Socio-Behavioural Barriers to Viral Suppression in the Older Adult Population in Rural South Africa.

South Africa has the largest share of people living with HIV in the world and this population is ageing. The social context in which people seek HIV care is often ignored. Apart from clinical interventions, socio-behavioural factors impact successful HIV care outcomes for older adults living with HIV. We use cross-sectional data linked with demographic household surveillance data, consisting of HIV positive adults aged above 40, to identify socio-behavioural predictors of a detectable viral load. Older adults were more likely to have a detectable viral load if they did not disclose their HIV positive status to close family members (aOR 2.56, 95% CI 1.89-3.46), resided in the poorest households (aOR 1.98, 95% CI 1.23-3.18), or were not taking medications other than ART (aOR 1.83, 95% CI 1.02-1.99) likely to have a detectable. Clinical interventions in HIV care must be supported by understanding the socio-behavioural barriers that occur outside the health facility. The importance of community health care workers in bridging this gap may offer more optimum outcomes for older adults ageing with HIV.

Broadening the ecology of fear: non-lethal effects arise from diverse responses to predation and parasitism.

Research on the 'ecology of fear' posits that defensive prey responses to avoid predation can cause non-lethal effects across ecological scales. Parasites also elicit defensive responses in hosts with associated non-lethal effects, which raises the longstanding, yet unresolved question of how non-lethal effects of parasites compare with those of predators. We developed a framework for systematically answering this question for all types of predator-prey and host-parasite systems. Our framework reveals likely differences in non-lethal effects not only between predators and parasites, but also between different types of predators and parasites. Trait responses should be strongest towards predators, parasitoids and parasitic castrators, but more numerous and perhaps more frequent for parasites than for predators. In a case study of larval amphibians, whose trait responses to both predators and parasites have been relatively well studied, existing data indicate that individuals generally respond more strongly and proactively to short-term predation risks than to parasitism. Apart from studies using amphibians, there have been few direct comparisons of responses to predation and parasitism, and none have incorporated responses to micropredators, parasitoids or parasitic castrators, or examined their long-term consequences. Addressing these and other data gaps highlighted by our framework can advance the field towards understanding how non-lethal effects impact prey/host population dynamics and shape food webs that contain multiple predator and parasite species.

Effects of temperature and viscosity on miracidial and cercarial movement of Schistosoma mansoni: ramifications for disease transmission.

Parasites with complex life cycles can be susceptible to temperature shifts associated with seasonal changes, especially as free-living larvae that depend on a fixed energy reserve to survive outside the host. The life cycle of Schistosoma, a trematode genus containing some species that cause human schistosomiasis, has free-living, aquatic miracidial and cercarial larval stages that swim using cilia or a forked tail, respectively. The small size of these swimmers (150-350 µm) dictates that their propulsion is dominated by viscous forces. Given that viscosity inhibits the swimming ability of small organisms and is inversely correlated with temperature, changes in temperature should affect the ability of free-living larval stages to swim and locate a host. By recording miracidial and cercarial movement of Schistosoma mansoni using a high-speed camera and manipulating temperature and viscosity independently, we assessed the role each factor plays in the swimming mechanics of the parasite. We found a positive effect of temperature and a negative effect of viscosity on miracidial and cercarial speed. Reynolds numbers, which describe the ratio of inertial to viscous forces exerted on an aquatic organism, were <1 across treatments. Q10 values were <2 when comparing viscosity treatments at 20 °C and 30 °C, further supporting the influence of viscosity on miracidial and cercarial speed. Given that both larval stages have limited energy reserves and infection takes considerable energy, successful transmission depends on both speed and lifespan. We coupled our speed data with mortality measurements across temperatures and discovered that the theoretical maximum distance travelled increased with temperature and decreased with viscosity for both larval stages. Thus, our results suggest that S. mansoni transmission is high during warm times of the year, partly due to improved swimming performance of the free-living larval stages, and that increases in temperature variation associated with climate change might further increase transmission.

A Novel Nanoconjugate of Landomycin A with C60 Fullerene for Cancer Targeted Therapy: In Vitro Studies.

INTRODUCTION: Landomycins are a subgroup of angucycline antibiotics that are produced by Streptomyces bacteria and possess strong antineoplastic potential. Literature data suggest that enhancement of the therapeutic activity of this drug may be achieved by means of creating specific drug delivery systems. Here we propose to adopt C60 fullerene as flexible and stable nanocarrier for landomycin delivery into tumor cells. METHODS: The methods of molecular modelling, dynamic light scattering and Fourier transform infrared spectroscopy were used to study the assembly of C60 fullerene and the anticancer drug Landomycin A (LA) in aqueous solution. Cytotoxic activity of this nanocomplex was studied in vitro towards two cancer cell lines in comparison to human mesenchymal stem cells (hMSCs) using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test and a live/dead assay. The morphology of the cells incubated with fullerene-drug nanoparticles and their uptake into target cells were studied by scanning electron microscopy and fluorescence light microscopy. RESULTS: The viability of primary cells (hMSCs, as a model for healthy cells) and cancer cell lines (human osteosarcoma cells, MG-63, and mouse mammary cells, 4T1, as models for cancer cells) was studied after incubation with water-soluble C60 fullerenes, LA and the mixture C60 + LA. The C60 + LA nanocomplex in contrast to LA alone showed higher toxicity towards cancer cells and lower toxicity towards normal cells, whereas the water-soluble C60 fullerenes at the same concentration were not toxic for the cells. CONCLUSIONS: The obtained physico-chemical data indicate a complexation between the two compounds, leading to the formation of a C60 + LA nanocomposite. It was concluded that immobilization of LA on C60 fullerene enhances selectivity of action of this anticancer drug in vitro, indicating on possibility of further preclinical studies of novel C60 + LA nanocomposites on animal tumor models.

Recurrent activating mutations of CD28 in peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation. We have identified recurrent mutations in CD28 in PTCLs. Two residues-D124 and T195-were recurrently mutated in 11.3% of cases of AITL and in one case of PTCL, not otherwise specified (PTCL-NOS). Surface plasmon resonance analysis of mutations at these residues with predicted differential partner interactions showed increased affinity for ligand CD86 (residue D124) and increased affinity for intracellular adaptor proteins GRB2 and GADS/GRAP2 (residue T195). Molecular modeling studies on each of these mutations suggested how these mutants result in increased affinities. We found increased transcription of the CD28-responsive genes CD226 and TNFA in cells expressing the T195P mutant in response to CD3 and CD86 co-stimulation and increased downstream activation of NF-κB by both D124V and T195P mutants, suggesting a potential therapeutic target in CD28-mutated PTCLs.

Comparative squamation of the lateral line canal pores in sharks.

The current study collected the first quantitative data on lateral line pore squamation patterns in sharks and assessed whether divergent squamation patterns are similar to experimental models that cause reduction in boundary layer turbulence. In addition, the hypothesis that divergent orientation angles are exclusively found in fast-swimming shark species was tested. The posterior lateral line and supraorbital lateral line pore squamation of the fast-swimming pelagic shortfin mako shark Isurus oxyrinchus and the slow-swimming epi-benthic spiny dogfish shark Squalus acanthias was examined. Pore scale morphology and pore coverage were qualitatively analysed and compared. In addition, pore squamation orientation patterns were quantified for four regions along the posterior lateral line and compared for both species. Isurus oxyrinchus possessed consistent pore scale coverage among sampled regions and had a divergent squamation pattern with multiple scale rows directed dorsally and ventrally away from the anterior margin of the pore with an average divergent angle of 13° for the first row of scales. Squalus acanthias possessed variable amounts of scale coverage among the sampled regions and had a divergent squamation pattern with multiple scale rows directed ventrally away from the anterior margin of the pore with an average angle of 19° for the first row of scales. Overall, the squamation pattern measured in I. oxyrinchus fell within the parameters used in the fluid flow analysis, which suggests that this pattern may reduce boundary layer turbulence and affect lateral line sensitivity. The exclusively ventral oriented scale pattern seen in S. acanthias possessed a high degree of divergence but the pattern did not match that of the fluid flow models. Given current knowledge, it is unclear how this would affect boundary layer flow. By studying the relationship between squamation patterns and the lateral line, new insights are provided into sensory biology that warrant future investigation due to the implications for the ecology, morphology and sensory evolution of sharks.

Examining shifts in Carabidae assemblages across a forest-agriculture ecotone.

Northeastern U.S. farms are often situated adjacent to forestland due to the heterogeneous nature of the landscape. We investigated how forested areas influence Carabidae diversity within nearby crop fields by establishing transects of pitfall traps. Trapping extended across a forest-agriculture ecotone consisting of maize, an intermediate mowed grass margin, and a forest edge. Carabidae diversity was compared among the three habitats, and community and population dynamics were assessed along the transect. We used a principal response curve to examine and visualize community change across a spatial gradient. The highest levels of richness and evenness were observed in the forest community, and carabid assemblages shifted significantly across the ecotone, especially at the forest-grass interface. Despite strong ecotone effects, population distributions showed that some species were found in all three habitats and seemed to thrive at the ecotone. Based on similarity indices, carabid assemblages collected in maize adjacent to forest differed from carabid assemblages in maize not adjacent to forest. We conclude that forest carabid assemblages exhibit high degrees of dissimilarity with those found in agricultural fields and forested areas should thus be retained in agricultural landscapes to increase biodiversity at the landscape scale. However, ecotone species found at forest edges can still noticeably influence carabid community composition within neighboring agricultural fields. Further studies should determine how these shifts in carabid assemblages influence agroecosystem services in relation to ecosystem services observed in fields embedded in an agricultural matrix.

Infection deflection: hosts control parasite location with behaviour to improve tolerance.

Anti-parasite behaviour can reduce parasitic infections, but little is known about how such behaviours affect infection location within the host's body and whether parasite distribution ultimately affects tolerance of infection. To assess these questions, we exposed both anaesthetized (no behaviour) and non-anaesthetized Hyla femoralis tadpoles to plagiorchiid cercariae (larval trematodes), and quantified resistance, tolerance (relationship between mass change and infection intensity) and encystment location. Non-anaesthetized tadpoles had significantly more infections in their tail region than anaesthetized tadpoles, which had the majority of their infections in the head. This pattern indicates that parasites preferred to infect the head, but that hosts shunted infections to the tail when possible. Furthermore, there was a significant effect of encystment location on tolerance, with head-infected tadpoles having poorer tolerance to infection than tail-infected tadpoles. Variance partitioning suggests that, among infected tadpoles, behaviour contributed more to tolerance than resistance. These results suggest that, in addition to using behaviour to resist parasites, H. femoralis tadpoles also use behaviour to enhance infection tolerance by deflecting infections posteriorly, away from their vital sensory organs. These findings highlight the need to assess how widespread and important behaviour is to the tolerance of infections.

Loss of trematode parthenitae in Planorbella trivolvis (Mollusca: Gastropoda).

Infection by trematode parthenitae (larval, asexual trematodes) has severe consequences for molluscan hosts, resulting in cessation of reproduction and early mortality. Here we present evidence that the freshwater snail Planorbella trivolvis can lose infections by trematode parthenitae. Of 8 P. trivolvis infected by reniferin parthenitae, 6 died within 2 wk, whereas the remaining 2 snails lost their infections within 82 days after initial examination. This phenomenon might suggest that molluscs can resist established trematode infections (i.e., "self-cure") or at least out-survive some trematode parthenitae.

Purification and structure elucidation of the by-product of new regulator of antibiotic production and differentiation of Streptomyces.

Streptomyces globisporus 1912, a producer of the antitumor antibiotic landomycin E, forms the new low-molecular signaling molecule N-methylphenylalanyl-dehydrobutyrine diketopiperazine (BDD) and its complex and unstable by-product which restore, like the A-factor in Streptomyces griseus 773, landomycin E and streptomycin biosynthesis, and sporulation of the defective mutants S. globisporus 1912-B2 and S. griseus 1439, respectively. Here, we report the purification and structure elucidation of two compounds with R(f)0.8 by HPLC, LC/MS and 1HMR analysis. These compounds have m/z 338 and 384, accordingly, and each of them is presented by two stereoisomers containing BDD in their structure. A hypothesis explaining the composition and regulatory properties of these unstable compounds is presented.

[Radiological comparison between two procedures for ventral spondylodesis: autologous iliac crest bone graft vs bovine bone graft]. / Radiologischer Vergleich zweier Verfahren zur ventralen Spondylodese: Autologer trikortikaler Beckenkammspan vs. boviner Spongiosablock.

BACKGROUND: The objective of this study was the radiological evaluation of osseous integration of autologous iliac crest graft and bovine bone graft after spondylodesis based on a standardized score. MATERIAL AND METHODS: Spondylodesis was performed on 18 sheep, divided into 2 groups, 1 with an autologous iliac crest graft and the other with a bovine bone graft. Computed tomography was performed 12 and 24 weeks postoperatively. The osseous integration was assessed by the Tübinger Score. RESULTS: The evaluation of the CT scans demonstrated a significantly better osseous integration of the autologous iliac crest graft compared to the bovine bone graft. CONCLUSIONS: Based on our results, the bovine bone graft as a transplant for spondylodesis is inadvisable.

Properties of lanK-based regulatory circuit involved in landomycin biosynthesis in Streptomyces cyanogenus S136.

LanK is TetR-like regulatory protein recently shown to regulate the export and glycosylation of landomycins in Streptomyces cyanogenus S136. Here, several properties of the lanK-mediated regulation were deciphered. LanK seems to function as oligomer as evident from experiments in vitro. In vivo, it is able to recognize various landomycins with altered aglycon structure and the minimal concentration of landomycin A sensed by LanK lies in low nanomolar range. Coexpression studies showed that the positive regulatory gene lanI upregulates lanK-dependent lan genes once the negative LanK-regulation is cancelled. Gene lanK can be useful for the construction of biosensor strains for sensitive and specific identification of producers of landomycin-like molecules with long glycosidic chains.

Co-occurring diagnoses among FMR1 premutation allele carriers.

Following the discovery of two disorders associated with premutation alleles of the fragile X mental retardation gene (FMR1), primary ovarian insufficiency [fragile X-associated primary ovarian insufficiency (FXPOI)] and a tremor/ataxia syndrome [fragile X-associated tremor/ataxia disorder (FXTAS)], numerous studies have examined other potential co-morbid conditions, including neuropsychological deficits. Here, the frequency of self-reported diagnoses obtained through medical history interviews from FMR1 premutation carriers and non-carriers aged 18-50 were analyzed. Study subjects included 537 women, 334 of whom carry the premutation and 151 men, 37 of whom carry the premutation. Men with the premutation did not report any medical conditions at higher rates compared with non-carriers, controlling for age, ethnicity/race, and household income. Women with the premutation reported mental health disorders [i.e. attention deficit hyperactivity disorder (ADHD), anxiety, depression] significantly more often than non-carriers. However, after adjusting for covariates, these increased rates were not statistically significant. Additional follow-up analyses examined the consequence of ovarian dysfunction as a cause of co-occurring conditions. Women with an indication of ovarian insufficiency (i.e. irregular cycles) reported higher rates of thyroid problems and depression/anxiety. Because only women, not men, reported these conditions more often, the relationship between FXPOI and hormone irregularities in women should be explored for a potential link with the increase in the reported medical conditions.

Conventional and seed-based insect management strategies similarly influence nontarget coleopteran communities in maize.

Seed-based pest management tools, such as transgenes and seed treatments, are emerging as viable alternatives to conventional insecticide applications in numerous crops, and often occur as coupled technologies. Seed-based technologies have been readily adopted in maize, for which ecological studies are needed to examine effects to farmland biodiversity. We compared the response of nontarget coleopteran communities in Cry1Ab/c sweet corn and Cry3Bb field corn to conventional pyrethroid applications and a control. Of particular interest was the Cry3Bb field corn, which was coupled with a neonicotinoid seed treatment and was not rotated across years. A functionally diverse subset of the coleopteran community, consisting of three families (Carabidae, Chrysomelidae, and Nitidulidae) and 9,525 specimens, was identified to species. We compared coleopteran diversity and dynamics using rarefaction and ordination techniques. There were no differences in species richness among treatments; however, higher activity densities were more common in the control. In the nonrotated field corn, principal response curves showed a consistent pattern of treatment communities deviating from the control communities over time, whereas crop rotation in the sweet corn negated treatment effects. Treatment effects could not be detected when beetles were grouped based on functional roles. Results indicate that neonicotinoid seed-based treatments may have effects on some nontarget coleopterans, but these effects are similar to conventional pyrethroid applications.

Reduced memory B cells in patients with hyper IgE syndrome.

Dominant-negative mutations in STAT-3 have recently been found in the majority of patients with sporadic or autosomal-dominant hyper IgE syndrome (HIES). Since STAT-3 plays a role in B cell development and differentiation, we analyzed memory B cells in 20 patients with HIES, 17 of which had STAT-3 mutations. All but four patients had reduced non-switched and/or class-switched memory B cells. No reduction in these B cell populations was found in 16 atopic dermatitis patients with IgE levels above 1000 KU/L. There was no correlation between the reduction of memory B cells and the ability to produce specific antibodies. Moreover, there was no correlation between the percentage of memory B cells and the infection history. Analysis of memory B cells can be useful in distinguishing patients with suspected HIES from patients with atopic disease, but probably fails to identify patients who are at high risk of infection.

Anti-Mullerian hormone indicates early ovarian decline in fragile X mental retardation (FMR1) premutation carriers: a preliminary study.

BACKGROUND: Women who carry the fragile X mental retardation (FMR1) premutation are at risk for fragile X-associated primary ovarian insufficiency. Past studies have shown that carriers who are still cycling have increased levels FSH compared with non-carriers. As anti-Mullerian hormone (AMH) has been shown as an excellent marker of ovarian decline, we examined AMH levels among premutation carriers to characterize their ovarian function. METHODS: We determined the level of FSH and AMH in serum samples collected during early follicular phase from women who carried longer FMR1 repeat alleles (defined as >or=70 repeats, n = 40) and those with shorter repeat alleles (<70 repeats, n = 75), identified by DNA analysis. Comparisons were made stratified by age and carrier status. RESULTS: For all age groups, AMH levels were significantly lower among longer repeat allele carriers compared to shorter repeat allele carriers (P = 0.002, 0.006 and 0.020 for women ages 18-30, 31-40 and 41-50 years, respectively). In contrast, increased FSH indicative of early ovarian decline was only evident for longer repeat allele carriers aged 31-40 years (P = 0.089, 0.001 and 0.261 for women ages 18-30, 31-40 and 41-50 years, respectively). CONCLUSIONS: These preliminary data suggest that AMH levels indicate early ovarian decline among women with longer FMR1 repeat alleles; moreover, AMH appears to be a better marker than FSH in identifying this early decline.

Surprising production of a new urdamycin derivative by S. fradiae Delta urdQ/R.

A strain (S. fradiae Delta urdQ/R) with mutations in urdQ and urdR encoding a dTDP-hexose-3,4-dehydratase and a dTDP-hexose-4-ketoreductase, respectively, produces a new urdamycin analogue (urdamycin X) with changes in the polyketide structure. The structure of urdamycin X has been elucidated by NMR spectroscopy. Urdamycin X was not detectable, even in small amounts, in either S. fradiae Delta urdQ, in S. fradiae DeltaurdR or in S. fradiae A0, a mutant lacking all glycosyltransferase genes. Complementation of S. fradiae Delta urdQ/R restored urdamycin A production indicating that the mutations did not cause any polar effect.

Transgenes sustain epigeal insect biodiversity in diversified vegetable farm systems.

Many ecological studies have focused on the effects of transgenes in field crops, but few have considered multiple transgenes in diversified vegetable systems. We compared the epigeal, or soil surface-dwelling, communities of Coleoptera and Formicidae between transgenic and isoline vegetable systems consisting of sweet corn, potato, and acorn squash, with transgenic cultivars expressing Cry1(A)b, Cry3, or viral coat proteins. Vegetables were grown in replicated split plots over 2 yr with integrated pest management (IPM) standards defining insecticide use patterns. More than 77.6% of 11,925 insects from 1,512 pitfall traps were identified to species, and activity density was used to compare dominance distribution, species richness, and community composition. Measures of epigeal biodiversity were always equal in transgenic vegetables, which required fewer insecticide applications than their near isolines. There were no differences in species richness between transgenic and isoline treatments at the farm system and individual crop level. Dominance distributions were also similar between transgenic and isoline farming systems. Crop type, and not genotype, had a significant influence on Carabidae and Staphylinidae community composition in the first year, but there were no treatment effects in the second year, possibly because of homogenizing effects of crop rotations. Communities were more influenced by crop type, and possibly crop rotation, than by genotype. The heterogeneity of crops and rotations in diversified vegetable farms seems to aid in preserving epigeal biodiversity, which may be supplemented by reductions in insecticide use associated with transgenic cultivars.

Field measurements and modeling of dilution in the wake of a US navy frigate.

A field measurement and computer modeling effort was made to assess the dilution field of pulped waste materials discharged into the wake of a US Navy frigate. Pulped paper and fluorescein dye were discharged from the frigate's pulper at known rates. The subsequent particle and dye concentration field was then measured throughout the wake by a following vessel using multiple independent measures. Minimum dilution of the pulped paper reached 3.2 x 10(5) within 1900 m behind the frigate, or about 8 min after discharge. Independent measures typically agreed within 25% of one another and within 20% of model predictions. Minimum dilution of dye reached 2.3 x 10(5) at a down-wake distance of approximately 3500 m, or roughly 15 min. Comparison to model measurements were again within 20%. The field test was not only successful at characterizing wake dilution under one set of at-sea conditions, but was successful at validating the computer model used for assessing a wide range of ships and conditions.

Patent foramen ovale, a possible cause of symptomatic migraine: a study of 74 patients with acute ischemic stroke.

Recent studies reported an increased prevalence of patent foramen ovale (PFO) in patients with migraine with aura (MA+). To investigate the possible relationship between MA+ and paradoxical embolism, we studied the prevalence of both conditions. Investigation of PFO was undertaken in 74 consecutive patients presenting with an acute stroke of undetermined origin. The patients were questioned about MA+ or migraine without aura (MA-) according to the criteria of the International Headache Society. Follow-up was performed to investigate the evolution of MA+ and MA- according to different treatments of stroke. PFO was found in 44 of 74 patients, 16 of whom had MA+ (36%), compared to 4 (13%) MA+ patients without PFO (p = 0.03). Of 25 patients in whom the PFO was considered to play a causal role in the stroke, 13 (52%) had MA+, whereas only 3 (16%) of 19 patients in whom PFO was considered unrelated had MA+ (p = 0.014). Thirty-nine of the patients with MA+ and MA- were studied over a mean follow-up of 13 months. Seven of 15 patients with MA+ and PFO, treated either with surgical closure or anticoagulants, noticed complete disappearance of MA+ attacks. The prevalence of MA+ is high among stroke patients with PFO. In patients with a high presumption of paradoxical embolism, the proportion of MA+ is increased, and this suggests a possible role of this association in the occurrence of the cerebrovascular event. Forty-seven percent of patients with PFO and MA+ reported complete suppression of their aura attacks after surgical closure or anticoagulant treatment. This finding suggests that at least in some patients, MA+ attacks may be due to paradoxical embolism.