Qualitatively different effect of repeated stress during adolescence on principal neuron morphology across lateral and basal nuclei of the rat amygdala.

Repeated stress can elicit symptoms of depression and anxiety. The amygdala is a significant contributor to the expression of emotion and the basolateral amygdala (BLA) is a major target for the effects of stress on emotion. The adolescent time period may be particularly susceptible to the effects of stress on emotion. While repeated stress has been demonstrated to modify the morphology of BLA neurons in adult rats, little is known about its effects on BLA neurons during adolescence. This study tests the effects of repeated stress during adolescence on BLA neuronal morphology, and whether these are similar to the effects of stress during adulthood. The BLA includes the basal (BA) and lateral (LAT) nuclei, which are differentially responsive to stress in adults. Therefore, effects of stress during adolescence were compared between the BA and LAT nuclei. Morphological features of reconstructed BLA neurons were examined using Golgi-Cox-stained tissue from control or repeated restraint stress-exposed rats. We found subtle dendritic growth coupled with loss of spines after repeated stress during adolescence. The magnitude and dendritic location of these differences varied between the BA and LAT nuclei in strong contrast to the stress-induced increases in spine number seen in adults. These results demonstrate that repeated stress during adolescence has markedly different effects on BLA neuronal morphology, and the extent of these changes is BLA nucleus-dependent. Moreover, altered neuroanatomy was associated with age-dependent effects of repeated stress on generalization of fear, and may point to the necessity for different approaches to target stress-induced changes in adolescents.

Repeated restraint stress exerts different impact on structure of neurons in the lateral and basal nuclei of the amygdala.

Chronic stress exacerbates and can induce symptoms of depression and anxiety disorders. Chronic stress causes amygdala hyperactivity, which may contribute to these detrimental effects. One potential mechanism for amygdala hyperactivity is an increase of excitatory drive after stress. Excitatory inputs to the amygdala predominantly synapse upon dendritic spines, and repeated stress has been demonstrated to increase dendritic spines in the basolateral amygdala (BLA). However, the BLA is comprised of several nuclei, including the lateral nucleus (LAT) and the basal nucleus (BA), which exert functionally distinct roles in amygdala-dependent behaviors. Furthermore, while an increase of dendritic spines can impart significant functional ramifications, a shift of spine distribution can also exert significant impact. However, differences in the effects of repeated stress on LAT and BA have not been examined, nor differential effects on spine distribution. This study examined the effects of repeated restraint stress on dendritic structure of principal neurons from the LAT and BA in Golgi-stained tissue. This study found that repeated stress increased spine number in LAT and BA, but in very distinct patterns, with proximal increases in LAT neurons and non-proximal increases in BA neurons. Furthermore, repeated stress increased dendritic length in the BA, but not the LAT, leading to a global change of spine density in BA, but a focal change in LAT. These distinct effects of repeated stress in the LAT and BA may exert significant functional effects on fear behavior, and may underlie differences in the effects of repeated stress on acquisition, contextual modulation and extinction of fear behavior.

Three years of operation of the urine diversion system at GTZ headquarters in Germany: user opinions and maintenance challenges.

In the main office building of GTZ in Eschborn, Germany a resource-oriented sanitation system containing urine diversion (UD) toilets and waterless urinals has been in operation since 2006. After 2.5 years of operating the system, a first overall evaluation of the system in terms of its acceptance amongst the users and the cleaning staff was conducted by carrying out two surveys and many interviews. The overall result is that most of the users appreciate the sanitation concept in theory but have problems with the technical design of the particular type of UD flush toilets installed here. The survey results also gave some directions towards which hygiene devices the users would appreciate in order to overcome their reluctance to sit down on the toilet seat in public buildings (the sitting being necessary for correct operation of the urine valve to separate urine from flush water). Also, it is difficult to convince the cleaning and facility maintenance staff of the necessity of special cleaning and preventative maintenance routines. Hence, before such systems can be widely used, clear cleaning routines and maintenance instruction are required as well as certain technical modifications of this type of UD flush toilets to optimise the urine/water separation and the flushing properties of the toilet.

Medical costs of osteoporosis in the elderly Medicare population.

UNLABELLED: Prior national cost estimates of osteoporosis and fractures in the USA have been based on diverse sets of provider data or selected commercial insurance claims. Based on a random population-based sample of older adults, the US medical cost of osteoporosis and fractures is estimated at $22 billion in 2008. INTRODUCTION: National cost estimates of osteoporosis and fractures in the USA have been based on diverse sets of provider data or selected commercial insurance claims. We sought to characterize prevalence and costs for osteoporosis using a random population-based sample of older adults. METHODS: A cross-sectional estimate of medical cost was made with 2002 data from the Medicare Current Beneficiary Survey (MCBS). MCBS combines health interviews with claims information from all payers to profile a random sample of 12,700 Medicare recipients. Three cohorts aged 65 or over were defined: (1) patients experiencing a fracture-related claim in 2002; (2) patients with a diagnosis, medication, or self-report for osteoporosis or past hip fracture; and (3) non-case controls. The total cost of patient claims was compared to that of controls using multiple regression. RESULTS: Of 30.2 million elderly Medicare recipients in 2002, 1.6 million (5%) were treated for a fracture that year, and an additional 7.2 million (24%) have osteoporosis without a fracture. The estimated mean impact of fractures on annual medical cost was $8,600 (95% confidence interval, $6,400 to $10,800), implying a US cost of $14 billion ($10 to $17 billion). Half of the non-fracture osteoporosis patients received drug treatment, averaging $500 per treated patient, or $2 billion nationwide. CONCLUSIONS: The annual cost of osteoporosis and fractures in the US elderly was estimated at $16 billion, using a national 2002 population-based sample. This amount corroborates previous estimates based on substantially different methodologies. Projected to 2008, the national cost of osteoporosis and fractures was $22 billion.

Work productivity loss due to flares in patients with chronic gout refractory to conventional therapy.

OBJECTIVE: Joint pain and swelling during gout flares may lead to considerable morbidity and disability, having an impact on patient work productivity and social participation. The objective of this study was to assess how gout flares affect these activities in patients with chronic gout refractory to conventional therapy. METHODS: A 1-year prospective observational study was conducted among patients with symptomatic disease in the United States in 2001. Inclusion criteria required patients (1) to be age 18 years or older, (2) to have documented, crystal-proven gout, (3) to have symptomatic gout, and (4) to be intolerant or unresponsive to conventional therapy, reflected by SUA ≥ 6.0 mg/dL. Patients were evaluated every 2 months. At each visit, patients completed a gout diary, which included number of flares experienced, duration and severity of each flare, and whether the flare caused: (1) work loss, (2) missed appointments or social events, or (3) impairment of self-care activities. The Short-Form Health Survey (SF-36) was also completed each visit. RESULTS: Analyses were restricted to those who completed the first 6 months of the study (n = 81). Mean number of flares per patient per year was 8.8. Of the patients who were <65 years, 78% reported at least 1 work day lost due to a gout attack during the year. Mean annual work day loss for those <65 years was 25.1 days. A total of 545 of patients reported at least one flare per year that impaired social activities, with a mean of 17.1 social days lost and 52% reported at least one flare per year that compromised normal self-care activities, with a mean of 16.9 days impairment. Correlations between the diary reports and activity-related questions from the SF-36 were significantly positive. LIMITATIONS: The study is limited by small sample size, lack of reference group, and inability to explicitly collect employment information. Age under 65 years was used as a proxy for employment eligibility. CONCLUSION: Flares in patients with chronic gout refractory to conventional therapy significantly affect patient work productivity and social activities.

Limitations of animal models of Parkinson's disease.

Most cases of Parkinson's disease (PD) are sporadic. When choosing an animal model for idiopathic PD, one must consider the extent of similarity or divergence between the physiology, anatomy, behavior, and regulation of gene expression between humans and the animal. Rodents and nonhuman primates are used most frequently in PD research because when a Parkinsonian state is induced, they mimic many aspects of idiopathic PD. These models have been useful in our understanding of the etiology of the disease and provide a means for testing new treatments. However, the current animal models often fall short in replicating the true pathophysiology occurring in idiopathic PD, and thus results from animal models often do not translate to the clinic. In this paper we will explain the limitations of animal models of PD and why their use is inappropriate for the study of some aspects of PD.

SmtB-DNA and protein-protein interactions in the formation of the cyanobacterial metallothionein repression complex: Zn2+ does not dissociate the protein-DNA complex in vitro.

The synechococcal metallothionein locus smt consists of two divergent genes: smtA coding for the metallothionein SmtA, and smtB coding for the trans-acting regulator SmtB. The latter binds at two inverted repeats, designated S1/S2 and S3/S4, in the overlapping promoter/operator sites between the two genes. We have determined the binding stoichiometries to the entire operator/promoter DNA and to the separate S1/S2 and S3/S4 half-operator oligonucleotides using sedimentation equilibrium and sedimentation velocity measurements. The full promoter/operator DNA binds two SmtB dimers. The hydrodynamic behavior of this complex supports a compact nucleoprotein structure. Each separate S1/S2 and S3/S4 operator sequence also binds two dimers. An equal molar mixture of separate S1/S2 and S3/S4 operator sequences, in excess SmtB, forms a S1/S2-SmtB:SmtB-S3/S4 bridge complex. Combining these results with previously published binding interference data, which showed consecutive S1/S2 and S3/S4 SmtB occupancy on the operator/promoter DNA, we have developed a model for the establishment of the repression complex that appears to involve significant DNA compaction, presumably DNA bending, stabilized by SmtB-SmtB bridge interactions. DNase I footprinting titrations also showed consecutive S1/S2 and S3/S4 SmtB occupancy. The footprints expand considerably in the presence of Zn2+. Hence, SmtB remains bound to the operator sites when Zn2+ ions are present. This result is further supported by gel retardation assay. Failure of the metal ions to dissociate SmtB from the DNA points to a hitherto unknown function of SmtB in the regulation of the smt locus.

The JACS study I: characteristics of a population of chemically dependent Jewish men and women.

In order to learn more about chemically dependent Jewish people, and to help dispel the misinformation about them, the authors surveyed individuals who were part of the JACS database. Data from 379 questionnaires were analyzed and compared with the findings of two general population surveys of Jews and a previous study of Jewish alcoholics. Seventy-one percent of respondents reported dependence on more than one substance. Alcohol was found to be the most prevalent drug of both primary (54.7%) and secondary (24.5%) dependence. The male:female ratios for all chemical dependents (1.08:1) and alcohol dependents (1:1.006) were lower than observed in national studies of American alcoholic populations, as was also found in a previous study of Jewish alcoholics. The hypotheses that alcoholic Jews suffer from lack of education, poor income, alienation or loss of religious conviction failed to be supported by the JACS study. Alcohol is the drug of choice for chemically dependent Jews. The JACS survey does not support previous ideas about causes of Jewish alcoholism. The relatively large proportion of women found deserves further study.

Technology assessment and the sociopolitics of health technologies.

In a growing number of countries, health technology assessment (HTA) has come to be seen as a vital component in policy making. Even though the assessment of the social, political, and ethical aspects of health technology is listed as one of its main objectives, in practice, the integration of such dimensions into HTA remains limited. Recent social scientific research on the inherently political nature of technology strongly supports such a comprehensive approach. The growing claims by and on behalf of consumer groups also suggest that HTA should be informed by a broader set of perspectives. Using the example of the cochlear implant in children, this essay compares the professed objectives of HTA with typical practice and explores possible explanations for the discrepancies observed. A second example, home telemonitoring for elderly persons, demonstrates how the types of evidence considered by HTA and the process through which assessments are produced may be reconsidered. We argue for the formal integration of the sociopolitical dimensions of health care technologies into assessments. The ability of HTA to more fully address important issues from a public policy point of view will increase by making explicit the sociopolitical nature of health care technologies.

Histories of cochlear implantation.

The cochlear implant, an electronic device by means of which some totally deaf people can be provided with a form of hearing, has been increasingly used since the early 1980s. The mass media have typically presented it as an example of the remarkable success of modern technological medicine. In France and The Netherlands, the countries on which this paper focuses, as in many others, deaf communities have rejected the technology. They have protested at its use with deaf children in particular. Rather than locating it in a history of medical progress, they have located it within a history of their own oppression. Each historical rendering is used to try to influence policy. The contest, however, is an unequal one.

The integral divalent cation within the intermolecular purine*purine. pyrimidine structure: a variable determinant of the potential for and characteristics of the triple helical association.

In vitro assembly of an intermolecular purine*purine.pyrimidine triple helix requires the presence of a divalent cation. The relationships between cation coordination and triplex assembly were investigated, and we have obtained new evidence for at least three functionally distinct potential modes of divalent cation coordination. (i) The positive influence of the divalent cation on the affinity of the third strand for its specific target correlates with affinity of the cation for coordination to phosphate. (ii) Once assembled, the integrity of the triple helical structure remains dependent upon its divalent cation component. A mode of heterocyclic coordination/chelation is favorable to triplex formation by decreasing the relative tendency for efflux of integral cations from within the triple helical structure. (iii) There is also a detrimental mode of base coordination through which a divalent cation may actively antagonize triplex assembly, even in the presence of other supportive divalent cations. These results demonstrate the considerable impact of the cationic component, and suggest ways in which the triple helical association might be positively or negatively modulated.

Molecular cDNA cloning and tissue distribution of mRNA encoding a novel ATP-binding cassette (ABC) half-transporter.

The majority of proteins belonging to the ATP-binding cassette (ABC) superfamily catalyzes translocation of substrates across biological membranes. Employing a reverse transcription-PCR approach with degenerate primers, we have identified a full-length cDNA from rat hepatocytes encoding a novel ABC transporter termed umat (ubiquitously expressed mammalian ABC half-transporter). The deduced sequence of 836 amino acids comprises an N-terminal membrane anchor domain and a single conserved C-terminal nucleotide binding fold, specifying umat as an ABC half-transporter. While the first 250 amino acid positions are highly divergent from other ABC transporters, clusters of conserved residues are evident along the rest of the protein. The greatest sequence similarity was observed with the fission yeast heavy metal tolerance protein hmt1 (44.5% identity in a 626-amino-acid overlap). Umat mRNA, expressed in all tissues analyzed, was most abundant in testis. Substantial umat mRNA expression in cultured primary rat hepatocytes suggests that hepatocyte cultures should represent an adequate model for investigation of umat function and regulation.

Divalent transition metal cations counteract potassium-induced quadruplex assembly of oligo(dG) sequences.

Nucleic acids containing tracts of contiguous guanines tend to self-associate into four-stranded (quadruplex) structures, based on reciprocal non-Watson-Crick (G*G*G*G) hydrogen bonds. The quadruplex structure is induced/stabilized by monovalent cations, particularly potassium. Using circular dichroism, we have determined that the induction/stabilization of quadruplex structure by K+is specifically counteracted by low concentrations of Mn2+(4-10 mM), Co2+(0.3-2 mM) or Ni2+(0.3-0.8 mM). G-Tract-containing single strands are also capable of sequence-specific non-Watson-Crick interaction with d(G. C)-tract-containing (target) sequences within double-stranded DNA. The assembly of these G*G.C-based triple helical structures is supported by magnesium, but is potently inhibited by potassium due to sequestration of the G-tract single strand into quadruplex structure. We have used DNase I protection assays to demonstrate that competition between quadruplex self-association and triplex assembly is altered in the presence of Mn2+, Co2+or Ni2+. By specifically counteracting the induction/stabilization of quadruplex structure by potassium, these divalent transition metal cations allow triplex formation in the presence of K+and shift the position of equilibrium so that a very high proportion of triplex target sites are bound. Thus, variation of the cation environment can differentially promote the assembly of multistranded nucleic acid structural alternatives.