How can we calculate the "E" in "CEA"?

Because full funding for HIV/AIDS prevention interventions is unlikely to occur in the near future, it is essential that the resources available are spent in the most effective way possible. This paper presents a matrix of effectiveness coefficients for HIV/AIDS-related prevention interventions that can be used as an integral part of the coordinated strategic planning process currently underway by the World Bank and UNAIDS, as the interventions in the matrix are harmonized with the interventions in that process. Coefficients for four types of sexual behavior change (condom use, partner reduction, sexually transmitted infection treatment-seeking behavior, age at first sex) across three different risk groups (high, medium, low) are presented, along with their interquartile ranges. Results indicate that: (1) impacts seem greater when an intervention includes interpersonal contact, rather than targeting a more general audience; (2) although significant impacts are observed in the columns measuring changing condom use, other impacts are lower, and sometimes are actually (measured) zero; and (3) additional studies have evaluations of the number of sexual partners and have found a greater impact than previous studies. Although progress has been made in increasing the number of evaluation studies that can be utilized in this impact matrix, particularly in the area of youth interventions, there are still empty cells in which no studies report impacts. Finally, it is important to note that issues such as quality differences and synergies between programmes could have an effect on the impacts calculated for a particular strategic plan.     

Flow motion waves with high and low frequency in severe ischaemia before and after percutaneous transluminal angioplasty

STUDY OF OBJECTIVE--The aim was to evaluate skin flux and prevalence of low and high frequency flow motion waves in patients with severe ischaemia due to peripheral arterial occlusive disease before and after percutaneous transluminal angioplasty (PTA) with and without local thrombolysis. DESIGN--Flow motion was recorded by the laser Doppler technique at the dorsum of the foot before, one day, and one month after PTA. The results were separately analysed in patients with successful and unsuccessful treatment. SUBJECTS--18 patients with rest pain or incipient gangrene were included. Mean pretreatment systolic ankle pressure was 55.8(SD 25.5) mm Hg, and mean transcutaneous PO2 at 43 degrees C was 5.2(9.4) mm Hg. Arteriography revealed relevant stenoses or occlusions of the femoropopliteal and calf arteries. MEASUREMENTS AND RESULTS--Before treatment two patterns of flow motion with characteristic frequency ranges were observed at the foot dorsum and at a probe temperature of 32 degrees C: low frequency (LF) waves with a mean frequency of 2.2(0.5) cycles.min-1 and a mean amplitude of 0.73(0.42) arbitrary units (AU) and high frequency (HF) waves with a mean frequency of 22.6(4.2) cycles.min-1 and a mean amplitude of 0.39(0.33) AU. PTA was successful in 11 of the 18 patients. After successful treatment, prevalence of HF waves decreased from 10/11 to 4/11 cases (p less than 0.001), but remained nearly unchanged after failed procedure. Prevalence of LF waves before and after PTA did not differ significantly. CONCLUSIONS--Our data support the hypothesis that HF waves represent a reaction of skin microcirculation to severe ischaemia. With reference to animal studies it is proposed that HF waves originate from terminal arterioles. They may function as a compensatory mechanism of flow regulation involved in pathophysiology of ischaemia.     

Human stem cell models of neurodegeneration: a novel approach to study mechanisms of disease development

The number of patients with neurodegenerative diseases is increasing significantly worldwide. Thus, intense research is being pursued to uncover mechanisms of disease development in an effort to identify molecular targets for therapeutic intervention. Analysis of postmortem tissue from patients has yielded important histological and biochemical markers of disease progression. However, this approach is inherently limited because it is not possible to study patient neurons prior to degeneration. As such, transgenic and knockout models of neurodegenerative diseases are commonly employed. While these animal models have yielded important insights into some molecular mechanisms of disease development, they do not provide the opportunity to study mechanisms of neurodegeneration in human neurons at risk and thus, it is often difficult or even impossible to replicate human pathogenesis with this approach. The generation of patient-specific induced pluripotent stem (iPS) cells offers a unique opportunity to overcome these obstacles. By expanding and differentiating iPS cells, it is possible to generate large numbers of functional neurons in vitro, which can then be used to study the disease of the donating patient. Here, we provide an overview of human stem cell models of neurodegeneration using iPS cells from patients with Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Huntington’s disease, spinal muscular atrophy and other neurodegenerative diseases. In addition, we describe how further refinements of reprogramming technology resulted in the generation of patient-specific induced neurons, which have also been used to model neurodegenerative changes in vitro.     

Podocyte Purinergic P2X4 Channels Are Mechanotransducers That Mediate Cytoskeletal Disorganization

Podocytes are specialized, highly differentiated epithelial cells in the kidney glomerulus that are exposed to glomerular capillary pressure and possible increases in mechanical load. The proteins sensing mechanical forces in podocytes are unconfirmed, but the classic transient receptor potential channel 6 (TRPC6) interacting with the MEC-2 homolog podocin may form a mechanosensitive ion channel complex in podocytes. Here, we observed that podocytes respond to mechanical stimulation with increased intracellular calcium concentrations and increased inward cation currents. However, TRPC6-deficient podocytes responded in a manner similar to that of control podocytes, and mechanically induced currents were unaffected by genetic inactivation of TRPC1/3/6 or administration of the broad-range TRPC blocker SKF-96365. Instead, mechanically induced currents were significantly decreased by the specific P2X purinoceptor 4 (P2X₄) blocker 5-BDBD. Moreover, mechanical P2X₄ channel activation depended on cholesterol and podocin and was inhibited by stabilization of the actin cytoskeleton. Because P2X₄ channels are not intrinsically mechanosensitive, we investigated whether podocytes release ATP upon mechanical stimulation using a fluorometric approach. Indeed, mechanically induced ATP release from podocytes was observed. Furthermore, 5-BDBD attenuated mechanically induced reorganization of the actin cytoskeleton. Altogether, our findings reveal a TRPC channel-independent role of P2X₄ channels as mechanotransducers in podocytes.     

Structure of the Trg protein: Homologies with and differences from other sensory transducers of Escherichia coli.

Transducer proteins are central to chemotaxis in Escherichia coli. Three transducer genes comprise a homologous gene family, while a fourth gene, trg, is more distantly related. We have determined the nucleotide sequence of trg. The deduced sequence of the Trg protein has features in common with other transducers as well as regions of significant divergence. The protein sequence suggests the same transmembrane structure postulated for other transducers: an extra cytoplasmic NH2-terminal domain connected by a membrane-spanning region to an intracellular COOH-terminal domain. The COOH-terminal domain of Trg exhibits substantial sequence identity with the corresponding domains of the other transducers, particularly near the sites of covalent modification. Trg appears to have the same five methyl-accepting sites identified in the Tsr protein. Two of those sites are glutamines that are deamidated to yield methyl-accepting glutamates, while the remainder are synthesized as glutamates. Conservation in number but not in position of modified glutamines in Trg compared to the other transducers is consistent with the notion that uncharged glutamines at a specific number of modification sites serve to balance the signaling state of newly synthesized transducers. The NH2-terminal domain of Trg exhibits no significant homology with other transducers, implying that trg may be a fusion of the common COOH-terminal transducer sequence with an unrelated NH2-terminal sequence. The location of specific mutations within trg provides support for the suggestion that ligand-binding sites are in the NH2-terminal domains.     

Correlates and trend of HIV prevalence among female sex workers attending sexually transmitted disease clinics in Pune, India (1993-2002)

In India, substantial efforts have been made to increase awareness about HIV/AIDS among female sex workers (FSWs). We assessed the impact of awareness regarding safe sex in a cohort of FSWs by studying trends in HIV prevalence, sexually transmitted diseases (STDs), and risk behaviors measured from 1993 to 2002 in Pune, India. A total of 1359 FSWs attending 3 STD clinics were screened for HIV infection, and data on demographics, sexual behaviors, and past and current STDs were obtained. The overall HIV prevalence among FSWs was 54%. Not being married (adjusted odds ratio [AOR] = 1.74, 95% confidence interval [CI]: 1.17 to 2.59), being widowed (AOR = 2.10, 95% CI: 1.16 to 3.80), inconsistent condom use (AOR = 1.60, 95% CI: 1.02 to 2.50), clinical presence of genital ulcer disease (GUD; AOR = 1.66, 95% CI: 1.07 to 2.56), and genital warts (AOR = 4.70, 95% CI: 1.57 to 14.08) were independently associated with HIV infection among FSWs. The prevalence of HIV remained stable over 10 years (46% in 1993 and 50% in 2002; P = 0.80). The prevalence of GUD decreased over time (P < 0.001), whereas that of observed genital discharge remained stable. Reported consistent condom use as well as the proportion of FSWs who refused sexual contact without condoms increased over time (P < 0.001). These data collectively suggest that safe sex interventions have had a positive impact on FSWs in Pune, India.     

Environmental allergens and asthma in urban elementary schools.

BACKGROUND: Asthma in school children is rising, and indoor allergens are very common triggers of asthma attacks; however, the risk of the school environment on asthma has not been well studied. OBJECTIVE: To determine the presence and the levels of common aeroallergens in schools, where asthma prevalence rates are high. METHODS: Settled dust samples were collected from 12 Baltimore City public elementary schools, and they were analyzed for the following allergens: cockroaches (Bla g 1/2), dust mites (Der f 1/p 1), dog (Can f 1), cat (Fel d 1), and mouse (Mus m 1). School asthma prevalence rates were correlated with allergen levels, and association between allergen levels and other risk factors present in the schools' environment was examined. RESULTS: The mean and range levels were 1.49 U/g (0 to 8) for Bla g 1/2; 0.38 microg/g (0 to 11.9) for the Der f 1/p 1; 1.44 microg/g (0.1 to 9.6) for Can f 1; 1.66 microg/g (0.2 to 12) for Fel d 1; and 6.24 microg/g (0.3 to 118.3) for Mus m 1. Dust mite, cat and dog allergens were significantly in rooms with carpet and/or area rugs, compared to rooms with bare floors (P < 0.05). Asthma prevalence rates varied from 11.8 to 20.8% between schools and positively correlation with the mean levels of Bla g 1/2 in the schools (P = 0.001). CONCLUSIONS: Common allergens that are known to trigger asthma were detected in all school environments, where asthma prevalence rates were high. However, the overall allergen levels were low, indicating that other factors, including exposures in the homes of asthmatic patients, may have more relevance to sensitization and symptoms than school exposures.     

Early dental caries risk assessment and prevention in pre-school children: evaluation of a new strategy for dental care in a field study

The aim of the present field study was to evaluate a new strategy for the dental care of pre-school children which includes an early caries risk assessment and early preventive care. One hundred and sixty-seven children were studied from 1 to 6 years of age (intervention group). A group of 125 children from the same clinic (historical control) was used as a comparison group. On the basis of the clinical examinations of the children and the interviews with the parents when the children were 3 years of age, the children in the intervention group were divided into four different risk groups: no (n = 95),low (n = 33), moderate (n = 30), and high caries risk (n = 9). Only 8 of the 95 children who had been placed in the no caries risk group at 3 years of age developed manifest carious lesions in their primary cuspids and molars by 6 years of age. At 6 years of age 81% in the intervention group were free of manifest carious lesions, compared with 55% in the comparison group (P < 0.001). Furthermore, the mean numbers of defs were 0.6 for children in the intervention group and 2.7 in the comparison group. Thus, this field study indicates that early primary prevention (before the onset of caries attack) and a structured and systematic approach to dental care for pre-school children result in good oral health for the children and may be economically profitable for a society with organized public dental service for pre-school children.     

The frequency histogram--a new method for the evaluation of laser Doppler flux motion

A digital filter system (DFS) was implemented to describe the frequency components of laser Doppler signals. The DFS calculates a frequency histogram on the basis of the prevalence of a certain frequency band during the sample period. This approach seems to be more suitable for the detection of low-power small-amplitude flux motion components recorded by laser Doppler as compared to the commonly used fast Fourier algorithm. Fourier analysis provides an amplitude-relevant frequency spectrum which may overlook relevant frequency components with small amplitude due to low power or short duration. DFS allows better detection of such signals as demonstrated by the initial clinical results of this study evaluating flux motion on the feet of 4 healthy controls and 10 patients with peripheral arterial occlusive disease. Three frequency components are easily distinguished corresponding to low (3.6 +/- 1.5 cycles/minute) and high (18.6 +/- 4.5 cycles/min) frequency flux motion and the pulsatile waves due to cardiac action.