The ZO-1 protein Polychaetoid as an upstream regulator of the Hippo pathway in Drosophila.

The generation of a diversity of photoreceptor (PR) subtypes with different spectral sensitivities is essential for color vision in animals. In the Drosophila eye, the Hippo pathway has been implicated in blue- and green-sensitive PR subtype fate specification. Specifically, Hippo pathway activation promotes green-sensitive PR fate at the expense of blue-sensitive PRs. Here, using a sensitized triple heterozygote-based genetic screening approach, we report the identification of the single Drosophila zonula occludens-1 (ZO-1) protein Polychaetoid (Pyd) as a new regulator of the Hippo pathway during the blue- and green-sensitive PR subtype binary fate choice. We demonstrate that Pyd acts upstream of the core components and the upstream regulator Pez in the Hippo pathway. Furthermore, We found that Pyd represses the activity of Su(dx), a E3 ligase that negatively regulates Pez and can physically interact with Pyd, during PR subtype fate specification. Together, our results identify a new mechanism underlying the Hippo signaling pathway in post-mitotic neuronal fate specification.

COVID-19 Test Allocation Strategy to Mitigate SARS-CoV-2 Infections across School Districts.

In response to COVID-19, schools across the United States closed in early 2020; many did not fully reopen until late 2021. Although regular testing of asymptomatic students, teachers, and staff can reduce transmission risks, few school systems consistently used proactive testing to safeguard return to classrooms. Socioeconomically diverse public school districts might vary testing levels across campuses to ensure fair, effective use of limited resources. We describe a test allocation approach to reduce overall infections and disparities across school districts. Using a model of SARS-CoV-2 transmission in schools fit to data from a large metropolitan school district in Texas, we reduced incidence between the highest and lowest risk schools from a 5.6-fold difference under proportional test allocation to 1.8-fold difference under our optimized test allocation. This approach provides a roadmap to help school districts deploy proactive testing and mitigate risks of future SARS-CoV-2 variants and other pathogen threats.

Massed v. standard prolonged exposure therapy for PTSD in military personnel and veterans: 12-month follow-up of a non-inferiority randomised controlled trial.

BACKGROUND: The utilisation of massed therapy for treating posttraumatic stress disorder (PTSD) is gaining strength, especially prolonged exposure. However, it is unknown whether massed prolonged exposure (MPE) is non-inferior to standard prolonged exposure (SPE) protocols in the long term. The current study aimed to assess whether MPE was non-inferior to SPE at 12 months post-treatment, and to ascertain changes in secondary measure outcomes. METHODS: A multi-site non-inferiority randomised controlled trial (RCT) compared SPE with MPE in 12 clinics. The primary outcome was PTSD symptom severity (CAPS-5) at 12 months post-treatment commencement. Secondary outcome measures included symptoms of depression, anxiety, anger, disability, and quality of life at 12 weeks and 12 months post-treatment commencement. Outcome assessors were blinded to treatment allocation. The intention-to-treat sample included 138 Australian military members and veterans and data were analysed for 134 participants (SPE = 71, MPE = 63). RESULTS: Reductions in PTSD severity were maintained at 12 months and MPE remained non-inferior to SPE. Both treatment groups experienced a reduction in depression, anxiety, anger, and improvements in quality of life at 12 weeks and 12 months post-treatment commencement. Treatment effects for self-reported disability in the SPE group at 12 weeks were not maintained, with neither group registering significant effects at 12 months. CONCLUSIONS: The emergence of massed protocols for PTSD is an important advancement. The current study provides RCT evidence for the longevity of MPE treatment gains at 12 months post-treatment commencement and demonstrated non-inferiority to SPE. Promisingly, both treatments also significantly reduced the severity of comorbid symptoms commonly occurring alongside PTSD.

Mental health across the early years in the military.

BACKGROUND: The mental health impact of the initial years of military service is an under-researched area. This study is the first to explore mental health trajectories and associated predictors in military members across the first 3-4 years of their career to provide evidence to inform early interventions. METHODS: This prospective cohort study surveyed Australian Defence personnel (n = 5329) at four time-points across their early military career. Core outcomes were psychological distress (K10+) and posttraumatic stress symptoms [four-item PTSD Checklist (PCL-4)] with intra-individual, organizational and event-related trajectory predictors. Latent class growth analyses (LCGAs) identified subgroups within the sample that followed similar longitudinal trajectories for these outcomes, while conditional LCGAs examined the variables that influenced patterns of mental health. RESULTS: Three clear trajectories emerged for psychological distress: resilient (84.0%), worsening (9.6%) and recovery (6.5%). Four trajectories emerged for post-traumatic stress, including resilient (82.5%), recovery (9.6%), worsening (5.8%) and chronic subthreshold (2.3%) trajectories. Across both outcomes, prior trauma exposure alongside modifiable factors, such as maladaptive coping styles, and increased anger and sleep difficulties were associated with the worsening and chronic subthreshold trajectories, whilst members in the resilient trajectories were more likely to be male, report increased social support from family/friends and Australian Defence Force (ADF) sources, and use adaptive coping styles. CONCLUSIONS: The emergence of symptoms of mental health problems occurs early in the military lifecycle for a significant proportion of individuals. Modifiable factors associated with wellbeing identified in this study are ideal targets for intervention, and should be embedded and consolidated throughout the military career.

Effect of massed v. standard prolonged exposure therapy on PTSD in military personnel and veterans: a non-inferiority randomised controlled trial.

BACKGROUND: A short, effective therapy for posttraumatic stress disorder (PTSD) could decrease barriers to implementation and uptake, reduce dropout, and ameliorate distressing symptoms in military personnel and veterans. This non-inferiority RCT evaluated the efficacy of 2-week massed prolonged exposure (MPE) therapy compared to standard 10-week prolonged exposure (SPE), the current gold standard treatment, in reducing PTSD severity in both active serving and veterans in a real-world health service system. METHODS: This single-blinded multi-site non-inferiority RCT took place in 12 health clinics across Australia. The primary outcome was PTSD symptom severity measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at 12 weeks. 138 military personnel and veterans with PTSD were randomised. 71 participants were allocated to SPE, with 63 allocated to MPE. RESULTS: The intention-to-treat sample included 138 participants, data were analysed for 134 participants (88.1% male, M = 46 years). The difference between the mean MPE and SPE group PTSD scores from baseline to 12 weeks-post therapy was 0.94 [95% confidence interval (CI) -4.19 to +6.07]. The upper endpoint of the 95% CI was below +7, indicating MPE was non-inferior to SPE. Significant rates of loss of PTSD diagnosis were found for both groups (MPE 53.8%, SPE 54.1%). Dropout rates were 4.8% (MPE) and 16.9% (SPE). CONCLUSIONS: MPE was non-inferior to SPE in significantly reducing symptoms of PTSD. Significant reductions in symptom severity, low dropout rates, and loss of diagnosis indicate MPE is a feasible, accessible, and effective treatment. Findings demonstrate novel methods to deliver gold-standard treatments for PTSD should be routinely considered.

Timing social distancing to avert unmanageable COVID-19 hospital surges.

Following the April 16, 2020 release of the Opening Up America Again guidelines for relaxing coronavirus disease 2019 (COVID-19) social distancing policies, local leaders are concerned about future pandemic waves and lack robust strategies for tracking and suppressing transmission. Here, we present a strategy for triggering short-term shelter-in-place orders when hospital admissions surpass a threshold. We use stochastic optimization to derive triggers that ensure hospital surges will not exceed local capacity and lockdowns are as short as possible. For example, Austin, Texas-the fastest-growing large city in the United States-has adopted a COVID-19 response strategy based on this method. Assuming that the relaxation of social distancing increases the risk of infection sixfold, the optimal strategy will trigger a total of 135 d (90% prediction interval: 126 d to 141 d) of sheltering, allow schools to open in the fall, and result in an expected 2,929 deaths (90% prediction interval: 2,837 to 3,026) by September 2021, which is 29% of the annual mortality rate. In the months ahead, policy makers are likely to face difficult choices, and the extent of public restraint and cocooning of vulnerable populations may save or cost thousands of lives.

A Declaration of Helsinki for animals.

OBJECTIVE: This article examines the ethical principles underlying the Declaration of Helsinki as an internationally agreed justificatory framework for human medical research. The aim of the analysis is to consider the potential usefulness of these principles for defining an internationally agreed ethical 'best practice' in clinical veterinary research (CVR). It is suggested that the specific ethical responsibilities of the clinician to protect the interests of their patient when conducting medical research may be translated into the veterinary setting. Through exploring risk and harm, unproven interventions, vulnerability and informed consent, the article identifies the ethical risks of CVR. It is shown that veterinary regulators in the UK and the European Union have addressed these concerns to varying degrees; however, disagreements over the appropriateness of specific CVR practices are identified. A commitment to collaborative exploration of the benefits and challenges of implementing a Declaration of Helsinki for Animals is proposed.

Solid-Phase Microextraction Techniques and Application in Food and Horticultural Crops.

Solid-phase microextraction (SPME) is a sample preparation technique which utilizes small amounts of an extraction phase for the extraction of target analytes from investigated sample matrices. Its simplicity of use, relatively short sample processing time, and fiber reusability have made SPME an attractive choice for many analytical applications. SPME has been widely applied to the sampling and analysis of environmental, food, aromatic, metallic, forensic, and pharmaceutical samples. Solid phase microextraction is used in horticultural crops, for example, to determine water and soil contaminants (pesticides, alcohols, phenols, amines, herbicides, etc.). SPME is also used in the food industry to separate biologically active substances in food products for various purposes, for example, disease prevention, determining the smell of food products, and analyzing tastes. SPME has been applied to forensic analysis to determine the alcohol concentration in blood and that of sugar in urine. This method has also been widely used in pharmaceutical analysis. It is a solvent-free sample preparation technique that integrates sampling, isolation, and concentration. This review focuses on recent work on the use of SPME techniques in the analysis of food and horticultural crops.

Bioassay-Guided Assessment of Antioxidative, Anti-Inflammatory and Antimicrobial Activities of Extracts from Medicinal Plants via High-Performance Thin-Layer Chromatography.

Natural products and their analogues have contributed significantly to treatment options, especially for anti-inflammatory and infectious diseases. Thus, the primary objective of this work was to compare the bioactivity profiles of selected medicinal plants that are historically used in folk medicine to treat inflammation and infections in the body. Chemical HPTLC fingerprinting was used to assess antioxidant, phenolic and flavonoid content, while bioassay-guided HPTLC was used to detect compounds with the highest antibacterial and anti-inflammatory activities. The results of this study showed that green tea leaf, walnut leaf, St. John's wort herb, wild thyme herb, European goldenrod herb, chamomile flower, and immortelle flower extracts were strong radical scavengers. Green tea and nettle extracts were the most active extracts against E. coli, while calendula flower extract showed significant potency against S. aureus. Furthermore, green tea, greater celandine, and fumitory extracts exhibited pronounced potential in suppressing COX-1 activity. The bioactive compounds from the green tea extract, as the most bioactive, were isolated by preparative thin-layer chromatography and characterized with their FTIR spectra. Although earlier studies have related green tea's anti-inflammatory properties to the presence of catechins, particularly epigallocatechin-3-gallate, the FTIR spectrum of the compound from the most intense bioactive zone showed the strongest anti-inflammatory activity can be attributed to amino acids and heterocyclic compounds. As expected, antibacterial activity in extracts was related to fatty acids and monoglycerides.

Attention-control training as an early intervention for veterans leaving the military: A pilot randomized controlled trial.

Transitioning out of the military can be a time of change and challenge. Research indicates that altered threat monitoring in military populations may contribute to the development of psychopathology in veterans, and interventions that adjust threat monitoring in personnel leaving the military may be beneficial. Australian Defence Force personnel (N = 59) transitioning from the military were randomized to receive four weekly sessions of either attention-control training or a placebo attention training. The primary outcome was symptoms of posttraumatic stress disorder (PTSD), as measured using the PTSD Checklist for DSM-5 (PCL-5) at posttreatment. Following training, participants who received attention-control training reported significantly lower levels of PTSD symptoms, Hedges' g = 0.86, 95% CI [0.37, 1.36], p = .004, and significantly improved work and social functioning, Hedges' g = 0.93, 95% CI [0.46, 1.39], p = .001, relative to those in the placebo condition. Moreover, no participants who received attention-control training worsened with regard to PTSD symptoms, whereas 23.8% of those who received the placebo attention training experienced an increase in PTSD symptoms. The preliminary findings from this pilot study add to a small body of evidence supporting attention-control training as a viable indicated early intervention approach for PTSD that is worthy of further research.

Development and Validation of an LC-MS/MS Method for Simultaneous Determination of Short Peptide-Based Drugs in Human Blood Plasma.

A novel HPLC-ESI-MS/MS method for simultaneous gonadotropin-releasing hormone (GnRH) analogs and somatostatin analog quantitation was developed and validated. The developed method was successfully applied to pharmacokinetic studies. The sample preparation process included solid-phase extraction (SPE). Effective chromatographic separation of the analytes and internal standard (dalargin) was achieved with a C18 column, using a gradient elution with two mobile phases: 0.1% v/v formic acid (aqueous solution) and 0.1% v/v formic acid (acetonitrile solution). The linearity of the method was demonstrated within a concentration range of 0.5-20 ng/mL, with correlation coefficients between 0.998-0.999 for goserelin, buserelin, triptorelin, and octreotide, respectively. The relative standard deviation (RSD, %) values for method accuracy and precision did not exceed 20% at the lower level of quantitation (LLOQ) or 15% at other concentration levels.

Selecting pharmacies for COVID-19 testing to ensure access.

Rapid diagnostic testing for COVID-19 is key to guiding social distancing orders and containing emerging disease clusters by contact tracing and isolation. However, communities throughout the US do not yet have adequate access to tests. Pharmacies are already engaged in testing, but there is capacity to greatly increase coverage. Using a facility location optimization model and willingness-to-travel estimates from US National Household Travel Survey data, we find that if COVID-19 testing became available in all US pharmacies, an estimated 94% of the US population would be willing to travel to obtain a test, if warranted. Whereas the largest chain provides high coverage in densely populated states, like Massachusetts, Rhode Island, New Jersey, and Connecticut, independent pharmacies would be required for sufficient coverage in Montana, South Dakota, and Wyoming. If only 1,000 ZIP code areas for pharmacies in the US are selected to provide testing, judicious selection, using our optimization model, provides estimated access to 29 million more people than selecting pharmacies simply based on population density.

HPTLC and ATR/FTIR Characterization of Antioxidants in Different Rosemary Extracts.

The effect of spontaneous fermentation by lactic acid bacteria on the extraction yield of bioactive compounds and antioxidant activity from rosemary leaf extracts was investigated using high-performance thin-layer chromatography (HPTLC). Brining and spontaneous fermentation with lactic acid bacteria more than doubled extraction of polyphenolics and antioxidants from the rosemary leaves. The results show that lactic acid fermentation enhances antioxidant activity in extracts by increasing the total phenolic content but does not increase extraction of phytosterols. Increased extraction of phenolic oxidants during fermentation assisted extraction, results from the in situ generated natural eutectic solvent from the plant sample. ATR-FTIR spectra from the bioactive bands suggests that this increased antioxidant activity is associated with increased extraction of rosmarinic acid, depolymerised lignin, abietane diterpenoids and 15-hydroxy-7-oxodehydroabietic acid.

HPTLC and FTIR Fingerprinting of Olive Leaves Extracts and ATR-FTIR Characterisation of Major Flavonoids and Polyphenolics.

The aim of this study was to analyse the effect of spontaneous microbial maceration on the release and extraction of the flavonoids and phenolics from olive leaves. Bioprofiling based on thin-layer chromatography effect-directed detection followed by ATR-FTIR spectroscopy proved to be a reliable and convenient method for simultaneous comparison of the extracts. Results show that fermentation significantly enhances the extraction of phenolic compounds and flavonoids. The polyphenolic content was increased from 6.7 µg GAE (gallic acid equivalents) to 25.5 µg GAE, antioxidants from 10.3 µg GAE to 25.3 µg GAE, and flavonoid content from 42 µg RE (rutin equivalents) to 238 µg RE per 20 µL of extract. Increased antioxidant activity of fermented ethyl acetate extracts was attributed to the higher concentration of extracted flavonoids and phenolic terpenoids, while increased antioxidant activity in fermented ethanol extract was due to increased extraction of flavonoids as extraction of phenolic compounds was not improved. Lactic acid that is released during fermentation and glycine present in the olive leaves form a natural deep eutectic solvent (NADES) with significantly increased solubility for flavonoids.

Highlighting DEM's Potential to Gauge Mechanistic Attributes of MUPS Tablet and Capsule Formulations.

Simulation of pharmaceutical unit operations by the discrete element method (DEM) has elevated our understanding of the impact of single-particle interactions on themselves, and on the entire tablets/powder. Studies in the past have shown how this knowledge helps to mitigate/solve multiple challenges during conventional formulation and process development/modernization/troubleshooting, with minimal use of active drug material. This communication adds to this- highlighting the tool's potential for a rapid preliminary assessment of the mechanistic attributes of multiple unit particle system (MUPS) based tablet and capsule drug products.

Opposing transcriptional and post-transcriptional roles for Scalloped in binary Hippo-dependent neural fate decisions.

The Hippo tumor suppressor pathway plays many fundamental cell biological roles during animal development. Two central players in controlling Hippo-dependent gene expression are the TEAD transcription factor Scalloped (Sd) and its transcriptional co-activator Yorkie (Yki). Hippo signaling phosphorylates Yki, thereby blocking Yki-dependent transcriptional control. In post-mitotic Drosophila photoreceptors, a bistable negative feedback loop forms between the Hippo-dependent kinase Warts/Lats and Yki to lock in green vs blue-sensitive neuronal subtype choices, respectively. Previous experiments indicate that sd and yki mutants phenocopy each other's functions, both being required for promoting the expression of the blue photoreceptor fate determinant melted (melt) and the blue-sensitive opsin Rh5. Here, we demonstrate that Sd ensures the robustness of this neuronal fate decision via multiple antagonistic gene regulatory roles. In Hippo-positive (green) photoreceptors, Sd directly represses both melt and Rh5 gene expression through defined TEAD binding sites, a mechanism that is antagonized by Yki in Hippo-negative (blue) cells. Additionally, in blue photoreceptors, Sd is required to promote the translation of the Rh5 protein through a 3'UTR-dependent and microRNA-mediated process. Together, these studies reveal that Sd can drive context-dependent cell fate decisions through opposing transcriptional and post-transcriptional mechanisms.

Distal nerve transfer for thenar palsy: A cadaveric study.

INTRODUCTION: Severe proximal median nerve palsies often result in irreversible thenar atrophy and thumb abduction function loss. Tendon transfer involves substantial limitations and challenges; but, distal nerve transfer may provide an alternative treatment. Our goal was to validate the anatomical suitability of two distal ulnar nerve branches for thenar muscle reanimation. MATERIALS AND METHODS: We assessed nerve transfer to the recurrent branch of median nerve (RMN) in 16 embalmed cadaveric hands. The ulnar motor branch to the flexor digiti minimi brevis (FDMBn) and the ulnar motor branch to the third lumbrical (3rdLn) were assessed for transfer. Coaptation success was measured by the overlap of the nerve donor with the RMN and correspondence of nerve diameters. RESULTS: The mean transferable length and width of the RMN were 20.7 ± 4.5 and 1.0 ± 0.3 mm, respectively. We identified an average of three branches in the branching anatomy from the ulnar nerve to the hypothenar muscles. The maximal transferable lengths and widths of the FDMBn and the 3rdLn were 13.8 ± 4.4 and 0.5 ± 0.1 mm and 24.1 ± 6.4 and 0.4 ± 0.1 mm, respectively. The overlap with the RMN of the FDMBn and 3rdLn was 9.0 ± 3.6 (2.0-15.3) and 17.8 ± 6.0 (4.7-27.5) mm, respectively. CONCLUSIONS: This anatomical study demonstrates the feasibility of distal nerve transfers between the ulnar and median nerves in the hand for reanimation of thenar muscles. Ulnar motor donors of the BrFDMBn and 3rdLn likely represent the least morbid donors with short distances for regeneration and a single coaptation repair.

WHO led the digital transformation of your company? A reflection of IT related challenges during the pandemic.

In this paper we reflect on a number of IT related challenges during the COVID19 pandemic, primarily from a CIO and IT professionals perspective. We consider three time periods, namely the period before the pandemic, the response to the pandemic and the period after it. For each period we discuss the key challenges that practitioners faced and outline important areas to consider for the future. Hopefully, the lessons learnt and the experiences gained will positively inform future academic research and practice.

Job satisfaction of nurses working in public hospitals: perceptions of nurse unit managers in South Africa.

BACKGROUND: Job satisfaction among nurses often determines whether they choose to remain in the profession or in the facility where they work. AIM: The study sought to explore and describe the job satisfaction of registered nurses in South Africa through the lens of their nurse unit managers. METHODS: A qualitative, exploratory, descriptive design was undertaken. Fourteen unit managers were interviewed and Tesch's method of data analysis was used. FINDINGS: Four themes emerged: 'staff shortages lead to nurses feeling overwhelmed and frustrated', 'nurses' work performance is undermined by limited resources and poor infrastructure', 'discontent among nurses with regard to poor top level and human resource management' and 'despite challenges, nurses experience rare moments of job satisfaction'. CONCLUSION: Unit managers need to find ways to enhance existing elements of job satisfaction by emphasising the nurse-patient relationship and teamwork among their staff in order to improve the overall job satisfaction of staff.

Ellis-van Creveld syndrome in a patient from Tanzania.

We report an African infant with Ellis-van Creveld (EVC) syndrome. EVC syndrome is a chondral and ectodermal dysplasia with autosomal recessive transmission. The baby presented with polydactyly, short limbs and atrioventricular septal defect, but was withdrawn from clinical follow up for the first year of life. Initial hematological abnormalities could not be explained and normalized later. EVC syndrome was confirmed by genetic analysis that showed two pathogenic mutations in the EVC2 gene, c.653_654del, p.Val218Glyfs*12 in exon 5, and c.2710C>T, p.Gln904* in exon 16. The variant c.653_654del; p.Val218Glyfs*12 in exon 5 has not been described before. Our review of medical literature suggested this is the first molecularly confirmed case of EVC syndrome in sub-Saharan Africa.