related to the development of this paper was supported by the National Institutes of Health, grants UL1 RR024926 pilot and HD080952-02, and by the American Cancer Society MRSG-08-110-01-CCE. The authors report no competing interests.

Moderators and mediators of the relationship between receiving versus being denied a pregnancy termination and subsequent binge drinking.

BACKGROUND: Women who terminate pregnancies drink more subsequent to the pregnancy than women who give birth, including women who give birth after seeking to terminate a pregnancy. METHODS: Data are from the Turnaway Study, a prospective, longitudinal study of 956 women who sought to terminate pregnancies at 30 U.S. facilities. This paper focuses on the 452 women who received terminations just below facility gestational limits and 231 who were denied terminations because they presented just beyond facility gestational limits. This study examined whether baseline characteristics moderate the relationship between termination and subsequent binge drinking and whether stress, feelings about the pregnancy, and number of social roles mediate the relationship. RESULTS: Only having had a previous live birth modified the termination-binge drinking relationship. Among women with previous live births, binge drinking was reduced among women carrying to term compared to terminating the pregnancy. Among women who had not had a previous live birth, however, the reduction in binge drinking among those denied termination was not sustained over time, and binge drinking of those who had and had not had terminations converged by 2.5 years. Neither stress, negative emotions, nor social roles mediated effects on binge drinking. Positive emotions at one week mediated effects on binge drinking at six months, although positive emotions at two years did not mediate effects on binge drinking at 2.5 years. CONCLUSIONS: Higher levels of binge drinking among those who terminate pregnancies do not appear due to stress or to negative emotions. Only parous women - and not nulliparous women - denied terminations experienced sustained reductions in binge drinking over time.

Which women are missed by primary health-care based interventions for alcohol and drug use?

BACKGROUND: Women of reproductive age who binge drink or have alcohol-related problem symptoms (APS) and who do not use contraception are considered at risk of an alcohol-exposed pregnancy (AEP). In the U.S., efforts to prevent AEPs focus largely on delivering interventions in primary health care settings. While research suggests that these interventions are efficacious for women reached, it is unclear to what extent these interventions are likely to reach women at risk of AEPs. METHODS: Data are from the Turnaway Study, a study of 956 women seeking pregnancy termination at 30 U.S. facilities between 2008 and 2010, some of whom received and some of whom were denied terminations because they were past the gestational limit. We examined associations between binge drinking, APS, and drug use prior to pregnancy recognition and having a usual source of health care (USOC). RESULTS: Overall, 59% reported having a USOC. A smaller proportion with than without an APS reported a USOC (44 vs. 60%, p<.05) and a smaller proportion using than not using drugs reported a USOC (51 vs. 61%, p<.05). This pattern was not observed for binge drinking. In multivariate analyses, an APS continued to be associated with lack of a USOC, while drug use was no longer associated with lack of a USOC. CONCLUSIONS: As more than 40% did not have a USOC, with higher proportions among women with an APS, primary health-care based approaches to AEP prevention seem unlikely to reach the majority of women who have an APS and are at risk of an unintended pregnancy.

Implications for women of Louisiana's law requiring abortion providers to have hospital admitting privileges.

BACKGROUND: In 2014, Louisiana passed a law requiring abortion providers to have hospital admitting privileges. This law is temporarily on hold while a court case challenging it continues. We aimed to describe the population who would be affected if the law goes into effect and how closures of between three and five Louisiana abortion facilities would affect the distance Louisiana women would need to travel for an abortion. STUDY DESIGN: We abstracted patient data from three of the five Louisiana abortion care facilities in the year before the law was scheduled to take effect. We then estimated distance traveled and distances women would need to travel if clinics close. FINDINGS: Half (53%) of women who had an abortion had no education beyond high school, most were black (62%) or white (30%), three fourths (73%) had a previous live birth, and most (89%) were having a first-trimester abortion. Seventy-nine percent resided in Louisiana and 15% in Texas. The parishes in which abortion patients resided had lower median income and higher percentage poverty than the Louisiana average. Abortion patients residing in Louisiana traveled a mean distance of 58 miles each way for an abortion. If all Louisiana facilities close, the mean distance women would need to travel would more than triple to 208 miles, and the proportion of Louisiana women of reproductive age who live more than 150 miles from an abortion facility would increase from 1% to 72%. CONCLUSION: The admitting privileges law will likely significantly increase the distance Louisiana women need to travel for an abortion. This burden is likely to disproportionately affect Louisiana's more vulnerable residents. IMPLICATIONS: If all Louisiana abortion facilities close due to Louisiana's hospital admitting privileges law, the mean distance women would need to travel for an abortion would more than triple from 58 to 208 miles. Louisiana's law would thus present a considerable burden on many Louisiana women, particularly those who are more vulnerable.

A comparison of depression and anxiety symptom trajectories between women who had an abortion and women denied one.

BACKGROUND: This study prospectively assesses the mental health outcomes among women seeking abortions, by comparing women having later abortions with women denied abortions, up to 2 years post-abortion seeking. METHOD: We present the first 2 years of a 5-year telephone interview study that is following 956 women who sought an abortion from 30 facilities throughout the USA. We use adjusted linear mixed-effects regression analyses to assess whether symptoms of depression and anxiety, as measured by the Brief Symptom Inventory-short form and the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire, differ over time among women denied an abortion due to advanced gestational age, compared with women who received abortions. RESULTS: Baseline predicted mean depressive symptom scores for women denied abortion (3.07) were similar to women receiving an abortion just below the gestational limit (2.86). Depressive symptoms declined over time, with no difference between groups. Initial predicted mean anxiety symptoms were higher among women denied care (2.59) than among women who had an abortion just below the gestational limit (1.91). Anxiety levels in the two groups declined and converged after 1 year. CONCLUSIONS: Women who received an abortion had similar or lower levels of depression and anxiety than women denied an abortion. Our findings do not support the notion that abortion is a cause of mental health problems.

Does adopting a prenatal substance use protocol reduce racial disparities in CPS reporting related to maternal drug use? A California case study.

OBJECTIVE: This study examined whether adopting a standardized prenatal substance use protocol (protocol) in a hospital labor and delivery unit reduced racial disparities in reporting to child protective services (CPS) related to maternal drug use during pregnancy. STUDY DESIGN: This study used an interrupted time series design with a non-equivalent control. One hospital adopted a protocol and another hospital group serving a similar geographic population did not change protocols. Data on CPS reporting disparities from these hospitals over 3.5 years were analyzed using segmented regression. RESULT: In the hospital that adopted the protocol, almost five times more black than white newborns were reported during the study period. Adopting the protocol was not associated with reduced disparities. CONCLUSION: Adopting a protocol cannot be assumed to reduce CPS reporting disparities. Efforts to encourage hospitals to adopt protocols as a strategy to reduce disparities may be misguided. Other strategies to reduce disparities are needed.

Comparison of sensorineural symptoms between UK orthopaedic surgeons and gynaecologists.

BACKGROUND: We have previously described significant differences in self-reported neurological symptoms of orthopaedic surgeons when compared to a group of gynaecologists. We suggested that this may be secondary to occupational sources of hand-transmitted vibration. The original study was intentionally brief and failed to address potential confounders. AIMS: To compare the prevalence of sensorineural symptoms between UK orthopaedic surgeons and gynaecologists and adjust for potential confounding factors. METHODS: Postal questionnaires were sent to 2040 members of the British Orthopaedic Association and 1797 members of the Royal College of Gynaecologists requesting information about demographics and self-reported neurological symptoms. Demographics of the orthopaedic surgeons and gynaecologists were compared using chi-squared tests and independent t-tests. Multiple logistic regressions were carried out to compare the prevalence of symptoms while adjusting for potential confounding factors. RESULTS: Differences in the demographic profile of the orthopaedic surgeons and gynaecologists were identified: orthopaedic surgeons were predominantly male, were more junior in grade, were younger, used double gloving more often, had larger glove size, were more likely to be ambidextrous, to use vibrating tools outside of work and to consume greater amounts of alcohol. Orthopaedic surgeons reported a higher prevalence of tingling and numbness of fingers while at work and at other times. These differences were significant even after adjusting for potential confounding factors. CONCLUSION: Observed differences could be related to exposure to hand-transmitted vibration at work. Further assessment of risk to orthopaedic surgeons from hand-held power tools used in the course of their work is recommended.

Correlations between heterozygosity and measures of genetic similarity: implications for understanding mate choice.

There is currently considerable interest in testing the effects of genetic compatibility and heterozygosity on animal mate preferences. Evidence for either effect is rapidly accumulating, although results are not always clear-cut. However, correlations between mating preferences and either genetic similarity or heterozygosity are usually tested independently, and the possibility that similarity and heterozygosity may be confounded has rarely been taken into account. Here we show that measures of genetic similarity (allele sharing, relatedness) may be correlated with heterozygosity, using data from 441 human individuals genotyped at major loci in the major histocompatibility complex, and 281 peafowl (Pavo cristatus) individuals genotyped at 13 microsatellite loci. We show that average levels of allele sharing and relatedness are each significantly associated with heterozygosity in both humans and peafowl, that these relationships are influenced by the level of polymorphism, and that these similarity measures may correlate with heterozygosity in qualitatively different ways. We discuss the implications of these inter-relationships for interpretation of mate choice studies. It has recently become apparent that mating preferences for 'good genes' and 'compatible genes' may introduce discordant choice amongst individuals, since the optimal mate for one trait may not be optimal for the other, and our results are consistent with this idea. The inter-relationship between these measures of genetic quality also carries implications for the way in which mate choice studies are designed and interpreted, and generates predictions that can be tested in future research.

A simple method for enhancing paclitaxel release from Taxus canadensis cell suspension cultures utilizing cell wall digesting enzymes.

Paclitaxel storage in Taxus suspension cell cultures was studied through the simple use of cell wall digesting enzymes. The application of cellulase (1%) and pectolyase (0.1%) to Taxus canadensis suspension cultures induced a significant increase in the paclitaxel present in the extracellular medium while maintaining membrane integrity, suggesting that paclitaxel is stored in the cell wall. The addition of cell wall digesting enzymes to a cell culture bioprocess may be an effective way of enhancing paclitaxel release to the extracellular medium and hence simplify product recovery.

Polyamine biosynthetic enzymes as drug targets in parasitic protozoa.

Molecular, biochemical and genetic characterization of ornithine decarboxylase, S -adenosylmethionine decarboxylase and spermidine synthase establishes that these polyamine-biosynthetic enzymes are essential for growth and survival of the agents that cause African sleeping sickness, Chagas' disease, leishmaniasis and malaria. These enzymes exhibit features that differ significantly between the parasites and the human host. Therefore it is conceivable that exploitation of such differences can lead to the design of new inhibitors that will selectively kill the parasites while exerting minimal, or at least tolerable, effects on the parasite-infected patient.

Genetic analysis of spermidine synthase from Leishmania donovani.

The polyamine biosynthetic pathway of protozoan parasites has been validated as a target in antiparasitic chemotherapy. To investigate this pathway at the biochemical and genetic level in a model parasite, the gene encoding spermidine synthase (SPDSYN), a key polyamine biosynthetic enzyme, has been cloned and sequenced from Leishmania donovani. The L. donovani SPDSYN gene encodes a polypeptide of 300 amino acids that exhibits 56% amino acid identity with the human counterpart. SPDSYN is present as a single copy gene in the leishmanial genome and encodes a 1.6 kb transcript. Employing SPDSYN flanking sequences to construct drug resistance cassettes, a Deltaspdsyn knockout strain of L. donovani was created by double targeted gene replacement. This Deltaspdsyn line could not convert putrescine to spermidine and was auxotrophic for polyamines. The polyamine auxotrophy could be circumvented by exogenous spermidine but not by putrescine (1,4-diaminobutane), cadaverine (1,5-diaminopentane), 1,3-diaminopropane, or spermine. Incubation of the null mutant in polyamine-deficient medium resulted in a rapid depletion in the intracellular spermidine level with a concomitant elevation of the putrescine pool. In addition, the level of trypanothione, a spermidine-containing thiol, was reduced, whereas the glutathione pool increased 3-4-fold. These data establish that SPDSYN is an essential enzyme in L. donovani promastigotes. The molecular and cellular reagents created in this investigation provide a foundation for subsequent structure-function and inhibitor design studies on this key polyamine biosynthetic enzyme.

Sensitivity and specificity of denaturing high-pressure liquid chromatography for unknown protein C gene mutations.

Screening methods for unknown DNA sequence variations are laborious, expensive, and relatively insensitive. To evaluate the sensitivity and specificity of denaturing high-pressure liquid chromatography (DHPLC) screening for unknown protein C gene (PROC) mutations, we studied 31 PROC-deficient patients. Eleven amplimers containing 4 kb of the PROC gene and spanning all exons, splice junctions, and the putative promoter and 3'-untranslated regions were amplified by PCR for each patient. Each amplimer (n = 341) was sequenced with a fluorescence-based method, and screened by DHPLC. Sequencing identified 10 unique mutations and three polymorphisms. Combining all mutations and polymorphisms, 227 amplimers were homozygous wildtype, and 63 and 51 were heterozygous and homozygous mutant, respectively. DHPLC screening correctly identified all amplimers (100% sensitivity and specificity). DHPLC is a rapid, automated, sensitive and specific screening method for unknown mutations within the PROC gene, and may be a useful screening method for unknown mutations within other genes.

Energetic constraints on the diet of terrestrial carnivores.

Species in the mammalian order Carnivora exhibit a huge diversity of life histories with body sizes spanning more than three orders of magnitude. Despite this diversity, most terrestrial carnivores can be classified as either feeding on invertebrates and small vertebrates or on large vertebrates. Small carnivores feed predominantly on invertebrates probably because they are a superabundant resource (sometimes 90% of animal biomass); however, intake rates of invertebrate feeders are low, about one tenth of those of vertebrate feeders. Although small carnivores can subsist on this diet because of low absolute energy requirements, invertebrate feeding appears to be unsustainable for larger carnivores. Here we show, by reviewing the most common live prey in carnivore diets, that there is a striking transition from feeding on small prey (less than half of predator mass) to large prey (near predator mass), occurring at predator masses of 21.5-25 kg. We test the hypothesis that this dichotomy is the consequence of mass-related energetic requirements and we determine the predicted maximum mass that an invertebrate diet can sustain. Using a simple energetic model and known invertebrate intake rates, we predict a maximum sustainable mass of 21.5 kg, which matches the point where predators shift from small to large prey.

Ornithine decarboxylase gene deletion mutants of Leishmania donovani.

A knockout strain of Leishmania donovani lacking both ornithine decarboxylase (ODC) alleles has been created by targeted gene replacement. Growth of Deltaodc cells in polyamine-deficient medium resulted in a rapid and profound depletion of cellular putrescine pools, although levels of spermidine were relatively unaffected. Concentrations of trypanothione, a spermidine conjugate, were also reduced, whereas glutathione concentrations were augmented. The Deltaodc L. donovani exhibited an auxotrophy for polyamines that could be circumvented by the addition of the naturally occurring polyamines, putrescine or spermidine, to the culture medium. Whereas putrescine supplementation restored intracellular pools of both putrescine and spermidine, exogenous spermidine was not converted back to putrescine, indicating that spermidine alone is sufficient to meet the polyamine requirement, and that L. donovani does not express the enzymatic machinery for polyamine degradation. The lack of a polyamine catabolic pathway in intact parasites was confirmed radiometrically. In addition, the Deltaodc strain could grow in medium supplemented with either 1,3-diaminopropane or 1, 5-diaminopentane (cadaverine), but polyamine auxotrophy could not be overcome by other aliphatic diamines or spermine. These data establish genetically that ODC is an essential gene in L. donovani, define the polyamine requirements of the parasite, and reveal the absence of a polyamine-degradative pathway.

Blind analysis of denaturing high-performance liquid chromatography as a tool for mutation detection.

Denaturing high-performance liquid chromatography (DHPLC) is a novel high-capacity technique for detecting new mutations. We have evaluated the sensitivity and specificity of this method in a blind analysis of exon H of the factor IX gene and exon 16 of the neurofibromatosis type 1 gene. Under a single set of conditions for each exon, 55/55 individuals carrying 48 unique mutations were correctly identified as were 55/55 individuals with wildtype alleles. We conclude that DHPLC is a highly sensitive and specific method for mutation detection.

Combined use of six-well polystyrene plates and thin layer chromatography for rapid development of optimal plant cell culture processes: application to taxane production byTaxus sp.

TwoTaxus (T. chinensis andT. baccata) cell suspension cultures were used as a model system to demonstrate the similarities of biomass accumulation and secondary metabolite (taxane) production obtained from cultures in six-well polystyrene plates and glass shake flasks (25 ml and 125 ml). Interference from binding of taxanes in cell-free culture broth to the polystyrene plates was minimal with 85% of the paclitaxel (Taxol®) and 100% of baccatin and 10-deacetyl-7-xylosyl-taxol remaining in the medium after 24 h beyond which no further binding was observed. A simple thin layer chromatography (TLC) procedure with a chloroform: acentonitrile (4:1) solvent system on silica gel was developed to simultaneously test up to 17 cultures for taxane production. The combination of six-well plate technology for experimentation and TLC for rapid taxane analysis can greatly accelerate the establishment of conditions for an optimalTaxus plant-cell culture process for taxane production.