Volvulus of the gastrointestinal tract.

Volvulus describes the twisting of the intestine or colon around its mesentery. Intestinal obstruction and/or ischaemia are the most common complications of volvulus. Within the gastrointestinal tract, there is a preponderance towards colonic volvulus. The sigmoid is the most commonly affected segment, followed by the caecum, small intestine and stomach. Distinguishing between the differing anatomical locations of gastrointestinal volvulus can be challenging, but is important for the management and prognosis. This article focuses on the main anatomical sites of gastrointestinal volvulus encountered in clinical practice. The aetiology, presentation, radiological features and management options for each are discussed to highlight the key differences.

Assaying Spontaneous Network Activity and Cellular Viability Using Multi-Well Microelectrode Arrays.

Microelectrode array (MEA) technology is a neurophysiological method that allows for the measurement of spontaneous or evoked neural activity to determine chemical effects thereon. Following assessment of compound effects on multiple endpoints that evaluate network function, a cell viability endpoint in the same well is determined using a multiplexed approach. Recently, it has become possible to measure electrical impedance of cells attached to the electrodes, where greater impedance indicates greater number of cells attached. This would allow rapid and repeated assessments of cell health as the neural network develops in longer exposure assays without impacting cell health. Typically, the lactate dehydrogenase (LDH) assay for cytotoxity and CellTiter-Blue® (CTB) assay for cell viability are only performed at the end of the chemical exposure period because these assays involve lysing of the cells. Procedures describing the multiplexed methods in acute and network formation screening are included in this chapter.

Impact of COVID-19 on the Mental Health and Well-Being of Latinx Caregivers of Children with Intellectual and Developmental Disabilities.

The COVID-19 pandemic has impacted the entire world in unprecedented ways. However, populations that have had a history of marginalization have experienced a more profound impact. One such group is Latinx families of children with intellectual and developmental disabilities (IDD) in the Unites States. In this study, we used a mixed methods approach to explore the impact of the pandemic on the mental health and well-being of Latinx caregivers of children with IDD. Specifically, we (1) identified which social determinants of health are correlated with maternal caregivers perceived general health, mental health, and well-being; (2) explored the impact of the pandemic on families' overall eating and physical activity routines; and (3) identified emergent themes from caregivers' experiences during the pandemic. Thirty-seven Latinx caregivers participated in three interviews in which several validated instruments were administered. The results indicated that perceived social support, annual family income, food security, and receipt of financial benefits were correlated with fewer depressive symptoms. Annual family income was also significantly correlated with perceived general health. Most caregivers reported that the pandemic had placed a strain on their economic situation; increased their isolation; and disrupted their child's therapeutic supports, online education, eating routines, and engagement in physical activity. Meanwhile, some caregivers reported positive changes as a result of the pandemic. Implications for future research and practice are discussed.

Changes in Emergency General Surgery During Covid-19 in Scotland: A Prospective Cohort Study.

INTRODUCTION: Covid-19 has had a significant impact on all aspects of health care. We aimed to characterise the trends in emergency general surgery at a district general hospital in Scotland. METHODS: A prospective cohort study was performed from 23/03/20 to 07/05/20. All emergency general surgery patients were included. Demographics, diagnosis and management were recorded along with Covid-19 testing and results. Thirty-day mortality and readmission rates were also noted. Similar data were collected on patients admitted during the same period in 2019 to allow for comparison. RESULTS: A total of 294 patients were included. There was a 58.3 per cent reduction in admissions when comparing 2020 with 2019 (85 vs 209); however, there was no difference in age (53.2 vs 57.2 years, p = 0.169) or length of stay (4.8 vs 3.7 days, p = 0.133). During 2020, the diagnosis of appendicitis increased (4.3 vs 18.8 per cent, p = < 0.05) as did severity (0 per cent > grade 1 vs 58.3 per cent > grade 1, p = < 0.05). The proportion of patients undergoing surgery increased (19.1 vs 42.3 per cent, p = < 0.05) as did the mean operating time (102.4 vs 145.7 min, p = < 0.05). Surgery was performed in 1 confirmed and 1 suspected Covid-19 patient. The latter died within 30 days. There were no 30-day readmissions with Covid-19 symptoms. CONCLUSION: Covid-19 has significantly impacted the number of admissions to emergency general surgery. However, emergency operating continues to be needed at pre-Covid-19 levels and as such provisions need to be made to facilitate this.

Interprofessional Education: TeamSTEPPS® and Simulation With Respiratory Therapy and Nursing Students in Their Final Year.

TeamSTEPPS is a curriculum designed to improve team communication to reduce medical errors and improve patient safety. This exploratory study used a questionnaire to explore differences in attitudes of 130 nursing and respiratory therapy students using a TeamSTEPPS-based interprofessional education seminar and simulation. Results support that students' attitudes regarding the principles Team Structure, Leadership, Situation Monitoring, Mutual Support, and Communication improved from Time 1 (preseminar) to Time 2 (postseminar; p < .05). This improvement was sustained at Time 3 (postsimulation) in all principles except for Mutual Support. Participation in a TeamSTEPPS seminar and simulation can influence attitudes among health care professional students.

Common neoplastic causes of paediatric and adolescent back pain.

Neoplasm of the spinal column in children is rare, but can involve either benign or malignant tumours. Early detection of malignant tumours is key to successful clinical outcome and long-term prognosis. In such cases, back pain is a common presenting symptom, but often has a non-neoplastic cause. Therefore, it is important for GPs and trainees who encounter paediatric patients to be aware of the clinical entity to be able to thoroughly assess them in clinical practice. This article discusses the types of paediatric spinal neoplasms, anatomical-based classification, clinical red flags, imaging modalities and outlines brief management options.

T cells promote microglia-mediated synaptic elimination and cognitive dysfunction during recovery from neuropathogenic flaviviruses.

T cells clear virus from the CNS and dynamically regulate brain functions, including spatial learning, through cytokine signaling. Here we determined whether hippocampal T cells that persist after recovery from infection with West Nile virus (WNV) or Zika virus (ZIKV) impact hippocampal-dependent learning and memory. Using newly established models of viral encephalitis recovery in adult animals, we show that in mice that have recovered from WNV or ZIKV infection, T cell-derived interferon-γ (IFN-γ) signaling in microglia underlies spatial-learning defects via virus-target-specific mechanisms. Following recovery from WNV infection, mice showed presynaptic termini elimination with lack of repair, while for ZIKV, mice showed extensive neuronal apoptosis with loss of postsynaptic termini. Accordingly, animals deficient in CD8+ T cells or IFN-γ signaling in microglia demonstrated protection against synapse elimination following WNV infection and decreased neuronal apoptosis with synapse recovery following ZIKV infection. Thus, T cell signaling to microglia drives post-infectious cognitive sequelae that are associated with emerging neurotropic flaviviruses.

Evaluation of Chemical Effects on Network Formation in Cortical Neurons Grown on Microelectrode Arrays.

Thousands of chemicals to which humans are potentially exposed have not been evaluated for potential developmental neurotoxicity (DNT), driving efforts to develop a battery of in vitro screening approaches for DNT hazard. Here, 136 unique chemicals were evaluated for potential DNT hazard using a network formation assay (NFA) in cortical cells grown on microelectrode arrays. The effects of chemical exposure from 2 h postplating through 12 days in vitro (DIV) on network formation were evaluated at DIV 5, 7, 9, and 12, with cell viability assessed at DIV 12. Only 82 chemicals altered at least 1 network development parameter. Assay results were reproducible; 10 chemicals tested as biological replicates yielded qualitative results that were 100% concordant, with consistent potency values. Toxicological tipping points were determined for 58 chemicals and were similar to or lower than the lowest 50% effect concentrations (EC50) for all parameters. When EC50 and tipping point values from the NFA were compared to the range of potencies observed in ToxCast assays, the NFA EC50 values were less than the lower quartile for ToxCast assay potencies for a subset of chemicals, many of which are acutely neurotoxic in vivo. For 13 chemicals with available in vivo DNT data, estimated administered equivalent doses based on NFA results were similar to or lower than administered doses in vivo. Collectively, these results indicate that the NFA is sensitive to chemicals acting on nervous system function and will be a valuable contribution to an in vitro DNT screening battery.

A Brief History of Awareness of the Link Between Alcohol and Fetal Alcohol Spectrum Disorder.

OBJECTIVE: Fetal alcohol spectrum disorder (FASD) is a medical term used to describe a range of mental and physical disabilities caused by maternal alcohol consumption. The role of alcohol as a teratogen and its effects on the cellular growth of the embryo and the fetus were not determined on scientific grounds until the late 1960s. However, the link between alcohol use during pregnancy and its harms to offspring might have been observed frequently over the many thousands of years during which alcohol has been available and used for social and other reasons. METHODS AND RESULTS: Using sources ranging from the biblical Book of Judges (pre-1700) up until the first public health bulletin (1977), we seek to provide an overview of the academic debate around early historical accounts ostensibly attributed to the awareness of alcohol as a prenatal teratogen as well as to describe the social and political influences that sculpted developments leading to the public recognition of FASD. CONCLUSIONS: Our analysis provides a brief overview of the discourse regarding historical awareness of the detrimental effects of prenatal alcohol exposure on fetal development leading to the formal recognition of FASD as a distinct clinical entity. Further research will be required to fully appreciate the scientific, medical, and societal ills associated with prenatal alcohol exposure.

The Standardization of Diagnostic Criteria for Fetal Alcohol Spectrum Disorder (FASD): Implications for Research, Clinical Practice and Population Health.

OBJECTIVE: Fetal Alcohol Spectrum Disorder (FASD) is a preventable disorder caused by maternal alcohol consumption and marked by a range of physical and mental disabilities. Although recognized by the scientific and medical community as a clinical disorder, no internationally standardized diagnostic tool yet exists for FASD. METHODS AND RESULTS: This review seeks to analyse the discrepancies in existing diagnostic tools for FASD, and the repercussions these differences have on research, public health, and government policy. CONCLUSIONS: Disagreement on the adoption of a standardised tool is reflective of existing gaps in research on the conditions and factors that influence fetal vulnerability to damage from exposure. This discordance has led to variability in research findings, inconsistencies in government messaging, and misdiagnoses or missed diagnoses. The objective measurement of the timing and level of prenatal alcohol exposure is key to bridging these gaps; however, there is conflicting or limited evidence to support the use of existing measures.

The burden of prostate cancer in Trinidad and Tobago: one of the highest mortality rates in the world.

PURPOSE: In Trinidad and Tobago (TT), prostate cancer (CaP) is the most commonly diagnosed malignancy and the leading cause of cancer deaths among men. TT currently has one of the highest CaP mortality rates in the world. METHODS: 6,064 incident and 3,704 mortality cases of CaP occurring in TT from January 1995 to 31 December 2009 reported to the Dr. Elizabeth Quamina Cancer population-based cancer registry for TT, were analyzed to examine CaP survival, incidence, and mortality rates and trends by ancestry and geography. RESULTS: The age-standardized CaP incidence and mortality rates (per 100,000) based on the 1960 world-standardized in 2009 were 64.2 and 47.1 per 100,000. The mortality rate in TT increased between 1995 (37.9 per 100,000) and 2009 (79.4 per 100,000), while the rate in the US decreased from 37.3 per 100,000 to 22.1 per 100,000 over the same period. Fewer African ancestry patients received treatment relative to those of Indian and mixed ancestry (45.7%, 60.3%, and 60.9%, respectively). CONCLUSIONS: Notwithstanding the limitations surrounding data quality, our findings highlight the increasing burden of CaP in TT and the need for improved surveillance and standard of care. Our findings highlight the need for optimized models to project cancer rates in developing countries like TT. This study also provides the rationale for targeted screening and optimized treatment for CaP to ameliorate the rates we report.

Defining toxicological tipping points in neuronal network development.

Measuring electrical activity of neural networks by microelectrode array (MEA) has recently shown promise for screening level assessments of chemical toxicity on network development and function. Important aspects of interneuronal communication can be quantified from a single MEA recording, including individual firing rates, coordinated bursting, and measures of network synchrony, providing rich datasets to evaluate chemical effects. Further, multiple recordings can be made from the same network, including during the formation of these networks in vitro. The ability to perform multiple recording sessions over the in vitro development of network activity may provide further insight into developmental effects of neurotoxicants. In the current study, a recently described MEA-based screen of 86 compounds in primary rat cortical cultures over 12 days in vitro was revisited to establish a framework that integrates all available primary measures of electrical activity from MEA recordings into a composite metric for deviation from normal activity (total scalar perturbation). Examining scalar perturbations over time and increasing concentration of compound allowed for definition of critical concentrations or "tipping points" at which the neural networks switched from recovery to non-recovery trajectories for 42 compounds. These tipping point concentrations occurred at predominantly lower concentrations than those causing overt cell viability loss or disrupting individual network parameters, suggesting tipping points may be a more sensitive measure of network functional loss. Comparing tipping points for six compounds with plasma concentrations known to cause developmental neurotoxicity in vivo demonstrated strong concordance and suggests there is potential for using tipping points for chemical prioritization.

From the Cover: Developmental Neurotoxicants Disrupt Activity in Cortical Networks on Microelectrode Arrays: Results of Screening 86 Compounds During Neural Network Formation.

Less than 1% of environmental chemicals have been evaluated for developmental neurotoxicity (DNT). Current guideline DNT studies are resource intensive and not amenable to screening large numbers of compounds for hazard. As part of evaluating a battery of more rapid and scalable in vitro assays for DNT hazard, 86 compounds were screened for their ability to alter function during cortical network development. Developing rat cortical networks were treated with a concentration series (usually 0.03-30 µM) of 86 compounds, 60 of which have known in vivo DNT effects ("DNT Reference Set"). Spontaneous network activity was monitored by microelectrode array recordings over 12 days in vitro, and 17 measures of network activity and synchrony were quantified. Following recordings on days in vitro 12, in-well cell assessment of metabolic activity (Alamar blue) and total cellular content (lactase dehydrogenase) were conducted. Of the 86 compounds tested, 64 perturbed cortical network function in a concentration-dependent manner; 49 of the 60 DNT Reference Set compounds (81.7%) altered network formation. Compounds were ranked by potency (network effect EC50) and selectivity (separation of network and cell viability EC50) for hazard prioritization. Machine learning indicates a combination of an overall network activity metric with a measure of network coordination is key in distinguishing network-disruptive from benign treatments. These data demonstrate that this microelectrode array-based assay for developing cortical network function is amenable to medium-throughput evaluation of environmental substances for DNT hazard and further prioritization. For comprehensive identification of compounds of concern, this assay will be a useful component of a battery of assays targeting independent neurodevelopmental processes.

Assaying Spontaneous Network Activity and Cellular Viability Using Multi-well Microelectrode Arrays.

Microelectrode array (MEA) technology is a neurophysiological method that allows for the spontaneous measure of activity in neural cultures and determination of drug and chemical effects thereon. Recent introduction of multi-well MEA (mwMEA) formats have dramatically increased the throughput of this technology, allowing more efficient compound screening. Rapid characterization of compounds for neuroactivity or neurotoxicity hazard evaluation following acute, chronic, or developmental exposures ideally would also consider compound effects on cell health, and to do so in the same well requires a multiplexed approach. Procedures describing the multiplexed method to acute and developmental screening are described in this chapter.

Editor's Highlight: Evaluation of a Microelectrode Array-Based Assay for Neural Network Ontogeny Using Training Set Chemicals.

Thousands of compounds in the environment have not been characterized for developmental neurotoxicity (DNT) hazard. To address this issue, methods to screen compounds rapidly for DNT hazard evaluation are necessary and are being developed for key neurodevelopmental processes. In order to develop an assay for network formation, this study evaluated effects of a training set of chemicals on network ontogeny by measuring spontaneous electrical activity in neural networks grown on microelectrode arrays (MEAs). Rat (0-24 h old) primary cortical cells were plated in 48 well-MEA plates and exposed to 6 compounds: acetaminophen, bisindolylmaleimide-1 (Bis-1), domoic acid, mevastatin, sodium orthovanadate, and loperamide for a period of 12 days. Spontaneous network activity was recorded on days 2, 5, 7, 9, and 12 and viability was assessed using the Cell Titer Blue assay on day 12. Network activity (e.g. mean firing rate [MFR], burst rate [BR], etc), increased between days 5 and 12. Random Forest analysis indicated that across all compounds and times, temporal correlation of firing patterns (r), MFR, BR, number of active electrodes and % of spikes in a burst were the most influential parameters in separating control from treated wells. All compounds except acetaminophen (≤ 30 µM) caused concentration-related effects on one or more of these parameters. Domoic acid and sodium orthovanadate altered several of these parameters in the absence of cytotoxicity. Although cytotoxicity was observed with Bis1, mevastatin, and loperamide, some parameters were affected by these compounds at concentrations below those resulting in cytotoxicity. These results demonstrate that this assay may be suitable for screening of compounds for DNT hazard identification.

Mass Balance Model for Sustainable Phosphorus Recovery in a US Wastewater Treatment Plant.

In response to limited phosphorus (P) reserves worldwide, several countries have demonstrated the prospect of recovering significant amounts of P from wastewater treatment plants (WWTPs). This technique uses enhanced biological P removal (EBPR) to concentrate P in sludge followed by chemical precipitation of P as struvite, a usable phosphate mineral. The present study models the feasibility of this enhanced removal and recovery technique in a WWTP in Arizona with design parameters typical of infrastructure in the United States. A mass balance was performed for existing treatment processes and modifications proposed to estimate the quantity of P that could be recovered under current and future flow conditions. Modeling results show that about 71 to 96% of the P being lost potentially could be recovered as struvite. About 491 ± 64 t yr of struvite may be recovered after process modification, which corresponds to $150,000 ± $20,000 yr in P sales to fertilizer industries. The process was projected to be economically feasible, with a payback period of 45 ± 30 yr in the studied WWTP and a much shorter duration of 3 ± 1 yr for WWTPs already using an EBPR process. Furthermore, modeling results suggest that P recovery can improve the quality of biosolids by favorably reducing the P:N ratio. Implementation of this strategy at US WWTPs may increase national security by reducing dependence of limited P resources. Considering all aspects of the recovery process with respect to environmental, economic, and social implications, the examined technique is concluded to represent a cost-attractive and sustainable method for P management in US WWTPs.