Development and validation of measures of pharmacists' acceptability and willingness to screen for perinatal depression.

BACKGROUND: While pharmacists' roles in mental healthcare are expanding, research exploring pharmacists' acceptability and willingness to provide mental health services is limited. This study developed and validated theory-driven measures of pharmacists' acceptability and willingness to screen for perinatal depression in community pharmacy settings. MATERIALS/METHODS: Items were developed using published literature and the Theoretical Framework of Acceptability (TFA), then content validated using consensus methods with experts who completed the content validity index (CVI). The revised items were disseminated to pharmacists in Australia. Responses were analysed descriptively. Exploratory factor analyses (EFA) were used to explore the factorial structure and generate scales. Multivariate regression analysis was conducted to explore predictors of willingness. RESULTS: A 58-item questionnaire was developed, encompassing the 7 domains of the TFA and an eighth domain (willingness). The average CVI was 0.92, domain range (0.88-0.96). The universal CVI was 56/58. Expert feedback informed item revision, creation and deletion. Pharmacists' responses (n = 157) to the final 42-item questionnaire indicated overall acceptance and willingness to conduct PND screening. However, perceived knowledge was lacking. The EFA resulted a two-factor solution (1 = acceptance; 2 = self-efficacy). The measurement scales created had good internal consistency. In multivariate regression analysis, 'Acceptance' (Beta = 0.949 (0.760-1.103)) and 'Self-Efficacy' (Beta = 0.107 (0.036-0.174)) were significant predictors of 'Willingness' and the model predicted 77 % of the variation in 'Willingness'. CONCLUSIONS: Psychometrically-sound measures of pharmacists' acceptability and willingness to screen for PND have been developed with stakeholder input. The questionnaire can be used for standardised measurement of these constructs across studies.

Sleep should not be this difficult: An interpretive descriptive study of older adults' perspectives on behaviour change elements in Sleepwell and experiences with benzodiazepine discontinuation.

Benzodiazepine receptor agonists are often used for insomnia in older adults contrary to current evidence. The harms outweigh the benefits, which are limited. Cognitive behavioural therapy for insomnia is the first-line recommended treatment. Sleepwell was created as a repository of evidence-based resources to promote cognitive behavioural therapy for insomnia and limit benzodiazepine receptor agonist use. This qualitative study uses an interpretive description design and reflexive thematic analysis to explore older adults' perspectives on behavioural change techniques used in Sleepwell resources. It also explores challenges and opportunities towards benzodiazepine receptor agonist discontinuation and cognitive behavioural therapy for insomnia use. Participants were recruited from the Sleepwell arm of a randomized controlled trial. Data were collected from 15 older adults using semi-structured interviews. Two main themes were developed: (1) sleep should not be this difficult; and (2) whether you know it, or learn it, drugs are bad. Two sub-themes were created within the first theme: (1) justification of benzodiazepine receptor agonist use to achieve sleep goals; (2) efforts of committing to cognitive behavioural therapy for insomnia. Several behavioural change techniques (e.g. information about consequences, anticipated regret, salience of consequences) were enablers of benzodiazepine receptor agonist-related behaviour change. For committing to cognitive behavioural therapy for insomnia, several behavioural change techniques (e.g. self-monitoring of behaviour, distraction, stimulus substitution) were beneficial, but social support, which was perceived as useful, was absent. Older adults experienced tension with benzodiazepine receptor agonist use and deprescribing, despite knowing or learning the potential consequences of benzodiazepine receptor agonists. Cognitive behavioural therapy for insomnia implementation was challenging. Embedded behavioural change techniques in the Sleepwell booklets were identified as helpful, but more (e.g. social support) are needed to optimize cognitive behavioural therapy for insomnia use.

Cardiovascular Fitness and Stride Acceleration in Race-Pace Workouts for the Prediction of Performance in Thoroughbreds.

In-training racehorse physiological data can be leveraged to further explore race-day performance prediction. To date, no large retrospective, observational study has analysed whether in-training speed and heart rate recovery can predict racehorse success. Speed (categorised as 'slow' to 'fast' according to the time taken to cover the last 600 m from a virtual finish line) and heart rate recovery (from gallop to 1 min after exercise) of flat racehorses (n = 485) of varying age, sex and type according to distance (e.g., sprinter, miler and stayer) were obtained using a fitness tracker from a single racing yard in Australia. Race-pace training sessions on turf comprised 'fast gallop' (n = 3418 sessions) or 'jumpout' (n = 1419). A posteriori racing information (n = 3810 races) for all 485 racehorses was extracted and combined with training data. Race performance was categorised as win/not-win or podium or not, each analysed by logistic regression. Colts (p < 0.001), stayers (p < 0.001) and being relatively fast over the last 600 m of a benchmark test in training (p < 0.008) were all predictive of race performance. Heart rate recovery after exercise (p = 0.21) and speed recorded at 600 m of a 1 km benchmark test in training (p = 0.94) were not predictive. In-training physiological data analytics used along with subjective experience may help trainers identify promising horses and improve decision-making.

Fetal growth delay caused by loss of non-canonical imprinting is resolved late in pregnancy and culminates in offspring overgrowth.

Germline epigenetic programming, including genomic imprinting, substantially influences offspring development. Polycomb Repressive Complex 2 (PRC2) plays an important role in Histone 3 Lysine 27 trimethylation (H3K27me3)-dependent imprinting, loss of which leads to growth and developmental changes in mouse offspring. In this study, we show that offspring from mouse oocytes lacking the PRC2 protein Embryonic Ectoderm Development (EED) were initially developmentally delayed, characterised by low blastocyst cell counts and substantial growth delay in mid-gestation embryos. This initial developmental delay was resolved as offspring underwent accelerated fetal development and growth in late gestation resulting in offspring that were similar stage and weight to controls at birth. The accelerated development and growth in offspring from Eed-null oocytes was associated with remodelling of the placenta, which involved an increase in fetal and maternal tissue size, conspicuous expansion of the glycogen-enriched cell population, and delayed parturition. Despite placental remodelling and accelerated offspring fetal growth and development, placental efficiency, and fetal blood glucose levels were low, and the fetal blood metabolome was unchanged. Moreover, while expression of the H3K27me3-imprinted gene and amino acid transporter Slc38a4 was increased, fetal blood levels of individual amino acids were similar to controls, indicating that placental amino acid transport was not enhanced. Genome-wide analyses identified extensive transcriptional dysregulation and DNA methylation changes in affected placentas, including a range of imprinted and non-imprinted genes. Together, while deletion of Eed in growing oocytes resulted in fetal growth and developmental delay and placental hyperplasia, our data indicate a remarkable capacity for offspring fetal growth to be normalised despite inefficient placental function and the loss of H3K27me3-dependent genomic imprinting.

Implementation of Agile in healthcare: methodology for a multisite home hospital accelerator.

BACKGROUND: The diffusion of innovation in healthcare is sluggish. Evidence-based care models and interventions take years to reach patients. We believe the healthcare community could deliver innovation to the bedside faster if it followed other sectors by employing an organisational framework for efficiently accomplishing work. Home hospital is an example of sluggish diffusion. This model provides hospital-level care in a patient's home instead of in a traditional hospital with equal or better outcomes. Home hospital uptake has steadily grown during the COVID-19 pandemic, yet barriers to launch remain for healthcare organisations, including access to expertise and implementation tools. The Home Hospital Early Adopters Accelerator was created to bring together a network of healthcare organisations to develop tools necessary for programme implementation. METHODS: The accelerator used the Agile framework known as Scrum to rapidly coordinate work across many different specialised skill sets and blend individuals who had no experience with one another into efficient teams. Its goal was to take 40 weeks to develop 20 'knowledge products',or tools critical to the development of a home hospital programme such as workflows, inclusion criteria and protocols. We conducted a mixed-methods evaluation of the accelerator's implementation, measuring teams' productivity and experience. RESULTS: 18 healthcare organisations participated in the accelerator to produce the expected 20 knowledge products in only 32 working weeks, a 20% reduction in time. Nearly all (97.4%) participants agreed or strongly agreed the Scrum teams worked well together, and 96.8% felt the teams produced a high-quality product. Participants consistently remarked that the Scrum team developed products much faster than their respective organisational teams. The accelerator was not a panacea: it was challenging for some participants to become familiar with the Scrum framework and some participants struggled with balancing participation in the Accelerator with their job duties. CONCLUSIONS: Implementation of an Agile-based accelerator that joined disparate healthcare organisations into teams equipped to create knowledge products for home hospitals proved both efficient and effective. We demonstrate that implementing an organisational framework to accomplish work is a valuable approach that may be transformative for the sector.

A maternal ketogenic diet alters oviduct fluid nutrients and embryo histone acetylation in mice.

In brief: A ketogenic diet (KD) elevates blood ß-hydroxybutyrate to concentrations that are known to perturb the development, metabolism, histone acetylation and viability of preimplantation mouse embryos in culture. This study shows that a maternal KD changes available nutrient levels in the oviduct, leading to altered embryo development and epigenetic state in vivo. Abstract: A ketogenic diet elevates blood ß-hydroxybutyrate to concentrations that perturb the development, metabolism, histone acetylation (H3K27ac) and viability of preimplantation mouse embryos in vitro. However, whether a ketogenic diet alters ß-hydroxybutyrate concentrations within female reproductive fluid is unknown. This study aimed to quantify glucose and ß-hydroxybutyrate within mouse blood and oviduct fluid following standard diet and ketogenic diet consumption and to assess whether a maternal periconceptional ketogenic diet impacts in vivo embryo development and blastocyst H3K27ac. Female C57BL/6 × CBA mice were fed a standard or ketogenic diet (n = 24 each) for 24-27 days. Glucose and ß-hydroxybutyrate were quantified in blood via an electronic monitoring system and in oviduct fluid via ultramicrofluorescence. The developmental grade of flushed blastocysts was recorded, and blastocyst cell number and H3K27ac were assessed via immunofluorescence. A maternal ketogenic diet elevated ß-hydroxybutyrate in day 24 blood (P < 0.001) and oviduct fluid (P < 0.05) compared with a standard diet, whereas glucose was unchanged. A periconceptional ketogenic diet did not impact blastocyst cell number; however, it significantly delayed blastocyst development (P < 0.05) and reduced trophectoderm-specific H3K27ac (P < 0.05) compared with standard diet-derived embryos. Maternal ketogenic diet consumption is, therefore, associated with reproductive tract nutrient changes and altered embryonic development and epigenetics in vivo. Future studies to assess whether periconceptional/gestational ketogenic diet consumption impacts human preimplantation, fetal, and long-term offspring development and health are warranted.

Evaluation of an artificial intelligence-facilitated sperm detection tool in azoospermic samples for use in ICSI.

RESEARCH QUESTION: Can artificial intelligence (AI) improve the efficiency and efficacy of sperm searches in azoospermic samples? DESIGN: This two-phase proof-of-concept study began with a training phase using eight azoospermic patients (>10,000 sperm images) to provide a variety of surgically collected samples for sperm morphology and debris variation to train a convolutional neural network to identify spermatozoa. Second, side-by-side testing was undertaken on two cohorts of non-obstructive azoospermia patient samples: an embryologist versus the AI identifying all the spermatozoa in the still images (cohort 1, n = 4), and a side-by-side test with a simulated clinical deployment of the AI model with an intracytoplasmic sperm injection microscope and the embryologist performing a search with and without the aid of the AI (cohort 2, n = 4). RESULTS: In cohort 1, the AI model showed an improvement in the time taken to identify all the spermatozoa per field of view (0.02 ± 0.30  ×  10-5s versus 36.10 ± 1.18s, P < 0.0001) and improved recall (91.95 ± 0.81% versus 86.52 ± 1.34%, P < 0.001) compared with an embryologist. From a total of 2660 spermatozoa to find in all the samples combined, 1937 were found by an embryologist and 1997 were found by the AI in less than 1000th of the time. In cohort 2, the AI-aided embryologist took significantly less time per droplet (98.90 ± 3.19 s versus 168.7 ± 7.84 s, P < 0.0001) and found 1396 spermatozoa, while 1274 were found without AI, although no significant difference was observed. CONCLUSIONS: AI-powered image analysis has the potential for seamless integration into laboratory workflows, to reduce the time to identify and isolate spermatozoa from surgical sperm samples from hours to minutes, thus increasing success rates from these treatments.

Temperature fluctuations during embryo transfer can be mitigated by optimizing transfer protocol.

RESEARCH QUESTION: What impact do variations in embryo transfer catheter loading and movement procedures have on temperature and pH fluctuations during embryo transfer? DESIGN: Mock embryo transfers were conducted to test the impact of air flow/movement, use of catheter coverings, and the type of workstation used for catheter loading on catheter temperature. A thermocouple probe inserted into the tip of the outer catheter or taped to the exterior of the inner catheter recorded temperature within the catheter every 5 s from time of mock embryo loading (TL) to 60 s (TL + 60 s) or from the start of transit (TT). Fluctuations in culture medium pH in embryo transfer dishes were monitored. RESULTS: The rate of cooling during transit was faster (all P < 0.05) when catheters were uncovered compared with all covering methods tested. This resulted in a lower catheter temperature at TL + 20 s (28.43 ± 0.30 °C) compared with catheters covered by plastic tubing (31.4 ± 0.30 °C), paper (31.0 ± 0.26 °C) or paper + thumb (31.1 ± 0.78 °C; all P ≤ 0.05). Temperature was maintained more effectively when catheters were loaded in a crib compared with a heated stage, until initiation of transit, when the rate of temperature decrease was similar. Culture medium pH increased more rapidly when embryo transfer dishes remained on a heated stage during the procedure compared with in an open crib. CONCLUSIONS: Temperature loss during the embryo transfer procedure can be mitigated by reducing the transit time and using catheter coverings. Use of a crib for catheter loading only improved temperature stability while the catheter remained in the crib, not during transit, and reduced pH fluctuations during the procedure.

Prescriber Acceptability of a Direct-to-Patient Intervention for Benzodiazepine Receptor Agonist Deprescribing and Behavioural Management of Insomnia in Older Adults.

Behavioural treatments are recommended first-line for insomnia, but long-term benzodiazepine receptor agonist (BZRA) use remains common and engaging patients in a deprescribing consultation is challenging. Few deprescribing interventions directly target patients. Prescribers' support of patient-targeted interventions may facilitate their uptake. Recently assessed in the Your Answers When Needing Sleep in New Brunswick (YAWNS NB) study, Sleepwell (mysleepwell.ca) was developed as a direct-to-patient behaviour change intervention promoting BZRA deprescribing and non-pharmacological insomnia management. BZRA prescribers of YAWNS NB participants were invited to complete an online survey assessing the acceptability of Sleepwell as a direct-to-patient intervention. The survey was developed using the seven construct components of the theoretical framework of acceptability (TFA) framework. Respondents (40/250, 17.2%) indicated high acceptability, with positive responses per TFA construct averaging 32.3/40 (80.7%). Perceived as an ethical, credible, and useful tool, Sleepwell also promoted prescriber-patient BZRA deprescribing engagements (11/19, 58%). Prescribers were accepting of Sleepwell and supported its application as a direct-to-patient intervention.

A step closer to parenthood with non-obstructive azoospermia: Unveiling the impact of microdissection testicular sperm extraction in Australia's largest single-centre study.

BACKGROUND: Non-obstructive azoospermia (NOA) diagnosis poses challenges for couples seeking parenthood. Microdissection testicular sperm extraction (MD-TESE) excels in retrieving testicular sperm cells for NOA cases. However, limited live birth data in Australian NOA patients hinders accurate counselling. AIMS: This study aimed to determine the likelihood of infertile couples with a male partner diagnosed with NOA conceiving biological children using MD-TESE / intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: A retrospective cohort study included 108 NOA men treated at a public fertility unit and a private fertility centre (May 2009-May 2022). PRIMARY OUTCOME: live birth rate (LBR); secondary outcomes: sperm retrieval rate, pregnancy rate, and neonatal outcomes. RESULTS: Among 108 patients undergoing MD-TESE, the positive sperm retrieval rate (PSRR) was 64.8% (70/108). Histology best predicted sperm retrieval success, with hypo-spermatogenesis yielding a 94.1% PSRR. Age, testicular volume, and hormonal parameters had no significant impact. Mean male age: 35.4 years; mean partner age: 32.7 years. Fertilisation rate: 50.7%. LBR per initiated cycle: 58.7% (37/63); per embryo transfer: 63.8% (37/58); per initially diagnosed NOA man: 34.3% (37/108). Cumulative LBR: 74.1% (43/58); twin rate: 10.8% (4/37). No neonatal deaths or defects were observed among 47 live offspring. CONCLUSION: This study provides valuable data for counselling NOA couples on the probability of conceiving biological offspring. MD-TESE and ICSI yielded favourable PSRR (64.8%) and LBR (63.8%). However, couples should be aware that once NOA is confirmed, the chance of taking home a baby is 34%.

A micro-fabricated device (microICSI) improves porcine blastocyst development and procedural efficiency for both porcine intracytoplasmic sperm injection and human microinjection.

PURPOSE: Intracytoplasmic sperm injection (ICSI) imparts physical stress on the oolemma of the oocyte and remains among the most technically demanding skills to master, with success rates related to experience and expertise. ICSI is also time-consuming and requires workflow management in the laboratory. This study presents a device designed to reduce the pressure on the oocyte during injection and investigates if this improves embryo development in a porcine model. The impact of this device on laboratory workflow was also assessed. METHODS: Porcine oocytes were matured in vitro and injected with porcine sperm by conventional ICSI (C-ICSI) or with microICSI, an ICSI dish that supports up to 20 oocytes housed individually in microwells created through microfabrication. Data collected included set-up time, time to align the polar body, time to perform the injection, the number of hand adjustments between controllers, and degree of invagination at injection. Developmental parameters measured included cleavage and day 6 blastocyst rates. Blastocysts were differentially stained to assess cell numbers of the inner cell mass and trophectoderm. A pilot study with human donated MII oocytes injected with beads was also performed. RESULTS: A significant increase in porcine blastocyst rate for microICSI compared to C-ICSI was observed, while cleavage rates and blastocyst cell numbers were comparable between treatments. Procedural efficiency of microinjection was significantly improved with microICSI compared to C-ICSI in both species. CONCLUSION: The microICSI device demonstrated significant developmental and procedural benefits for porcine ICSI. A pilot study suggests human ICSI should benefit equally.

Does video e-learning improve pharmacy teams' attitudes and preparedness towards suicide prevention?

Background: Evidence on the role of pharmacy teams in suicide prevention is growing. To support pharmacy teams, a video e-learning was produced by the Centre for Pharmacy Postgraduate Education (CPPE) involving an 'on-the-sofa' style group interview with people with personal and professional experience of suicide and suicide research. Objective: The objective was to measure any change in attitudes and preparedness for suicide prevention, following a video e-learning produced for pharmacy staff. Methods: People working in any sector of pharmacy in England and who accessed the training video were invited to complete a pre- and post- training questionnaire, between September 2019 and March 2021. Question types included demographics, experiences, attitudes as measured by the Attitudes to Suicide Prevention (ASP) scale, and preparedness. Descriptive statistics were used to summarize demographics and experience and paired t-tests were used to compare pre- and post- questionnaire responses. Results: Both questionnaires were completed by 147 people. Most worked in community pharmacy (88%) and were pharmacists (64%) or pharmacy technicians (20%). Attitudes to suicide prevention improved significantly (pre:31.20 (SD 6.04); post:28.40 (SD 6.50), p < 0.0001) after watching the video, as did self-reported preparedness. Conclusions: Pharmacy teams' self-reported attitudes and preparedness for suicide prevention improved after watching this suicide awareness video compared to baseline. Suicide awareness training tailored to pharmacy teams may be valuable, but the longitudinal impact of any suicide prevention training requires further exploration.

Vertical transmission of maternal DNA through extracellular vesicles associates with altered embryo bioenergetics during the periconception period.

The transmission of DNA through extracellular vesicles (EVs) represents a novel genetic material transfer mechanism that may impact genome evolution and tumorigenesis. We aimed to investigate the potential for vertical DNA transmission within maternal endometrial EVs to the pre-implantation embryo and describe any effect on embryo bioenergetics. We discovered that the human endometrium secretes all three general subtypes of EV - apoptotic bodies (ABs), microvesicles (MVs), and exosomes (EXOs) - into the human endometrial fluid (EF) within the uterine cavity. EVs become uniformly secreted into the EF during the menstrual cycle, with the proportion of different EV populations remaining constant; however, MVs contain significantly higher levels of mitochondrial (mt)DNA than ABs or EXOs. During the window of implantation, MVs contain an eleven-fold higher level of mtDNA when compared to cells-of-origin within the receptive endometrium, which possesses a lower mtDNA content and displays the upregulated expression of mitophagy-related genes. Furthermore, we demonstrate the internalization of EV-derived nuclear-encoded (n)DNA/mtDNA by trophoblast cells of murine embryos, which associates with a reduction in mitochondrial respiration and ATP production. These findings suggest that the maternal endometrium suffers a reduction in mtDNA content during the preconceptional period, that nDNA/mtDNA become packaged into secreted EVs that the embryo uptakes, and that the transfer of DNA to the embryo within EVs occurs alongside the modulation of bioenergetics during implantation.

A rare case of mosaic Klinefelter syndrome in a 45-year-old man leading to successful live birth through ejaculated spermatozoa: a case report and literature review.

Background: Men diagnosed with Klinefelter syndrome (KS) commonly exhibit non-obstructive azoospermia or rarely having sperm in their ejaculate, rendering them traditionally considered sterile prior to the introduction of intracytoplasmic sperm injection (ICSI). The presence of mosaic KS may mask the classical phenotype, resulting in underdiagnosis throughout their lifetime. Surgical sperm retrieval through Microdissection Testicular Sperm Extraction (Micro-TESE) combined with ICSI has become the gold standard approach, maximizing reproductive outcomes in these individuals. However, it is noteworthy that approximately 7% of men with KS may exhibit sperm in their ejaculate, providing an opportunity for them to achieve biological parenthood through ICSI. Case Presentation: In this report, we present an exceptional case of a 45-year-old man with Mosaic KS and severe oligozoospermia who successfully achieved pregnancy utilizing ICSI with freshly ejaculated sperm. Remarkably, this case represents the oldest recorded instance of a man with Klinefelter syndrome fathering his own biological child using sperm derived from fresh ejaculate. Conclusion: Although this case is exceedingly rare, it underscores the critical importance of exhausting all possibilities to facilitate biological parenthood in men with KS before considering alternative options such as sperm donation or adoption. By recognizing the potential for successful conception using ejaculated sperm in this population, we can provide individuals with mosaic KS the opportunity to fulfill their desire for biological offspring.

Perinatal depression screening in community pharmacy: Exploring pharmacists' roles, training and resource needs using content analysis.

BACKGROUND: Perinatal depression (PND) screening is often recommended in primary care settings, which includes the community pharmacy setting. However, there is limited research exploring pharmacists' perspectives on their roles in screening for perinatal mental illness. AIM: This study aimed to explore pharmacists' views of pharmacists' roles in PND screening, as well as training and resource needs for PND screening in community pharmacy settings. METHOD: A questionnaire including three open-ended questions focusing on pharmacists' perspectives of their role in PND screening, their training, and resource needs in this area, was disseminated to pharmacists across Australia via professional organisations and social media. Each open-ended question was separately analysed by inductive content analysis. Subcategories were deductively mapped to the Theoretical Framework of Acceptability. RESULTS: Responses (N = 149) from the first open-ended question about pharmacists' roles in PND screening resulted in three categories (PND screening in primary care settings will support the community, community pharmacy environment, and system and policy changes) and ten subcategories. Responses to question two on training needs (n = 148) were categorised as: training content, training length, and training delivery while responses about resource needs (n = 147) fell into three categories: adapting community pharmacy operating structures, pharmacist-specific resources, and consumer-specific resources. CONCLUSION: While some pharmacists were accepting of a role in PND screening due to pharmacists' accessibility and positive relationships with consumers, others had concerns regarding whether PND screening was within pharmacists' scope of practice. Further training and resources are needed to facilitate pharmacists' roles in PND screening, referral and care.

Second International Consensus Study of Antipsychotic Dosing (ICSAD-2).

BACKGROUND: Expert consensus-based clinically equivalent dose estimates and dosing recommendations can provide valuable support for the use of drugs for psychosis in clinical practice and research. AIMS: This second International Consensus Study of Antipsychotic Dosing provides dosing equivalencies and recommendations for newer drugs for psychosis and previously reported drugs with low consensus. METHODS: We used a two-step Delphi survey process to establish and update consensus with a broad, international sample of clinical and research experts regarding 26 drug formulations to obtain dosing recommendations (start, target range, and maximum) and estimates of clinically equivalent doses for the treatment of schizophrenia. Reference agents for equivalent dose estimates were oral olanzapine 20 mg/day for 15 oral and 7 long-acting injectable (LAI) agents and intramuscular haloperidol 5 mg for 4 short-acting injectable (SAI) agents. We also provide a contemporary list of equivalency estimates and dosing recommendations for a total of 44 oral, 16 LAI, and 14 SAI drugs for psychosis. RESULTS: Survey participants (N = 72) from 24 countries provided equivalency estimates and dosing recommendations for oral, LAI, and SAI formulations. Consensus improved from survey stages I to II. The final consensus was highest for LAI formulations, intermediate for oral agents, and lowest for SAI formulations of drugs for psychosis. CONCLUSIONS: As randomized, controlled, fixed, multiple-dose trials to optimize the dosing of drugs for psychosis remain rare, expert consensus remains a useful alternative for estimating clinical dosing equivalents. The present findings can support clinical practice, guideline development, and research design and interpretation involving drugs for psychosis.

Preimplantation embryo exposure to ketone bodies exerts sex-specific effects on mouse fetal and placental transcriptomes.

RESEARCH QUESTION: Does in vitro exposure of preimplantation mouse embryos to the ketone bodies ß-hydroxybutyrate (ßOHB) and acetoacetate (AcAc) impact post-transfer fetal and placental gene expression? DESIGN: Blastocysts cultured in vitro with or without 2 mmol/l ßOHB alone ('ßOHB') or combined with 0.8 mmol/l AcAc ('Keto') underwent embryo transfer. Transcriptional profiles of sexed placenta, liver and brain at gestational day 14.5 were examined via RNA sequencing and DAVID functional analysis. RESULTS: A sexually dimorphic response to in vitro ketone exposure was observed. Both ßOHB and Keto exposure down-regulated genes related to oxidative phosphorylation specifically in female liver. ßOHB down-regulated female placental steroid biosynthetic processes, while Keto treatment up-regulated genes relevant to blood vessel formation and cell migration in male placenta. Brain transcriptomes were minimally affected. X-linked genes and chromatin modifiers were identified as differentially expressed in both liver and placenta, alluding to a sex-specific regulatory mechanism. CONCLUSIONS: Transient preimplantation ketone exposure perturbs sex-specific fetal liver and placental gene expression, demonstrating a developmental programming effect that warrants future investigation of the postnatal metabolic health of male and female offspring.

Detrimental actions of obesity-associated advanced glycation end-products on endometrial epithelial cell proliferation are alleviated by antioxidants.

RESEARCH QUESTION: Advanced glycation end-products (AGE) are elevated in the uterine environment of obese infertile women. Can the detrimental effects of AGE on endometrial epithelial cells be mitigated with therapeutics, and recapitulated in a more physiologically relevant primary model (organoids)? DESIGN: Human endometrial epithelial cells (ECC-1) were exposed to AGE at concentrations physiologically representative of uterine fluid in lean or obese individuals, and three potential therapeutics: 25 nmol/l receptor for AGE (RAGE) antagonist FPS-ZM1, 100 µmol/l metformin, or a combination of antioxidants (10 µmol/l N-acetyl-l-cysteine, 10 µmol/l N-acetyl-l-carnitine and 5 µmol/l α-lipoic acid). Real-time cell analysis (xCELLigence, ACEA Biosciences) determined the rate of adhesion and proliferation. The proliferation of organoid-derived cells and secretion of cytokines from organoids was characterized in the presence of AGE (n = 5). The uterine fluid of women undergoing assisted reproduction was profiled for AGE-associated inflammatory markers (n = 77). RESULTS: ECC-1 proliferation was reduced by AGE from obese versus lean conditions and vehicle control (P = 0.04 and P < 0.001, respectively), and restored to a proliferation corresponding to lean conditions by antioxidants. AGE influenced organoid derived primary endometrial epithelial cell proliferation in a donor-dependent manner. AGE increased the organoid secretion of the proinflammatory cytokine CXCL16 (P = 0.006). Clinically, CXCL16 correlated positively to maternal body mass index (R = 0.264, P = 0.021) and intrauterine glucose concentration (R = 0.736, P < 0.0001). CONCLUSIONS: Physiologically relevant concentrations of AGE alter endometrial epithelial cell function. Antioxidants restore the rate of proliferation of AGE-treated endometrial epithelial (ECC-1) cells. Primary endometrial epithelial cells, cultured as organoids, demonstrate altered proliferation and CXCL16 secretion in the presence of AGE equimolar with the uterine fluid from obese individuals.

Pharmacist Administration of Long-Acting Injectable Antipsychotics to Community-Dwelling Patients: A Scoping Review.

Long-acting injectable antipsychotics (LAIAs) have demonstrated positive outcomes for people with serious mental illnesses. They are underused, and access to LAIAs can be challenging. Pharmacies could serve as suitable environments for LAIA injection by pharmacists. To map and characterize the literature regarding the administration of LAIAs by pharmacists, a scoping review was conducted. Electronic-database searches (e.g., PsycINFO, Ovid Medline, Scopus, and Embase) and others including ProQuest Dissertations & Theses Global and Google, were conducted. Citation lists and cited-reference searches were completed. Zotero was used as the reference-management database. Covidence was used for overall review management. Two authors independently screened articles and performed full-text abstractions. From all sources, 292 studies were imported, and 124 duplicates were removed. After screening, 13 studies were included for abstraction. Most articles were published in the US since 2010. Seven studies used database and survey methods, with adherence and patient satisfaction as the main patient-outcomes assessed. Reporting of pharmacists' and patients' perspectives surrounding LAIA administration was minimal and largely anecdotal. Financial analyses for services were also limited. The published literature surrounding pharmacist administration of LAIAs is limited, providing little-to-no guidance for the development and implementation of this service by others.