Implementation of an Enhanced Recovery after Surgery Pathway to Reduce Inpatient Opioid Consumption after Cesarean Delivery.

OBJECTIVE: Opioid prescription after cesarean delivery is excessive and can lead to chronic opioid use disorder. We assessed the impact of an enhanced recovery after surgery (ERAS) pathway on inpatient opioid consumption after cesarean delivery. STUDY DESIGN: An ERAS pathway was implemented as a quality improvement initiative in December 2019. Preintervention (PRE) data were collected from March to May 2019 to assess baseline opioid consumption. Postintervention (POST) data were collected from January to March 2020. The primary outcome was inpatient postoperative opioid consumption in morphine milligram equivalents (MME). Secondary outcomes included the consumption of any opioids, postpartum length of stay, and opioid prescription at discharge. RESULTS: A total of 92 women were in the PRE group and 91 were in the POST group. Inpatient opioid consumption decreased by 87.3% from PRE to POST, from 124.7 (interquartile range [IQR]: 10-181.6) MME to 15.8 (IQR: 0-75) MME (p < 0.001). There was no difference in median postpartum length of stay (3.4 days PRE vs. 3.3 days POST; p = 0.12). The proportion of women who did not consume any opioids increased by 75.4% from PRE to POST (p = 0.02). The proportion of women discharged with an opioid prescription decreased by 25.6% from PRE to POST (p = 0.007), despite no formal change to prescribing practices. After adjustment for differences in race/ethnicity and gravidity, there was still a reduction in total inpatient opioid consumption (p < 0.001) and an increase in the proportion of women not consuming any opioids (adjusted relative risk (RR): 2.14, 95% confidence interval [CI]: 1.18-3.87), but the difference in rate of prescription of opioids at discharge was no longer statistically significant (adjusted RR: 0.70, 95% CI: 0.48-1.02). CONCLUSION: Adoption of an ERAS pathway for cesarean delivery resulted in a marked reduction in inpatient opioid consumption. Such a pathway can be implemented across institutions and may be a powerful tool in combating the opioid epidemic. KEY POINTS: · ERAS after cesarean reduces inpatient opioid consumption.. · ERAS after cesarean increases the proportion of women not consuming any opioids.. · This pathway can be feasibly adopted elsewhere..

Surviving and thriving - a mixed-methods study of staff experiences of occupational wellbeing in a psychiatric place of safety service.

BACKGROUND: Under the S136 of the UK Mental Health Act, people experiencing a mental health crisis may be taken to a locally agreed location (Place of Safety) by police for urgent assessment. Research has shown that mental health professionals (MHPs) face high levels of burnout, but we know very little about the particular challenges staff who work in extreme clinical settings such as a Place of Safety service face. AIM: This study aimed to fill this gap by exploring the wellbeing experiences of staff in a Place of Safety service. METHOD: A mixed-methods approach was used, with quantitative data on job satisfaction (Job Satisfaction Survey) and burnout (Maslach Burnout Inventory-Human Services Survey) and qualitative data from focus groups. Purposive sampling was used. Qualitative data was analysed using thematic analysis and descriptive statistics were calculated for the quantitative data. RESULTS: Twenty staff scored within the moderate range for emotional exhaustion, depersonalisation and personal accomplishment, and in the satisfied range for job satisfaction. Three overarching themes were identified: (i) united as insiders, (ii) surviving and thriving, and (iii) narratives of coping. CONCLUSIONS: Despite unique setting-related stressors, participants showed comparable levels of wellbeing to other MHPs. Implications are discussed.

Epistemic injustice amongst clinical and non-clinical voice-hearers: A qualitative thematic analysis study.

OBJECTIVES: Research has suggested people who hear voices may be at risk of epistemic injustice. This is a form of discrimination whereby someone is unfairly judged to be an unreliable knower (testimonial injustice) or is unable to contribute to, and therefore access, concepts that make sense of their experience within mainstream society (hermeneutical injustice). Voice-hearing occurs both in people who are mental health service users and in the general population (clinical and non-clinical voice-hearers, respectively). The degree of distress and impairment associated with voices has been shown to relate to how individuals make sense of their experiences and how others respond to their identity as a voice-hearer. The aim of this study was to explore people's experiences of epistemic injustice in relation to voice-hearing and to understand how these may differ between clinical and non-clinical voice-hearers. DESIGN: A qualitative design was used. METHOD: Eight clinical and nine non-clinical voice-hearers partook in semi-structured interviews, which were analysed using thematic analysis. RESULTS: Three pairs of themes related to (i) identity, (ii) relationships and (iii) power and position were constructed across the clinical and non-clinical groups, and two shared themes within both groups were created relating to testimonial and hermeneutical injustice. CONCLUSION: Both clinical and non-clinical voice-hearers described experiencing epistemic injustice in wider society. The presence of a 'safe haven' (e.g. spiritualist churches) for non-clinical voice-hearers ameliorated the impact of this to some degree, by allowing people to make connections with others with similar experiences within a non-judgemental and accepting community.

Ultrasonography and CT of the vas deferens in a neutered male dog with chronic exogenous estrogen exposure.

A 2-year-old male neutered Rat Terrier was presented for alopecia, recurrent urinary tract infections, and urinary incontinence. Abdominal ultrasound and CT identified a thin, tubular, paired structure arising from the craniodorsal aspect of an enlarged, cystic prostate. An atypical uterus masculinus was initially suspected, however it was then identified that the patient had chronic exogenous estrogen exposure, and surgical resection and histopathology was consistent with an enlarged and inflamed vas deferens. Vas deferens enlargement and vasitis secondary to chronic hyperestrogenism should be considered for a tubular, paired structure arising from the craniodorsal prostate in a male dog.

Neutral lineage tracing of proliferative embryonic and adult mammary stem/progenitor cells.

Mammary gland development occurs over multiple phases, beginning in the mammalian embryo and continuing throughout reproductive life. The remarkable morphogenetic capacity of the mammary gland at each stage of development is attributed to the activities of distinct populations of mammary stem cells (MaSCs) and progenitor cells. However, the relationship between embryonic and adult MaSCs, and their fate during different waves of mammary gland morphogenesis, remains unclear. By employing a neutral, low-density genetic labelling strategy, we characterised the contribution of proliferative stem/progenitor cells to embryonic, pubertal and reproductive mammary gland development. Our findings further support a model of lineage restriction of MaSCs in the postnatal mammary gland, and highlight extensive redundancy and heterogeneity within the adult stem/progenitor cell pool. Furthermore, our data suggest extensive multiplicity in their foetal precursors that give rise to the primordial mammary epithelium before birth. In addition, using a single-cell labelling approach, we revealed the extraordinary capacity of a single embryonic MaSC to contribute to postnatal ductal development. Together, these findings provide tantalising new insights into the disparate and stage-specific contribution of distinct stem/progenitor cells to mammary gland development.

Efficacy of a Modified Health Assessment Utilized on Two Genetically Distinct Stocks of Rainbow Trout.

The Rainbow Trout Oncorhynchus mykiss is a salmonid fish that is maintained in aquaculture facilities and used as a source of protein around the world. Veterinarians need accurate, efficient tools and straightforward assessments to evaluate the health status of fish, like Rainbow Trout, that are cultivated on farms. In this study, two genetically distinct broodstock lines of Rainbow Trout originally obtained from two different U.S. states but propagated at Rushing Waters Trout Farm (Palmyra, Wisconsin) were evaluated. Groups originating from both states (State A: n = 20; State B: n = 20) were surveyed with a modified health assessment in a prospective, randomized, single-blind study. The adapted health assessment included external and internal gross evaluations, skin scrapes, gill clips, intestinal scrapes, and calculated indices, including condition factor and the hepatosomatic index. Generally, there were few significant differences in health assessment values between State A and State B fish. When this information was presented to the producer, it was discovered that perceived differences between groups were due to management errors in calculated growth rates. The results of this study add validity to the use of standardized health assessments for evaluating fish within aquaculture.

Imaging the mammary gland and mammary tumours in 3D: optical tissue clearing and immunofluorescence methods.

BACKGROUND: High-resolution 3D imaging of intact tissue facilitates cellular and subcellular analyses of complex structures within their native environment. However, difficulties associated with immunolabelling and imaging fluorescent proteins deep within whole organs have restricted their applications to thin sections or processed tissue preparations, precluding comprehensive and rapid 3D visualisation. Several tissue clearing methods have been established to circumvent issues associated with depth of imaging in opaque specimens. The application of these techniques to study the elaborate architecture of the mouse mammary gland has yet to be investigated. METHODS: Multiple tissue clearing methods were applied to intact virgin and lactating mammary glands, namely 3D imaging of solvent-cleared organs, see deep brain (seeDB), clear unobstructed brain imaging cocktails (CUBIC) and passive clarity technique. Using confocal, two-photon and light sheet microscopy, their compatibility with whole-mount immunofluorescent labelling and 3D imaging of mammary tissue was examined. In addition, their suitability for the analysis of mouse mammary tumours was also assessed. RESULTS: Varying degrees of optical transparency, tissue preservation and fluorescent signal conservation were observed between the different clearing methods. SeeDB and CUBIC protocols were considered superior for volumetric fluorescence imaging and whole-mount histochemical staining, respectively. Techniques were compatible with 3D imaging on a variety of platforms, enabling visualisation of mammary ductal and lobulo-alveolar structures at vastly improved depths in cleared tissue. CONCLUSIONS: The utility of whole-organ tissue clearing protocols was assessed in the mouse mammary gland. Most methods utilised affordable and widely available reagents, and were compatible with standard confocal microscopy. These techniques enable high-resolution, 3D imaging and phenotyping of mammary cells and tumours in situ, and will significantly enhance our understanding of both normal and pathological mammary gland development.

The Evolution of Simplifying Heuristics in Visual Cognition: Categorization, Specialization, and Visual Illusions.

Animals live in visually complex environments. As a result, visual systems have evolved mechanisms that simplify visual processing and allow animals to focus on the information that is most relevant to adaptive decision making. This review explores two key mechanisms that animals use to efficiently process visual information: categorization and specialization. Categorization occurs when an animal's perceptual system sorts continuously varying stimuli into a set of discrete categories. Specialization occurs when particular classes of stimuli are processed using distinct cognitive operations that are not used for other classes of stimuli. We also describe a nonadaptive consequence of simplifying heuristics: visual illusions, where visual perception consistently misleads the viewer about the state of the external world or objects within it. We take an explicitly comparative approach by exploring similarities and differences in visual cognition across human and nonhuman taxa. Considering areas of convergence and divergence across taxa provides insight into the evolution and function of visual systems and associated perceptual strategies.

Kintsugi-Identity change and reconstruction following an episode of psychosis: A systematic review and thematic synthesis.

AIM: Research has shown that experiences of psychosis can have a significant impact on an individual's identity. Moreover, the way those who experience psychosis make sense of these changes appears to affect their recovery journey and hold clinical significance. However, this area of research is still very much developing, and there is a need for reviews, which look to synthesise and understand this process of identity change to guide clinicians working in this area as well as future research. This study looks to meet that gap and aims to synthesise qualitative literature exploring the lived experience of identity change amongst people who experience psychosis. METHODS: A systematic review using thematic synthesis was carried out. The PRISMA and ENTREQ guidelines were followed in reporting the study. RESULTS: Ninety-one papers were identified which met criteria for inclusion and 31 papers included in the synthesis at which point conceptual saturation was judged to have been reached. Five themes were created: psychosis as an obliteration of the old self; the futile fight against psychosis; mourning for who I was; the battle for self as a battle against disempowerment; and recovery as rebirth. CONCLUSIONS: Results highlighted the substantive impact an experience of psychosis has on an individual's identity, the key role sense making around these identity changes plays in recovery and the crucial impact of clinicians on the sense-making process. The implications for theory, future research and clinical practice are discussed.

Trainee life under COVID-19: A systemic case report.

The coronavirus disease 2019 (COVID-19) pandemic has had implications for all of us. For those of us studying on clinical psychology doctorates, and similar psychotherapeutic training courses, this pandemic has led to some particular challenges. This article explores the experiences of a group of clinical psychology trainees, who are also completing intermediate systemic qualification, during the COVID-19 pandemic using a systemic case study approach. We consider the challenges we faced in relation to systemic theory and the intervention we would have used if we were clients in a family therapy clinic. This enabled us to reflect on the importance of self-reflexivity and self-care during these challenging times. Practitioner points: Using systemic thinking and ideas can help organisations make sense of how the system has had to adapt to working during a pandemic and can bring to light some of the challenges.During the pandemic and at other times of crisis, opportunities for students and staff to reflect together are likely to be beneficial.When working independently, as necessitated by the pandemic, finding ways to remain connected to our colleagues will be especially important.Providing opportunities for individuals to give feedback regarding their experiences and to influence organisational change will help individuals gain a sense of agency during a time when they are likely otherwise to feel disempowered.

Integrating elements of teddy bear therapy into cognitive behavioral therapy for a child with obsessive-compulsive disorder: A case study.

PROBLEM: Childhood obsessive-compulsive disorder (OCD) can chronically affect functioning across a multitude of areas. Cognitive behavioral therapy (CBT) is well-evidenced as an effective treatment option, however, there is less research on how CBT for OCD can best be adapted to meet the specific needs of younger children. Integrating CBT with forms of therapy that incorporate play and externalization may be particularly appropriate for this age group. However, more research is needed detailing how this could be carried out in clinical settings. METHODS: This study meets this need by describing the treatment of an 8-year-old boy with OCD. An evidence-based CBT approach was used integrated with teddy-bear therapy (TBT). This study employs a single-case A-B design to explore the acceptability and benefits of using an integrated CBT/TBT treatment approach. FINDINGS AND CONCLUSIONS: A reduction in ritualistic behavior and anxiety was seen following treatment, with qualitative feedback from the client and his family showing the inclusion of TBT to be experienced as acceptable and useful. All therapy goals were met by the end of treatment, though the parental scores on the Revised Child Anxiety and Depression Scale indicated ongoing clinically significant OCD symptoms. Implications for clinical practice and future research are discussed.

Beyond Cognitive Templates: Re-Examining Template Metaphors Used for Animal Recognition and Navigation.

The term "cognitive template" originated from work in human-based cognitive science to describe a literal, stored, neural representation used in recognition tasks. As the study of cognition has expanded to nonhuman animals, the term has diffused to describe a wider range of animal cognitive tools and strategies that guide action through the recognition of and discrimination between external states. One potential reason for this nonstandardized meaning and variable employment is that researchers interested in the broad range of animal recognition tasks enjoy the simplicity of the cognitive template concept and have allowed it to become shorthand for many dissimilar or unknown neural processes without deep scrutiny of how this metaphor might comport with underlying neurophysiology. We review the functional evidence for cognitive templates in fields such as perception, navigation, communication, and learning, highlighting any neural correlates identified by these studies. We find that the concept of cognitive templates has facilitated valuable exploration at the interface between animal behavior and cognition, but the quest for a literal template has failed to attain mechanistic support at the level of neurophysiology. This may be the result of a misled search for a single physical locus for the "template" itself. We argue that recognition and discrimination processes are best treated as emergent and, as such, may not be physically localized within single structures of the brain. Rather, current evidence suggests that such tasks are accomplished through synergies between multiple distributed processes in animal nervous systems. We thus advocate for researchers to move toward a more ecological, process-oriented conception, especially when discussing the neural underpinnings of recognition-based cognitive tasks.

Dynamic architectural interplay between leucocytes and mammary epithelial cells.

The adult mammary gland undergoes dynamic changes during puberty and the postnatal developmental cycle. The mammary epithelium is composed of a bilayer of outer basal, or myoepithelial, cells and inner luminal cells, the latter lineage giving rise to the milk-producing alveolar cells during pregnancy. These luminal alveolar cells undergo Stat3-mediated programmed cell death following the cessation of lactation. It is established that immune cells in the microenvironment of the gland have a role to play both in the ductal outgrowth during puberty and in the removal of dead cells and remodelling of the stroma during the process of postlactational regression. However, most studies have focussed on the role of the stromal immune cell compartment or have quantified immune cell populations in tissue extracts. Our recent development of protocols for deep imaging of the mammary gland in three dimensions (3D) has enabled the architectural relationship between immune cells and the epithelium to be examined in detail, and we have discovered a surprisingly dynamic relationship between the basal epithelium and leucocytes. Furthermore, we have observed morphological changes in the myoepithelial cells, as involution progresses, which were not revealed by previous work in 2D tissue sections and whole tissue. This dynamic architecture suggests a role for myoepithelial cells in the orderly progression of involution. We conclude that deep imaging of mammary gland and other tissues is essential for analysing complex interactions between cellular compartments.

Core-shell nanospheres behind the blue eyes of the bay scallop Argopecten irradians.

The bay scallop Argopecten irradians (Mollusca: Bivalvia) has dozens of iridescent blue eyes that focus light using mirror-based optics. Here, we test the hypothesis that these eyes appear blue because of photonic nanostructures that preferentially scatter short-wavelength light. Using transmission electron microscopy, we found that the epithelial cells covering the eyes of A. irradians have three distinct layers: an outer layer of microvilli, a middle layer of random close-packed nanospheres and an inner layer of pigment granules. The nanospheres are approximately 180 nm in diameter and consist of electron-dense cores approximately 140 nm in diameter surrounded by less electron-dense shells 20 nm thick. They are packed at a volume density of approximately 60% and energy-dispersive X-ray spectroscopy indicates that they are not mineralized. Optical modelling revealed that the nanospheres are an ideal size for producing angle-weighted scattering that is bright and blue. A comparative perspective supports our hypothesis: epithelial cells from the black eyes of the sea scallop Placopecten magellanicus have an outer layer of microvilli and an inner layer of pigment granules but lack a layer of nanospheres between them. We speculate that light-scattering nanospheres help to prevent UV wavelengths from damaging the internal structures of the eyes of A. irradians and other blue-eyed scallops.

Neuronal ceroid lipofuscinosis in a German Shorthaired Pointer associated with a previously reported CLN8 nonsense variant.

Two littermate German Shorthaired Pointers, a male and a female, were adopted as puppies from an animal shelter. Both puppies developed normally until approximately 11 months of age when the male began to exhibit neurological signs including ataxia, vision loss, and behavioral changes indicative of cognitive decline. These signs increased in severity over time. The female remained neurologically normal and healthy. The affected dog was euthanized at approximately 21 months of age. Autofluorescent cytoplasmic storage bodies were detected in neurons in unstained tissue sections from the cerebellum, the cerebrum, and the retina. Electron micrographs of these storage bodies showed that they were membrane bound and that most contained tightly packed aggregates of membranous whorls along with a variety of other ultrastructural features. This ultrastructure, along with the autofluorescence and the clinical signs supported a diagnosis of neuronal ceroid lipofuscinosis (NCL). Unlike earlier investigated forms of canine NCL with causal alleles in ATP13A2, TPP1, MFSD8 and CLN5 that had autofluorescent cytoplasmic storage bodies in cardiac muscle, no autofluorescence was detected in cardiac muscle from the affected German Shorthaired Pointer. A 39-fold average coverage whole genome sequence indicated that the affected German Shorthaired Pointer was homozygous for the A allele of a G > A transversion at position 30,895,648 chromosome 37. This 37:30895648G > A mutation created a CLN8 termination codon that had been previously reported to cause NCL in a mixed breed dog with Australian Shepherd and Australian Cattle Dog ancestry. This nonsense allele was heterozygous in the clinically normal female sibling, while archived DNA samples from 512 other German Shorthaired Pointers were all homozygous for the reference allele. The affected German Shorthaired Pointer and the previously diagnosed mixed breed dog with the same nonsense mutation shaired an identical homozygous haplotype that extended for 4.41 Mb at the telomeric end of chromosome 37, indicating the both dogs inherited the nonsense mutation from a common ancestor.

Mammary Stem Cells: Premise, Properties, and Perspectives.

Adult mammary stem cells (MaSCs) drive postnatal organogenesis and remodeling in the mammary gland, and their longevity and potential have important implications for breast cancer. However, despite intense investigation the identity, location, and differentiation potential of MaSCs remain subject to deliberation. The application of genetic lineage-tracing models, combined with quantitative 3D imaging and biophysical methods, has provided new insights into the mammary epithelial hierarchy that challenge classical definitions of MaSC potency and behaviors. We review here recent advances - discussing fundamental unresolved properties of MaSC potency, dynamics, and plasticity - and point to evolving technologies that promise to shed new light on this intractable debate. Elucidation of the physiological mammary differentiation hierarchy is paramount to understanding the complex heterogeneous breast cancer landscape.

BMP2/BMPR1A is linked to tumour progression in dedifferentiated liposarcomas.

Bone Morphogenic Protein 2 (BMP2) is a multipurpose cytokine, important in the development of bone and cartilage, and with a role in tumour initiation and progression. BMP2 signal transduction is dependent on two distinct classes of serine/threonine kinase known as the type I and type II receptors. Although the type I receptors (BMPR1A and BMPR1B) are largely thought to have overlapping functions, we find tissue and cellular compartment specific patterns of expression, suggesting potential for distinct BMP2 signalling outcomes dependent on tissue type. Herein, we utilise large publicly available datasets from The Cancer Genome Atlas (TCGA) and Protein Atlas to define a novel role for BMP2 in the progression of dedifferentiated liposarcomas. Using disease free survival as our primary endpoint, we find that BMP2 confers poor prognosis only within the context of high BMPR1A expression. Through further annotation of the TCGA sarcoma dataset, we localise this effect to dedifferentiated liposarcomas but find overall BMP2/BMP receptor expression is equal across subsets. Finally, through gene set enrichment analysis we link the BMP2/BMPR1A axis to increased transcriptional activity of the matrisome and general extracellular matrix remodelling. Our study highlights the importance of continued research into the tumorigenic properties of BMP2 and the potential disadvantages of recombinant human BMP2 (rhBMP2) use in orthopaedic surgery. For the first time, we identify high BMP2 expression within the context of high BMPR1A expression as a biomarker of disease relapse in dedifferentiated liposarcomas.

Single-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny.

The mammary gland undergoes cycles of growth and regeneration throughout reproductive life, a process that requires mammary stem cells (MaSCs). Whilst recent genetic fate-mapping studies using lineage-specific promoters have provided valuable insights into the mammary epithelial hierarchy, the true differentiation potential of adult MaSCs remains unclear. To address this, herein we utilize a stochastic genetic-labelling strategy to indelibly mark a single cell and its progeny in situ, combined with tissue clearing and 3D imaging. Using this approach, clones arising from a single parent cell could be visualized in their entirety. We reveal that clonal progeny contribute exclusively to either luminal or basal lineages and are distributed sporadically to branching ducts or alveoli. Quantitative analyses suggest that pools of unipotent stem/progenitor cells contribute to adult mammary gland development. Our results highlight the utility of tracing a single cell and reveal that progeny of a single proliferative MaSC/progenitor are dispersed throughout the epithelium.

PACAP in the BNST produces anorexia and weight loss in male and female rats.

Recent gene association studies have implicated pituitary adenylate cyclase-activating peptide (PACAP) systems in several psychiatric disorders associated with stressor exposure, and we have argued that many of the behavioral consequences of repeated stressor exposure may depend on the expression of PACAP in the bed nucleus of the stria terminalis (BNST). One behavioral consequence of the activation of stress systems can be anorexia and subsequent weight loss, and both the activation of central PACAP systems as well as neuronal activity in the BNST have also been associated with anorexic states in rodents. Hence, we investigated the regulation of food and water intake and weight loss following BNST PACAP infusion. BNST PACAP38 dose-dependently decreased body weight, as well as food and water intake in the first 24 h following infusion. Because different BNST subregions differentially regulate stress responding, we further examined the effects of PACAP38 in either the anterior or posterior BNST. Anterior BNST PACAP38 infusion did not alter weight gain, whereas posterior PACAP38 infusion resulted in weight loss. PACAP38 infused into the lateral ventricles did not alter weight, suggesting that the effects of BNST-infused PACAP were not mediated by leakage into the ventricular system. These data suggest that PACAP receptor activation in posterior BNST subregions can produce anorexia and weight loss, and corroborate growing data implicating central PACAP activation in mediating the consequences of stressor exposure.

Qaraqara-Charka Mallku, Inka y Rey en la provincia de Charcas (siglos XV-XVII): Historia antropologica de una confederacion aymara

El libro representa un notable adelanto en la construccion de la historia de los pueblos andinos y sera de util consulta para todos aquellos que se interesan en la formacion de los antiguos Estados americanos y su integracion al estado colonial europeo