A global overview of midwives' working conditions: A rapid review of literature on positive practice environment.

BACKGROUND: In the United Kingdom (UK), a critical shortage of midwives puts pressure on the already overworked midwives working in maternity services. Considering the challenges that midwives in the UK face, this rapid review was conducted to inform a larger-scale initiative to improve the working conditions of midwives in an acute NHS Trust in the Midlands area of the UK. OBJECTIVE: To describe midwives' perceptions and experiences of positive practice environments. METHODS: A search strategy to identify literature about midwives' perceptions and experiences of positive practice environments was conducted in Medline, CINAHL Plus and Embase databases. Literature screening was conducted independently in two steps using an eligibility tool. The articles' quality assessment was conducted using the Mixed Method Appraisal Tool. Data were extracted using the Job Quality framework and managed using NVivo12. RESULTS: Seventy articles were included in this review. Midwives' working conditions can be improved in all seven areas of the Job Quality framework. Most articles in the review reported the negative aspects of midwives' working environments, making it challenging for the team to define a positive practice environment for midwives. Despite this, authors discuss that a positive practice environment is at least sustained by ensuring midwives' ability to provide care; providing good employment conditions; developing respectful organisations; and increasing team resources, such as those that improve team resilience. CONCLUSIONS: Midwives' working conditions are universally challenging. Failure to address the situation will compromise recruitment and retention, increasing the shortage of midwives. Provision of safe and respectful care appears to be directly linked to midwives' safe and respectful working conditions.

Guava (Psidium guajava L.): a glorious plant with cancer preventive and therapeutic potential.

Guava (Psidium guajava L.) tree (Myrtaceae family) bears fruit rich in vitamins, fiber, and other nutrients. While native to Latin America, guava is grown in many tropical and subtropical regions across the globe where it has long been used in traditional medicine to treat a myriad of ailments. Guava has been shown to exhibit a number of biological and pharmacological activities, such as antioxidant, anti-inflammatory, immunomodulatory, antimicrobial, antidiabetic, and anticancer properties. Several parts of the plant, including the leaves, fruits, seeds, peels, pulp, bark, and oil, produce phytochemicals with medicinal properties. Emerging research has found that guava bioactive phytochemicals exert antitumorigenic effects against various human malignancies through multiple mechanisms. While there are numerous individual studies that document the anticancer effects of guava constituents, an up-to-date, comprehensive, and critical review of available research data has not been performed. Therefore, the purpose of this review is to present a complete analysis of the cancer preventive and anticancer therapeutic potential of guava-derived products and guava constituents, with a focus on the cellular and molecular mechanisms of action. The bioavailability, pharmacokinetics, and toxicity of guava as well as limitations, challenges, and future directions of research have also been discussed.

Papaya (Carica papaya L.) for cancer prevention: Progress and promise.

Cancer is a leading cause of morbidity and mortality across the globe. Emerging evidence suggests that consumption of a well-balanced diet containing a wide variety of vegetables, fruits, and whole grains can prevent the development of, halt, or reverse cancer progression. Carica papaya L. (papaya) has a wide distribution throughout many countries. Although the fruits of C. papaya are primarily consumed as food, various parts of this tree, including the bark, fruits, latex, seeds, and roots, have been used in traditional medicine for health promotion and disease mitigation. While numerous individual studies have investigated anticancer efficacies of various products and constituents of C. papaya, an up-to-date, comprehensive, and critical evaluation of available research data covering its role in the prevention and intervention of various human malignancies has not been conducted according to our knowledge. The purpose of this review is to present a systematic, comprehensive, and critical analysis of the cancer-preventive potential of C. papaya extracts, fractions, and isolated phytochemicals with a special emphasis on the cellular and molecular mechanisms of action. Moreover, the bioavailability, pharmacokinetics, and safety profiles of individual phytochemicals of C. papaya, as well as current limitations, challenges, and future directions of research, have also been discussed.

Field Evaluation of Tiletamine-Zolazepam-Medetomidine for Immobilization of Raccoons (Procyon lotor) and Striped Skunks (Mephitis mephitis).

The effectiveness of tiletamine-zolazepam (1.7 mg/kg) plus medetomidine (0.07 mg/kg; TZM) as an immobilizing combination in raccoons (Procyon lotor; n=43) and striped skunks (Mephitis mephitis; n=7) was evaluated during October 2019. Mean (±SD) induction time for raccoons was 15.0±6.6 min. First signs of recovery (head up) occurred 12.9±6.0 min after receiving atipamezole reversal (0.35 mg/kg) and animals were standing in 30.3±16.1 min. Mean induction time for skunks was 11.7±5.8 min. Following reversal, skunks first raised their heads in 6.7±4.3 min and stood in 17.1±12.9 min. Recovery in skunks and female raccoons was not related to length of time immobilized, but male raccoons that were immobilized for longer periods of time stood faster after reversal. Raccoon heart rate (HR) remained steady during immobilization, but respiration rate (RR) and rectal temperature (RT) declined. The HR and RR were similar among males and females, but RT of male raccoons were, on average, 0.5 C higher than those of females, and rate of temperature decline was slower for males. The HR, RR, and RT of skunks declined during immobilization. Although induction times for both raccoons and skunks were longer than expected, induction and recovery were smooth, side effects were few, analgesia was adequate for nonsurgical procedures, and reversal reduced time in captivity.

Xanthohumol for Human Malignancies: Chemistry, Pharmacokinetics and Molecular Targets.

Xanthohumol (XH) is an important prenylated flavonoid that is found within the inflorescence of Humulus lupulus L. (Hop plant). XH is an important ingredient in beer and is considered a significant bioactive agent due to its diverse medicinal applications, which include anti-inflammatory, antimicrobial, antioxidant, immunomodulatory, antiviral, antifungal, antigenotoxic, antiangiogenic, and antimalarial effects as well as strong anticancer activity towards various types of cancer cells. XH acts as a wide ranging chemopreventive and anticancer agent, and its isomer, 8-prenylnaringenin, is a phytoestrogen with strong estrogenic activity. The present review focuses on the bioactivity of XH on various types of cancers and its pharmacokinetics. In this paper, we first highlight, in brief, the history and use of hops and then the chemistry and structure-activity relationship of XH. Lastly, we focus on its prominent effects and mechanisms of action on various cancers and its possible use in cancer prevention and treatment. Considering the limited number of available reviews on this subject, our goal is to provide a complete and detailed understanding of the anticancer effects of XH against different cancers.

Neuroprotective Potential of Ellagic Acid: A Critical Review.

Ellagic acid (EA) is a dietary polyphenol present in various fruits, vegetables, herbs, and nuts. It exists either independently or as part of complex structures, such as ellagitannins, which release EA and several other metabolites including urolithins following absorption. During the past few decades, EA has drawn considerable attention because of its vast range of biological activities as well as its numerous molecular targets. Several studies have reported that the oxidative stress-lowering potential of EA accounts for its broad-spectrum pharmacological attributes. At the biochemical level, several mechanisms have also been associated with its therapeutic action, including its efficacy in normalizing lipid metabolism and lipidemic profile, regulating proinflammatory mediators, such as IL-6, IL-1ß, and TNF-α, upregulating nuclear factor erythroid 2-related factor 2 and inhibiting NF-κB action. EA exerts appreciable neuroprotective activity by its free radical-scavenging action, iron chelation, initiation of several cell signaling pathways, and alleviation of mitochondrial dysfunction. Numerous in vivo studies have also explored the neuroprotective attribute of EA against various neurotoxins in animal models. Despite the increasing number of publications with experimental evidence, a critical analysis of available literature to understand the full neuroprotective potential of EA has not been performed. The present review provides up-to-date, comprehensive, and critical information regarding the natural sources of EA, its bioavailability, metabolism, neuroprotective activities, and underlying mechanisms of action in order to encourage further studies to define the clinical usefulness of EA for the management of neurological disorders.

Correction: MicroRNA regulation of persistent stress-enhanced memory.

A correction to this paper has been published and can be accessed via a link at the top of the paper.

MicroRNA regulation of persistent stress-enhanced memory.

Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stress disorder (PTSD) and related syndromes, which develop in a subset of individuals following a traumatic event. We previously developed a stress-enhanced fear learning (SEFL) paradigm in inbred mice that produces PTSD-like characteristics in a subset of mice, including persistently enhanced memory and heightened cFos in the basolateral amygdala complex (BLC) with retrieval of the remote (30-day-old) stress memory. Here, the contribution of BLC microRNAs (miRNAs) to stress-enhanced memory was investigated because of the molecular complexity they achieve through their ability to regulate multiple targets simultaneously. We performed small-RNA sequencing (smRNA-Seq) and quantitative proteomics on BLC tissue collected from mice 1 month after SEFL and identified persistently changed microRNAs, including mir-135b-5p, and proteins associated with PTSD-like heightened fear expression. Viral-mediated overexpression of mir-135b-5p in the BLC of stress-resilient animals enhanced remote fear memory expression and promoted spontaneous renewal 14 days after extinction. Conversely, inhibition of BLC mir-135b-5p in stress-susceptible animals had the opposite effect, promoting a resilient-like phenotype. mir-135b-5p is highly conserved across mammals and was detected in post mortem human amygdala, as well as human serum samples. The mir-135b passenger strand, mir-135b-3p, was significantly elevated in serum from PTSD military veterans, relative to combat-exposed control subjects. Thus, miR-135b-5p may be an important therapeutic target for dampening persistent, stress-enhanced memory and its passenger strand a potential biomarker for responsivity to a mir-135-based therapeutic.

microRNA mir-598-3p mediates susceptibility to stress enhancement of remote fear memory.

microRNAs (miRNAs) have emerged as potent regulators of learning, recent memory, and extinction. However, our understanding of miRNAs directly involved in regulating complex psychiatric conditions perpetuated by aberrant memory, such as in posttraumatic stress disorder (PTSD), remains limited. To begin to address the role of miRNAs in persistent memories, we performed small-RNA sequencing on basolateral amygdala (BLA) tissue and identified miRNAs altered by auditory fear conditioning (FC) one month after training. mir-598-3p, a highly conserved miRNA previously unstudied in the brain, was down-regulated in the BLA. Further decreasing BLA mir-598-3p levels did not increase strength of the remote fear memory. Given that stress is a critical component in PTSD, we next assessed the impact of stress and stress-enhanced fear learning (SEFL) on mir-598-3p levels, finding the miRNA is elevated in the BLA of male, but not female, mice susceptible to the effects of stress in SEFL. Accordingly, intra-BLA inhibition of mir-598-3p interfered with expression and extinction of the remote fear memory in male, but not female, mice. This effect could not be attributed to an anxiolytic effect of miRNA inhibition. Finally, bioinformatic analysis following quantitative proteomics on BLA tissue collected 30 d post-SEFL training identified putative mir-598-3p targets and related pathways mediating the differential susceptibility, with evidence for regulation of the actin cytoskeleton, the core mediator of structural plasticity. Taken together, the results suggest BLA mir-598-3p may be recruited by stress to mediate a critical switch from a salient remote fear memory to one that is enhanced and extinction-resistant.

ONRAB® oral rabies vaccine is shed from, but does not persist in, captive mammals.

ONRAB® is a human adenovirus rabies glycoprotein recombinant vaccine developed to control rabies in wildlife. To support licensing and widespread use of the vaccine, safety studies are needed to assess its potential residual impact on wildlife populations. We examined the persistence of the ONRAB® vaccine virus in captive rabies vector and non-target mammals. This research complements work on important rabies vector species (raccoon, striped skunk, and red fox) but also adds to previous findings with the addition of some non-target species (Virginia opossum, Norway rats, and cotton rats) and a prolonged period of post vaccination monitoring (41 days). Animals were directly inoculated orally with the vaccine and vaccine shedding was monitored using quantitative real-time PCR applied to oral and rectal swabs. ONRAB® DNA was detected in both oral and rectal swabs from 6 h to 3 days post-inoculation in most animals, followed by a resurgence of shedding between days 17 and 34 in some species. Overall, the duration over which ONRAB® DNA was detectable was shorter for non-target mammals, and by day 41, no animal had detectable DNA in either oral or rectal swabs. All target species, as well as cotton rats and laboratory-bred Norway rats, developed robust humoral immune responses as measured by competitive ELISA, with all individuals being seropositive at day 31. Similarly, opossums showed good response (89% seropositive; 8/9), whereas only one of nine wild caught Norway rats was seropositive at day 31. These results support findings of other safety studies suggesting that ONRAB® does not persist in vector and non-target mammals exposed to the vaccine. As such, we interpret these data to reflect a low risk of adverse effects to wild populations following distribution of ONRAB® to control sylvatic rabies.

Serum prolactin and testosterone levels in captive and wild brown kiwi (Apteryx mantelli) during the prebreeding, breeding, and incubation periods.

In brown kiwi (Apteryx mantelli), the male is the primary incubator, a trait that is relatively rare among birds. The maintenance of avian incubation behavior is controlled by the protein hormone prolactin (PRL). Although steroid hormone concentrations in both wild and captive kiwi have previously been reported, this study is the first to report levels of PRL in captive and wild male and female kiwi through the prebreeding and breeding seasons, and to directly compare testosterone (T) concentrations between captive and wild males during the breeding and incubation periods. Female PRL concentrations increased at the time of oviposition, whereas male PRL concentrations rose gradually between the prebreeding and incubation periods. Although males are considered the main incubator, an increase in PRL levels could help females maintain behaviors such as nest guarding, or to take over incubation the event of mate loss. A gradual increase in PRL allows the male to be ready for incubation during the long breeding season. Interestingly, T concentrations in captive males did not decrease during incubation and was significantly higher than in wild males. Continual elevated T could have an impact on sperm production through negative feedback, thereby contributing to the low egg fertility seen in captive kiwi. Therefore, determining the underlying reason for the differences in hormone levels could be significant, if not vital, for improving the success of captive kiwi breeding programs.

Bioinformatic analysis of long-lasting transcriptional and translational changes in the basolateral amygdala following acute stress.

Stress profoundly impacts the brain and increases the risk of developing a psychiatric disorder. The brain's response to stress is mediated by a number of pathways that affect gene expression and protein function throughout the cell. Understanding how stress achieves such dramatic effects on the brain requires an understanding of the brain's stress response pathways. The majority of studies focused on molecular changes have employed repeated or chronic stress paradigms to assess the long-term consequences of stress and have not taken an integrative genomic and/or proteomic approach. Here, we determined the lasting impact of a single stressful event (restraint) on the broad molecular profile of the basolateral amygdala complex (BLC), a key brain region mediating emotion, memory and stress. Molecular profiling performed thirty days post-restraint consisted of small RNA sequencing, RNA sequencing and quantitative mass spectrometry and identified long-lasting changes in microRNA (miRNA), messenger RNA (mRNA) and proteins. Alignment of the three datasets further delineated the regulation of stress-specific pathways which were validated by qPCR and Western Blot analysis. From this analysis, mir-29a-5p was identified as a putative regulator of stress-induced adaptations in the BLC. Further, a number of predicted mir-29a-5p targets are regulated at the mRNA and protein level. The concerted and long-lasting disruption of multiple molecular pathways in the amygdala by a single stress event is expected to be sufficient to alter behavioral responses to a wide array of future experiences, including exposure to additional stressors.

Social stress-potentiated methamphetamine seeking.

Human studies of substance use disorder show that psychological stress and drug availability interact following rehabilitation, contributing to the high relapse potential. Social stressors trigger particularly strong motivation for drug, but how this affects neuronal function to increase relapse is unknown. Animal models, which allow for the dissection of neural mechanisms, primarily utilize physical stressors to trigger relapse. To recapitulate psychosocial post-rehabilitation challenges in animals, we developed a model of social stress-potentiated methamphetamine (METH) seeking. Rats receive a single social defeat (SD) session after completion of self-administration and extinction of lever pressing. While a reminder of the SD was insufficient to reinstate METH seeking on its own, rats that received a reminder of SD followed by a METH-priming injection displayed potentiated reinstatement over METH-priming alone. Examination of neuronal activation patterns of the METH-primed reinstatement session identified c-Fos-immunoreactivity in the basolateral amygdala (BLA) as correlated with SD score, a measure of defeat latency. Rapidly defeated rats showed potentiated METH-primed reinstatement and elevated BLA c-Fos compared with controls. Conversely, rats that were undefeated during the social stress did not show potentiated METH-primed reinstatement or elevated BLA c-Fos. Interestingly, inactivation of the BLA with baclofen/muscimol prior to the stress reminder and METH-priming generated a potentiation of METH seeking in the undefeated rats, suggesting the BLA may mediate resilience to the stressor. This model provides a tool for the further dissection of neural mechanisms mediating social stress-potentiated relapse and for the development of relapse-reducing therapeutics.

Susceptibility and Resilience to Posttraumatic Stress Disorder-like Behaviors in Inbred Mice.

BACKGROUND: The limited neurobiological understanding of posttraumatic stress disorder (PTSD) has been partially attributed to the need for improved animal models. Stress-enhanced fear learning (SEFL) in rodents recapitulates many PTSD-associated behaviors, including stress-susceptible and stress-resilient subgroups in outbred rats. Identification of subgroups requires additional behavioral phenotyping, a confound to mechanistic studies. METHODS: We employed a SEFL paradigm in inbred male and female C57BL/6 mice that combines acute stress with fear conditioning to precipitate traumatic-like memories. Extinction and long-term retention of extinction were examined after SEFL. Further characterization of SEFL effects on male mice was performed with additional behavioral tests, determination of regional activation by Fos immunofluorescence, and RNA sequencing of the basolateral amygdala. RESULTS: Stressed animals displayed persistently elevated freezing during extinction. While more uniform in females, SEFL produced male subgroups with differential susceptibility that were identified without posttraining phenotyping. Additional phenotyping of male mice revealed PTSD-associated behaviors, including extinction-resistant fear memory, hyperarousal, generalization, and dysregulated corticosterone in stress-susceptible male mice. Altered Fos activation was also seen in the infralimbic cortex and basolateral amygdala of stress-susceptible male mice after remote memory retrieval. Key behavioral outcomes, including susceptibility, were replicated by two independent laboratories. RNA sequencing of the basolateral amygdala revealed transcriptional divergence between the male subgroups, including genes with reported polymorphic association to patients with PTSD. CONCLUSIONS: This SEFL model provides a tool for development of PTSD therapeutics that is compatible with the growing number of mouse-specific resources. Furthermore, use of an inbred strain allows for investigation into epigenetic mechanisms that are expected to critically regulate susceptibility and resilience.

Thin-Film Carbon Nanofuses for Permanent Data Storage.

In this study, we have fabricated nanofuses from thin-film, arc-deposited carbon for use in permanent data storage. Thin-film carbon fuses have fewer fabrication barriers and retain the required resistivity and structural stability to act as a data-storage medium. Carbon thin films were characterized for their electrical, microstructural, and chemical bonding properties. Annealing these films in an argon environment at 400 °C reduced the resistivity from about 4 × 10-2 Ω cm as deposited to about 5 × 10-4 Ω cm, allowing a lower blowing voltage. Nanofuses with widths ranging from 200 to 60 nm were fabricated and tested. They blow with voltages between 2 and 5.5 V, and the nanofuses remain stable in both "1" and "0" states under a constantly applied read voltage of 1 V for over 90 h.

Iatrogenic Femoral Neck Fracture After Closed Reduction of Anterior Hip Dislocation in the Emergency Department.

This is a case report detailing an iatrogenic femoral neck fracture (FNF) after closed reduction of an anterior hip dislocation. While iatrogenic FNF is a known complication of closed reduction, there are few published reports of the circumstances surrounding these fractures, and there has been no discussion of possible risk factors predisposing to this injury. This case report and review of the literature identifies the current incidence of FNF with closed reduction of anterior dislocations of the hip, as well as possible antecedent risk factors for this complication. As a result of this case report, we have changed our protocol for treatment of these injuries.

Leg hammock for closed reduction of tibial shaft fractures.

Tibial shaft fractures are common injuries in emergency departments (EDs). Although many of these fractures require surgery, nearly all are stabilized in the ED with a long leg splint or bivalved cast. Long leg splinting is often challenging for a single health care provider. Further, even with assistance or previously described techniques for fracture reduction and stabilization, fracture angulation may occur, potentially leading to pain for the patient, fracture displacement, or further soft tissue injury. The authors propose a method for splinting tibial fractures that avoids fracture angulation, is cost-effective and quick, and can be easily performed by a single health care provider.

Prevalence of marine debris in marine birds from the North Atlantic.

Marine birds have been found to ingest plastic debris in many of the world's oceans. Plastic accumulation data from necropsies findings and regurgitation studies are presented on 13 species of marine birds in the North Atlantic, from Georgia, USA to Nunavut, Canada and east to southwest Greenland and the Norwegian Sea. Of the species examined, the two surface plungers (great shearwaters Puffinus gravis; northern fulmars Fulmarus glacialis) had the highest prevalence of ingested plastic (71% and 51%, respectively). Great shearwaters also had the most pieces of plastics in their stomachs, with some individuals containing as many of 36 items. Seven species contained no evidence of plastic debris. Reporting of baseline data as done here is needed to ensure that data are available for marine birds over time and space scales in which we see changes in historical debris patterns in marine environments (i.e. decades) and among oceanographic regions.

Do purely capital layers exist among flying birds? Evidence of exogenous contribution to arctic-nesting common eider eggs.

The strategy of relying extensively on stored resources for reproduction has been termed capital breeding and is in contrast to income breeding, where needs of reproduction are satisfied by exogenous (dietary) resources. Most species likely fall somewhere between these two extremes, and the position of an organism along this gradient can influence several key life-history traits. Common eiders (Somateria mollissima) are the only flying birds that are still typically considered pure capital breeders, suggesting that they depend exclusively on endogenous reserves to form their eggs and incubate. We investigated the annual and seasonal variation in contributions of endogenous and exogenous resources to egg formation in eiders breeding at the East Bay colony in the Canadian Arctic. We collected prey items along with females and their eggs during various stages of breeding and used two complementary analytical approaches: body reserve dynamics and stable isotope [δ(13)C, δ(15)N] mixing models. Indices of protein reserves remained stable from pre-laying to post-laying stages, while lipid reserves declined significantly during laying. Similarly, stable isotope analyses indicated that (1) exogenous nutrients derived from marine invertebrates strongly contributed to the formation of lipid-free egg constituents, and (2) yolk lipids were constituted mostly from endogenous lipids. We also found evidence of seasonal variation in the use of body reserves, with early breeders using proportionally more exogenous proteins to form each egg than late breeders. Based on these results, we reject the hypothesis that eiders are pure capital layers. In these flying birds, the fitness costs of a strict capital breeding strategy, such as temporary loss of flight capability and limitation of clutch and egg size, may outweigh benefits such as a reduction in egg predation rate.

Dialectical behaviour therapy in an Irish community mental health setting.

OBJECTIVES: Dialectical behaviour therapy (DBT) is a recommended treatment of patients with borderline personality disorder, yet there are few descriptions of the approach in public community mental health settings where the majority of such patients present. This study describes the development and evaluation of a DBT programme in an Irish setting. METHODS: The DBT programme was run over a six month period. Participants were assessed at baseline and post intervention with the following instruments: The Structured Clinical Interview for DSM III R personality disorders (SCID II), the clinical Outcomes in Routine Evaluation (CORE) and the symptom checklist 90 Revised (SCL-90-Revised). Inpatient bed usage was determined from case note review. RESULTS: Outcome data was available for eight subjects. Significant improvement (p < 0.005) was seen on all CORE subscales. SCL-90-R showed significant improvement (p < 0.05) on the global severity index and on the positive symptom distress index. A decrease in self harming behaviour was found. Subjects' inpatient bed days dropped from a mean of 58 in the year pre intervention to a mean of four days in the year post intervention. A novel finding was that 43% of subjects who originally fulfilled criteria for avoidant personality disorder no longer did so post intervention. CONCLUSIONS: The study found that DBT can be applied in a community mental health setting with benefits similar to more specialist settings. Significant difficulties were encountered in implementing the programme. The clinical implications are that specialist psychotherapy services need to be an integral part of psychiatric services to achieve better outcomes for patients with borderline personality disorder.