The American Association for Pediatric Ophthalmology and Strabismus workforce distribution project.

PURPOSE: To describe data sources and functional utility of the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) workforce database and associated map files. METHODS: Population data from the 2000 U.S. Census and current listings from the AAPOS and American Academy of Ophthalmology (AAO) databases were organized to demonstrate and analyze practitioner-to-population relationships for metropolitan statistical areas nationwide. An interactive map was developed to provide an intuitive graphical display of the data. RESULTS: A total of 749 active AAPOS members were distributed in 154 of 280 defined metropolitan statistical areas. Within these areas, a 0- to 20-year age subgroup varied from 17.8% to 42.6%, with an average of 30.4%. The AAPOS member-to-million-person ratio varied from 1.3 to 27, with higher numbers generally representing regions with population bases inadequately defined by Census Bureau statistical area definitions. Ratios for a majority of larger, better-defined areas ranged from 3 to 4 AAPOS members per million persons. Sizable areas with no AAPOS member presence were identified and tabulated. AAO members with a specified pediatric practice focus who were not AAPOS members were identified in 103 areas, possibly influencing patient choices and practitioner referrals for these regions. CONCLUSIONS: The AAPOS workforce database and related interactive map display practitioner and population data that may assist physicians and planners in targeting practice development and identifying potentially underserved areas.     

Antisense inhibition of methylenetetrahydrofolate reductase reduces cancer cell survival in vitro and tumor growth in vivo.

PURPOSE: Many cancer lines are methionine dependent and decrease proliferation when methionine supply is limited. Methylenetetrahydrofolate reductase (MTHFR) generates the folate derivative for homocysteine remethylation to methionine. We investigated the effect of antisense-mediated inhibition of MTHFR on survival of human cancer cells. EXPERIMENTAL DESIGN: We examined the in vitro and in vivo anticancer effects of a combination of MTHFR antisense and standard cytotoxic drugs. RESULTS: Specific antisense against MTHFR (EX5) showed significant inhibitory effects on growth of human colon, lung, breast, prostate, and neuroblastoma tumor cells in vitro compared with that of the control oligonucleotide. Cytotoxic drugs (5-fluorouracil, cisplatin, or paclitaxel) potentiated the effect of EX5. In vivo, antisense alone or in combination with cytotoxic drugs inhibited the growth of human colon and lung carcinoma xenografts. In comparison with control oligonucleotide, treatment with EX5 inhibited growth of colon tumors and lung tumors by 60% and 45%, respectively. EX5 with 5-fluorouracil decreased growth of colon tumors by an additional 30% compared with EX5 alone, and EX5 with cisplatin decreased growth of lung tumors by an additional 40% compared with cisplatin alone. Growth inhibition by EX5 was associated with decreased amounts of MTHFR protein and with increased amounts of an apoptosis marker. CONCLUSIONS: Our results confirm that MTHFR inhibition decreases tumor growth and suggest that inhibition of MTHFR by antisense or small molecules may be a novel anticancer approach.     

Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part III. Apigenin, baicalelin, kaempherol, luteolin and quercetin

Flavonoids are found universally in plants and act as free radical scavenging and chelating agents with antiinflammatory, antiischemic, vasodilating and chemoprotective properties. In this study, the antilipoperoxidative and cytoprotective effects of apigenin, baicalein, kaempferol, luteolin and quercetin against doxorubicin-induced oxidative stress were investigated in isolated rat heart cardiac myocytes, mitochondria and microsomes. After preincubation of cardiomyocytes with the test compounds for 1 h the cardiomyocytes were treated with the toxic agent, doxorubicin (100 micro M for 8 h). Cardiomyocyte protection was assessed by extracellular LDH and cellular ADP and ATP production. Cytoprotection was concentration dependent for baicalein > luteolin congruent with apigenin > quercetin > kaempferol. All test compounds had signi fi cantly better protective effects than dexrazoxan, an agent currently used for adjuvant therapy during anthracycline antibiotic therapy. In microsomes/mitochondria the IC(50) values of lipid peroxidation inhibition for quercetin, baicalein, kaempferol, luteolin, and apigenin were 3.1 +/- 0.2/8.2 +/- 0.6, 3.3 +/- 0.3/9.6 +/- 0.5, 3.9 +/- 0.3/10.1 +/- 0.8, 22.9 +/- 1.7/18.2 +/- 0.7, and 338.8 +/- 23.1/73.1 +/- 6.4 mM, respectively. The antilipoperoxidative activity of apigenin differed from its cytoprotective effects, but correlated with the free radical scavenging of 2,2-diphenyl-1-picrylhydrazyl radical and half peak oxidation potential (E(p/2)). Apigenin was the least effective of the flavonoids studied in all models except the cardiomyocyte model where its cardiomyocyte cytoprotective effect was comparable to other compounds.     

Changes in antioxidant,inflammatory and metabolic markers during 1 week cultivation of human skin explants

Human skin explant (HSE) seems to be a useful model for dermatological/cosmetic testing. HSE prepared from donor superfluous skin from plastic surgery operations is cheap and easily obtainable compared to reconstructed models. The HSE use, however, may be limited by the degeneration processes during cultivation. The aim was to monitor changes in metabolic activity and selected apoptotic, inflammatory and antioxidant parameters during 7 day cultivation. The significant changes were found in the superoxide dismutase‐2 level from day 5, glutathione S‐reductase level from day 6, metabolic activity and fibulin‐5 level from day 4, cyclooxygenase‐2, interleukin‐6 and interleukin‐10 from day 1 to 2. Other selected markers (lipid peroxidation products and glutathione level, glutathione S‐transferase, catalase, superoxide dismutase and glutathione S‐reductase activity, glutathione peroxidase and glutathione S‐reductase levels) were not modified significantly due to high inter‐individual variability of skin donors. The HSE microstructure as well as cytokeratin‐10 and proliferation marker Ki67 expression was also only minimally affected during cultivation. Collectively, the results demonstrate that HSE represents a good model for short‐term studies focused on the physical and chemical agent toxicity, protective potential of compounds or metabolic biotransformation. However, reduced metabolic activity, increased inflammation and the high inter‐individual variability and sensitivity of donors have to be taken into consideration.     

Coat as a Dagger: The Use of Capsid Proteins to Perforate Membranes during Non-Enveloped DNA Viruses Trafficking

To get access to the replication site, small non-enveloped DNA viruses have to cross the cell membrane using a limited number of capsid proteins, which also protect the viral genome in the extracellular environment. Most of DNA viruses have to reach the nucleus to replicate. The capsid proteins involved in transmembrane penetration are exposed or released during endosomal trafficking of the virus. Subsequently, the conserved domains of capsid proteins interact with cellular membranes and ensure their efficient permeabilization. This review summarizes our current knowledge concerning the role of capsid proteins of small non-enveloped DNA viruses in intracellular membrane perturbation in the early stages of infection.     

The Relationship among Cognition,Psychological Well-being,Physical Activity and Demographic Data in People over 80 Years of Age

Objectives: It is the main goal of this study to investigate the relationships between physical abilities, cognitive abilities and the aspects of psychological well-being in people aged 80 or older. In contrast to other studies, we focus on the executive functions and mental rotation while investigating cognitive performance; this is because it is well known in the literature investigating younger participants that these functions relate to some kind of motor or physical activity.

Methods: 41 independently living persons over 80 years were enrolled. Physical activities (German Physical Activity Questionnaire 50+), balance (One leg stand), psychological well-being (Resilience, General depressions scale), cognitive abilities (Flanker task, Mental rotation, Number connection test) as well as the influence of gender and education status were analyzed.

Results: Higher physical activity correlates with higher resilience. Persons with higher education and men show better values on the depression scale. Better mental rotation ability could be detected in persons with higher education.

Discussion: This first experimental study with people only over 80 years demonstrates the importance of education and physical activity for different aspects of psychological well-being. Due to the aim of investigating participants only over 80 years living independently the sample size is small so the study should be further enlarged.     

White matter alteration and cerebellar atrophy are hallmarks of brain MRI in alpha-mannosidosis

ObjectiveDespite profound neurological symptomatology there are only few MRI studies focused on the brain abnormalities in alpha-mannosidosis (AM). Our aim was to characterize brain MRI findings in a large cohort of AM patients along with clinical manifestations.MethodsTwenty-two brain MRIs acquired in 13 untreated AM patients (8 M/5F; median age 17 years) were independently assessed by three experienced readers and compared to 16 controls.ResultsFocal and/or diffuse hyperintense signals in the cerebral white matter were present in most (85%) patients. Cerebellar atrophy was common (62%), present from the age of 5 years. Progression was observed in two out of 6 patients with follow-up scans. Cortical atrophy (62%) and corpus callosum thinning (23%) were already present in a 13-month-old child. The presence of low T₂ signal intensity in basal ganglia and thalami was excluded by the normalized signal intensity profiling. The enlargement of perivascular spaces in white matter (38%), widening of perioptic CSF spaces (62%), and enlargement of cisterna magna (85%) were also observed. Diploic space thickening (100%), mucosal thickening (69%) and sinus hypoplasia (54%) were the most frequent non-CNS abnormalities.ConclusionWhite matter changes and cerebellar atrophy are proposed to be the characteristic brain MRI features of AM. The previously reported decreased T₂ signal intensity in basal ganglia and thalami was not detected in this quantitative study. Rather, this relative MR appearance seems to be related to the diffuse high T₂ signal in the adjacent white matter and not the gray matter iron deposition that has been hypothesized.     

Single injections of apoA-I acutely improve in vivo glucose tolerance in insulin-resistant mice

Aims/hypothesis

Apolipoprotein A-I (apoA-I), the main protein constituent of HDL, has a central role in the reverse cholesterol-transport pathway, which together with the anti-inflammatory properties of apoA-I/HDL provide cardioprotection. Recent findings of direct stimulation of glucose uptake in muscle by apoA-I/HDL suggest that altered apoA-I and HDL functionality may be a contributing factor to the development of diabetes. We have studied the in vivo effects of short treatments with human apoA-I in a high-fat diet fed mouse model. In addition to native apoA-I, we investigated the effects of the cardioprotective Milano variant (Arg173Cys).

Methods

Male C57Bl6 mice on a high-fat diet for 2 weeks that received a single injection of human apoA-I proteins (wild-type and Milano) were analysed for blood glucose and insulin levels during a 3 h incubation followed by glucose tolerance tests. Incorporation of injected human apoA-I protein into HDLs was analysed by native gel electrophoresis.

Results

ApoA-I treatment significantly improved insulin secretion and blood glucose clearance in the glucose tolerance test, with an efficiency exceeding that of lean control animals, and led to decreased basal glucose during the 3 h incubation. Notably, the two apoA-I variants triggered insulin secretion and glucose clearance to the same extent.

Conclusions/interpretation

ApoA-I treatment leads to insulin- and non-insulin-dependent effects on glucose homeostasis. The experimental model of short-term (2 weeks) feeding of a high-fat diet to C57Bl6 mice provides a suitable and time-efficient system to unravel the resulting tissue-specific mechanisms of acute apoA-I treatment that lead to improved glucose homeostasis.     

Patterns of surface temperatures in two mole-rats (Bathyergidae) with different social systems as revealed by IR-thermography

Furred subterranean mammals face the problem of dissipating heat to the environment because high humidity and absence of air flow in sealed belowground tunnels constrain heat loss from body by convection and evaporation. In order to detect body areas responsible for heat loss, surface temperatures in two species of African mole-rats were measured at different ambient air temperatures by infrared thermography. Fur characteristics were also evaluated. Thinner pelage of the ventrum, its moderate temperature and large size suggest that ventral side of the body is the main thermal avenue for heat loss in both species. Interspecific differences could be explained by different fur characteristics connected with social thermoregulation. Compared to the social Fukomys mechowii, the solitary Heliophobius argenteocinereus has denser and longer fur on most of its body; its surface temperature was thus lower than in F. mechowii at lowered ambient temperatures. On the other hand, the denser and longer hair cover in H. argenteocinereus impedes heat dissipation at highest ambient temperatures (and probably also during digging activity) resulting in increase of core body temperature. H. argenteocinereus seems to be more sensitive to overheating than F. mechowii. At lower air temperatures, the social species may uses huddling to combat hypothermia.