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Point of care (PoC) diagnostics are at the focus of government initiatives, NGOs and fundamental research alike. In high-income countries, the hope is to streamline the diagnostic procedure, minimize costs and make healthcare processes more efficient and faster, which, in some cases, can be more a matter of convenience than necessity. However, in resource-limited settings such as low-income countries, PoC-diagnostics might be the only viable route, when the next laboratory is hours away. Therefore, it is especially important to focus research into novel diagnostics for these countries in order to alleviate suffering due to infectious disease. In this review, the current research describing the use of PoC diagnostics in resource-limited settings and the potential bottlenecks along the value chain that prevent their widespread application is summarized. To this end, we will look at literature that investigates different parts of the value chain, such as fundamental research and market economics, as well as actual use at healthcare providers. We aim to create an integrated picture of potential PoC barriers, from the first start of research at universities to patient treatment in the field. Results from the literature will be discussed with the aim to bring all important steps and aspects together in order to illustrate how effectively PoC is being used in low-income countries. In addition, we discuss what is needed to improve the situation further, in order to use this technology to its fullest advantage and avoid “leaks in the pipeline”, when a promising device fails to take the next step of the valorization pathway and is abandoned.

Study objective:To investigate prospectively the associations between depression and cognitive social capital (social trust, sense of belonging, mutual aid) and structural social capital (volunteer work and community participation).Methods:This was a prospective study that was carried out in the USA. The participants were a nationally representative sample of 724 English-speaking non-institutionalised adults (25–74 years old) who participated in the National Survey of Midlife Development in the United States (MIDUS) in 1995–6 and the MIDUS Psychological Experience Follow-Up study in 1998.Main results:In multivariable adjusted logistic regression analyses, those who trusted their neighbours were less likely to develop major depression (MD) during follow-up than those who reported low levels of social capital on these dimensions (adjusted OR of MD for high vs low trust = 0.43; 95% CI 0.20 to 0.93, adjusted for MD at baseline, age, gender, race, education, working status, marital status, physical health and extroversion traits). Structural dimensions of social capital were not associated with MD in adjusted models.Conclusions:Perceptions of higher levels of cognitive social capital (trust of neighbours) are associated with lower risks of developing MD during 2–3 year follow-up. However, after excluding participants with MD at the baseline, the association between trust and MD became non-significant. Structural dimensions were not associated with MD.

Mental health problems in adolescence are increasingly prevalent and have tremendous impacts on life-long health and mortality. Although household poverty is a known risk factor for adolescent mental health, evidence of the timing hypothesis is scarce. We aimed to examine the longitudinal associations of poverty across childhood with mental health in adolescence, focusing on the timing of exposure. We used the data of 5,671 children from a Japanese population-based longitudinal cohort, which recruited the first graders (aged 6-7 years) and followed biannually until eighth grade (aged 13-14 years) in Adachi, Tokyo. Household poverty was defined as households having any of the following experiences: annual income less than Japanese yen 3 million, payment difficulties and material deprivations, measured in first, second, fourth, sixth and eighth grades. Adolescent mental health included parent-report internalizing and externalizing problems (the Strengths and Difficulties Questionnaire), self-report depression (the Patient Health Questionnaire-9) and self-esteem (the Japanese version Children's Perceived Competence Scale) in eighth grade. We applied g-estimation of structural nested mean modelling to account for time-varying confounders. If adolescents were exposed to household poverty at any grade across childhood, on average, they would report more severe depressive symptoms (ψ = 0.32 [95% CI 0.13; 0.51]) and lower self-esteem (ψ = -0.41 [-0.62; -0.21]) in eighth grade. There were also average associations of household poverty at any grade with more internalizing (ψ = 0.19 [0.10; 0.29]) and externalizing problems (ψ = 0.10 [0.002; 0.19]). Although the associations between household poverty and mental health were stronger in younger ages (e.g., poverty in the second grade → depression: ψ = 0.54 [-0.12; 1.19] vs. poverty in the eighth grade → depression: ψ = -0.01 [-0.66; 0.64]), overlapping 95% CIs indicated no statistically significantly different associations by the timing of exposure. We found the average effect of exposure to household poverty at any grade on mental health outcomes in eighth grade, failing to support the timing hypothesis. The findings indicate that the effects of household poverty accumulate over time in childhood and impact adolescent mental health (cumulative hypothesis) rather than the effects differ by the timing of exposure. While cumulative effects suggest a persistent intervention in poor households across childhood, we highlight intervention at any timing in childhood may be effective in alleviating adolescent mental health problems.

Unlike in urban areas where intensive water reclamation systems are available, development of decentralized technologies and systems is required for water use to be sustainable in agricultural areas. To overcome various water quality issues in those areas, a research project entitled ‘Development of an innovative water management system with decentralized water reclamation and cascading material-cycle for agricultural areas under the consideration of climate change’ was launched in 2009. This paper introduces the concept of this research and provides detailed information on each of its research areas: (1) development of a diffuse agricultural pollution control technology using catch crops; (2) development of a decentralized differentiable treatment system for livestock and human excreta; and (3) development of a cascading material-cycle system for water pollution control and value-added production. The author also emphasizes that the innovative water management system for agricultural areas should incorporate a strategy for the voluntary collection of bio-resources.

Background: We hypothesized that children from lower income households and in households experiencing a negative income change in connection to the global economic crisis in 2008 would be at increased risk of adverse weight status during the subsequent years of economic downturn. Methods: Data were obtained from a nationwide longitudinal survey comprising all children born during 2 weeks of 2001. For 16,403 boys and 15,206 girls, information about anthropometric measurements and household characteristics was collected from 2001 to 2011 on multiple occasions. Interactions between the crisis onset (September 2008) and household income group, as well as the crisis onset and a >30% negative income change in connection to the crisis, were assessed with respect to risk of childhood over- and underweight. Results: Adjusted for household and parental characteristics, boys and girls in the lower household income quartiles had a larger increase in risk of overweight after the crisis onset relative to their peers in the highest income group. (Odds ratio (95% confidence interval) for interaction term in boys=1.23 (1.02–1.24); girls=1.35 (1.23–1.49) comparing the lowest with the highest income group.) Among girls, an interaction between the crisis onset and a >30% negative change in household income with respect to risk of overweight was observed (odds ratio for interaction term=1.23 (1.09–1.38)). Girls from the highest income group had an increased risk of underweight after the crisis onset compared with girls from the lowest income group. Conclusions: Boys and girls from lower household income groups and girls from households experiencing a negative income change in connection to the global economic crisis in 2008, may be at increased risk of overweight. Vulnerability to economic uncertainty could increase risk of overweight in preadolescence.

Summary This study investigated the long-term survival and incidence of secondary fractures after fragility hip fractures. The 5-year survival rate was 62%, and the mortality risk was seen in patients with GNRI < 92. The 5-year incidence of secondary fracture was 22%, which was significantly higher in patients with a BMI < 20. Background Malnutrition negatively influences the postoperative survival of patients with fragility hip fractures (FHFs); however, little is known about their association over the long term. Objective This study evaluated the ability of the geriatric nutritional risk index (GNRI) as a risk factor for long-term mortality after FHFs. Methods This study included 623 Japanese patients with FHFs over the age of 60 years. We prospectively collected data on admission and during hospitalization and assessed the patients’ conditions after discharge through a questionnaire. We examined the long-term mortality and the incidence of secondary FHFs and assessed the prognostic factors. Results The mean observation period was 4.0 years (range 0–7 years). The average age at the time of admission was 82 years (range 60–101 years). The overall survival after FHFs (1 year, 91%; 5 years, 62%) and the incidence of secondary FHFs were high (1 year, 4%; 5 years, 22%). The multivariate Cox proportional hazard analysis revealed the risk factors for mortality as older age (hazard ratio [HR] 1.04), male sex (HR 1.96), lower GNRI score (HR 0.96), comorbidities (malignancy, HR 2.51; ischemic heart disease, HR 2.24; revised Hasegawa dementia scale ≤ 20, HR 1.64), no use of active vitamin D3 on admission (HR 0.46), and a lower Barthel index (BI) (on admission, HR 1.00; at discharge, HR 0.99). The GNRI scores were divided into four risk categories: major risk (GNRI, < 82), moderate risk (82–91), low risk (92–98), and no risk (> 98). Patients at major and moderate risks of GNRI had a significantly lower overall survival rate ( p < 0.001). Lower body mass index (BMI) was also identified as a prognostic factor for secondary FHFs (HR 0.88 [ p = 0.004]). Conclusions We showed that older age, male sex, a lower GNRI score, comorbidities, and a lower BI are risk factors for mortality following FHFs. GNRI is a novel and simple predictor of long-term survival after FHFs.

Boron (B) is required for cross linking of the pectic polysaccharide rhamnogalacturonan II (RG-II) and is consequently essential for the maintenance of cell wall structure. Arabidopsis (Arabidopsis thaliana) BOR1 is an efflux B transporter for xylem loading of B. Here, we describe the roles of BOR2, the most similar paralog of BOR1. BOR2 encodes an efflux B transporter localized in plasma membrane and is strongly expressed in lateral root caps and epidermis of elongation zones of roots. Transfer DNA insertion of BOR2 reduced root elongation by 68%, whereas the mutation in BOR1 reduced it by 32% under low B availability (0.1 μM), but the reduction in shoot growth was not as obvious as that in the BOR1 mutant. A double mutant of BOR1 and BOR2 exhibited much more severe growth defects in both roots and shoots under B-limited conditions than the corresponding single mutants. All single and double mutants grew normally under B-sufficient conditions. These results suggest that both BOR1 and BOR2 are required under B limitation and that their roles are, at least in part, different. The total B concentrations in roots of BOR2 mutants were not significantly different from those in wild-type plants, but the proportion of cross-linked RG-II was reduced under low B availability. Such a reduction in RG-II cross linking was not evident in roots of the BOR1 mutant. Thus, we propose that under B-limited conditions, transport of boric acid/borate by BOR2 from symplast to apoplast is required for effective cross linking of RG-II in cell wall and root cell elongation.

Chloroplasts, or photosynthetic plastids, multiply by binary fission, forming a homogeneous population in plant cells. In Arabidopsis thaliana, the division apparatus (or division ring) of mesophyll chloroplasts includes an inner envelope transmembrane protein ARC6, a cytoplasmic dynamin-related protein ARC5 (DRP5B), and members of the FtsZ1 and FtsZ2 families of proteins, which co-assemble in the stromal mid-plastid division ring (FtsZ ring). FtsZ ring placement is controlled by several proteins, including a stromal factor MinE (AtMinE1). During leaf mesophyll development, ARC6 and AtMinE1 are necessary for FtsZ ring formation and thus plastid division initiation, while ARC5 is essential for a later stage of plastid division. Here, we examined plastid morphology in leaf epidermal pavement cells (PCs) and stomatal guard cells (GCs) in the arc5 and arc6 mutants using stroma-targeted fluorescent proteins. The arc5 PC plastids were generally a bit larger than those of the wild type, but most had normal shapes and were division-competent, unlike mutant mesophyll chloroplasts. The arc6 PC plastids were heterogeneous in size and shape, including the formation of giant and mini-plastids, plastids with highly developed stromules, and grape-like plastid clusters, which varied on a cell-by-cell basis. Moreover, unique plastid phenotypes for stomatal GCs were observed in both mutants. The arc5 GCs rarely lacked chlorophyll-bearing plastids (chloroplasts), while they accumulated minute chlorophyll-less plastids, whereas most GCs developed wild type-like chloroplasts. The arc6 GCs produced large chloroplasts and/or chlorophyll-less plastids, as previously observed, but unexpectedly, their chloroplasts/plastids exhibited marked morphological variations. We quantitatively analyzed plastid morphology and partitioning in paired GCs from wild-type, arc5, arc6, and atminE1 plants. Collectively, our results support the notion that ARC5 is dispensable in the process of equal division of epidermal plastids, and indicate that dysfunctions in ARC5 and ARC6 differentially affect plastid replication among mesophyll cells, PCs, and GCs within a single leaf.

Myxoid/round cell (RC) liposarcomas (MLS) were originally classified into two distinct populations based on histological differences; a myxoid component and a RC component. It is notable that, depending on an increase of the RC component, the prognosis significantly differs. Hence, the RC component is associated with metastasis and poor prognosis. However, the molecular mechanisms that contribute to the malignancy of the RC component still remain largely unknown. Here, we report microRNA-135b (miR-135b), a key regulator of the malignancy, highly expressed in the RC component and promoting MLS cell invasion in vitro and metastasis in vivo through the direct suppression of thrombospondin 2 (THBS2). Decreased THBS2 expression by miR-135b increases the total amount of matrix metalloproteinase 2 (MMP2) and influences cellular density and an extracellular matrix structure, thereby resulting in morphological change in tumor. The expression levels of miR-135b and THBS2 significantly correlated with a poor prognosis in MLS patients. Overall, our study reveals that the miR-135b/THBS2/MMP2 axis is tightly related to MLS pathophysiology and has an important clinical implication. This work provides noteworthy evidence for overcoming metastasis and improving patient outcomes, and sheds light on miR-135b and THBS2 as novel molecular targets for diagnosis and therapy in MLS.

Background: Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, and metastasis occurs in up to one-third of cases. However, the mechanisms of invasion and metastasis remain unclear. Tumour-associated macrophages (TAMs) have important roles in tumour invasion, metastasis, and/or poor prognosis. The aim of this study was to investigate the relationship between TAMs and MLS. Methods: Using 78 primary MLS samples, the association between clinical prognosis and macrophage infiltration was evaluated by immunochemistry. The effects of macrophages on cell growth, cell motility, and invasion of MLS cell lines were investigated in vitro . In addition, clinicopathological factors were analysed to assess their prognostic implications in MLS. Results: Higher levels of CD68-positive macrophages were associated with poorer overall survival in MLS samples. Macrophage-conditioned medium enhanced MLS cell motility and invasion by activating epidermal growth factor receptor (EGFR), with the key ligand suggested to be heparin-binding EGF-like growth factor (HB-EGF). The phosphoinositide 3-kinase/Akt pathway was mostly involved in HB-EGF-induced cell motility and invasion of MLS. The expression of phosphorylated EGFR in MLS clinical samples was associated with macrophage infiltration. In addition, more significant macrophage infiltration was associated with poor prognosis even in multivariate analysis. Conclusions: Macrophage infiltration in MLS predicts poor prognosis, and the relationship between TAMs and MLS may be a new candidate for therapeutic targets of MLS.