Breast milk transmission of flaviviruses in the context of Zika virus: A systematic review

Background

Since the Zika virus epidemic in the Americas began in 2015, Zika virus transmission has occurred throughout the Americas. However, limited information exists regarding possible risks of transmission of Zika virus and other flaviviruses through breast feeding and human milk. We conducted a systematic review of the evidence regarding flaviviruses detection in and transmission through milk, specifically regarding Zika virus, Japanese encephalitis virus, tick‐borne encephalitis virus, Powassan virus, West Nile virus, dengue virus, and yellow fever virus.

Methods

Medline, Embase, Global Health, CINAHL , Cochrane Library, Scopus, Popline, Virtual Health Library, and WorldCat were searched through June 2017. Two authors independently screened potential studies for inclusion and extracted data. Human and nonhuman (animal) studies describing: 1) confirmed or suspected cases of mother‐to‐child transmission through milk; or 2) the presence of flavivirus genomic material in milk.

Results

Seventeen studies were included, four animal models and thirteen observational studies. Dengue virus, West Nile virus, and Zika virus viral ribonucleic acid was detected in human milk, including infectious Zika virus and dengue virus viral particles. Human breast‐feeding transmission was confirmed for only yellow fever virus. There was evidence of milk‐related transmission of dengue virus, Powassan virus, and West Nile virus in animal studies.

Conclusions

Because the health advantages of breast feeding are considered greater than the potential risk of transmission, the World Health Organization recommends that mothers with possible or confirmed Zika virus infection or exposure continue to breast feed. This review did not identify any data that might alter this recommendation.

     

ASO Research Letter: Trends in Location of Death for Individuals with Pancreatic Cancer in the United States

Annals of Surgical Oncology -     

Sertraline effects on cerebrospinal fluid monoamines and species-typical socioemotional behavior of female cynomolgus monkeys

Rationale

Although widely prescribed, little is known about the effects of selective serotonin reuptake inhibitors (SSRIs) on social behavior and cerebrospinal fluid (CSF) monoamines in female primates.

Objective

The objective of this study was to determine the effects of sertraline on agonistic and affiliative behavior.

Methods

Twenty-one adult female cynomolgus monkeys were housed in small, stable social groups, trained to participate in oral dosing, and began a 5-week cumulative dose–response study. Serial doses of 0, 5, 10, 15, and 20 mg/kg of sertraline were administered orally for 1 week each. Behavior was recorded daily during 10-min observations before and 4 h after dosing. On the seventh day of dosing, circulating sertraline/desmethylsertraline and CSF monoamines/metabolites were determined 4 h after the last dose.

Results

At 20 mg/kg, circulating sertraline/desmethylsertraline was in the therapeutic range. CSF 5-hydroxyindole acetic acid decreased by 33 % (p?<?0.05). Overall aggression, submission, locomotion, and time alone decreased, whereas affiliative behaviors (body contact, grooming) increased (all p values <0.05). Effects of sertraline on aggression and submission were social status-dependent, reducing aggression in dominants and submission in subordinates.

Conclusions

A clinically relevant oral dose of sertraline resulted in CSF metabolite changes similar to those observed in patients and altered the socioemotional behavior of female monkeys. Changes in CSF 5-HT and dopamine are novel observations that may be sex-specific. The robust effects of sertraline on aggression and affiliation may explain the efficacy of SSRIs on a range of human behavioral pathologies that share the characteristics of increased aggression and decreased sociality.     

Intracerebroventricular corticotropin-releasing factor increases limbic glucose metabolism and has social context-dependent behavioral effects in nonhuman primates

Corticotropin-releasing factor (CRF) is a neuropeptide involved in integrating the behavioral, autonomic, and hormonal responses to stress within the central nervous system. Patients suffering from depression have abnormal activity in stress responsive brain regions and elevated cerebrospinal fluid CRF. The DSM-IV criteria for major depressive disorder include behavioral changes such as depressed mood, anhedonia, and psychomotor agitation/retardation. We studied the effects of 434 microgram of CRF given intracerebroventricularly over 40 min in group and individually housed monkeys to examine the role of elevated levels of central CRF on behavior. CRF elicited a wide range of behaviors, which fell into three broad categories: anxiety-like, depressive-like, and externally oriented. Externally oriented behaviors decreased, and anxiety-like behaviors increased regardless of how the animals were housed. Interestingly, increased depressive-like behaviors were only observed when the animals were socially housed. In a separate experiment, we examined the effects of the same dose of CRF on the regional cerebral glucose metabolism of lightly anesthetized monkeys by using positron emission tomography and [(18)F]fluorodeoxyglucose. CRF infusion increased glucose metabolism in the pituitary/infundibulum, the amygdala, and hippocampus. These results indicate that increased central CRF tone affects primate behavior in a context-dependent manner, and that it activates limbic and stress-responsive regions. The fact that intracerebroventricular CRF increases depressive-like behavior in socially housed animals and increases activity in limbic brain regions may help explain the behavioral and metabolic alterations in humans with affective disorders, and this model could therefore have significant value in the development of novel antidepressant treatments.     

Structural approaches for prevention of sexually transmitted HIV in general populations: definitions and an operational approach

Introduction

Although biomedical HIV prevention efforts have seen a number of recent promising developments, behavioural interventions have often been described as failing. However, clear lessons have been identified from past efforts, including the need to address influential social, economic and legal structures; to tailor efforts to local contexts; and to address multiple influencing factors in combination. Despite these insights, there remains a pervasive strategy to try to achieve sexual behaviour change through single, decontextualized, interventions or sets of activities. With current calls for structural approaches to HIV as part of combination HIV prevention, though, there is a unique opportunity to define a structural approach to HIV prevention as one which moves beyond these past limitations and better incorporates our knowledge of the social world and the lessons from past efforts.

Discussion

A range of interlinked concepts require delineation and definition within the broad concept of a structural approach to HIV. This includes distinguishing between “structural factors,” which can be seen as any number of elements (other than knowledge) which influence risk and vulnerability, and “structural drivers,” which should be reserved for situations where an empirically established relationship to a target group is known. Operationalizing structural approaches similarly can take different paths, either working to alter structural drivers or alternatively working to build individual and community resilience to infection. A “structural diagnostic approach” is further defined as the process one undertakes to develop structural intervention strategies tailored to target groups.

Conclusions

For three decades, the HIV prevention community has struggled to reduce the spread of HIV through sexual risk behaviours with limited success, but equally with limited engagement with the lessons that have been learned about the social realities shaping patterns of sexual practices. Future HIV prevention efforts must address the multiple factors influencing risk and vulnerability, and they must do so in ways tailored to particular settings. Clarity on the concepts, terminology and approaches that can allow structural HIV prevention efforts to achieve this is therefore essential to improve the (social) science of HIV prevention.     

Effects of aging on lower urinary tract and pelvic floor function in nulliparous women

OBJECTIVE: To evaluate the effects of aging, independent of parity, on pelvic organ and urethral support, urethral function, and levator function in a sample of nulliparous women. METHODS: A cohort of 82 nulliparous women, aged 21-70 years, were recruited from the community through advertisements. Subjects underwent pelvic examination using pelvic organ prolapse quantification, urethral angles by cotton-tipped swab, and multichannel urodynamics and uroflow. Vaginal closure force was quantified using an instrumented vaginal speculum. Subjects were grouped into five age categories and analyses performed using t tests, Fisher exact tests, Kruskal-Wallace, and Pearson correlation coefficients. Multiple linear regression modeling was performed to adjust for factors that might confound the results of our primary outcomes. RESULTS: Increasing age was associated with decreasing maximal urethral closure pressure (r=-0.758, P<.001) with a 15-cm-H(2)O decrease in pressure per decade. Pelvic organ support as measured by pelvic organ prolapse quantification did not differ by age group. Levator function as measured by resting vaginal closure force and augmentation of vaginal closure force also did not change with increasing age. CONCLUSION: In a sample of nulliparous women between 21 and 70 years of age maximal urethral closure pressure in the senescent urethra was 40% of that in the young urethra; increasing age did not affect clinical measures of pelvic organ support, urethral support, and levator function. LEVEL OF EVIDENCE: III.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Plant immunity: Rice XA21-mediated resistance to bacterial infection

In this article, we describe the development of the plant immunity field, starting with efforts to understand the genetic basis for disease resistance, which ∼30 y ago led to the discovery of diverse classes of immune receptors that recognize and respond to infectious microbes. We focus on knowledge gained from studies of the rice XA21 immune receptor that recognizes RaxX (required for activation of XA21 mediated immunity X), a sulfated microbial peptide secreted by the gram-negative bacterium Xanthomonas oryzae pv. oryzae. XA21 is representative of a large class of plant and animal immune receptors that recognize and respond to conserved microbial molecules. We highlight the complexity of this large class of receptors in plants, discuss a possible role for RaxX in Xanthomonas biology, and draw attention to the important role of sulfotyrosine in mediating receptor–ligand interactions.

Perception of extracellular signals by cell-surface receptors is of central importance to eukaryotic development and immunity. For example, in the absence of an adaptive immune system, plants rely on a repertoire of innate immune receptors to recognize potential pathogens and initiate defensive responses. A key research focus of the P.R. laboratory is to understand the principles and mechanisms that underlie the processes governing the immune response.Here we describe our 30-y effort to dissect the genetic and molecular basis of the innate immune response in the staple food crop and model organism rice Oryza sativa.