Medium-Chain Acyl-CoA Dehydrogenase Deficiency in Adulthood: A Potential Diagnosis in a Patient with Mental Status Changes Suspected of Drug Toxicity.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a rare but important component of the differential diagnosis for adults with a history of premortem mental status changes and the postmortem finding of hepatic steatosis. This case report describes a 30-year-old white man who, following a period of nausea and vomiting, was admitted to the hospital with sudden mental status deterioration followed rapidly by clinical deterioration and death. Treating physicians in this case suspected acute illicit drug toxicity with synthetic cathinones based on social history. Clinicians and medical examiners should be aware that the presentation, signs, and symptoms described may indicate an underlying inborn error of metabolism such as MCAD deficiency and take action accordingly.

An agent-based model of the population dynamics of Anopheles gambiae.

BACKGROUND: Agent-based models (ABMs) have been used to model the behaviour of individual mosquitoes and other aspects of malaria. In this paper, a conceptual entomological model of the population dynamics of Anopheles gambiae and the agent-based implementations derived from it are described. Hypothetical vector control interventions (HVCIs) are implemented to target specific activities in the mosquito life cycle, and their impacts are evaluated. METHODS: The core model is described in terms of the complete An. gambiae mosquito life cycle. Primary features include the development and mortality rates in different aquatic and adult stages, the aquatic habitats and oviposition. The density- and age-dependent larval and adult mortality rates (vector senescence) allow the model to capture the age-dependent aspects of the mosquito biology. Details of hypothetical interventions are also described. RESULTS: Results show that with varying coverage and temperature ranges, the hypothetical interventions targeting the gonotrophic cycle stages produce higher impacts than the rest in reducing the potentially infectious female (PIF) mosquito populations, due to their multi-hour mortality impacts and their applicability at multiple gonotrophic cycles. Thus, these stages may be the most effective points of target for newly developed and novel interventions. A combined HVCI with low coverage can produce additive synergistic impacts and can be more effective than isolated HVCIs with comparatively higher coverages. It is emphasized that although the model described in this paper is designed specifically around the mosquito An. gambiae, it could effectively apply to many other major malaria vectors in the world (including the three most efficient nominal anopheline species An. gambiae, Anopheles coluzzii and Anopheles arabiensis) by incorporating a variety of factors (seasonality cycles, rainfall, humidity, etc.). Thus, the model can essentially be treated as a generic Anopheles model, offering an excellent framework for such extensions. The utility of the core model has also been demonstrated by several other applications, each of which investigates well-defined biological research questions across a variety of dimensions (including spatial models, insecticide resistance, and sterile insect techniques).

Going rogue in the spatial cuing paradigm: high spatial validity is insufficient to elicit voluntary shifts of attention.

Voluntary shifts of attention are often motivated in experimental contexts by using well-known symbols that accurately predict the direction of targets. The authors report 3 experiments, which showed that the presentation of predictive spatial information does not provide sufficient incentive to elicit voluntary shifts of attention. For instance, when allowed to spontaneously choose between using a 100%-valid spatial word cue versus searching without the aid of the cue, observers consistently searched for a unique target without the aid of the cue. Another experiment showed that observers' choice to use spatial word cues could be biased by providing dedicated time to process the cue before the target display appeared (i.e., nonzero, cue-target SOAs). Although this dedicated processing time has routinely been included in spatial cuing experiments, its incentive-inducing role has never been acknowledged. Implications for theories of both voluntary and involuntary control are discussed.

Sudden and unexpected death in three cases of Ehlers-Danlos syndrome type IV.

Ehlers-Danlos syndrome (EDS) type IV is a connective tissue disorder characterized by the inability to produce sufficient amounts of collagen or a defect in the structure of collagen. The most serious complications include a rupture of a viscus or vascular rupture with or without mural dissection. Death may result from internal hemorrhage. This report describes three cases of sudden and unexpected death caused by EDS type IV. Two cases involved hemothorax as a result of dissection of the subclavian artery and aorta, respectively. The third case represented spontaneous pulmonary rupture and hemorrhage. A detailed family history should be sought, and additional specimens collected to confirm the diagnosis, including skin fibroblasts for collagen testing and blood for DNA testing. The forensic pathologist should consider the possibility of EDS type IV upon discovery of spontaneous visceral or arterial rupture and should alert the family members of this hereditary and potentially fatal condition.

Death of a toddler due to ingestion of sulfuric acid at a clandestine home methamphetamine laboratory.

Exposure to strong acids such as sulfuric acid to either the skin or the gastrointestinal or respiratory mucosa will result respectively in significant-occasionally fatal-cutaneous chemical burns as well as devastating corrosive damage to the respiratory and gastrointestinal tracts. Most injuries are accidental, but there are reports of using acids as weapons or as a means of suicide. The primary mechanism of acid injury is coagulative necrosis of the tissues. Sulfuric acid is a chemical often used in industrial and chemical laboratories, and it is an ingredient in household products like drain cleaner. Easily accessible, over-the-counter, household drain cleaner is one of several common materials used to manufacture methamphetamine. With increasing clandestine methamphetamine laboratories in the United States, exposure to methamphetamine and the toxic chemicals used for its production is a growing problem. In many instances, children living in these laboratories qua homes are at risk for injury and death. We report the death of an unattended toddler, who ingested sulfuric acid drain cleaner in his home. The gross and histopathological autopsy findings in this case are similar to those of previously described cases of sulfuric acid injury.

Sudden death in a child with Carpenter Syndrome. Case report and literature review.

Carpenter syndrome (Acrocephalopolysyndactyly type II) is a rare disorder characterized by acrocephaly, mental retardation, congenital heart disease, syndactyly, preaxial polydactyly, obesity, cryptorchidism, hypogenitalism, bony abnormalities, and umbilical hernia. We present a case of unexpected death of a 7-year-old boy with Carpenter Syndrome complicated by twin and premature birth as well as repaired congenital heart disease.

Fatal rhizopus pneumonia in allogeneic stem cell transplant patients despite posaconazole prophylaxis: two cases and review of the literature.

Posaconazole is a triazole with broad spectrum of activity against multiple fungi including members of the fungal order Mucorales. This activity has been shown both in clinical and in vitro studies, which are critically reviewed here. It has become very popular in prophylaxis in acute myelogenous leukemia (AML) induction and in the graft-versus-host disease (GVHD) settings after 2 recent prospective trials that showed advantage of posaconazole prophylaxis compared to fluconazole or itraconazole. In this report, 2 patients are presented, in whom, despite posaconazole prophylaxis, invasive and ultimately fatal Rhizopus pulmonary infections developed. These cases are similar to a previously reported case of Rhizopus infection in a stem cell transplant recipient who also received posaconazole, indicating a potential newly recognized pattern of breakthrough infections in patients receiving posaconazole prophylaxis.

Symbolic control of visual attention: semantic constraints on the spatial distribution of attention.

Humans routinely use spatial language to control the spatial distribution of attention. In so doing, spatial information may be communicated from one individual to another across opposing frames of reference, which in turn can lead to inconsistent mappings between symbols and directions (or locations). These inconsistencies may have important implications for the symbolic control of attention because they can be translated into differences in cue validity, a manipulation that is known to influence the focus of attention. This differential validity hypothesis was tested in Experiment 1 by comparing spatial word cues that were predicted to have high learned spatial validity ("above/below") and low learned spatial validity ("left/right"). Consistent with this prediction, when two measures of selective attention were used, the results indicated that attention was less focused in response to "left/right" cues than in response to "above/below" cues, even when the actual validity of each of the cues was equal. In addition, Experiment 2 predicted that spatial words such as "left/right" would have lower spatial validity than would other directional symbols that specify direction along the horizontal axis, such as "<--/-->" cues. The results were also consistent with this hypothesis. Altogether, the present findings demonstrate important semantic-based constraints on the spatial distribution of attention.

Human cerebral neuropathology of Type 2 diabetes mellitus.

The cerebral neuropathology of Type 2 diabetes (CNDM2) has not been positively defined. This review includes a description of CNDM2 research from before the 'Pubmed Era'. Recent neuroimaging studies have focused on cerebrovascular and white matter pathology. These and prior studies about cerebrovascular histopathology in diabetes are reviewed. Evidence is also described for and against the link between CNDM2 and Alzheimer's disease pathogenesis. To study this matter directly, we evaluated data from University of Kentucky Alzheimer's Disease Center (UK ADC) patients recruited while non-demented and followed longitudinally. Of patients who had come to autopsy (N = 234), 139 met inclusion criteria. These patients provided the basis for comparing the prevalence of pathological and clinical indices between well-characterized cases with (N = 50) or without (N = 89) the premortem diagnosis of diabetes. In diabetics, cerebrovascular pathology was more frequent and Alzheimer-type pathology was less frequent than in non-diabetics. Finally, a series of photomicrographs demonstrates histopathological features (including clinical-radiographical correlation) observed in brains of persons that died after a history of diabetes. These preliminary, correlative, and descriptive studies may help develop new hypotheses about CNDM2. We conclude that more work should be performed on human material in the context of CNDM2.

Cardiomyopathy of unknown etiology: Barth syndrome unrecognized.

This is a report of a child who died at 20 months from what was clinically thought to be cardiomyopathy of unknown etiology. Barth syndrome, an X-linked mitochondrial cardioskeletal myopathy, was diagnosed by genetic testing at autopsy. Barth syndrome presents in infancy or childhood with cardiomyopathy, hypotonia, growth delays, and cyclic neutropenia. Other associated laboratory findings can include hypocholesterolemia, relative monocytosis, low prealbumin, low plasma carnitine, and lactic acidosis. The classic echocardiogram finding is left ventricular noncompaction, although not always present. Until recently, the most reliable biochemical finding has been 3-methylglutaconic aciduria. However, quantitative analysis must be specifically requested for results to be reliable. Recently, a confirmatory tetralinoleoyl cardiolipin high-pressure liquid chromotography-tandem mass spectrometry blood test has become available. Genetic testing is also confirmatory and details the underlying mutation. Diagnosis is often missed or delayed and early diagnosis improves survival. The purpose of this case report is to encourage physicians to include Barth syndrome in the differential for cardiomyopathy of uncertain etiology in males, especially in the presence of growth delays, hypotonia, neutropenia, and/or family history of pediatric male death of unknown etiology.

Cortical sulci and bipolar disorder.

The width of cortical sulci in bipolar patients (n=19) and healthy controls (n=35) was examined using a novel automated technique involving magnetic resonance imaging. All sulci were wider for bipolar patients than for healthy controls. Bipolar-control differences were largest for the superior and intermediate frontal sulci, smallest for the occipital and cingulate sulci, and intermediate in magnitude for the other sulci (intraparietal, inferior frontal, and central sulci). The results were interpreted in terms of neurodegenerative-illness-related processes, which could produce cortical atrophy and result in wider sulci.

A method for making estimates of the benefit of the late use of letrozole in patients completing 5 years of tamoxifen.

This article discusses the rationale for 2 methods of making estimates of the benefit of letrozole as extended adjuvant hormonal therapy after 5 years of tamoxifen. It uses information from the Overview metaanalyses to develop general rules for making estimates of remaining risk of relapse for women completing 5 years of adjuvant tamoxifen without relapse. The first derived method shows that the expected benefit for such a woman is approximately one tenth of her risk of relapse in years 0-10 if untreated. The second method uses a modification of Adjuvant!, a decision support tool, and makes similar estimates. The decision tool supplies needed estimates of initial risk and allows adjustment for competing mortality. Uncertainties involved in making these estimates are also discussed.

Accidental electrocution during autoeroticism: a shocking case.

A case of atypical autoerotic death is described. An 18-year-old white man clad in two brassieres was found dead in his bedroom by his brother. Two wet green terry cloths were under the brassiere cups, connected to the house current via two metal washers and a bifid electrical cord. Literature depicting nude women was found near the victim. Autopsy revealed second-degree and third-degree burns of the mammary regions. Death was attributed to accidental self-electrocution. The authors will discuss typical and atypical forms of autoerotic death.