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The fog of Alzheimer’s is a commonly used metaphor, and I think it’s a pretty good one. It refers to the loss of mental acuity, disorientation, and forgetfulness that are common in Alzheimer’s. But one aspect of the metaphor that is not emphasized is that like the fog bank on the ocean, the fog of Alzheimer’s can come and go. It does for me. Sometimes there is an obvious cause such as running a fever, getting too tired, or having a second glass of wine. On the day after I got my second Covid-19 vaccination I was not mentally sharp and had trouble concentrating despite not having any other side effects. Once or twice a week on first awakening in the morning, I think I am in my childhood bedroom. It only takes a few seconds to get reoriented, and it actually is a pleasant rather than scary experience. Sometimes the fog comes in for no apparent reason, lasts a few minutes or a few hours, and then goes away. I wonder what is behind these mysterious, seemingly unprovoked but temporary episodes of cognitive impairment.
To describe cognitive impairment in out-of-hospital cardiac arrest (OHCA) survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA.
Participants and Methods:
This was a prospective case control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. We administered an extensive neuropsychological assessment at approximately 7 months post-cardiac event, including a neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes. Z-scores of individual tests were converted to neuropsychological composite scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions). Between-group differences on the neuropsychological composite scores were investigated with linear regression. Associations between anxiety, depression, fatigue, insomnia, hypertension, diabetes, and the neuropsychological composite scores among OHCA survivors were calculated with Spearman’s rho.
Results:
Of 184 eligible OHCA survivors, 108 were included (mean age = 62, 88% male), with 92 MI controls enrolled (mean age = 64, 89% male). Amongst OHCA survivors, 29% performed z <-1 indicating at least borderline-mild impairment in >2 cognitive domains, and 14% performed z <-2 exhibiting major impairment in >1 cognitive domain. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = -0.37, 95% confidence intervals [-0.61, -0.12]), verbal (MD = -0.34 [-0.62, -0.07]), and visual/constructive functions (MD = -0.26 [-0.47, -0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, processing speed (MD = -0.41 [-0.74, -0.09]) and executive functions (MD = -0.69 [-1.13, -0.24]) were also worse following OHCA. Depressive symptoms were associated with worse executive functions (rs = -0.37, p <0.001) and worse processing speed (rs = -0.27, p = 0.01) post-OHCA. Anxiety symptoms (rs = -0.21, p = 0.01) and general fatigue (rs = -0.24, p = 0.01) were associated with worse executive functions. Diabetes was associated with worse processing speed (rs = -0.20, p = 0.03), visual/constructive (rs = -0.29, p <0.001) and executive functions (rs = -0.25, p = 0.02), while hypertension and insomnia were not significantly associated with neuropsychological test performance.
Conclusions:
Cognitive impairment is generally mild following OHCA, but most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed worse than MI controls. We suggest that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue.
Sickle cell disease (SCD) is caused by an autosomal recessive mutation in the β-globin chain of hemoglobin A (HbA), causing the mutated hemoglobin S (HbS). In a vaso-occlusive crisis (VOC), sickled red blood cells (RBCs) increase the viscosity of blood and cause microvascular occlusion, contributing to hypoxia, acidosis and further sickling. The clinical manifestations of SCD are diverse and are related to chronic hemolysis with periodic episodes of vascular occlusion that can affect nearly every organ system.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the pandemic declared in March 2020. While many of the manifestations (i.e., acute respiratory distress syndrome [ARDS]) are similar to other severe respiratory viruses, there is an increasing number of specific therapeutics found to be effective in combating coronavirus disease 2019 (COVID-19). As data emerge on the optimal treatment of COVID-19, the recommendations in this chapter are based on the current consensus from large global health and infectious disease authorities but are subject to evolution of the evidence.
Edited by
Dan Chamberlain, University of Turin,Aleksi Lehikoinen, Finnish Museum of Natural History, University of Helsinki,Kathy Martin, University of British Columbia, Vancouver
Alpine birds face many challenges to live in habitats characterized by low temperatures, high winds, short growing seasons and delayed breeding schedules. Breeding in alpine environments is always a race against time due to the shortened egg laying period and frequent storms that may result in delayed development or reproductive failure. Since daily temperatures in the alpine zone can range from below freezing to >450C, developing embryos may require cooling as well as heating to maintain homeothermy. To cope with such conditions, birds breeding in alpine habitats have developed physiological, morphological and behavioural adaptations, and have adopted a slower lifestyle where they may produce fewer offspring each year compared to populations at low elevations, but may live longer. In the northern hemisphere, only a few birds live exclusively in the alpine zone, with many mountain species breeding in both alpine and lower elevation habitats, while in the Southern Andes, most alpine birds breed exclusively above the treeline. In summary, there may be high ecological costs to living in open habitats at high elevations. However, alpine birds likely experience lower levels of interspecific competition, habitat degradation and parasites and diseases than birds living at lower elevations.
Sudden infant death syndrome (SIDS) is multifactorial, associated with inadequate cardiac, breathing, autonomic and/or arousal control. Although cases are usually found collapsed in the early hours of the morning, collapse can occur in daytime. If resuscitation is successful, these infants may die later (delayed SIDS). In these circumstances, hypoxic ischaemic injury to vital organs, including the central nervous system will likely develop: haemorrhages (subdural (SDH), intradural, subgaleal, subarachnoid and/or brain), oedema, spinal and/or retinal haemorrhages (RH). The SDH and encephalopathy are well described in young infants dying of natural causes, especially following successful advanced resuscitation. Infants who develop the triad of SDH, RH, and encephalopathy share many epidemiological features with infants dying of SIDS: age, male sex, prematurity, small for gestational age, young mothers, multiple births, high parity, low socioeconomic status, smoking during pregnancy, minor respiratory infections. Hence, it seems reasonable to hypothesise that there is an overlap between some features in SIDS and SBS, and that the latter may correspond to a resuscitated SIDS.
The high-medieval demographic and economic growth in which fishers and their customers shared had detectable environmental consequences. Prevailing agricultural practices plus increased human and other wastes damaged river systems and polluted both flowing and still waters. Contemporaries were aware of some such effects; others emerge only in modern scientific archaeology. Rulers and others blamed perceived declines in the quantity and quality of fish on overfishing. Present-day studies of long-running assemblages of fish remains detect local depletion of favoured varieties and shrinking average size of more common species. Some fishes (eel) and some fisheries (for herring) of previously limited importance increased their contribution to European diets. An exotic species, common carp, hitherto present in Europe only in the lower Danube, spread westwards into waters made warmer and siltier by human activities. In large thirteenth-century assemblages (but with regional variations), more accessible herring, eel, codfishes, and small cyprinids become dominant. Not all change had human origin; natural dynamics also played a role. High medieval centuries saw the crest, then decline, of climatic warming, with concomitant regional differences in precipitation, seasonality, riverine and estuarine hydrology, and even shifts in stratification and water chemistry of the Baltic. Changed habitats let heat-tolerant fishes spread west, while a herring-dominated regime in the Baltic peaked and slowly yielded to greater presence of cod. Knowingly or not, humans and animals had to adapt.
Coastal eutrophication and hypoxia remain a persistent environmental crisis despite the great efforts to reduce nutrient loading and mitigate associated environmental damages. Symptoms of this crisis have appeared to spread rapidly, reaching developing countries in Asia with emergences in Southern America and Africa. The pace of changes and the underlying drivers remain not so clear. To address the gap, we review the up-to-date status and mechanisms of eutrophication and hypoxia in global coastal oceans, upon which we examine the trajectories of changes over the 40 years or longer in six model coastal systems with varying socio-economic development statuses and different levels and histories of eutrophication. Although these coastal systems share common features of eutrophication, site-specific characteristics are also substantial, depending on the regional environmental setting and level of social-economic development along with policy implementation and management. Nevertheless, ecosystem recovery generally needs greater reduction in pressures compared to that initiated degradation and becomes less feasible to achieve past norms with a longer time anthropogenic pressures on the ecosystems. While the qualitative causality between drivers and consequences is well established, quantitative attribution of these drivers to eutrophication and hypoxia remains difficult especially when we consider the social economic drivers because the changes in coastal ecosystems are subject to multiple influences and the cause–effect relationship is often non-linear. Such relationships are further complicated by climate changes that have been accelerating over the past few decades. The knowledge gaps that limit our quantitative and mechanistic understanding of the human-coastal ocean nexus are identified, which is essential for science-based policy making. Recognizing lessons from past management practices, we advocate for a better, more efficient indexing system of coastal eutrophication and an advanced regional earth system modeling framework with optimal modules of human dimensions to facilitate the development and evaluation of effective policy and restoration actions.
We report a preliminary study that compared decisions made in an oxygen depleted environment with those made in a normoxic environment. Participants were presented with a series of choices that involved either losses or gains. For each choice they were forced to choose between a sure thing and a gamble of the same expected value. For choices involving losses, participants were more risk seeking in the oxygen depleted environment; for those involving gains, no difference was found.
Low atmospheric pressure stunning (LAPS) is a slaughter technique which may be less stressful for pigs (Sus scrofa domestica) than current commercial stunning and slaughter methods. The main methods used currently for slaughtering pigs are electric and carbon dioxide stunning, both of which are widely recognised as stressful for pigs. There is currently no published research on the use of LAPS for stunning adult pigs, however there is a significant body of relevant experience from investigations into the effects of low pressure and hypoxia on humans, hypoxia for killing pigs and the use of LAPS for killing poultry, rats and piglets. In this paper, the basic physics and biology of LAPS is briefly reviewed and relevant experience from research with humans, poultry, rats and piglets is presented. On the basis of this information, some initial parameters for LAPS trials with pigs are proposed, potential welfare issues identified and an approach to achieving LAPS at a commercially viable speed is outlined. While the effects of LAPS on pigs is, at present, uncertain, the evidence from research with humans and other animals suggests that healthy, fasted pigs undergoing LAPS are unlikely to suffer from air hunger or from pain. Any pigs suffering from upper respiratory tract disease, tooth decay or excess gas in the alimentary canal may, however, experience pain. A total killing cycle is likely to require 9 to 14 min. To implement LAPS in a commercial, high throughput processing plant will require the use of multiple decompression cylinders. The evidence available suggests that LAPS could be commercially viable for pig slaughter and that for most pigs it will be less stressful than current commercial slaughter methods.
Long coronavirus disease 2019 (LC) is a chronic sequel of acute COVID-19. The exact pathophysiology of the affective, chronic fatigue and physiosomatic symptoms (labelled as “physio-affective phenome”) of LC has remained elusive.
Objective:
The current study aims to delineate the effects of oxygen saturation (SpO2) and body temperature during the acute phase on the physio-affective phenome of LC.
Method:
We recruited 120 LC patients and 36 controls. For all participants, we assessed the lowest SpO2 and peak body temperature during acute COVID-19, and the Hamilton Depression and Anxiety Rating Scale (HAMD/HAMA) and Fibro Fatigue (FF) scales 3–4 months later.
Results:
Lowered SpO2 and increased body temperature during the acute phase and female sex predict 60.7% of the variance in the physio-affective phenome of LC. Using unsupervised learning techniques, we were able to delineate a new endophenotype class, which comprises around 26.7% of the LC patients and is characterised by very low SpO2 and very high body temperature, and depression, anxiety, chronic fatigue, and autonomic and gastro-intestinal symptoms scores. Single latent vectors could be extracted from both biomarkers, depression, anxiety and FF symptoms or from both biomarkers, insomnia, chronic fatigue, gastro-intestinal and autonomic symptoms.
Conclusion:
The newly constructed endophenotype class and pathway phenotypes indicate that the physio-affective phenome of LC is at least in part the consequence of the pathophysiology of acute COVID-19, namely the combined effects of lowered SpO2, increased body temperature and the associated immune-inflammatory processes and lung lesions.
Fetal or neonatal hypoxia (FoNH) is a known risk factor for schizophrenia. It has been hypothesized that FoNH induced expression of schizophrenia susceptibility genes (Schmidt-Kastner et al. 2012, Giannopoulou et al. 2018).
Objectives
To test this hypothesis, we explore the effects of FoNH and some genetic variants on age at onset (AAO) of schizophrenia.
Methods
The study included 1670 patients (women 1021 (61.1%), mean age 34.6 (SD 13.6), mean age at disease onset 25.4 (10.5) years) with ICD-10 diagnosis of schizophrenia or schizoaffective psychosis. The effects of FoNH in interaction with sex, family history (FH) and genetic variants on AAO of schizophrenia were evaluated. Polymorphisms rs2514218 DRD2 (n=943), Val66Met BDNF (n=820) and VNTR AS3MT (n=804) were genotyped.
Results
Among all patients studied 179 (10.8%) had experienced FoNH. Regression model showed that FoNH, sex and FH of schizophrenia contribute significantly (p=0.000) to AAO. In the FoNH group, AAO was lower compared to the group without FoNH (20.7 (6.2) vs 25.5 (10.) years). When comparing men and women, there was a difference between FoNH and non- FoNH subgroups only in women (p=0.000). No interaction between FH and FoNH was observed though positive FH had an effect on AAO. There was the interaction effect of VNTR AS3MT and FoNH on AAO. In the FoNH group, carriers of 2 repeats had younger AAO compared to the carriers homozygous for 3 repeat variant (19.6 (4.9) vs 22. (7.6) years).
Conclusions
We demonstrate the interaction effects of FoNH and VNTR AS3MT polymorphism on AAO of schizophrenia.
Ionising radiotherapy is a well-established, effective cancer treatment modality, whose efficacy has improved with the application of newer technological modalities. However, patient outcomes are governed and potentially limited by aspects of tumour biology that are associated with radioresistance. Patients also still endure treatment-associated toxicities owed to the action of ionising radiation in normoxic tissue adjacent to the tumour mass. Tumour hypoxia is recognised as a key component of the tumour microenvironment and is well established as leading to therapy resistance and poor prognosis. In this review, we outline the current understanding of hypoxia-mediated radiotherapy resistance, before exploring targeting tumour hypoxia for radiotherapy sensitisation to improve treatment outcomes and increase the therapeutic window. This includes increasing oxygen availability in solid tumours, the use of hypoxia-activated prodrugs, targeting of hypoxia-regulated or associated signalling pathways, as well as the use of high-LET radiotherapy modalities. Ultimately, targeting hypoxic radiobiology combined with precise radiotherapy delivery modalities and modelling should be associated with improvement to patient outcomes.
I had been working on the endocrine and signalling role of white adipose tissue (WAT) since 1994 following the identification of the ob (Lep) gene(1), this after some 15 years investigating the physiological role of brown adipose tissue. The ob gene, a mutation in which it is responsible for the profound obesity of ob/ob (Lepob/Lepob) mice, is expressed primarily in white adipocytes and encodes the pleiotropic hormone leptin. The discovery of this adipocyte hormone had wide-ranging implications, including that white fat has multiple functions that far transcend the traditional picture of a simple lipid storage organ.
A 33-year-old nulligravid woman is undergoing hysteroscopic removal of a 5 cm FIGO type 1 submucosal myoma due to heavy menstrual bleeding and mild anemia. She is otherwise in good health and has no significant medical or surgical history. She is not on any medications and denies drug allergy. The patient receives general anesthesia without difficulty. The procedure commences with use of a fluid management system and a bipolar resectoscope to remove myoma fragments. Approximately 30 minutes into the surgery, the anesthesiologist becomes concerned due to sudden decrease of oxygen saturation to 87%. The total fluid deficit is approaching 2300 mL. The anesthesiologist administers intravenous (IV) furosemide and asks the surgeon to terminate the procedure. Several minutes later, oxygen saturations increase to 92%. The patient is awakened from anesthesia and proceeds to the recovery room in a stable condition.
1. Drowning is a leading global killer of children and young adults.
2. Outcomes from drowning are uncertain, principally determined by the time of cerebral anoxia, and not the extent of pulmonary aspiration and soiling.
3. Trauma should be considered as a potential cause or consequence of drowning; hence, protective C-spine measures should be considered.
4. Rescue breaths should be administered to both adult and paediatric drowned patients with or without spontaneous circulation.
5. Hypothermia is commonplace in drowned patients and should be managed with active rewarming to 34°C.
Prenatal fetal monitoring allows for the detection of abnormal physiologic conditions in the fetus. The different available methods can detect abnormalities in utero-placental perfusion, as well as physiologic changes during and after in-utero fetal surgery. Basic antepartum fetal monitoring in viable fetuses has advanced over the years and now involves not only the nonstress test but more advanced methods which also take into account the ultrasound findings. Comprehension of the different fetal heart rate tracings allow for rapid intervention where necessary. Unfortunately, while many modes of surveillance exist, no single method can accurately identify a fetus that will progress to being stillbirth.
Persistent pulmonary hypertension of the neonate can cause acute and life-threatening hypoxia, but preterm neonates are not suitable candidate to extra-corporeal life support. We report the unique case of an extremely preterm neonates with life-threatening persistent pulmonary hypertension refractory to triple vasodilator therapy (nitric oxide, iloprost, and bosentan), which has been successfully treated with the addition of adenosine continuous infusion.
Severe acute respiratory syndrome (SARS) is a highly contagious viral respiratory illness associated with hypoxia and dyspnea. Many of those who contracted and recovered from SARS during the 2002–2003 outbreak reported persistent physical, psychological, and cognitive difficulties. Here, we investigated the residual influences of SARS on cognition for a subset of healthcare professionals who recovered and were referred for neuropsychological evaluation through their workplace insurance.
Method:
Twenty-eight healthcare professionals were evaluated on neuropsychological and mood functioning approximately 1.5 years post-recovery from a severe respiratory illness. Test scores were compared with age-matched normative data, and correlations were examined between mood, self-report memory scales, subjective complaints (e.g., poor concentration, pain, fatigue), illness severity (i.e., length of hospitalization, oxygen use during hospital stay), and cognitive performance.
Results:
Participants performed within age expectations on the majority of cognitive measures including overall memory ability. Although processing speed was generally within normal limits, 43% showed significant speed–accuracy trade-offs favoring accuracy over maintaining speed. Deficits were observed on measures of complex attention, such as working memory and the ability to sustain attention under conditions of distraction. Participants endorsed poorer memory ability than same-age peers on a meta-memory measure and mild to moderate depression and anxiety symptoms. Objective test performance was largely uncorrelated with self-reports, mood, or illness severity, except for moderate correlations between complex attention and participants’ subjective ratings of Everyday Task-Oriented Memory.
Conclusions:
These findings demonstrate specific long-term cognitive deficits associated with SARS and provide further evidence of the cognitive effects of hypoxic illnesses.
Environmental hypoxia exposure causes fertility problems in human and animals. Compelling evidence suggests that chronic hypoxia impairs spermatogenesis and reduces sperm motility. However, it is unclear whether paternal hypoxic exposure affects fertilization and early embryo development. In the present study, we exposed male mice to high altitude (3200 m above sea level) for 7 or 60 days to evaluate the effects of hypoxia on sperm quality, zygotic DNA methylation and blastocyst formation. Compared with age-matched controls, hypoxia-treated males exhibited reduced fertility after mating with normoxic females as a result of defects in sperm motility and function. Results of in vitro fertilization (IVF) experiments revealed that 60 days’ exposure significantly reduced cleavage and blastocyst rates by 30% and 70%, respectively. Immunohistochemical staining of pronuclear formation indicated that the pronuclear formation process was disturbed and expression of imprinted genes was reduced in early embryos after paternal hypoxia. Overall, the findings of this study suggested that exposing male mice to hypoxia impaired sperm function and affected key events during early embryo development in mammals.