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Understanding the factors contributing to optimal cognitive function throughout the aging process is essential to better understand successful cognitive aging. Processing speed is an age sensitive cognitive domain that usually declines early in the aging process; however, this cognitive skill is essential for other cognitive tasks and everyday functioning. Evaluating brain network interactions in cognitively healthy older adults can help us understand how brain characteristics variations affect cognitive functioning. Functional connections among groups of brain areas give insight into the brain’s organization, and the cognitive effects of aging may relate to this large-scale organization. To follow-up on our prior work, we sought to replicate our findings regarding network segregation’s relationship with processing speed. In order to address possible influences of node location or network membership we replicated the analysis across 4 different node sets.
Participants and Methods:
Data were acquired as part of a multi-center study of 85+ cognitively normal individuals, the McKnight Brain Aging Registry (MBAR). For this analysis, we included 146 community-dwelling, cognitively unimpaired older adults, ages 85-99, who had undergone structural and BOLD resting state MRI scans and a battery of neuropsychological tests. Exploratory factor analysis identified the processing speed factor of interest. We preprocessed BOLD scans using fmriprep, Ciftify, and XCPEngine algorithms. We used 4 different sets of connectivity-based parcellation: 1)MBAR data used to define nodes and Power (2011) atlas used to determine node network membership, 2) Younger adults data used to define nodes (Chan 2014) and Power (2011) atlas used to determine node network membership, 3) Older adults data from a different study (Han 2018) used to define nodes and Power (2011) atlas used to determine node network membership, and 4) MBAR data used to define nodes and MBAR data based community detection used to determine node network membership.
Segregation (balance of within-network and between-network connections) was measured within the association system and three wellcharacterized networks: Default Mode Network (DMN), Cingulo-Opercular Network (CON), and Fronto-Parietal Network (FPN). Correlation between processing speed and association system and networks was performed for all 4 node sets.
Results:
We replicated prior work and found the segregation of both the cortical association system, the segregation of FPN and DMN had a consistent relationship with processing speed across all node sets (association system range of correlations: r=.294 to .342, FPN: r=.254 to .272, DMN: r=.263 to .273). Additionally, compared to parcellations created with older adults, the parcellation created based on younger individuals showed attenuated and less robust findings as those with older adults (association system r=.263, FPN r=.255, DMN r=.263).
Conclusions:
This study shows that network segregation of the oldest-old brain is closely linked with processing speed and this relationship is replicable across different node sets created with varied datasets. This work adds to the growing body of knowledge about age-related dedifferentiation by demonstrating replicability and consistency of the finding that as essential cognitive skill, processing speed, is associated with differentiated functional networks even in very old individuals experiencing successful cognitive aging.
This study was designed to investigate the physiological responses induced in sheep (n = 18) by two different loading techniques followed by a short road journey. All animals were prepared with venous catheters, to minimize the disturbing effects of blood sampling, and nine sheep were fitted with heart rate monitors. The animals were loaded onto a transport vehicle in groups of three, alternately using a conventional tailgate ramp or a crate raised with a hydraulic lift. When all of the sheep were loaded, they were taken on a journey lasting 195min. Blood samples were collected in the home pen, directly after loading, and at 15min intervals during the journey. Measurements were made of plasma concentrations of Cortisol, prolactin and catecholamines (adrenaline and noradrenaline). The results indicated that heart rate increased during loading, regardless of the method used. No changes in concentrations of Cortisol or the catecholamines were detected, although a small increase in prolactin was noted when animals were loaded using the ramp. During transport, all sheep exhibited increases in plasma Cortisol concentrations which were greatest during the first 2h of the journey. The results suggest that, under the conditions employed in this experiment, the effects of the two loading procedures were similar and that transport appeared to be more stressful than loading.
For animals undergoing rehabilitation it is vital to monitor welfare in a way that is feasible, practical, and limits stress to the animal. The industry gold standard is to assess welfare under the Five Domains model, including nutrition, environment, physical health, and behaviour as the first four physical domains and mental domain as the fifth. Feasibility and effectiveness of these domains for assessing welfare of sea turtles undergoing rehabilitation were reviewed and it was determined that the mental state can be best assessed through behavioural changes. A scoping review of the literature was conducted using Scopus and Web of Science to investigate use of environmental enrichment devices (EEDs) as a measure of welfare in sea turtles. Behavioural assessments using EEDs were found to be well-documented; however, most EED studies pertained largely to livestock or zoo animals. Furthermore, studies rarely concentrated on reptiles, and specifically sea turtles. Results also showed that certain welfare assessment methods may be less appropriate for short-term captivity experienced during rehabilitation. Additionally, the hospital environment limits the ability to address some of the domains (ie biosecurity, feasibility, safety of turtle, etc, might be compromised). This review shows that only three of the nine environmental enrichment strategies described in the literature suit the specific requirements of sea turtles in rehabilitation: feeding, tactile, and structural. It is documented that turtles display behaviours that would benefit from EEDs and, therefore, more specific studies are needed to ensure the best welfare outcomes for sea turtles undergoing rehabilitation.
This study seeks the opinions of qualified doctors on what they feel medical students should learn about otolaryngology. It aims to identify both the content deemed relevant and the performance levels for medical students in otolaryngology.
Methods
A national survey developed from a content analysis of undergraduate otolaryngology curricula from the UK was undertaken, accompanied by a review of the literature and input from an expert group. Data were collected from a wide range of doctors.
Results
Participants felt that graduating students should be able to: recognise, assess and initiate management for common and life-threatening acute conditions; take an appropriate patient history; and perform an appropriate examination for the majority of otolaryngology clinical conditions but manage only a select few.
Conclusion
This study reports performance levels for otolaryngology topics at an undergraduate level. Participating doctors felt that a higher level of performance should be expected of students treating life-threatening, acute and common otolaryngology conditions.
To examine the factors that are associated with changes in depression in people with type 2 diabetes living in 12 different countries.
Methods
People with type 2 diabetes treated in out-patient settings aged 18–65 years underwent a psychiatric assessment to diagnose major depressive disorder (MDD) at baseline and follow-up. At both time points, participants completed the Patient Health Questionnaire (PHQ-9), the WHO five-item Well-being scale (WHO-5) and the Problem Areas in Diabetes (PAID) scale which measures diabetes-related distress. A composite stress score (CSS) (the occurrence of stressful life events and their reported degree of ‘upset’) between baseline and follow-up was calculated. Demographic data and medical record information were collected. Separate regression analyses were conducted with MDD and PHQ-9 scores as the dependent variables.
Results
In total, there were 7.4% (120) incident cases of MDD with 81.5% (1317) continuing to remain free of a diagnosis of MDD. Univariate analyses demonstrated that those with MDD were more likely to be female, less likely to be physically active, more likely to have diabetes complications at baseline and have higher CSS. Mean scores for the WHO-5, PAID and PHQ-9 were poorer in those with incident MDD compared with those who had never had a diagnosis of MDD. Regression analyses demonstrated that higher PHQ-9, lower WHO-5 scores and greater CSS were significant predictors of incident MDD. Significant predictors of PHQ-9 were baseline PHQ-9 score, WHO-5, PAID and CSS.
Conclusion
This study demonstrates the importance of psychosocial factors in addition to physiological variables in the development of depressive symptoms and incident MDD in people with type 2 diabetes. Stressful life events, depressive symptoms and diabetes-related distress all play a significant role which has implications for practice. A more holistic approach to care, which recognises the interplay of these psychosocial factors, may help to mitigate their impact on diabetes self-management as well as MDD, thus early screening and treatment for symptoms is recommended.
Clinicians treating patients with Major Depressive Disorder (MDD) might favor one second-generation antidepressant (SGA) because of perceived benefits for the accompanying symptoms of MDD.
Objectives
To compare the efficacy of bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine for the treatment of the accompanying symptoms of MDD.
Methods
This review is part of a larger review on the comparative effectiveness of SGAs for MDD. We searched MEDLINE, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts up to May 2010. Two persons independently reviewed the literature, abstracted data, and rated the risk of bias.
Results
We located 26 head-to-head and 7 placebo-controlled trials that provided evidence for this review. We did not locate any studies on treating accompanying appetite change, low energy, melancholia, or psychomotor change. There was no evidence for many comparisons and we were unable to conduct quantitative analysis for any comparisons. For the comparisons that were studied, we concluded that the SGAs are similarly efficacious for treating anxiety, insomnia, pain, and somatization. The strength of the evidence for these conclusions is low (meaning further research is very likely to have an important impact on our confidence in the estimate of the effect and is likely to change the estimate).
Conclusions
Our findings indicate that the existing evidence does not warrant the choice of one second-generation antidepressant over another based on greater efficacy for the accompanying symptoms of depression.
Extended-release formulations of antidepressants have been marketed as a strategy to increase patient adherence. Changes in the formulation of drugs, however, could be related to changes in efficacy and tolerability. Among second-generation antidepressants, bupropion, fluoxetine, mirtazapine, paroxetine, and venlafaxine are available in immediate- and extended-release formulations.
Objectives
To compare the efficacy, tolerability, and adherence of immediate- versus extended-release formulations of second-generation antidepressants for the treatment of major depressive disorder (MDD) in adults.
Aim
To provide an evidence base for clinicians when choosing immediate- or extended-release formulations of antidepressants for the treatment of MDD.
Methods
We conducted a comparative effectiveness review for the U.S. Agency for Healthcare Research and Quality searching PubMed, EMBASE, The Cochrane Library, and the International Pharmaceutical Abstracts up to May 2010. Two people independently reviewed the literature, abstracted data, and rated the risk of bias.
Results
Six RCTs and one observational study provided evidence about the comparative efficacy, tolerability, and adherence of bupropion SR (sustained release) versus bupropion XL (extended release), fluoxetine daily vs. fluoxetine weekly, paroxetine IR (immediate release) versus paroxetine CR (continuous release), and venlafaxine IR versus venlafaxine XR (extended release). Overall, no substantial differences in efficacy and safety could be detected. Open-label and observational evidence indicated better adherence for bupropion XL and fluoxetine weekly than for immediate-release medications. No differences in adherence could be detected between paroxetine IR and paroxetine CR.
Conclusions
Our findings indicate similar efficacy and tolerability between immediate- and extended-release formulations. Whether extended-release formulations lead to better adherence remains unclear.
Life in the terrestrial and marine subsurface has adapted and evolved mechanisms to survive under extremes of energy limitation, temperature, pressure, radiation, and/or water availability. New developments in nucleic acid sequencing, high-pressure biochemistry, and high-pressure biophysics have expanded our understanding of the mechanisms used by deep life. This chapter synthesizes these new developments and highlights remaining gaps in understanding.
Knowledge of the solid-phase speciation of As in Bengali sediments associated with hazardous As-rich groundwaters is crucial to understanding the processes controlling As release. The local coordination environment of As in such a sediment has been probed using K-edge As EXAFS. This revealed that As exists predominantly in its oxidized form, As(V), probably adsorbed as bidentate arsenate tetrahedra on metal (Fe and/or Al) oxide/hydroxide surfaces, although incorporation of As into a metal oxide structure cannot be ruled out. Arsenic was found to occur in several different coordination environments and this, together with the low concentration (<10 μg g–1) of As in the sediment prevented the unambiguous assignment of the second coordination sphere. The EXAFS analysis of the sediment after incubation under anaerobic conditions in the presence of added electron donor for metal reduction indicated changes in the relative concentrations of different solid-phase As species, providing circumstantial evidence for differential susceptibility to microbial action.
Arsenic mobilization and Fe(III) reduction in acetate-amended sediments collected from a range of depths from an aquifer with elevated groundwater arsenic concentrations in West Bengal were monitored over a 1 month period. Significant arsenic release was noted in sediment collected from 24 m and 45 m depth, with some Fe(III) reduction also observed in the 24 m sample. The structure of the microbial communities present in the sediments prior to incubation showed marked differences down the sediment column. Profiling of the microbial community in the 24 m and 45 m samples revealed a relatively complex make-up, with Acinetobacter species comprising the bulk of the 24 m sedimentary bacterial population, but no previously characterized As(V)-reducers were detected in either sample.
Previous studies from our laboratory have suggested a role for indigenous metal-reducing bacteria in the reduction of sediment-bound As(V), and have also shown that a stable enrichment culture of Fe(III)-reducing bacteria was able to mobilize arsenic (as As(III)) from sediments collected from West Bengal (Islam et al., 2004). To identify the Fe(III)-reducing bacteria that may play a role in the reduction of As(V) and mobilization of As(III), we made a detailed molecular analysis of this enrichment culture. It was dominated by a close relative of Geothrix fermentans, but the type strain of this organism was unable to conserve energy for growth via the dissimilatory reduction of As(V), or reduce As(V) present in a defined medium containing fumarate as the electron acceptor. Furthermore, when the cells were grown using soluble Fe(III)-citrate as an electron acceptor in the presence of As(V), bacterial Fe(III) reduction resulted in the precipitation of the Fe(II)-bearing mineral vivianite in 2 weeks. This was accompanied by the efficient removal of As from solution. These results demonstrate that Geothrix fermentans, in common with other key Fe(III)-reducing bacteria such as Geobacter sulfurreducens, does not reduce As(V) enzymatically, but can capture arsenic in Fe(II) minerals formed during respiration using Fe(III) as an electron acceptor. Thus, the reduction of arsenic-bearing Fe(III) oxide minerals is not sufficient to mobilize arsenic, but may result in the formation of Fe(II) biominerals that could potentially act as sinks for arsenic in sediments. Additional mechanisms, including dissimilatory As(V) reduction by other specialist anaerobic bacteria, are implicated in the mobilization of arsenic from sediments.
Persistence of the embryonic “fifth aortic arch” in postnatal life is a rare, enigmatic – and at times controversial – condition, with variable anatomical forms and physiological consequences. First described in humans over 40 years ago by Van Praagh, the condition was labelled the “great pretender” by Gerlis 25 years later, because of its apparent propensity to mimic anatomically similar structures. Despite many subsequent case reports citing the condition, the true developmental origin of these structures remains unresolved, and has been the subject of debate among embryologists for more than a century. A persistent fifth aortic arch has been defined as an extrapericardial structure, arising from the ascending aorta opposite or proximal to the brachiocephalic artery, and terminating in the dorsal aorta or pulmonary arteries via a persistently patent arterial duct. This description may therefore encompass various anatomical forms, such as a unilateral double-lumen aortic arch, an unrestrictive aortopulmonary shunt, or a critical vascular channel for either the systemic or pulmonary circulation. The physiological properties of these vessels, such as their response to prostaglandins, may also be unpredictable. In this article, we demonstrate a number of cases that fulfil the contemporary definition of “persistent fifth aortic arch” while acknowledging the embryological controversies associated with this term. We also outline the key diagnostic features, particularly with respect to the use of new cross-sectional imaging techniques.
The study aim was to establish and quantify suicide risk following acute admissions for all major physical illnesses, for confirmatory purposes, from two independent information sources from different countries.
Methods
Record linkage of inpatient and death certificate data for 11 004 389 acute admissions for physical illnesses in England and 713 496 in Wales. The main outcome measure was standardised mortality ratios (SMRs) for suicide at 1 year following discharge from hospital.
Results
There were 1781 suicides within 1 year of discharge in England (SMR = 1.7; 95% = 1.6–1.8) and 131 in Wales (SMR = 2.0; 1.7–2.3). Of 48 major physical illnesses that were associated with at least eight suicides in either country, there was high consistent suicide mortality (significant SMR >3) in both countries for constipation (SMR = 4.1 in England, 7.5 in Wales), gastritis (4.4 and 4.9) and upper gastrointestinal bleeding (3.4 and 4.5). There was high suicide mortality in one country for alcoholic liver disease, other liver disease and chronic pancreatitis; for epilepsy and Parkinson's disease; for diabetes, hypoglycaemia and hypo-osmolality & hyponatraemia; and for pneumonia, back pain and urinary tract infections.
Conclusions
There is little or no increased suicide mortality following acute admissions for most physical illnesses. Much of the increased suicide mortality relates to gastrointestinal disorders that are often alcohol related or specific chronic conditions, which may be linked to side effects from certain therapeutic medications. Acute hospital admissions for physical illnesses may therefore provide an opportunity for targeted suicide prevention among people with certain conditions, particularly alcohol related disorders.
The final effort of the CLIMAP project was a study of the last interglaciation, a time of minimum ice volume some 122,000 yr ago coincident with the Substage 5e oxygen isotopic minimum. Based on detailed oxygen isotope analyses and biotic census counts in 52 cores across the world ocean, last interglacial sea-surface temperatures (SST) were compared with those today. There are small SST departures in the mid-latitude North Atlantic (warmer) and the Gulf of Mexico (cooler). The eastern boundary currents of the South Atlantic and Pacific oceans are marked by large SST anomalies in individual cores, but their interpretations are precluded by no-analog problems and by discordancies among estimates from different biotic groups. In general, the last interglacial ocean was not significantly different from the modern ocean. The relative sequencing of ice decay versus oceanic warming on the Stage 6/5 oxygen isotopic transition and of ice growth versus oceanic cooling on the Stage 5e/5d transition was also studied. In most of the Southern Hemisphere, the oceanic response marked by the biotic census counts preceded (led) the global ice-volume response marked by the oxygen-isotope signal by several thousand years. The reverse pattern is evident in the North Atlantic Ocean and the Gulf of Mexico, where the oceanic response lagged that of global ice volume by several thousand years. As a result, the very warm temperatures associated with the last interglaciation were regionally diachronous by several thousand years. These regional lead-lag relationships agree with those observed on other transitions and in long-term phase relationships; they cannot be explained simply as artifacts of bioturbational translations of the original signals.
A pneumocele occurs when an aerated cranial cavity pathologically expands; a pneumatocele occurs when air extends from an aerated cavity into adjacent soft tissues forming a secondary cavity. Both pathologies are extremely rare with relation to the mastoid. This paper describes a case of a mastoid pneumocele that caused hypoglossal nerve palsy and an intracranial pneumatocele.
Case report:
A 46-year-old man presented, following minor head trauma, with hypoglossal nerve palsy secondary to a fracture through the hypoglossal canal. The fracture occurred as a result of a diffuse temporal bone pneumocele involving bone on both sides of the hypoglossal canal. Further slow expansion of the mastoid pneumocele led to a secondary middle fossa pneumatocele. The patient refused treatment and so has been managed conservatively for more than five years, and he remains well.
Conclusion:
While most patients with otogenic pneumatoceles have presented acutely in extremis secondary to tension pneumocephalus, our patient has remained largely asymptomatic. Aetiology, clinical features and management options of temporal bone pneumoceles and otogenic pneumatoceles are reviewed.
Two cases of hospital-acquired listeriosis were linked to a commercially produced, pasteurized ice cream mix. Manufacturers should implement safety measures from the Food Safety Modernization Act to minimize the risk of Listeria contamination. Dietary guidelines for persons at high risk of listeriosis may need revision to recognize the potential risk from pasteurized products.
To systematically summarise the peer-reviewed literature relating to the aetiology, clinical presentation, investigation and treatment of geniculate neuralgia.
Data sources:
Articles published in English between 1932 and 2012, identified using Medline, Embase and Cochrane databases.
Methods:
The search terms ‘geniculate neuralgia’, ‘nervus intermedius neuralgia’, ‘facial pain’, ‘otalgia’ and ‘neuralgia’ were used to identify relevant papers.
Results:
Fewer than 150 reported cases were published in English between 1932 and 2012. The aetiology of the condition remains unknown, and clinical presentation varies. Non-neuralgic causes of otalgia should always be excluded by a thorough clinical examination, audiological assessment and radiological investigations before making a diagnosis of geniculate neuralgia. Conservative medical treatment is always the first-line therapy. Surgical treatment should be offered if medical treatment fails. The two commonest surgical options are transection of the nervus intermedius, and microvascular decompression of the nerve at the nerve root entry zone of the brainstem. However, extracranial intratemporal division of the cutaneous branches of the facial nerve may offer a safer and similarly effective treatment.
Conclusion:
The response to medical treatment for this condition varies between individuals. The long-term outcomes of surgery remain unknown because of limited data.
Community-onset methicillin resistant Staphylococcus aureus (CO-MRSA) became a prominent cause of infection in North America in 2003, with a peak in the epidemic noted by multiple groups in the USA between 2005 and 2007. We reviewed rates of MRSA in two hospitals in Vancouver, Canada, to observe changes in epidemiology from 2003 to 2011. Episodes of emergency department (ED) MRSA bacteraemia and wounds were extracted from the laboratory database, with rates calculated per 10 000 ED visits. All cases were assumed to be community onset, as they were diagnosed in the ED. A peak in ED MRSA bacteraemias occurred in 2005, at 7·8/10 000 ED visits. By 2011, rates of ED bacteraemia declined significantly to 3·3/10 000 ED visits (P⩽0·03). MRSA wound rates peaked at 82·2 cases/10 000 ED visits in 2007 with a subsequent significant decline to 34·3 cases in 2011 (P = 0·04). We have demonstrated a significant decline in CO-MRSA within our population, consistent with reports from the USA, suggesting a substantial change in the epidemiology of CO-MRSA in certain North American cities.
Risk factors to prolonged fatigue syndromes (PFS) are controversial. Pre-morbid and/or current psychiatric disturbance, and/or disturbed cell-mediated immunity (CMI), have been proposed as etiologic factors. Self-report measures of fatigue and psychologic distress and three in vitro measures of CMI were collected from 124 twin pairs. Crosstwincrosstrait correlations were estimated for the complete monozygotic (MZ; 79 pairs) and dizygotic (DZ; 45 pairs) twin groups. Multivariate genetic and environmental models were fitted to explore the patterns of covariation between etiologic factors. For fatigue, the MZ correlation was more than double the DZ correlation (0.49 versus 0.16) indicating strong genetic control of familial aggregation. By contrast, for in vitro immune activation measures MZ and DZ correlations were similar (0.49–0.69 versus 0.42–0.53) indicating the etiologic role of shared environments. As small univariate associations were noted between prolonged fatigue and the in vitro immune measures (r = −0.07 to −0.12), multivariate models were fitted. Relevant etiologic factors included: a common genetic factor accounting for 48% of the variance in fatigue which also accounted for 4%, 6% and 8% reductions in immune activation; specific genetic factors for each of the in vitro immune measures; a shared environment factor influencing the three immune activation measures; and, most interestingly, unique environmental influences which increased fatigue but also increased markers of immune activation. PFS that are associated with in vitro measures of immune activation are most likely to be the consequence of current environmental rather than genetic factors. Such environmental factors could include physical agents such as infection and/or psychologic stress.