A systematic review of the effects of temperature and precipitation on pollen concentrations and season timing, and implications for human health.

Climate and weather directly impact plant phenology, affecting airborne pollen. The objective of this systematic review is to examine the impacts of meteorological variables on airborne pollen concentrations and pollen season timing. Using PRISMA methodology, we reviewed literature that assessed whether there was a relationship between local temperature and precipitation and measured airborne pollen. The search strategy included terms related to pollen, trends or measurements, and season timing. For inclusion, studies must have conducted a correlation analysis of at least 5 years of airborne pollen data to local meteorological data and report quantitative results. Data from peer-reviewed articles were extracted on the correlations between seven pollen indicators (main pollen season start date, end date, peak date, and length, annual pollen integral, average daily pollen concentration, and peak pollen concentration), and two meteorological variables (temperature and precipitation). Ninety-three articles were included in the analysis out of 9,679 articles screened. Overall, warmer temperatures correlated with earlier and longer pollen seasons and higher pollen concentrations. Precipitation had varying effects on pollen concentration and pollen season timing indicators. Increased precipitation may have a short-term effect causing low pollen concentrations potentially due to "wash out" effect. Long-term effects of precipitation varied for trees and weeds and had a positive correlation with grass pollen levels. With increases in temperature due to climate change, pollen seasons for some taxa in some regions may start earlier, last longer, and be more intense, which may be associated with adverse health impacts, as pollen exposure has well-known health effects in sensitized individuals.

Impact of prescription drugs on second fragility fractures among US Medicare patients.

Drugs that increase the risk of fracture are commonly prescribed to survivors of a fragility fracture. This study shows that starting new high-risk medications after fracture increases the risk of a second, potentially preventable fracture. For most drug classes, however, it is safe to continue medications taken before the fracture. INTRODUCTION: Most patients who survive a fragility fracture are subsequently exposed to prescription drugs that have been linked to increased fracture risk. This study was designed to quantify the extent to which current prescribing practices result in potentially preventable second fractures. METHODS: We analyzed a cohort of 138,526 Medicare beneficiaries who returned to the community after a fragility fracture. Post-fracture drug use was defined using retail pharmacy fills. The risk of second fracture associated with individual drug classes was analyzed using Cox proportional hazard models. Data were further analyzed to determine whether there is a difference in risk between continuing previous therapy and initiating new therapy after fracture. RESULTS: Many drug classes previously identified as increasing fracture risk were not associated with increased fracture risk in this cohort. Discontinuing therapy at the time of fracture was only beneficial for patients taking selective serotonin reuptake inhibitors; however, initiating therapy in previous non-users increased second fracture risk for five classes of drugs (selective serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics, proton pump inhibitors, and non-benzodiazepine hypnotics). CONCLUSION: Discontinuing high-risk drugs after fracture was not generally protective against subsequent fractures. Preventing the addition of new medications may result in greater improvements in post-fracture care.

Regional anesthesia decreases complications and resource utilization in shoulder arthroplasty patients.

BACKGROUND: Regional anesthesia can be used as part of the anesthetic to optimize anesthesia and analgesia during shoulder arthroplasty, but little is known about the overall effect that regional anesthesia has on perioperative outcomes and resource utilization. We hypothesized that regional anesthesia may decrease complication rates and resource utilization in shoulder arthroplasty patients. METHODS: We examined administrative data from 588 US hospitals from 2010 to 2015. Logistic regression was used to examine the relationship between type of anesthesia and perioperative complications. RESULTS: Among patients who underwent shoulder arthroplasty, 79.1% (53,243) had general anesthesia alone, 17.8% (12,011) had general anesthesia and a nerve block, and 3.1% (2062) had a nerve block alone. Overall, the complication rate was 13.3% and 30-day mortality was 1.2 per 1000 (95% CI 0.9, 1.4). In adjusted analyses, patients who had general anesthesia alone (compared to general anesthesia and nerve block) had a 16% increase in all cause infectious complications (OR 1.16, 95% CI: 1.03, 1.31) and were 2.6 times more likely to develop pulmonary complications (OR 2.6, 95% CI: 1.14, 5.78). General anesthesia alone (relative to either block only or general anesthesia and block) was associated with substantial increases in the likelihood of blood transfusions, intensive care unit transfers, and prolonged length of stay. CONCLUSION: Patients receiving regional anesthesia for shoulder arthroplasty may have a reduction in perioperative complications, the need for intensive care unit transfers, blood transfusions, and prolonged hospital stays.

Relating coccidioidomycosis (valley fever) incidence to soil moisture conditions.

Coccidioidomycosis (also called Valley fever) is caused by a soilborne fungus, Coccidioides spp., in arid regions of the southwestern United States. Though some who develop infections from this fungus remain asymptomatic, others develop respiratory disease as a consequence. Less commonly, severe illness and death can occur when the infection spreads to other regions of the body. Previous analyses have attempted to connect the incidence of coccidioidomycosis to broadly available climatic measurements, such as precipitation or temperature. However, with the limited availability of long-term, in situ soil moisture data sets, it has not been feasible to perform a direct analysis of the relationships between soil moisture levels and coccidioidomycosis incidence on a larger temporal and spatial scale. Utilizing in situ soil moisture gauges throughout the southwest from the U.S. Climate Reference Network and a model with which to extend those estimates, this work connects periods of higher and lower soil moisture in Arizona and California between 2002 and 2014 to the reported incidence of coccidioidomycosis. The results indicate that in both states, coccidioidomycosis incidence is related to soil moisture levels from previous summers and falls. Stated differently, a higher number of coccidioidomycosis cases are likely to be reported if previous bands of months have been atypically wet or dry, depending on the location.

Second fractures among older adults in the year following hip, shoulder, or wrist fracture.

UNLABELLED: We report on second fracture occurrence in the year following a hip, shoulder or wrist fracture using insurance claims. Among 273,330 people, 4.3 % had a second fracture; risk did not differ by first fracture type. Estimated adjusted second fracture probabilities may facilitate population-based evaluation of secondary fracture prevention strategies. INTRODUCTION: The purpose of this study was estimate second fracture risk for the older US population in the year following a hip, shoulder, or wrist fracture. METHODS: Observational cohort study of Medicare fee-for-service beneficiaries with an index hip, shoulder, or wrist fragility fracture in 2009. Time-to-event analyses using Cox proportional hazards models to characterize the relationship between index fracture type (hip, shoulder, wrist) and patient factors (age, gender, and comorbidity) on second fracture risk in the year following the index fracture. RESULTS: Among 273,330 individuals with fracture, 11,885 (4.3 %) sustained a second hip, shoulder or wrist fracture within one year. Hip fracture was most common, regardless of the index fracture type. Comparing adjusted second fracture risks across index fracture types reveals that the magnitude of second fracture risk within each age-comorbidity group is similar regardless of the index fracture. Men and women face similar risks with frequently overlapping confidence intervals, except among women aged 85 years or older who are at greater risk. CONCLUSIONS: Regardless of index fracture type, second fractures are common in the year following hip, shoulder or wrist fracture. Secondary fracture prevention strategies that take a population perspective should be informed by these estimates which take competing mortality risks into account.

Application of a Novel Brain Arteriovenous Malformation Endovascular Grading Scale for Transarterial Embolization.

BACKGROUND AND PURPOSE: The advent of modern neuroendovascular techniques has highlighted the need for a simple, effective, and reliable brain arteriovenous malformation endovascular grading scale. A novel scale of this type has recently been described. It incorporates the number of feeding arteries, eloquence, and the presence of an arteriovenous fistula component. Our aim is to assess the validity of this grading scale. MATERIALS AND METHODS: We retrospectively reviewed all suspected brain arteriovenous malformations at Massachusetts General Hospital from 2005 to 2013, identifying 126 patients who met the inclusion criteria. Spearman correlations between endovascular and Spetzler-Martin grading scales and long-term outcomes were performed. Median endovascular grades were compared between treatment modalities and endovascular outcomes. Binary regression analysis was performed with major endovascular complications as a dichotomized dependent variable. Intraclass correlation coefficients were calculated for interobserver reliability of the endovascular grading scale. RESULTS: A significant Spearman correlation between the endovascular grade and the Spetzler-Martin grade was demonstrated (ρ = 0.5, P < .01). Differences in the median endovascular grades between the endovascular cure (median = 2) and endovascular complication groups (median = 4) (P < .05) and between the endovascular cure and successful multimodal treatment groups (median = 3) (P < .05) were demonstrated. The endovascular grade was the only independent predictor of complications (OR = 0.5, P < .01). The intraclass correlation coefficient of the endovascular grade was 0.71 (P < .01). CONCLUSIONS: Validation of a brain arteriovenous malformation endovascular grading scale demonstrated that endovascular grades of ≤II were associated with endovascular cure, while endovascular grades of ≤III were associated with multimodal cure or significant lesion reduction and favorable outcome. The endovascular grade provides useful information to refine risk stratification for endovascular and multimodal treatment.

N-methyl-d-aspartate receptors, learning and memory: chronic intraventricular infusion of the NMDA receptor antagonist d-AP5 interacts directly with the neural mechanisms of spatial learning.

Three experiments were conducted to contrast the hypothesis that hippocampal N-methyl-d-aspartate (NMDA) receptors participate directly in the mechanisms of hippocampus-dependent learning with an alternative view that apparent impairments of learning induced by NMDA receptor antagonists arise because of drug-induced neuropathological and/or sensorimotor disturbances. In experiment 1, rats given a chronic i.c.v. infusion of d-AP5 (30 mm) at 0.5 µL/h were selectively impaired, relative to aCSF-infused animals, in place but not cued navigation learning when they were trained during the 14-day drug infusion period, but were unimpaired on both tasks if trained 11 days after the minipumps were exhausted. d-AP5 caused sensorimotor disturbances in the spatial task, but these gradually worsened as the animals failed to learn. Histological assessment of potential neuropathological changes revealed no abnormalities in d-AP5-treated rats whether killed during or after chronic drug infusion. In experiment 2, a deficit in spatial learning was also apparent in d-AP5-treated rats trained on a spatial reference memory task involving two identical but visible platforms, a task chosen and shown to minimise sensorimotor disturbances. HPLC was used to identify the presence of d-AP5 in selected brain areas. In Experiment 3, rats treated with d-AP5 showed a delay-dependent deficit in spatial memory in the delayed matching-to-place protocol for the water maze. These data are discussed with respect to the learning mechanism and sensorimotor accounts of the impact of NMDA receptor antagonists on brain function. We argue that NMDA receptor mechanisms participate directly in spatial learning.

Characterization of a novel bidirectional distraction spinal cord injury animal model.

Scoliosis corrective surgery requires the application of significant multidirectional stress forces, including distraction, for correction of the curved spine deformity and the application of fixation rods. If excessive, spine distraction may result in the development of new neurological deficits, some as severe as permanent paralysis. Current animal models of spinal cord injury, however, are limited to contusion, transection, or unidirectional distraction injuries, which fail to replicate the multidirectional forces that occur during spine corrective surgery. To address such limitation, we designed a novel device that relies on intervertebral grip fixation and linear actuators to induce controllable bidirectional distraction injuries to the spine. The device was tested in three (i.e., 3, 5, and 7 mm) distention paradigms of the rat T9-T11 vertebra, and the resulting injuries were evaluated through electrophysiological, behavioral, and histological analysis. As expected, 3mm bilateral spine distractions showed no neurological deficit. In contrast, those with 5 and 7 mm showed partial and complete paralysis, respectively. The relationship between the severity of the spine distraction and injury to the spinal cord tissue was determined using glial fibrillary acidic protein immunocytochemistry for visualization of reactive astrocytes and labeling of ED1-positive activated macrophages/microglia. Our results demonstrate that this device can produce bidirectional spine distraction injuries with high precision and control and, thus, may be valuable in contributing to the testing of neuroprotective strategies aimed at preventing unintended new neurological damage during corrective spine surgery.

Mineralocorticoid receptor mRNA expression is increased in human hippocampus following brief cerebral ischaemia.

BACKGROUND: We have previously reported that neuronal endangerment in vitro and hypothermic transient global ischaemia in vivo each result in increased mineralocorticoid receptor (MR) expression. In both models MR induction is associated with increased neuronal survival, and blocking MR signalling reduces neuronal survival. Furthermore, transgenic overexpression of human MR promotes neuronal survival both in vitro and in vivo. AIMS: Here we have assessed whether brief periods of cerebral ischaemia in human subjects, such as occurs in cardiac arrest from which successful resuscitation is achieved, are associated with a sustained increase in hippocampal MR mRNA expression. METHODS: Human post-mortem brain sections from patients who had died in the weeks following cardiac arrest were analysed for MR mRNA expression by in situ hybridization. RESULTS: Sustained upregulation of MR mRNA expression was observed in the dentate gyrus region of human hippocampus following a brief episode of cerebral ischaemia. CONCLUSIONS: This confirms that MR mRNA expression is regulated following neuronal injury in human brain, and suggests that the benefits of increased MR expression seen in animal models of ischaemia may also be observed in humans.

The Neuropathology of HIV/AIDS.

The introduction of Highly Active Anti-retroviral Therapy (HAART) has resulted in significant decreases in morbidity and mortality for subjects infected with HIV. The brain is a major target organ for HIV resulting in significant neuropathological changes in most HIV infected subjects and a wide range of clinical neurological symptoms including HIV associated dementia. In the pre-HAART era HIV associated dementia was a common complication of AIDS. However, since the introduction of HAART the incidence of HIV associated dementia has fallen, but the prevelance has actually risen due to the increasing number of infected subjects and increased life expectancy. HIV associated dementia correlates most closely with neuroinflammation rather than directly with viral load or HIV encephalitis. HIV related clinical and neuropathological disorders are more prevalent in drug abusers than in other risk groups. This review focuses on the shifting pathology observed in HIV infected subjects since the introduction of HAART, discussing the clinical manifestations of these and the influence of confounding factors such as drug abuse and Hepatitis C co-infection.

Infective dementias.

A wide range of infectious diseases can result in dementia, although the identity and nature of these diseases has changed over time. Two of the most significant current groups in terms of scientific complexity are HIV/AIDS and prion diseases. In these disorders, dementia occurs either as a consequence of targeting the brain and selectively damaging neurones, or by an indirect effect of neuroinflammation. In prion diseases, both direct neurotoxicity and neuroinflammation may act to result in neuronal damage. In HIV encephalitis, the progression of the dementia is slower, perhaps reflecting indirect damage that appears to result from neuroinflammation as a main cause of neuronal death. An ever-increasing range of model systems is now available to study the neuronal damage in infectious dementias, ranging from cell culture systems to animal models, some of which, particularly in the case of prion diseases, are very well characterised and amenable to controlled manipulation in terms of both host and agent parameters. As valuable as these experimental models are, they do not allow a direct approach to an understanding of dementia, the complexities of which cannot readily be studied in vitro or in animal models, but they do allow studies of interventions and therapeutic strategies. This review summarises the current state of knowledge regarding the major infective dementias.

Tissue and organ donation for research in forensic pathology: the MRC Sudden Death Brain and Tissue Bank.

Novel methodological approaches to the investigation of brain and non-central nervous system disorders have led to increased demand for well-characterized, high quality human tissue samples, particularly from control cases. In the setting of the new Human Tissue legislation, we sought to determine whether relatives who have been suddenly bereaved are willing to grant authorization for research use of post mortem tissue samples and organs in sufficient numbers to support the establishment of a brain and tissue bank based in the forensic service. Research authorization was sought from families on the day prior to forensic post mortem examination followed up by written confirmation. We have to date selected individuals who have died suddenly (age range 1-89 years) and who were likely to have normal brains or who had displayed symptoms of a CNS disorder of interest to researchers, including psychiatric disorders. One hundred and eleven families have been approached during the first 2 years of this project. Research use of tissue samples was authorized by 96% of families and 17% agreed to whole brain donation. Audit of families' experience does not suggest that they are further distressed by being approached. Respondents expressed a clear view that the opportunity for research donation should be open to all bereaved families. Despite the sometimes long post mortem intervals, the quality of tissue samples is good, as assessed by a range of markers including Agilent BioAnalyzer quantification of RNA integrity (mean value 6.4). We conclude that the vast majority of families are willing to support research use of post mortem tissues even in the context of sudden bereavement and despite previous adverse publicity. The potential for acquisition of normal CNS and non-CNS tissues and of various hard-to-get CNS disorders suggests that efforts to access the forensic post mortem service for research material are eminently worthwhile.

How a neuropsychiatric brain bank should be run: a consensus paper of Brainnet Europe II.

The development of new molecular and neurobiological methods, computer-assisted quantification techniques and neurobiological investigation methods which can be applied to the human brain, all have evoked an increased demand for post-mortem tissue in research. Psychiatric disorders are considered to be of neurobiological origin. Thus far, however, the etiology and pathophysiology of schizophrenia, depression and dementias are not well understood at the cellular and molecular level. The following will outline the consensus of the working group for neuropsychiatric brain banking organized in the Brainnet Europe II, on ethical guidelines for brain banking, clinical diagnostic criteria, the minimal clinical data set of retrospectively analyzed cases as well as neuropathological standard investigations to perform stageing for neurodegenerative disorders in brain tissue. We will list regions of interest for assessments in psychiatric disorder, propose a dissection scheme and describe preservation and storage conditions of tissue. These guidelines may be of value for future implementations of additional neuropsychiatric brain banks world-wide.

Dura mater-associated Creutzfeldt-Jakob disease: experience from surveillance in the UK.

Between 1970 and 2003, seven cases of human dura mater-associated Creutzfeldt-Jakob disease (CJD) were identified in the UK. Furthermore, we identified a case of CJD in a porcine dura graft recipient. The mean incubation period of the human dura mater cases was 93 (range 45-177) months. The clinico-pathological features of the cases are described and compared with cases previously reported in the world literature.

The Scottish Perinatal Neuropathology Study--clinicopathological correlation in stillbirths.

OBJECTIVE: To examine the neuropathology of fetuses dying before birth, to determine the timing of any brain damage seen and to ascertain clinical associations of pre-existing brain damage. DESIGN: Population-based observational study. SETTING: All 22 delivery units within Scotland, 1995-1998. SAMPLE: All stillborn fetuses > or =24 weeks of gestation excluding those with chromosomal abnormality or central nervous system/cardiothoracic malformation. METHODS: Clinical detail was collected on all stillborn fetuses. Requests for postmortem included separate request for detailed neuropathological examination. Stillborn fetuses were classified as full term antepartum (normal growth/growth restricted), preterm antepartum (normal growth/growth restricted), intrapartum (full term/preterm), multiple births and stillborn fetuses following abruptions. Clinicopathological correlation attempted to define the timing of brain insult. Placentas were examined for each case where available. MAIN OUTCOME MEASURES: Presence of established and/or recent brain damage. RESULTS Clinical details were available for 471 stillborn fetuses, and detailed neuropathology was possible in 191 cases. Of these 191, 13 were multiple births, 9 died following abruption, 12 were intrapartum deaths and 157 were antepartum stillborn fetuses (99 preterm and 58 full term). Recent or established brain damage was seen in 66% of the entire cohort. Thirty-five percent of all cases showed well-established hypoxic damage predating the last evidence of fetal life, and this was more common in preterm fetuses (P = 0.015), those fetuses with evidence of recent damage (P < 0.001), in pregnancies complicated by pregnancy-induced hypertension (P = 0.044) and those in whom the placenta was <10th centile (P = 0.002). CONCLUSIONS: Brain damage is commonly seen in stillborn infants, and in around one-third of cases, damage predates the period immediately before death. Factors suggesting suboptimal placental function are associated with such damage. Early identification of placental impairment may lead to improved pregnancy outcome.

An immune control model for viral replication in the CNS during presymptomatic HIV infection.

The brain is targeted by human immunodeficiency virus type 1 (HIV-1) during the course of untreated infection, leading to cognitive impairment, neurological damage and HIV encephalitis (HIVE). To study early dynamics of HIV entry into the brain, we examined a unique autopsy series of samples obtained from 15 untreated individuals who died in the presymptomatic stages of infection from non-HIV causes. HIV was detected and quantified by limiting dilution PCR and genetically characterized in the V3 region of env. Limiting dilution was shown to be essential for correct estimation of genetic partitioning between brain- and lymphoid-associated HIV populations. While no actively expressing HIV-infected cells were detected by immunohistochemistry, variable and generally extremely low levels of proviral DNA were detected in presymptomatic brain samples. V3 region sequences were frequently genetically distinct from lymphoid-associated HIV variants, with association index (AI) values similar to those observed in cases of HIVE. Infiltration of CD8 lymphocytes in the brain was strongly associated with expression of activation markers (MHCII; R = 0.619; P < 0.05), the presence of HIV-infected cells (proviral load; R = 0.608; P < 0.05) and genetic segregation of brain variants from populations in lymphoid tissue (AI value, R = -0.528; P approximately 0.05). CD8 lymphocytes may thus limit replication of HIV seeded into the brain in early stages of infection. Neurological complications in AIDS occur when this control breaks down, due to systemic immunosuppression from HIV that destroys CD8 lymphocyte function and/or through the evolution of more aggressive neuropathogenic variants.

Third ventricular chordoid glioma: clinicopathological study of two cases with evidence for a poor clinical outcome despite low grade histological features.

Chordoid glioma of the third ventricle is a rare glial tumour whose precise histogenesis remains uncertain. We describe two cases that presented recently to our department and review the background literature. The neoplasm tends to occur in women and its clinical presentation is variable, resulting from acute hydrocephalus or impingement upon local structures. However, the radiological appearance is distinct, with an ovoid shape, hyperdensity and uniform contrast enhancement on computerized tomography and magnetic resonance imaging. Intraoperative smear diagnosis is difficult because of the lack of specific features, although the presence of metachromatic extracellular mucin may be useful. The characteristic histological appearance is that of cords and clusters of cohesive, oval-to-polygonal epithelioid cells with abundant eosinophilic cytoplasm and a mucinous background. There is often a mixed chronic inflammatory infiltrate with lymphocytes and plasma cells with Russell bodies. The main differentials for histological diagnosis include chordoid meningiomas, pilocytic astrocytomas and ependymomas. An immunohistochemical panel including antibodies to glial fibrillary acidic protein, CD 34, epithelial membrane antigen, pan cytokeratin, S100 and vimentin can be used to distinguish between these possibilities. Ultrastructurally the tumour cells have basal lamina and microvilli, reminiscent of ependymomas. The clinical outcome in our cases was poor because of the location of the lesion and its close relation to the hypothalamus. Limited follow-up after surgery with or without radiotherapy suggests that as-full-as-possible resection favours a better outcome, although surgery in this area carries significant operative risks.

Hyperphosphorylated tau and amyloid precursor protein deposition is increased in the brains of young drug abusers.

Drug abuse is a major problem worldwide. The incidence of drug-related deaths attributed to opiate abuse is increasing annually. Apart from routine examination, little is known of the neuropathology of drug abuse. We, and others, have shown previously that drug abuse is associated with microglial activation. We hypothesised that neuroinflammation might lead to premature neurodegeneration in drug abusers. We investigated the brains of young opiate abusers (n=34, all<40 years) for the presence of proteins associated with neurodegenerative diseases and compared them with the brains of age-matched, non-drug users (n=16) all of whom died suddenly. Detailed immunohistochemical analysis of the hippocampus, brainstem and basal ganglia for hyperphosphorylated tau, beta-amyloid, beta-amyloid precursor protein (betaAPP) and ubiquitin demonstrated an excess of AT 8-positive neurofibrillary tangles (NFT) in the drug abusers. These were not only more prevalent in the drug abusers than in controls (44%vs. 19%) but also involved more brain areas. In controls NFT were confined to the entorhinal cortex whereas in drug users they were also found in the subiculum, temporal neocortex, nucleus basalis of Meynert and the locus coeruleus. Virtually no amyloid plaques were present but betaAPP positivity was again much more common in drug abusers than controls (73%vs. 20% in the brainstem and 59%vs. 23% in the temporal lobe). There is no suggestion that these drug abusers had displayed major cognitive impairment although detailed neuropsychological assessment is difficult in this subject group. Likely causes of hyperphosphorylated tau deposition in drug abuse include hypoxic-ischaemic injury, microglial-associated cytokine release and possibly drug-associated neurotoxicity or hepatitis. Head injury, which is another major risk factor, does not appear to have contributed to our findings. Genetic factors also merit consideration. It is unclear at present how much of the hyperphosphorylated tau detected in these young drug abusers represents a transitory phenomenon.

Influence of HAART on HIV-related CNS disease and neuroinflammation.

Neuroinflammation has an established link with AIDS-related dementia but has not been investigated in the post-highly active anti-retroviral therapy (HAART) era. In this autopsy study we examined post-HAART cases in Edinburgh for the presence of HIV-related pathology and in well-treated cases for evidence of neuroinflammation. We focused on basal ganglia and the hippocampus, 2 key areas of the brain for cognitive functioning and compared pre- and post-HAART cases for neuroinflammatory status. We find evidence, post-HAART, that there is a high level of microglial/macrophage activation that is comparable with the levels seen, pre-HAART, in HIV encephalitis (HIVE) and AIDS cases. This result was maximal in the hippocampus where microglial/macrophage upregulation in the HAART-treated group exceeded that seen in HIVE. In the basal ganglia, HAART-treated cases showed significantly higher levels of CD68-positive microglia/macrophages than in control brains (p = 0.004), and in the hippocampus levels were significantly higher than those seen in control cases, pre-HAART AIDS, and presymptomatic brains (p = 0.01). However, lymphocyte levels in the areas examined were low in HAART-treated cases. We conclude that there is a surprising degree of ongoing neuroinflammation in HAART-treated patients, particularly in the hippocampus. This may pose a threat for the future health of individuals maintained long-term on HAART therapy.

Distribution of apolipoprotein E alleles in a Scottish healthy newborn population.

The different alleles of the human apolipoprotein E polymorphism, ApoE epsilon2, epsilon3, epsilon4, have important implications for systemic lipid metabolism, immunological function and for the brain in maintenance and in response to injury. Few studies have focussed on their role in early life. The ApoE alleles and genotypes were ascertained in the cord blood of 371 full-term and normal Scottish newborn infants using PCR methodology. The results were compared to previously published data for Scottish adults in late middle age. There was a marginally significant over-representation of epsilon4 and under-representation of epsilon3 alleles in healthy infants as compared with adults. Inspection of the individual genotypes confirms the over-representation of ApoE 4/4 and 2/4 with a reduction in ApoE 2/3 and 3/3 when compared with Scottish adults. Although these results may have occurred by chance, the ApoE epsilon4 allele may confer an increased risk of premature death.