QCD and strongly coupled gauge theories: challenges and perspectives.

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.

Information needs across the colorectal cancer care continuum: scoping the literature.

Because cancer care requires a multifaceted approach, providing useful and timely information to people with colorectal cancer may be fragmented and inconsistent. Our interest was in examining what has and has not captured the attention of researchers speaking to the information needs of people with colorectal cancer. We followed Arksey and O'Malley's framework for the methodology of scoping review. Focusing solely on colorectal cancer, we analysed 239 articles to get a picture of which information needs and sources of information, as well as the timing of providing information, were attended to. Treatment-related information received the most mentions (26%). Healthcare professionals (49%) were mentioned as the most likely source of information. Among articles focused on one stage of the care continuum, post-treatment (survivorship) received the most attention (16%). Only 27% of the articles consulted people with colorectal cancer and few attended to diet/nutrition and bowel management. This study examined the numerical representation of issues to which researchers attend, not the quality of the mentions. We ponder, however, on the relationship between the in/frequency of mentions and the actual information needs of people with colorectal cancer as well as the availability, sources and timing of information.

Astrophysics: quark matter in compact stars?

In a theoretical interpretation of observational data from the neutron star EXO 0748-676, Ozel concludes that quark matter probably does not exist in the centre of neutron stars. However, this conclusion is based on a limited set of possible equations of state for quark matter. Here we compare Ozel's observational limits with predictions based on a more comprehensive set of proposed quark-matter equations of state from the literature, and conclude that the presence of quark matter in EXO 0748-676 is not ruled out.

Smoking affects the phenotype of Alzheimer disease.

Because epidemiologic and in vitro evidence conflict, the authors studied the association between smoking and Alzheimer disease (AD) in 46 never, 47 former, and 15 active smokers with AD followed to autopsy. Disease parameters were examined by smoking status and amount smoked in bivariate tests and in multivariate models controlling for age, sex, education, and APOE status. Smoking status was not associated with cognitive or neuropathologic measures. However, active smokers were significantly younger at death and higher levels of smoking were associated with shorter disease duration.

Clinical and genetic linkage analysis of a large Venezuelan kindred with Usher syndrome.

OBJECTIVE: To undertake a comprehensive investigation into the very high incidence of congenital deafness on the Macano peninsula of Margarita Island, Venezuela. METHODS: Numerous visits were made to the isolated island community over a 4-year-period. During these visits, it became apparent that a significant number of individuals complained of problems with hearing and vision. Socioeconomic assessments, family pedigrees and clinical histories were recorded on standard questionnaires. All individuals underwent thorough otolaryngologic and ophthalmologic examinations. Twenty milliliters of peripheral venous blood was obtained from each participant. A genome-wide linkage analysis study was performed. Polymorphic microsatellite markers were amplified by polymerase chain reaction and separated on polyacrylamide gels. An ABI 377XL sequencer was used to separate fragments and LOD scores were calculated by using published software. RESULTS: Twenty-four families were identified, comprising 329 individuals, age range 1-80 years, including 184 children. All families were categorized in the lower two (least affluent) socioeconomic categories. A high incidence of consanguinity was detected. Fifteen individuals (11 adults, 4 children) had profound congenital sensorineural hearing loss, vestibular areflexia and retinitis pigmentosa. A maximum LOD score of 6.76 (Linkage >3.0), between markers D11s4186 and D11s911, confirmed linkage to chromosome 11q13.5. The gene myosin VIIA (MYO7A) was confirmed in the interval. Clinical and genetic findings are consistent with a diagnosis of Usher syndrome 1B for those with hearing and vision problems. CONCLUSIONS: We report 15 Usher syndrome 1B individuals from a newly detected Latin American socio-demographic origin, with a very high prevalence of 76 per 100,000 population.

Impact of APOE genotype on neuropathologic and neurochemical markers of Alzheimer disease.

BACKGROUND: The APOE epsilon4 allele has emerged as a major genetic factor for Alzheimer disease (AD), and its presence has been associated with an increase in beta-amyloid senile plaques (SPs) and neuritic plaques (NPs). Whether it affects neurofibrillary tangle (NFT) accumulation or cholinergic losses in AD remains controversial. In contrast, the epsilon2 allele has been reported to decrease the risk for AD. However, its effect on neuropathologic and neurochemical markers of disease is unclear. OBJECTIVE: To investigate the relationship between APOE genotype and both pathologic severity and cholinergic dysfunction in AD. METHODS: In an autopsy series of 296 patients with AD, APOE genotype was determined in blood or postmortem brain tissue. NPs and NFTs were counted in the midfrontal (MF), inferior parietal (IP), and superior temporal (ST) cortices and the hippocampus. Choline acetyltransferase (ChAT) activity was assessed in the MF, IP, and ST cortices. RESULTS: Compared with patients with no epsilon4 alleles, epsilon4 carriers (patients with either one or two epsilon4 alleles) did not differ significantly with regard to any pathologic or neurochemical measures, except for increased ST NPs. However, when cases were stratified into three groups according to the number of epsilon4 alleles, patients with two epsilon4 alleles had significantly more NPs and NFTs in all neocortical regions than those with either one or no epsilon4 alleles. The association of the epsilon4/4 genotype with neocortical pathologic severity remained significant even after adjusting for age at onset or age at death. In contrast, there were no significant group differences with regard to neocortical ChAT activity. When pathologic and neurochemical measures were compared between patients with the epsilon2 allele and those without, a strong relationship emerged between the epsilon2 allele and decreased NPs in all neocortical regions. CONCLUSIONS: The epsilon4 allele does not predict cholinergic decline in AD. Although the presence of a single epsilon4 allele appears to have no effect, the presence of two epsilon4 alleles is an important determinant of both NP and NFT accumulation. A putative protective role for the epsilon2 allele in AD may be mediated by reduced plaque burden.

Alzheimer disease without neocortical neurofibrillary tangles: "a second look".

OBJECTIVE: To compare the clinical and pathologic features of plaque only Alzheimer disease (POAD) with plaque and tangle Alzheimer disease (PTAD). METHODS: An autopsy series of 16 patients with POAD and 32 subjects with PTAD on whom extensive antemortem neuropsychological testing was available. Plaques, tangles, and cerebral amyloid angiopathy were examined in the neocortex and hippocampus using thioflavin S staining. In addition, immunocytochemical analysis with AT8 for phosphorylated tau was performed. Midfrontal (MF) synaptic density, MF choline acetyltransferase (ChAT) activity, and apolipoprotein E genotyping were also assessed. RESULTS: Initial neuropsychological test scores and rates of cognitive decline on the Mini-Mental State Examination and Blessed Information-Memory-Concentration were similar between the two groups. However, compared to PTAD, POAD patients tended to deteriorate more slowly on the Mattis Dementia Rating Scale. Furthermore, they were somewhat less impaired on all these measures at last examination. There was an older age at onset and death, and a trend toward a shorter disease duration, in POAD compared to PTAD patients. POAD subjects, by definition, had no neocortical neurofibrillary tangles (NFT) (Braak stages IV or less). In addition, they also had fewer hippocampal NFT, fewer neuritic plaques, and higher mean MF ChAT activity than PTAD subjects. On the other hand, the two groups did not differ significantly in brain weight or MF synaptic density. Although lacking overt tangle formation, the POAD group displayed abnormal phosphorylated tau immunoreactivity in neocortical pyramidal neurons. CONCLUSIONS: Dementing syndromes virtually indistinguishable from each other can, and do, develop in the presence or absence of neocortical NFT. Patients without neocortical NFT are, on average, older at disease onset and death, and show a trend toward a shorter disease duration with somewhat slower deterioration. Although neocortical NFT per se are not obligatory for the development of clinical dementia, more subtle neocortical cytoskeletal tau pathology may contribute to cognitive decline in these subjects.

Abeta1-42 promotes cholinergic sprouting in patients with AD and Lewy body variant of AD.

BACKGROUND: The neurodegenerative process in Alzheimer's disease (AD) and in the Lewy body variant of AD (LBV) patients is characterized by cholinergic dysfunction and deposition of amyloid beta-peptide (Abeta) 1-40 and 1-42; however, the differential effects of Abeta species on the cholinergic system are not completely clear. OBJECTIVE: To better understand the relationship between levels of Abeta1-40 and 1-42 on cholinergic deficits in AD and LBV patients. METHODS: Levels of choline acetyltransferase (ChAT) activity and ChAT immunoreactivity in the plaques in the frontal cortex of patients with AD and LBV were correlated with Abeta1-42 and 1-40 levels determined by ELISA and with neuropathologic and neurologic markers. RESULTS: Although the overall levels of ChAT activity were reduced in AD and LBV cases, there was a direct correlation with Abeta1-42 levels. Furthermore, patients with high Abeta1-42 levels had more abundant cholinergic dystrophic neurites in the plaques than cases with lower Abeta1-42. CONCLUSION: Abeta1-42 may also trigger cholinergic dysfunction by promoting aberrant neuritic sprouting.

Early and persistent alterations in prefrontal cortex MAO A and B in Alzheimer's disease.

Both monoamine oxidase (MAO) A and MAO B in the brain have been implicated in the etiology of Alzheimer's disease. MAO B is elevated in plaque-associated glia in Alzheimer brain. Elevations in MAO A in Alzheimer neurons have been linked to increases in neurotoxic metabolites and neuron loss. We investigated the relationship between cognitive function in Alzheimer patients and post-mortem prefrontal cortex MAO A and B activities. Prefrontal cortex tissue from 92 Alzheimer patients and 74 neurologically normal subjects was obtained at autopsy and analyzed for activities of MAO A and B by radioenzymatic methods. Mini Mental Status Exam was performed on Alzheimer patients within 1 year of death. Alzheimer brains were analyzed for Braak stage, tangles, plaques and choline acetyltransferase activity. Prefrontal cortex MAO B activity was significantly increased by 16% in Alzheimer patients versus normals, whereas MAO A activity was significantly decreased by 17% in these same patients. Neither MAO A nor MAO B activities correlated with cognitive function (MMSE score), choline acetyltransferase activity, plaques, neurofibrillary tangles, Braak stage, or age of disease onset in the Alzheimer patients. With increasing Alzheimer duration or increasing Braak stage, MMSE scores and choline acetyltransferase activity declined, but levels of MAO A and B in prefrontal cortex were unchanged. Patients in the upper quintile for MAO A or B activity did not differ significantly from those in the lowest quintile with respect to MMSE scores or age of Alzheimer disease onset. We conclude that the changes in MAO A and B in the prefrontal cortex occur very early in Alzheimer's disease and remain relatively constant as the disease progresses.

Effects of Cerebrolysin on amyloid-beta deposition in a transgenic model of Alzheimer's disease.

We investigated the potential mechanisms through which Cerebrolysin, a neuroprotective noothropic agent, might affect Alzheimer's disease pathology. Transgenic (tg) mice expressing mutant human (h) amyloid precursor protein 751 (APP751) cDNA under the Thy-1 promoter (mThy1-hAPP751) were treated for four weeks with this compound and analyzed by confocal microscopy to asses its effects on amyloid plaque formation and neurodegeneration. In this model, amyloid plaques in the brain are found much earlier (beginning at 3 months) than in other tg models. Quantitative computer-aided analysis with anti-amyloid-beta protein (A beta) antibodies, revealed that Cerebrolysin significantly reduced the amyloid burden in the frontal cortex of 5-month-old mice. Furthermore, Cerebrolysin treatment reduced the levels of A beta(1-42). This was accompanied by amelioration of the synaptic alterations in the frontal cortex of mThy1-hAPP751 tg mice. In conclusion, the present study supports the possibility that Cerebrolysin might have neuroprotective effects by decreasing the production of A beta(1-42) and reducing amyloid deposition.

Correlation of nicotinic receptor binding with clinical and neuropathological changes in Alzheimer's disease and dementia with Lewy bodies.

We investigated the relationship between the loss of nicotinic acetylcholine receptors (nAChR) and the cognitive decline or neuropathological changes seen in Alzheimer's Disease (AD) and dementia with Lewy bodies (DLB). Midfrontal (MF) cortex of 31 AD, 24 DLB and 11 non-demented controls was examined. Total plaque (TP), neuritic plaque (NP) and neurofibrillary tangle (NFT) counts were obtained. NAChR binding was assayed using 3H-epibatidine [3H-EPI]. Last Blessed Information-Memory-Concentration scores (BIMC), Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale (DRS) scores were collected. There were no correlations between 3H-EPI binding and TP, NP, NFTs counts in either AD or DLB. Last BIMC, MMSE, DRS scores did not correlate with 3H-EPI binding in AD or DLB. Thus, decline in cognitive function does not correlate with loss of nAChR in DLB or AD at the end of life suggesting that later in these diseases, loss of nAChR binding is not a reliable marker of cognitive function in AD or DLB. Loss of nAChR activity does not appear to be related to plaques or NFTs in AD or DLB.

Cholinergic deficits in the brains of patients with parkinsonism-dementia complex of Guam.

Patients with parkinsonism-dementia complex (PDC) of Guam showed moderate loss of choline acetyl transferase activity in the midfrontal and inferior parietal cortex, and severe loss in the superior temporal cortex. This deficit was similar to that seen in Alzheimer's disease and less severe than Lewy body disease. Thus, cholinergic deficits in the neocortex might contribute to some of the cognitive alterations in PDC of Guam.

Predictive value of the initial quantified relative afferent pupillary defect in 19 consecutive patients with traumatic optic neuropathy.

PURPOSE: To study the predictive value of the initial quantified relative afferent pupillary defect (RAPD) in patients with indirect traumatic neuropathy as it relates to final visual outcome. METHODS: The RAPD was measured and quantified by neutral density filters in patients with unilateral indirect traumatic neuropathy. All patients were treated with megadose methylprednisolone by of the protocol established by the Second National Acute Spinal Cord Injury Study. Patients were followed twice daily during treatment and then at 3-month intervals. RESULTS: Nineteen patients were enrolled over a 23-month period. Patients ranged in age from 12 to 78 years old; 18 of the 19 patients were male. No patient with an RAPD of 2.1 log units or greater had visual recovery to better than hand motion vision. The 7 patients with an initial RAPD of less than 2.1 log units showed improvement in their RAPD and were found to have vision of 20/30 or better during the follow-up period. CONCLUSIONS: In patients treated with megadose methylprednisolone with an initial RAPD of less than 2.1 log units, visual acuity improved to 20/30 or better; however, patients with an initial RAPD of 2.1 or greater showed little visual improvement. The initial quantified RAPD appears to have a predictive value related to final visual outcome.

Role of apolipoprotein E receptors in regulating the differential in vivo neurotrophic effects of apolipoprotein E.

Apolipoprotein E (apoE) is known to bind to at least five receptors, including the low-density lipoprotein (LDL) receptor-related protein (LRP), very low density LDL receptor (VLDL-R), LDL-R, apoE receptor 2 (apoER2), and megalin/gp330. In this context, the main objective of the present study was to better understand the contributions of LRP and LDL-R to the in vivo neurotrophic effects of apoE. For this purpose, apoE-deficient and receptor-associated protein (RAP)-deficient mice were infused with recombinant apoE3, RAP, or saline. Infusion of apoE3 into apoE-deficient mice resulted in amelioration of degenerative alterations of pyramidal neurons, but had no effect on somatostatin-producing interneurons. In contrast, infusion of apoE3 into RAP-deficient mice resulted in amelioration of degenerative alterations of somatostatin-producing interneurons. LRP and LDL-R levels were significantly reduced in RAP-deficient mice, but significantly increased in the apoE-deficient mice. In contrast, levels of apoE were reduced in the RAP-deficient mice compared to wildtype controls, suggesting that neurotrophic effects of apoE3 in the RAP-deficient mice were related to a combined deficit in endogenous apoE and selected apoE receptors. Furthermore, in apoE-deficient mice, infusion of apoE3 had a neurotrophic effect on somatostatin-producing interneurons only when combined with RAP, suggesting that increased expression of apoE receptors in apoE-deficient mice prevented apoE from rescuing somatostatin-producing neurons. This study supports the contention that some of the in vivo neurotrophic effects of apoE are mediated by LRP and LDL-R and that a critical balance between levels of apoE and its receptors is necessary for the differential neurotrophic effects to appear.

Tipificación del virus del papiloma humano en papilomatosis laríngea recurrente juvenil / Typing of papillomavirus human in juvenile laryngeal papillomatosis relapsing juvenile

El objetivo del presente estudio fue el detectar los tipos de VPH en muestras de tejido laríngeo de 15 pacientes entre 3 y 20 años de edad con diagnóstico clínico e histopatológico de papilomatosis laríngea juvenil (PLJ), por medio de la prueba de reacción de cadena de la polimerasa (PCR), con mezcla de ADN genómicos de VPH 6, 11, 16, 18, 31, 33 y 35, en el Servicio de Otorrinolaringología del Hospital Universitario de Caracas, período 1994-1999. En el 53 por ciento de las muestras procesadas se determinaron serotipos de VPH, 4 del tipo VPH 6 y 4 del tipo VPH 11, coincidiendo estos datos con lo descrito en la literatura mundial. En el resto de muestras (47 por ciento) la determinación del VPH fue negativa. No se detectó ninguno de los otros serotipos investigados ni se evidenció coinfección viral

Altered expression of synaptic proteins occurs early during progression of Alzheimer's disease.

The expression levels of three synaptic proteins (synaptophysin, synaptotagmin, and growth-associated protein 43 [GAP43]) in AD cases clinically classified by Clinical Dementia Rating (CDR) score were analyzed. Compared with control subjects (CDR = 0), mild (early) AD (CDR = 0.5 to 1) cases had a 25% loss of synaptophysin immunoreactivity. Levels of synaptotagmin and GAP43 were unchanged in mild AD, but cases with CDR of >1 had a progressive decrement in these synaptic proteins. Thus, synaptic injury in frontal cortex is an early event in AD.

The decline in synapses and cholinergic activity is asynchronous in Alzheimer's disease.

OBJECTIVE: To determine the timing of cholinergic loss and reduction of synapses in AD. BACKGROUND: Decrements in neocortical synapses and cholinergic function occur in AD and correlate with cognitive decline. However, how early in the disease process these changes appear remains unclear. METHODS: An autopsy series of 89 demented patients with pathologically confirmed AD (National Institute on Aging and Consortium to Establish a Registry for Alzheimer's Disease criteria) and 18 normal control subjects (NC). The AD cases were stratified according to their last Mini-Mental State Examination (MMSE) score prior to death as mild (MMSE = 20; n = 14), moderate (MMSE = 10 to 19; n = 20), severe (MMSE = 1 to 9; n = 29), and very severe (MMSE = 0; n = 26). Midfrontal (MF) synapse density was assessed by dot-immunobinding assay for synaptophysin (Syn), and MF choline acetyltransferase (ChAT) activity was determined using standard protocols. RESULTS: Compared with those in NC, neither Syn nor ChAT was appreciably reduced in patients with mild AD at death. Decline of ChAT was significant only in AD patients who died in the late stages of the disease and was maximal in those who had more severely deteriorated. In contrast, decline of Syn was significant and almost maximal in patients in intermediate or moderate stages. Consequently, the last MMSE score prior to death correlated more strongly with ChAT than Syn when the AD cohort included more impaired patients (r = 0.46 versus 0.40). The reverse occurred when only less impaired patients (MMSE = 10) were included in the analyses (r = 0.28 versus 0.64). There was only a modest correlation between Syn and ChAT activity. CONCLUSIONS: The results imply an asynchronous pattern of decline of synapses and cholinergic activity, with Syn loss preceding ChAT decrements. However, neither MF synapse reduction nor cholinergic dysfunction appears to be an early event in AD.

Gapless color superconductivity

We present the dispersion relations for quasiparticle excitations about the color-flavor locked ground state of QCD at high baryon density. In the presence of condensates which pair light and strange quarks there need not be an energy gap in the quasiparticle spectrum. This raises the possibility of gapless color superconductivity, with a Meissner effect but no minimum excitation energy. Analysis within a toy model suggests that gapless color superconductivity may occur only as a metastable phase.

Adenocarcinoma of the esophagus presenting as orbital cellulitis.

A 56-year-old man was seen with signs and symptoms consistent with orbital cellulitis. Computed tomographic scan showed a localized bony defect in the sphenoid wing, on which a biopsy was performed through a lateral orbitotomy. Pathologic examination of the surgical specimen revealed mucinous adenocarcinoma, and metastatic workup revealed an extensive lower esophageal malignant neoplasm. Arch Ophthalmol. 2000;118:986-988

Abnormal glutamate transport function in mutant amyloid precursor protein transgenic mice.

Recent studies have shown that amyloid precursor protein (APP), which plays a central role in Alzheimer's disease (AD), protects against excitotoxic neuronal injuries by regulating the function of the glial glutamate transporters. The mechanisms underlying these effects and their relationship to the neurodegenerative process in AD are under intense scrutiny. In this context, the main objective of the present study was to determine if overexpression of mutant human APP in transgenic mouse brains results in altered functioning of the excitatory amino acid transporters (EAATs). Transgenic mice expressing the 695 amino acid form of the human APP from the Thy-1 promoter showed a significant decrease in B(max) and K(D) for aspartate uptake when compared to nontransgenic controls. This decrease in glutamate transporter activity was associated with decreased protein expression of glial specific glutamate transporters, EAAT1 and 2, but did not affect mRNA levels. These results suggest that expression of mutant forms of APP disturbs astroglial transport of excitatory amino acids at the posttranscriptional level leading, in turn, to increased susceptibility to glutamate toxicity.