The Effect of COVID-19 Endemicity on the Mental Health of Health Workers.

OBJECTIVES: A major surge in COVID-19 cases despite Singapore's high vaccination has strained the health care system in October 2021. Our aim was to assess and compare Healthcare Worker (HCW) mental well-being in 2021 against a previously published cohort in 2020. DESIGN: Cross-sectional survey study. SETTING AND PARTICIPANTS: HCWs from 4 public hospitals and a primary health care system over a 4-week duration in 2021 coinciding with a major surge compared with a similar period in 2020. METHODS: A survey comprising of the Oldenburg Burnout Inventory (OLBI), Hospital Anxiety and Depression Scale (HADS), and Safety Attitudes Questionnaire (SAQ) was distributed via email. Primary endpoints were the proportion meeting OLBI thresholds for both disengagement and exhaustion and being at risk for both Anxiety and Depression using HADS. Multivariate analysis identified significant predictors among demographic, workplace, and SAQ data. Subgroup analysis of overseas HCWs was performed. RESULTS: We surveyed 1475 HCWs. Significantly more HCWs met primary outcomes using OLBI and HADS than in 2020 (84.1% and 39.6% vs 68.2% and 23.3%, respectively; P < .001). Burnout levels were uniformly high. A HADS score ≥8 in either subscale was significantly associated with meeting burnout thresholds (P < .001). Overseas HCWs (P = .002), South Asian ethnicity (P = .004), preuniversity educational qualifications (P = .026), and longer shift workhours of 8 to <12 (P = .015) and ≥12 (P = .001) were significantly associated with meeting HADS thresholds. Among overseas HCWs (n=407), seeing family more than a year ago was significantly associated with worse OLBI disengagement scores and a greater proportion meeting HADS thresholds vs seeing them within a year or being local HCWs (47.2% vs 37.2% and 35.6%, respectively; P = .001). CONCLUSIONS AND IMPLICATIONS: HCW mental health has objectively worsened between 2020 and 2021 in the pandemic's second year. Avoiding prolonged shifts, adopting preventive mental health strategies, improving patient safety, and attention to HCWs of minority ethnicity, from overseas, and with preuniversity education may help.

Depression, anxiety, and associated psychological outcomes in living organ transplant donors: A systematic review.

With increasing demands for living organ donations, understanding the prevalence of depression and anxiety, which are the commonest psychiatric disorders in donors following organ transplantation, will serve to improve psychiatric care to safeguard donors' mental wellbeing. This descriptive systematic review examines all observational studies in English investigating prevalence of depression and anxiety in adult transplant donors using bibliographic databases. Sixty-two papers were included (kidney, n = 25; liver, n = 25; bone marrow, n = 7; uterus, n = 2; lung, n = 1; kidney and lung concurrently, n = 2). Post-transplantation depression and anxiety prevalence rates (Depression: 0-46.9%, Anxiety: 0-66.7%) did not differ significantly from pre-transplantation and were largely comparable to the general population. Other psychiatric disorders observed included bipolar disorder, conversion disorder, adjustment disorder and sleep disorder. Other psychological outcomes observed included lower quality of life, lower satisfaction of life and regret after donation. Pre-donation risk factors such as poor physical/psychological health status, and post-donation risk factors such as complicated post-surgical recovery and poor physical/psychological health in recipients were identified, predisposing donors to poor psychological outcomes. Individuals with risk factors should be monitored and provided with social support, psychoeducation, psychotherapy and long-term follow up. Future studies should adopt consistent methodological approaches to improve comparability between various studies. More research investigating poor psychological outcomes in other organ donors besides kidney and liver donors, donors who have past psychiatric history, unrelated and parent donors is warranted.

Burnout and Associated Factors Among Health Care Workers in Singapore During the COVID-19 Pandemic.

OBJECTIVES: The strain on health care systems due to the COVID-19 pandemic has led to increased psychological distress among health care workers (HCWs). As this global crisis continues with little signs of abatement, we examine burnout and associated factors among HCWs. DESIGN: Cross-sectional survey study. SETTING AND PARTICIPANTS: Doctors, nurses, allied health professionals, administrative, and support staff in 4 public hospitals and 1 primary care service in Singapore 3 months after COVID-19 was declared a global pandemic. METHODS: Study questionnaire captured demographic and workplace environment information and comprised 3 validated instruments, namely the Oldenburg Burnout Inventory (OLBI), Safety Attitudes Questionnaire (SAQ), and Hospital Anxiety and Depression Scale (HADS). Multivariate mixed model regression analyses were used to evaluate independent associations of mean OLBI-Disengagement and -Exhaustion scores. Further subgroup analysis was performed among redeployed HCWs. RESULTS: Among 11,286 invited HCWs, 3075 valid responses were received, giving an overall response rate of 27.2%. Mean OLBI scores were 2.38 and 2.50 for Disengagement and Exhaustion, respectively. Burnout thresholds in Disengagement and Exhaustion were met by 79.7% and 75.3% of respondents, respectively. On multivariate regression analysis, Chinese or Malay ethnicity, HADS anxiety or depression scores ≥8, shifts lasting ≥8 hours, and being redeployed were significantly associated with higher OLBI mean scores, whereas high SAQ scores were significantly associated with lower scores. Among redeployed HCWs, those redeployed to high-risk areas in a different facility (offsite) had lower burnout scores than those redeployed within their own work facility (onsite). A higher proportion of HCWs redeployed offsite assessed their training to be good or better compared with those redeployed onsite. CONCLUSIONS AND IMPLICATIONS: Every level of the health care workforce is susceptible to high levels of burnout during this pandemic. Modifiable workplace factors include adequate training, avoiding prolonged shifts ≥8 hours, and promoting safe working environments. Mitigating strategies should target every level of the health care workforce, including frontline and nonfrontline staff. Addressing and ameliorating burnout among HCWs should be a key priority for the sustainment of efforts to care for patients in the face of a prolonged pandemic.

Diagnostic and Predictive Applications of Functional Near-Infrared Spectroscopy for Major Depressive Disorder: A Systematic Review.

INTRODUCTION: Major depressive disorder (MDD) is a global psychiatric disorder with no established biomarker. There is growing evidence that functional near-infrared spectroscopy (fNIRS) has the ability to aid in the diagnosis and prediction of the treatment response of MDD. The aim of this review was to systematically review, and gather the evidence from existing studies that used fNIRS signals in the diagnosis of MDD, correlations with depression symptomatology, and the monitoring of treatment response. METHODS: PubMed, EMBASE, ScienceDirect, and Cochrane Library databases were searched for published English articles from 1980 to June 2019 that focused on the application of fNIRS for (i) differentiating depressed versus nondepressed individuals, (ii) correlating with depression symptomatology, and in turn (iii) monitoring treatment responses in depression. Studies were included if they utilized fNIRS to evaluate cerebral hemodynamic variations in patients with MDD of any age group. The quality of the evidence was assessed using the Newcastle-Ottawa quality assessment scale. RESULTS: A total of 64 studies were included in this review, with 12 studies being longitudinal, while the rest were cross-sectional. More than two-thirds of the studies (n = 49) had acceptable quality. fNIRS consistently demonstrated attenuated cerebral hemodynamic changes in depressed compared to healthy individuals. fNIRS signals have also shown promise in correlating with individual symptoms of depression and monitoring various treatment responses. CONCLUSIONS: This review provides comprehensive updated evidence of the diagnostic and predictive applications of fNIRS in patients with MDD. Future studies involving larger sample sizes, standardized methodology, examination of more brain regions in an integrative approach, and longitudinal follow-ups are needed.

WITHDRAWN: Psychosis: A Presentation of COVID-19?

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Dangers of Mixed Martial Arts in the Development of Chronic Traumatic Encephalopathy.

Chronic traumatic encephalopathy (CTE) was first discovered in professional boxers after they exhibited memory impairments, mood and behavioral changes after years of boxing. However, there is now a growing acceptance that CTE can develop in athletes of other sports due to the repetitive head trauma they receive. We present a case of a middle-aged male who presented with worsening memory, poor concentration, and behavioral changes for a year. On further cognitive testing, it was revealed that he had difficulties with short-term memory and processing speed as well as difficulties in organizing and multitasking. He had been practicing mixed martial arts (MMA) for 10 years, and later was an instructor of the sport. Through a detailed examination of his history, it was discovered that he sustained recurrent minor head concussions due to his line of work. To date, there has been limited large-scale research on head trauma in MMA. There is thus an urgent need for more studies in this area as CTE can be a chronic and debilitating illness with incapacitating neuropsychiatric sequelae. This case highlights the importance of public awareness of the risks of MMA and the dangers it poses to the brain, especially with more young people being attracted to this sport.

Extrinsic tension results in FGF-2 release, membrane permeability change, and intracellular Ca++ increase in immature cranial sutures.

There are numerous studies cataloging the temporal profiles of the various growth factors during the morphogenesis of cranial sutures. There are also many clearly documented mutations of the receptors of some of these growth factors such as fibroblast growth factor (FGF)R-2 and FGFR-3 in clinical craniosynostosis. It is obvious, and often concluded, that growth factors play a role or are involved in craniofacial development. However, precisely what that role is, what causes the changes in the growth factor levels, and why these changes occur in the particular temporal and spatial patterns observed remains elusive. Using simple physics, we applied a plasma membrane disruption model and the principles of complex adaptive systems to arrive at a conjecture of calvarial morphogenesis. The purpose of this article is to introduce the concept of complex adaptive systems, to propose our conjecture, and to provide experimental proof of some key steps in this conjecture: tension induces rapid and demonstrable physiological responses in some cells within the immature cranial sutures. These responses include increases of intracellular Ca++, plasma membrane permeability, and the release of growth factors, e.g., FGF-2. Paired coronal sutures from 1-week-old Sprague-Dawley rat pups were subjected to either 0.59 N of tensile force or no force for 5 minutes in a protein-free medium. FGF-2 levels in the media were measured by slot blot analysis. Western blot analysis was used to determine FGF-2 levels in the sutures. To determine cell membrane permeability changes, fluorescein-conjugated dextran, with a molecular weight of 10 kd, was added to the media during the 5 minutes with or without tensile force. Laser confocal microscopy was used to compare the amount of entry of this impermeant tracer and the pattern of permeability change at the tissue level. To determine the intracellular pCa++, the sutures were first loaded with a calcium indictor, FURA-2 AM, and then subjected isotonically to 0.059 N of tension. The intracellular pCa++ was expressed as ratio of Ca++-bound FURA-2 to Ca++-free FURA-2. The experimental findings were as follows: 1) Sutures, in response to tension, release FGF-2. 2) Sutures contain higher levels of FGF-2 when strained. 3) There is an increase in the sutural cell membrane permeability as a result of tensile strain. 4) The cells along the leading edges of the ossification fronts (at the insertion sites of Sharpey's fibers) demonstrated the maximum permeability increase. 5) There was an immediate (within seconds) increase in intracellular Ca++. and 6) This increase in intracellular Ca++ caused by tension was reversible and independent of the extracellular Ca++ ion availability. In summary, these data support, in part, the conjecture that growth of the brain places strain on the cells within the immature sutures, which causes the iteration of a set of cellular subroutines. These subroutines integrate to generate the emergent property of directed cranial expansion with dissipation of the initiating strains.

Effects of sodium and chloride on neuronal survival after neurite transection.

An in vitro investigation was undertaken to study the roles of Na+ and Cl- in mammalian spinal cord (SC) neuron deterioration and death after injury involving physical disruption of the plasma membrane. Individual SC neurons in monolayer cultures were subjected to UV laser microbeam transection of a primary dendrite. Neurons lesioned in modified ionic environments (MIEs) where 50%-75% of the NaCl was replaced with sucrose had higher survival (65%-75%) than neurons lesioned in medium with normal (125 mM) NaCl (28%; p < 0.001). Subsequent experiments found a comparable increase in lesioned neuron survival in MIEs in which only Na+ was replaced with specific ionic substitutes; however, replacement of Cl- was not protective. Electron microscope examinations of neurons fixed <16 min after lesioning showed a dramatic decrease in vesiculation of the smooth endoplasmic reticulum and Golgi apparatus in the low NaCl or low Na+ MIEs. It is hypothesized that Na+ entry after membrane disruption may stimulate elevation of [Ca+2]i leading to ultrastructural disruption and death of injured neurons. The results of these studies suggest that a low NaCl MIE may be useful as an irrigant to limit damage spread and cell death within CNS tissues during surgery or after trauma.

Inosine and guanosine preserve neuronal and glial cell viability in mouse spinal cord cultures during chemical hypoxia.

Murine spinal cord primary mixed cultures were treated with the respiratory inhibitor, rotenone, to mimic hypoxic conditions. Under these conditions neurons rapidly underwent oncosis (necrosis) with a complete loss in viability occurring within 260 min; however, astrocytes, which accounted for most of the cell population, died more slowly with 50% viability occurring at 565 min. Inosine preserved both total cell and neuronal viability in a concentration-dependent manner. The time of inosine addition relative to hypoxic insult was critical with the most effective protection occurring when inosine was added just prior to or within 5 min after insult. Inosine was ineffective when added 30 min after hypoxic insult. The effect of guanosine was similar to that of inosine. Treatment of cultures with BCX-34, a purine nucleoside phosphorylase inhibitor, prevented protection by inosine or guanosine, suggesting involvement of a purine nucleoside phosphorylase in the nucleoside protective effect.

The endogenous antioxidant glutathione as a factor in the survival of physically injured mammalian spinal cord neurons.

Glutathione is part of the system of cellular defenses against lipid peroxidation and other free radical-mediated damage. An established in vitro trauma model was utilized to evaluate whether glutathione is a factor in the survival of mammalian spinal cord neurons following physical injury. Cultured murine spinal neurons were subjected to a standard lesion: transection of a primary dendrite 100 microm from the perikaryon. Prior reduction of glutathione with ethacrynic acid or buthionine sulfoximine caused a dose-dependent decrease in neuronal survival 24 hours after dendrotomy. Prior glutathione augmentation with gamma-glutamylcysteine or L-2-oxo-4-thiazolidine carboxylic acid significantly increased survival, but N-acetyl-cysteine was not protective. Gamma glutamylcysteine effected the most rapid increase in glutathione (peak at 10 min), and survival was 72% +/- 10 when 0.2 mM gamma-glutamylcysteine was added immediately after dendrotomy compared with 38% +/- 4 in the control group (p < 0.0001). These results indicate that the level of glutathione is a factor in spinal cord neuron survival after physical trauma, and that glutathione augmentation may be an effective acute phase spinal cord injury (SCI) intervention strategy.

Increased jun immunoreactivity in an in vitro model of mammalian spinal neuron physical injury.

Dendrites were transected from murine spinal neurons. Unlesioned neurons showed dark nucleolar and patchy cytoplasmic jun immunostaining. By 0.5 and 2 h, most lesioned neurons stained intensely throughout the soma. However, at 24 h only dead neurons displayed intense somal staining, and 100% of the surviving cells stained like unlesioned controls. Correlation of immunostaining patterns with viability, injury, and death suggests jun gene expression may influence the survival of neurons after physical injury.

Recurrent synovial chondromatosis treated with meniscectomy and synovectomy.

Synovial chondromatosis is a rare benign intraarticular metaplasia of synovium. This process may result in the production of detached particles of highly cellular cartilage in the involved joint spaces. It is most often reported in the larger joints of the body including the knee, hip, elbow, and ankle. Since Axhausen in 1993 reported the first case affecting the temporomandibular joint, several articles have been listed in the literature regarding the presentation, diagnosis, and management of this form of an arthropathy. This is a case of a recurrent synovial chondromatosis that was approached with a meniscectomy and a complete synovectomy.

The effects of ciliary neurotrophic factor on murine spinal cord neurons subjected to dendrite transection injury.

Ciliary neurotrophic factor (CNTF) has been found to increase neuronal survival during development and after axotomy. The present study tested the effects of CNTF on lesioned and uninjured mouse spinal cord (SC) neurons grown in tissue culture. An initial toxicity study found that a 24-72 h exposure of SC cultures to concentrations of CNTF above 1000 ng/ml caused stress and death of unlesioned neurons and glia. Pre-selected SC neurons were then subjected to transection of a primary dendrite 100 microns from the edge of the perikaryon (approximately 50% average survival at 24 h). Application of CNTF at concentrations ranging from 0.5 to 1000 ng/ml immediately after lesioning had no statistically significant effects on SC neuron survival 24 h after dendrotomy. Separation of control (no CNTF) and CNTF-treated cells into groups of putative alpha-motor (multipolar with somal diameters > or = 25 microns) and non-alpha-motor neurons (< 25 microns somal diameters) also failed to reveal any significant differences in survival. The lack of protection by CNTF of lesioned SC neurons in mature (21-28 DIV) cultures may reflect a loss of sensitivity to CNTF that occurs with development. Alternatively, protection by CNTF may require co-factors or factors that are released from target or other cells after injury but that are not present in SC cultures.

The role of excitatory amino acids in hypothermic injury to mammalian spinal cord neurons.

Hypothermia has been reported to be beneficial in CNS physical injury and ischemia. We previously reported that posttraumatic cooling to 17 degrees C for 2 h increased survival of mouse spinal cord (SC) neurons subjected to physical injury (dendrite transection) but that cooling below 17 degrees C caused a lethal NMDA receptor-linked stress to both lesioned and uninjured neurons. The present study tested whether cooling below 17 degrees C increases extracellular levels of excitatory amino acids (EAA). SC cultures were placed at 10 degrees C or 37 degrees C. Glutamate (Glu) and aspartate (Asp) levels were higher in the medium of the cooled cultures after 0.5 h (23 +/- 4 nM/microgram vs. 4 +/- 1 nM/microgram and 4 +/- 1 nM/microgram vs. 1 +/- 0 nM/microgram, respectively). The concentration of each EAA then declined and reached a plateau at 2-4 h that was still significantly higher than control levels (p < 0.0001, two-factor ANOVA, three cultures per group). Other amino acids (glycine, asparagine, glutamine, serine) showed an opposite pattern, with higher levels in the 37 degrees C group. Both NMDA and non-NMDA antagonists prevented the lethal cold injury. Survival of SC neurons cooled at 10 degrees C for 2 h and rewarmed for 22 h was 58% +/- 25% in the control group, 94% +/- 5% in the CNQX-treated group, 97% +/- 5% in the DAPV-treated group, and 99% +/- 2% in the group treated with both antagonists [p < 0.0006, one factor ANOVA, five cultures (> 120 neurons) per group]. These results show that death of neurons cooled to 10 degrees C is caused by elevated extracellular Glu and Asp and requires activation of both the NMDA and non-NMDA receptor subtypes.

Reduction of NaCl increases survival of mammalian spinal neurons subjected to dendrite transection injury.

Neurites were transected from spinal neurons in media with normal (125 microM) or reduced NaCl (sucrose substitution). After 12 h the normal ionic environment (conditioned medium with serum) was restored. A one-factor ANOVA comparison found a significant difference in 48 h survival (P = 0.0001). Survival was highest when NaCl was reduced 50% (74% +/- 19 vs. 22% +/- 19 in normal NaCl). Na(+)- and Cl-mediated deterioration may contribute to both gray and white matter injury in CNS trauma.

Effects of methylprednisolone on lesioned and uninjured mammalian spinal neurons: viability, ultrastructure, and network electrophysiology.

An in vitro investigation was undertaken to provide information regarding the effectiveness of methylprednisolone sodium succinate (MPSS) as a treatment for the primary mechanical injury of spinal cord (SC) trauma. Exposure of uninjured mouse SC cells to MPSS for 24 h caused neuronal stress when the concentration exceeded 150 micrograms/mL; neuronal death occurred at concentrations above 600 micrograms/mL. The concentration range for MPSS protection of SC neurons subjected to a defined physical injury (laser microbeam transection of a primary dendrite 100 microns from the perikaryon) was very narrow: survival in the 30 micrograms/mL group differed significantly from the untreated control group (68.5% +/- 14.1 vs. 47.1% +/- 14.1), treatment with 20 or 60 micrograms/mL MPSS did not increase survival, and treatment with 100 micrograms/mL MPSS accelerated ultrastructural deterioration and increased the likelihood of death. Enhanced survival of lesioned neurons was observed when 30 micrograms/mL MPSS was applied within 15 min of dendrotomy but not when MPSS was administered 2 h after lesioning. Multimicroelectrode plate (MMEP) studies of SC network electrical activity indicated that MPSS associated readily with neuronal membranes. This finding was consistent with the hypothesis that MPSS may protect lesioned neurons by stabilizing damaged membranes, enhancing lesion resealing, and limiting the spread of ion-mediated damage. However, comparisons of neurite die-back 24 h after dendrotomy found no significant difference between MPSS-treated and control neurons. Application of 30 or 100 micrograms/mL MPSS increased the spontaneous burst activity of SC networks grown on MMEPs, however, there was no evidence that the increased excitability at these concentrations was the result of specific actions of MPSS on GABA or NMDA synapses.

Responsiveness to ATP with an increase in intracellular free Ca2+ is not a distinctive feature of calbindin-D28 immunoreactive neurons in myenteric ganglia.

The aim of this study was to test the hypothesis that ATP elevates cytosolic free Ca2+ levels ([Ca2+]i) in myenteric neurons expressing the Ca2+ binding protein, calbindin-D28. A laser microbeam marked the location of cultured neurons on coverslips and provided unequivocal relocation of ATP-responsive neurons after immunocytochemistry. All myenteric multipolar neurons displayed ATP Ca2+ transients, and 42% also expressed calbindin-D28 reactivity. Statistical analysis of the kinetics and shape of ATP Ca2+ transients revealed no differences between calbindin and non-calbindin neurons. The identity of other responsive neurons is unknown. Less than 8% of ganglion cells with ATP Ca2+ transients were immunopositive for the glial protein S-100. We conclude that one of the actions of ATP in myenteric ganglia is to increase [Ca2+]i which may activate gKCa leading to membrane hyperpolarization in AH, Dogiel Type II neurons expressing calbindin-D28. An efficient buffering mechanism for handling large purinergic Ca2+ loads is a common feature of all types of myenteric ganglion cells.