Epidemiology of Brucellosis and Q Fever in Linked Human and Animal Populations in Northern Togo

BACKGROUND: Although brucellosis (Brucella spp.) and Q Fever (Coxiella burnetii) are zoonoses of global importance, very little high quality data are available from West Africa. METHODS/PRINCIPAL FINDINGS: A serosurvey was conducted in Togo's main livestock-raising zone in 2011 in 25 randomly selected villages, including 683 people, 596 cattle, 465 sheep and 221 goats. Additionally, 464 transhumant cattle from Burkina Faso were sampled in 2012. The serological analyses performed were the Rose Bengal Test and ELISA for brucellosis and ELISA and the immunofluorescence assay (IFA) for Q Fever Brucellosis did not appear to pose a major human health problem in the study zone, with only 7 seropositive participants. B. abortus was isolated from 3 bovine hygroma samples, and is likely to be the predominant circulating strain. This may explain the observed seropositivity amongst village cattle (9.2%, 95%CI:4.3-18.6%) and transhumant cattle (7.3%, 95%CI:3.5-14.7%), with an absence of seropositive small ruminants. Exposure of livestock and people to C. burnetii was common, potentially influenced by cultural factors. People of Fulani ethnicity had greater livestock contact and a significantly higher seroprevalence than other ethnic groups (Fulani: 45.5%, 95%CI:37.7-53.6%; non-Fulani: 27.1%, 95%CI:20.6-34.7%). Appropriate diagnostic test cut-off values in endemic settings requires further investigation. Both brucellosis and Q Fever appeared to impact on livestock production. Seropositive cows were more likely to have aborted a foetus during the previous year than seronegative cows, when adjusted for age. This odds was 3.8 times higher (95%CI: 1.2-12.1) for brucellosis and 6.7 times higher (95%CI: 1.3-34.8) for Q Fever. CONCLUSIONS: This is the first epidemiological study of zoonoses in Togo in linked human and animal populations, providing much needed data for West Africa. Exposure to Brucella and C. burnetii is common but further research is needed into the clinical and economic impact.

Asthma and allergies: is the farming environment (still) protective in Poland? The GABRIEL Advanced Studies

BACKGROUND Evidence exists that a farming environment in childhood may provide protection against atopic respiratory disease. In the GABRIEL project based in Poland and Alpine regions of Germany, Austria and Switzerland, we aimed to assess whether a farming environment in childhood is protective against allergic diseases in Poland and whether specific exposures explain any protective effect. METHODS In rural Poland, 23 331 families of schoolchildren completed a questionnaire enquiring into farming practices and allergic diseases (Phase I). A subsample (n = 2586) participated in Phase II involving a more detailed questionnaire on specific farm exposures with objective measures of atopy. RESULTS Farming differed between Poland and the Alpine centres; in the latter, cattle farming was prevalent, whereas in Poland 18% of village farms kept ≥1 cow and 34% kept ≥1 pig. Polish children in villages had lower prevalences of asthma and hay fever than children from towns, and in the Phase II population, farm children had a reduced risk of atopy measured by IgE (aOR = 0.72, 95% CI 0.57, 0.91) and skin prick test (aOR = 0.65, 95% CI 0.50, 0.86). Early-life contact with grain was inversely related to the risk of atopy measured by IgE (aOR = 0.66, 95% CI 0.47, 0.92) and appeared to explain part of the farming effect. CONCLUSION While farming in Poland differed from that in the Alpine areas as did the exposure-response associations, we found in communities engaged in small-scale, mixed farming, there was a protective farming effect against objective measures of atopy potentially related to contact with grain or associated farm activities.

Secondary Forests and Local Livelihoods along a Gradient of Accessibility: A Case Study in Northern Laos

Rural livelihoods in developing countries can be enhanced by improving access to natural resources, services, and markets. In remote rural areas of the humid or semihumid tropics, forests represent an important resource for livelihoods. In countries like Laos, where most primary forest has been converted to secondary forest, and where an intricate and interlinked mosaic of forest and farmland prevails, people depend on secondary forests as a prime source of goods and services. The linkages between local livelihoods and secondary forest resources are subject to changes caused by improving accessibility. This article studies how accessibility affects the condition of forests and local livelihoods by comparing three villages along a gradient of accessibility in Phonxay district, Luang Prabang province, northern Laos. The results of this research show that accessibility strengthens the influence of the government and of markets, and that local livelihoods improve with increasing accessibility, while forest condition deteriorates.

Biactantial agreement in the Gongduk transitive verb in the broader Tibeto-Burman context

The Gongduk language is spoken in an enclave in south central Bhutan comprising several villages and hamlets in the mountains west of the Kurichu. The language occupies a distinct phylogenetic position within the Tibeto-Burman language family. The intransitive verb agrees for person and number with the subject, and the transitive shows biactantial agreement for person and number with both agent and patient. A morphological analysis has identified the individual agreement morphemes, their precise grammatical meaning and their patterns of allomorphy. The cognacy of the greater part of the desinences of the Gongduk verb with morphemes identifiable in the biactantial agreement systems of other Tibeto-Burman languages supports the view that at least a portion of such conjugational morphology must be reconstructed to the common ancestral language.

L’archéologie entre glaciers et sommets. Dernières découvertes dans les Alpes Bernoises (Cantons de Berne et du Valais, Suisse)

Connus sous le nom populaire de palafittes, les habitats préhistoriques construits sur les rives des lacs subalpins du Néolithique à l’aube de l’âge du Fer (entre 5300 et 700 av. J.-C.) offrent des informations exceptionnelles sur l’évolution culturelle d’une importante région européenne, grâce à la préservation remarquable des matériaux organiques, en particulier du bois. À partir de la deuxième moitié du XXe siècle, le perfectionnement des techniques de fouille subaquatiques et de la dendrochronologie permettront la construction d’un schéma chronologique précis pour l’Europe nord-alpine. Les recherches contribueront à des observations d’ordre écologique à l’échelle locale et régionale et à l’identification des rythmes de développement des villages. Sous l’égide de l'UNESCO, les années 2010 verront la constitution d’un inventaire vaste et uniforme des sites préhistoriques des lacs circumalpins, classés Patrimoine culturel mondial en juin 2011. De nombreux objets préhistoriques, romains et médiévaux ont été découverts entre 2003 et 2010, au Schnidejoch, un col des Alpes bernoises occidentales à 2756 m d’altitude, à la frontière entre les cantons de Berne et du Valais. Les hautes températures de l'été 2003 ont provoqué la fonte d'un petit champ de glace et mis en lumière les vestiges. Les recherches ont été programmées à la suite d’une série d’informations fournies par des randonneurs. Les objets en matière organique (bois, écorce de bouleau, cuir, fibres végétales) revêtent une très grande importance car ils ont permis l’obtention de plus d’une cinquantaine de datations radiocarbone ; elles indiquent le passage du col entre la moitié du Ve millénaire av. J.-C. et l’année 1000 de notre ère. En outre, les séries de datations suggèrent l’alternance de périodes de praticabilité et d’inaccessibilité du col. Le Schnidejoch est actuellement le plus ancien témoignage de la traversée des Alpes, reliant l‘Oberland bernois par les vallées de la Simme et du Rhône.

Adapting to climate change through sustainable land management: experiences of a pilot project in Tajikistan

Tajikistan is particularly exposed to the risks of climate change. Its widely degraded landscapes are badly prepared to cope with changes in precipitation patterns, increased temperatures, droughts, and the spread of pests and disease. Sustainable land management (SLM) provides a “basket of opportunities” to address these challenges, particularly for increasing land productivity, improving livelihoods, and protecting ecosystems. Within the Pilot Program for Climate Resilience (PPCR) in Tajikistan 70 SLM technologies and approaches on how to implement SLM were documented with the World Overview of Conservation Approaches and Technologies (WOCAT ) tools in 2011. For this purpose a climate change adaptation module was developed and tested in order to enhance the understanding about climate change resilience of SLM practices and community workshops conducted to on adaptation mechanisms by rural communities in Tajikistan. The analysis came up with four guiding principles for applying SLM for adapting to climate change: 1. Diversification of land use technologies and farm incomes; 2. Intensification of use of natural resources; 3. Expansion of highly productive land use technologies; 4. Protection of land and livelihoods from extreme weather events. Furthermore, SLM must be up-scaled from isolated plots to entire zones or landscapes and the project developed the concept of three concentric villages zones, the in-, near- and off-village zones. Land users, advisors, and decision- and policy makers face the task of finding management practices that best suit site-specific conditions. This task is most efficiently addressed in collaborative effort, and building up and managing a respective knowledge platform.

P2X7 receptors mediate resistance to toxin-induced cell lysis

In the majority of cells, the integrity of the plasmalemma is recurrently compromised by mechanical or chemical stress. Serum complement or bacterial pore-forming toxins can perforate the plasma membrane provoking uncontrolled Ca(2+) influx, loss of cytoplasmic constituents and cell lysis. Plasmalemmal blebbing has previously been shown to protect cells against bacterial pore-forming toxins. The activation of the P2X7 receptor (P2X7R), an ATP-gated trimeric membrane cation channel, triggers Ca(2+) influx and induces blebbing. We have investigated the role of the P2X7R as a regulator of plasmalemmal protection after toxin-induced membrane perforation caused by bacterial streptolysin O (SLO). Our results show that the expression and activation of the P2X7R furnishes cells with an increased chance of surviving attacks by SLO. This protective effect can be demonstrated not only in human embryonic kidney 293 (HEK) cells transfected with the P2X7R, but also in human mast cells (HMC-1), which express the receptor endogenously. In addition, this effect is abolished by treatment with blebbistatin or A-438079, a selective P2X7R antagonist. Thus blebbing, which is elicited by the ATP-mediated, paracrine activation of the P2X7R, is part of a cellular non-immune defense mechanism. It pre-empts plasmalemmal damage and promotes cellular survival. This mechanism is of considerable importance for cells of the immune system which carry the P2X7R and which are specifically exposed to toxin attacks.

Integrated reconstruction of Holocene millennial-scale environmental changes in Tierra del Fuego, southernmost South America

This study presents new paleoenvironmental data obtained from sedimentary cores from Lago Fagnano, an elon- gated lake located at 54°S in southernmost South America. Data from palynomorphs (pollen, spores and algae) and associated palynofacies as well as from diatom taxa retrieved from these cores compared with other regional proxies contribute to evaluate the similarities and differences in the climate patterns based on different proxies from southernmost Patagonia. The pollen analysis reveals that a grass steppe environment existed during the early Holocene (11,300–~8000 cal a BP) followed by a major vegetation change characterized by development of forest-steppe ecotone communities between ~8000 and ~6500 cal a BP, under more humid conditions. Between ~ 6500 and ~ 4000 cal a BP, expansion and colonization by Nothofagus forests reflect an increase in effec- tive moisture levels, while openness in the forest communities characterizes the region after ~ 1100 cal a BP. The palynological organic matter combined with the algal content reflects hydrological changes occurring in the lake and its nutrient status, probably in close relation with past climate oscillations. All these past ecological changes are closely related to oscillations in precipitation and temperature as a response to the variations in the latitudinal position and/or strength of the Southern Westerlies wind belt during the Holocene.

Genetically determined heterogeneity of lung disease in a mouse model of airway mucus obstruction

Mucus clearance is an important airway innate defense mechanism. Airway-targeted overexpression of the epithelial Na(+) channel β-subunit [encoded by sodium channel nonvoltage gated 1, beta subunit (Scnn1b)] in mice [Scnn1b-transgenic (Tg) mice] increases transepithelial Na(+) absorption and dehydrates the airway surface, which produces key features of human obstructive lung diseases, including mucus obstruction, inflammation, and air-space enlargement. Because the first Scnn1b-Tg mice were generated on a mixed background, the impact of genetic background on disease phenotype in Scnn1b-Tg mice is unknown. To explore this issue, congenic Scnn1b-Tg mice strains were generated on C57BL/6N, C3H/HeN, BALB/cJ, and FVB/NJ backgrounds. All strains exhibited a two- to threefold increase in tracheal epithelial Na(+) absorption, and all developed airway mucus obstruction, inflammation, and air-space enlargement. However, there were striking differences in neonatal survival, ranging from 5 to 80% (FVB/NJ

Natriuretic peptides and nitric oxide stimulate cGMP synthesis in different cellular compartments.

Cyclic nucleotide-gated (CNG) channels are a family of ion channels activated by the binding of cyclic nucleotides. Endogenous channels have been used to measure cyclic nucleotide signals in photoreceptor outer segments and olfactory cilia for decades. Here we have investigated the subcellular localization of cGMP signals by monitoring CNG channel activity in response to agonists that activate either particulate or soluble guanylyl cyclase. CNG channels were heterologously expressed in either human embryonic kidney (HEK)-293 cells that stably overexpress a particulate guanylyl cyclase (HEK-NPRA cells), or cultured vascular smooth muscle cells (VSMCs). Atrial natriuretic peptide (ANP) was used to activate the particulate guanylyl cyclase and the nitric oxide donor S-nitroso-n-acetylpenicillamine (SNAP) was used to activate the soluble guanylyl cyclase. CNG channel activity was monitored by measuring Ca2+ or Mn2+ influx through the channels using the fluorescent dye, fura-2. We found that in HEK-NPRA cells, ANP-induced increases in cGMP levels activated CNG channels in a dose-dependent manner (0.05-10 nM), whereas SNAP (0.01-100 microM) induced increases in cGMP levels triggered little or no activation of CNG channels (P < 0.01). After pretreatment with 100 microM 3-isobutyl-1-methylxanthine (IBMX), a nonspecific phosphodiesterase inhibitor, ANP-induced Mn2+ influx through CNG channels was significantly enhanced, while SNAP-induced Mn2+ influx remained small. In contrast, we found that in the presence of IBMX, both 1 nM ANP and 100 microM SNAP triggered similar increases in total cGMP levels. We next sought to determine if cGMP signals are compartmentalized in VSMCs, which endogenously express particulate and soluble guanylyl cyclase. We found that 10 nM ANP induced activation of CNG channels more readily than 100 muM SNAP; whereas 100 microM SNAP triggered higher levels of total cellular cGMP accumulation. These results suggest that cGMP signals are spatially segregated within cells, and that the functional compartmentalization of cGMP signals may underlie the unique actions of ANP and nitric oxide.

Partial volume correction incorporating Rb-82 positron range for quantitative myocardial perfusion PET based on systolic-diastolic activity ratios and phantom measurements.

BACKGROUND: Quantitative myocardial PET perfusion imaging requires partial volume corrections. METHODS: Patients underwent ECG-gated, rest-dipyridamole, myocardial perfusion PET using Rb-82 decay corrected in Bq/cc for diastolic, systolic, and combined whole cycle ungated images. Diastolic partial volume correction relative to systole was determined from the systolic/diastolic activity ratio, systolic partial volume correction from phantom dimensions comparable to systolic LV wall thicknesses and whole heart cycle partial volume correction for ungated images from fractional systolic-diastolic duration for systolic and diastolic partial volume corrections. RESULTS: For 264 PET perfusion images from 159 patients (105 rest-stress image pairs, 54 individual rest or stress images), average resting diastolic partial volume correction relative to systole was 1.14 ± 0.04, independent of heart rate and within ±1.8% of stress images (1.16 ± 0.04). Diastolic partial volume corrections combined with those for phantom dimensions comparable to systolic LV wall thickness gave an average whole heart cycle partial volume correction for ungated images of 1.23 for Rb-82 compared to 1.14 if positron range were negligible as for F-18. CONCLUSION: Quantitative myocardial PET perfusion imaging requires partial volume correction, herein demonstrated clinically from systolic/diastolic absolute activity ratios combined with phantom data accounting for Rb-82 positron range.

Glutamate receptors expressed in {\it Xenopus\/} oocytes: Studies in function and regulation

The amino acid glutamate is the primary excitatory neurotransmitter for the CNS and is responsible for the majority of fast synaptic transmission. Glutamate receptors have been shown to be involved in multiple forms of synaptic plasticity such as LTP, LTD, and the formation of specific synaptic connections during development. In addition to contributing to the plasticity of the CNS, glutamate receptors also are involved in, at least in part, various pathological conditions such as epilepsy, ischemic damage due to stroke, and Huntington's chorea. The regulation of glutamate receptors, particularly the ionotropic NMDA and AMPA/KA receptors is therefore of great interest. In this body of work, glutamate receptor function and regulation by kinase activity was examined using the Xenopus oocyte which is a convenient and faithful expression system for exogenous proteins. Glutamate receptor responses were measured using the two-electrode voltage clamp technique in oocytes injected with rat total forebrain RNA. NMDA elicited currents that were glycine-dependent, subject to block by Mg$\sp{2+}$ in a voltage-dependent manner and sensitive to the specific NMDA antagonist APV in a manner consistent with those types of responses found in neural tissue. Similarly, KA-evoked currents were sensitive to the specific AMPA/KA antagonist CNQX and exhibited current voltage relationships consistent with the calcium permeable type II KA receptors found in the hippocampus. There is evidence to indicate that NMDA and AMPA/KA receptors are regulated by protein kinase A (PKA). We explored this by examining the effects of activators of PKA (forskolin, 1-isobutyl-3-methylxanthine (IBMX) and 8-Br-cAMP) on NMDA and KA currents in the oocyte. In buffer where Ca$\sp{2+}$ was replaced by 2 mM Ba$\sp{2+},$ forskolin plus IBMX and 8-Br-cAMP augmented currents due to NMDA application but not KA. This augmentation was abolished by pretreating the oocytes in the kinase inhibitor K252A. The use of chloride channel blockers resulted in attenuation of this effect indicating that Ba$\sp{2+}$ influx through the NMDA channel was activating the endogenous calcium-activated chloride current and that the cAMP mediated augmentation was at the level of the chloride channel and not the NMDA channel. This was confirmed by (1) the finding that 8-Br-cAMP increased chloride currents elicited via calcium channel activation while having no effect on the calcium channels themselves and (2) the fact that lowering the Ba$\sp{2+}$ concentration to 200 $\mu$M abolished the augmentation NMDA currents by 8-Br-cAMP. Thus PKA does not appear to modulate ionotropic glutamate receptors in our preparation. Another kinase also implicated in the regulation of NMDA receptors, calcium/phospholipid-dependent protein kinase (PKC), was examined for its effects on the NMDA receptor under low Ba$\sp{2+}$ (200 $\mu$M) conditions. Phorbol esters, activators of PKC, induced a robust potentiation of NMDA currents that was blockable by the kinase inhibitor K252A. Furthermore activation of metabotropic receptors by the selective agonist trans-ACPD, also potentiated NMDA albeit more modestly. These results indicate that neither NMDA nor KA-activated glutamate receptors are modulated by PKA in Xenopus oocytes whereas NMDA receptors appear to be augmented by PKC. Furthermore, the endogenous chloride current of the oocyte was found to be responsive to Ba$\sp{2+}$ and in addition is enhanced by PKA. Both of these latter findings are novel. In conclusion, the Xenopus oocyte is a useful expression system for the analysis of ligand-gated channel activity and the regulation of those channels by phosphorylation. ^

The door of the tomb is open: Participatory action research to assess the impact of strengthened community capacity on maternal health care in rural Mali

This participatory action-research project addressed the hypothesis that strengthened community and women's capacity for self-development will lead to action to address maternal health problems and the prevention of maternal morbidity and mortality in Mali. Research objectives were: (1) to undertake a comparative cross-sectional study of the association of community capacity with improved maternal health in rural areas of Sanando, Mali, where capacity building interventions have taken place in some villages but not in others. (2) to describe women's maternal health status, access to and use of maternal health services given their residence in program or comparison communities.^ The participatory action research project was an integrated qualitative and quantitative study using participatory rural appraisal exercises, semi-structured group interviews and a cross-sectional survey.^ Factors related to community capacity for self-development were identified: community harmony; an understanding of the benefits of self-development; dynamic leadership; and a structure to implement collective activities.^ A distinct difference between the program and comparison villages was the commitment to train and support traditional birth attendants (TBAs). The TBAs in the program villages work in the context of the wider, integrated self-development program and, 10 years after their initial training, the TBAs continue to practice.^ Many women experience labor and childbirth alone or are attended by an untrained relative in both program and comparison villages. Nevertheless a significant change is apparent, with more women in program villages than in comparison villages being assisted by the TBAs. The delivery practices of the TBAs reveal the positive impact of their training in the "three cleans" (clean hands of the assistant, clean delivery surface and clean cord-cutting). The findings of this study indicate a significant level of unmet need for child spacing methods in all villages.^ The training and support of TBAs in the program villages yielded significant improvements in their delivery practices, and resulting outcomes for women and infants. However, potential exists for further community action. Capacities for self-development have not yet been directed toward an action plan encompassing other Safe Motherhood interventions, including access to family planning services and emergency obstetric care services. ^

Assessing dynamics of forced livestock movements, livelihoods and future development options for pastoralists/agro-pastoralists in Ruvuma and Lindi Regions, in the Southern Tanzania

The study that aimed at understanding the dynamics of forced livestock movements and pastoral livelihood and development options was conducted in Lindi and Ruvuma regions, using both formal and informal approaches. Data were collected from 60 randomly selected Agro-pastoralists/Pastoralists and native farmers using a structured questionnaire. Four villages were involved; two in Lindi region (Matandu and Mkwajuni) and the other two in Ruvuma region (Gumbiro and Muhuwesi). Data were analyzed using descriptive statistics of SPSS to generate means and frequencies. The results indicate that a large number of animals moved into the study area following the eviction order of the government in Ihefu wetlands in 2006/2007. Lindi region was earmarked by the government to receive all the evicted pastoralists. However, by 2008 only 30% of the total cattle that were expected to move into the region had been received. Deaths of many animals on transit, selling of the animals to pay for transportation and other costs while on transit and many pastoralists settling in Coastal and Ruvuma regions before reaching their destinations were reported to be the reasons for the discrepancy observed. To mitigate anticipated conflicts between farmers and pastoralists, Participatory Land Use Management (PLUM) plans were developed in all the study villages in order to demarcate village land area into different uses, including grazing, cropping, settlement and forests. Land units for grazing were supposed to be provided with all necessary livestock infrastructures (dips, charcoal dams, livestock markets and stock routes). However, the land use plans were not able to prevent the anticipated conflicts because most of the livestock infrastructures were lacking, the land use boundaries were not clearly demarcated and there was limited enforcement of village by-laws, since most had not been enacted by the respective district councils. Similarly, the areas allocated for grazing were inadequate for the number of livestock available and thus the carrying capacity exceeded. Thus, land resource-based conflicts between farmers and pastoralists were emerging in the study areas for the reason that most of the important components in the PLUM plans were not in place. Nevertheless, the arrival of pastoralists in the study areas had positive effects on food security and growth of social interactions between pastoralists and farmers including marriages between them. Environmental degradations due to the arrival of livestock were also not evident. Thus, there is a need for the government to purposely set aside enough grazing land with all necessary infrastructures in place for the agro-pastoral/pastoral communities in the country.

Shifting cultivation stability and change: Contrasting pathways of land use and livelihood change in Laos

Rural areas in Laos are experiencing a rapid transformation from traditional rice-based shifting cultivation systems to more permanent and diversified market-oriented cultivation systems. The consequences of these changes for local livelihoods are not well known. This study analyzes the impact of shifting cultivation change on the livelihood of rural people in six villages in three districts of northern and central Laos. Focus group discussions and household interview questionnaires were employed for data collection. The study reveals that the shifting cultivation of rice is still important in these communities, but it is being intensified as cash crops are introduced. Changes in shifting cultivation during the past ten years vary greatly between the communities studied. In the northern study sites, it is decreasing in areas with rubber expansion and increasing in areas with maize expansion, while it is stable in the central site, where sugarcane is an important cash crop. The impacts of land use change on livelihoods are also diverse. Cash crop producers hold more agricultural land than non-cash crop producers, and rubber and sugarcane producers have fewer rice shortages than non-producers. In the future, livelihood improvements in the central study site may be replicated in the northern sites, but this depends to a large extent on the economic and agricultural settings into which cash crops and other development opportunities are introduced. Moreover, the expansion of cash crops appears to counteract Lao policies aimed at replacing shifting cultivation areas with forests.