Household resilience among fish value chain actors during the COVID-19 pandemic in Malawi.

We analyse household resilience capacities during the COVID-19 pandemic in the fishing communities along Lake Malawi by using FAO's resilience index measurement assessment (RIMA) methodology. The study is based on a sample of 400 households, and we employ the multiple indicators multiple causes (MIMIC) model to estimate resilience capacities. The model uses household food security indicators as development outcomes. Our findings show that the COVID-19 pandemic significantly reduces household food security and resilience capacity. COVID-19 shocks that significantly reduce household resilience capacities are death and illness of a household member. Important pillars for resilience building are assets, access to basic services and adaptive capacity. These findings point to the need to build assets of the households, build their adaptive capacity, and identify innovative ways of improving access to basic services to build household resilience capacities in the fishing communities. We recommend providing external support to households that have been directly affected by the pandemic through the death or illness of a member because their capacities to bounce back on their own significantly declines.

Impoverishing effects of catastrophic health expenditures in Malawi.

BACKGROUND: Out of pocket (OOP) health spending can potentially expose households to risk of incurring large medical bills, and this may impact on their welfare. This work investigates the effect of catastrophic OOP on the incidence and depth of poverty in Malawi. METHODS: The paper is based on data that was collected from 12,271 households that were interviewed during the third Malawi integrated household survey (IHS-3). The paper considered a household to have incurred a catastrophic health expenditure if the share of health expenditure in the household's non-food expenditure was greater than a given threshold ranging between 10 and 40%. RESULTS: As we increase the threshold from 10 to 40%, we found that OOP drives between 9.37 and 0.73% of households into catastrophic health expenditure. The extent by which households exceed a given threshold (mean overshoot) drops from 1.01% of expenditure to 0.08%, as the threshold increased. When OOP is accounted for in poverty estimation, additional 0.93% of the population is considered poor and the poverty gap rises by almost 2.54%. Our analysis suggests that people in rural areas and middle income households are at higher risk of facing catastrophic health expenditure. CONCLUSION: We conclude that catastrophic health expenditure increases the incidence and depth of poverty in Malawi. This calls for the introduction of social insurance system to minimize the incidence of catastrophic health expenditure especially to the rural and middle income population.

Anti-inflammatory effects of infliximab in mice are independent of tumour necrosis factor α neutralization.

Infliximab (IFX) has been used repeatedly in mouse preclinical models with associated claims that anti-inflammatory effects are due to inhibition of mouse tumour necrosis factor (TNF)-α. However, the mechanism of action in mice remains unclear. In this study, the binding specificity of IFX for mouse TNF-α was investigated ex vivo using enzyme-linked immunosorbent assay (ELISA), flow cytometry and Western blot. Infliximab (IFX) did not bind directly to soluble or membrane-bound mouse TNF-α nor did it have any effect on TNF-α-induced nuclear factor kappa B (NF-κB) stimulation in mouse fibroblasts. The efficacy of IFX treatment was then investigated in vivo using a TNF-α-independent Trichuris muris-induced infection model of chronic colitis. Infection provoked severe transmural colonic inflammation by day 35 post-infection. Colonic pathology, macrophage phenotype and cell death were determined. As predicted from the in-vitro data, in-vivo treatment of T. muris-infected mice with IFX had no effect on clinical outcome, nor did it affect macrophage cell phenotype or number. IFX enhanced apoptosis of colonic immune cells significantly, likely to be driven by a direct effect of the humanized antibody itself. We have demonstrated that although IFX does not bind directly to TNF-α, observed anti-inflammatory effects in other mouse models may be through host cell apoptosis. We suggest that more careful consideration of xenogeneic responses should be made when utilizing IFX in preclinical models.

Inflammatory cues enhance TGFß activation by distinct subsets of human intestinal dendritic cells via integrin αvß8.

Regulation of intestinal T-cell responses is crucial for immune homeostasis and prevention of inflammatory bowel disease (IBD). A vital cytokine in regulating intestinal T cells is transforming growth factor-ß (TGFß), which is secreted by cells as a latent complex that requires activation to function. However, how TGFß activation is regulated in the human intestine, and how such pathways are altered in IBD is completely unknown. Here we show that a key activator of TGFß, integrin αvß8, is highly expressed on human intestinal dendritic cells (DCs), specifically on the CD1c+ but not the CD141+ intestinal DC subset. Expression was significantly upregulated on intestinal DC from IBD patients, indicating that inflammatory signals may upregulate expression of this key TGFß-activating molecule. Indeed, we found that the Toll-like receptor 4 ligand lipopolysaccharide upregulates integrin αvß8 expression and TGFß activation by human DC. We also show that DC expression of integrin αvß8 enhanced induction of FOXP3 in CD4+ T cells, suggesting functional importance of integrin αvß8 expression by human DC. These results show that microbial signals enhance the TGFß-activating ability of human DC via regulation of integrin αvß8 expression, and that intestinal inflammation may drive this pathway in patients with IBD.

Measuring and Valuing Informal Care for Economic Evaluation of HIV/AIDS Interventions: Methods and Application in Malawi.

BACKGROUND: Economic evaluation studies often neglect the impact of disease and ill health on the social network of people living with HIV (PLHIV) and the wider community. An important concern relates to informal care requirements which, for some diseases such as HIV/AIDS, can be substantial. OBJECTIVES: To measure and value informal care provided to PLHIV in Malawi. METHODS: A modified diary that divided a day into natural calendar changes was used to measure informal care time. The monetary valuation was undertaken by using four approaches: opportunity cost (official minimum wage used to value caregiving time), modified opportunity cost (caregiver's reservation wage), willingness to pay (amount of money caregiver would pay for care), and willingness to accept (amount of money caregiver would accept for providing care to someone else) approaches. Data were collected from 130 caregivers of PLHIV who were accessing antiretroviral therapy from six facilities in Phalombe district in southeast Malawi. RESULTS: Of the 130 caregivers, 62 (48%) provided informal care in the survey week. On average, caregivers provided care of 8 h/wk. The estimated monetary values of informal care provided per week were US $1.40 (opportunity cost), US $2.41 (modified opportunity cost), US $0.40 (willingness to pay), and US $2.07 (willingness to accept). CONCLUSIONS: Exclusion of informal care commitments may be a notable limitation of many applied economic evaluations. This work demonstrates that inclusion of informal care in economic evaluations in a low-income context is feasible.

Health and vulnerability to poverty in Ghana: evidence from the Ghana Living Standards Survey Round 5.

BACKGROUND: An understanding of the complex relationship between health status and welfare is crucial for critical policy interventions. However, the focus of most policies in developing regions has been on current welfare to the neglect of forward-looking welfare analysis. The absence of adequate research in the area of future poverty or vulnerability to poverty has also contributed to the focus on current welfare. The objectives of this study were to estimate vulnerability to poverty among households in Ghana and examine the relationship between health status and vulnerability to poverty. METHOD: The study used cross section data from the Fifth Round of the Ghana Living Standards Survey (GLSS 5) with a nationally representative sample of 8,687 households from all administrative regions in Ghana. A three-step Feasible Generalized Least Squares (FGLS) estimation procedure was employed to estimate vulnerability to poverty and to model the effect of health status on expected future consumption and variations in future consumption. Vulnerability to poverty estimates were also examined against various household characteristics. RESULTS: Using an upper poverty line, the estimates of vulnerability show that about 56% of households in Ghana are vulnerable to poverty in the future and this is higher than the currently observed poverty level of about 29%. Households with ill members were vulnerable to poverty. Moreover, households with poor hygiene conditions were also vulnerable to future poverty. The vulnerability to poverty estimates were, however, sensitive to the poverty line used and varied with household characteristics. CONCLUSION: The results imply that policies directed towards poverty reduction need to take into account the vulnerability of households to future poverty. Also, hygienic conditions and health status of households need not be overlooked in poverty reduction strategies.

An asset-based approach to vulnerability: the case of small-scale fishing areas in Cameroon and Nigeria.

This paper analyses vulnerability to poverty of rural small-scale fishing communities using cross-section data from 295 households in Cameroon and 267 in Nigeria. We propose a vulnerability measure that incorporates the idea of asset poverty into the concept of expected poverty, which allows decomposing expected poverty into expected structural-chronic, structural-transient, and stochastic-transient poverty. The findings show that most households in our study areas are expected to be structurally-chronic and structurally-transient poor. This underlines the importance of asset formation for long-term poverty reduction strategies. Further refinements are possible with longitudinal data and information about future states of nature.

Colonic transcriptional profiling in resistance and susceptibility to trichuriasis: phenotyping a chronic colitis and lessons for iatrogenic helminthosis.

BACKGROUND: Helminth therapy is advocated to restore and maintain control of inflammatory responses, particularly chronic colitis. However, helminths can induce chronic colitis in susceptible individuals. Susceptibility has an immunogenetic basis: defining this is essential if nematode therapy is to be successfully and safely targeted in inflammatory bowel disease (IBD). To validate a preclinical mouse model we phenotyped the response to Trichuris muris in mice. We determined colonic transcriptional activity in naïve and infected mice and linked differential gene expression to mechanistic pathways. METHODS: T. muris-infected resistant (BALB/c) and susceptible (AKR) mice were studied to a chronic colitic timepoint (day 35). Colonic genome-wide expression was performed by microarray. Significant transcriptional changes were analyzed by cluster and gene ontology filtering and KEGG pathway mapping. RESULTS: Day 35 infected AKR displayed chronic diarrhea, weight loss, and transmural colonic inflammation; BALB/c remained asymptomatic, cleared the infection, and demonstrated normal histology. Compared to BALB/c mice, infected AKR upregulated gene expression clusters were overrepresented by immune response, chemotaxis, and apoptosis pathways. Cellular/tissue homeostasis and tight junction pathways dominated downregulated AKR expression clusters. Infected AKR T-helper cell development/polarization markers demonstrated predominant T(H) 1/T(H) 17 transcriptional activity. Colitic AKR data mirrored established murine models and human colitis. CONCLUSIONS: T. muris infection in the mouse shows striking phenotypic and transcriptional similarities to widely used models of IBD and human IBD. This preclinical mouse model presents a platform to examine biological commonalities among chronic colitides. However, these data urge caution in untargeted therapeutic helminth use until risk/benefit in susceptible individuals is more fully understood.

Rescue of a living donor with liver transplantation.

Postoperative liver failure is a rare complication after living donor liver resection. This is a case report of a 22-year-old healthy donor who was rescued with liver transplantation 11 days after right hemihepatectomy. Nine months later the patient is alive, and has fully recovered from his multiple organ failure. According to a review of the literature, there are four additional living liver donors, who received a liver transplant. Our own patient is the only survivor, so far. This case demonstrates that even in supposedly healthy living donors postoperative complications cannot be completely prevented. Although liver failure is rare in these patients, timely transplantation may need to be considered as the only life-saving treatment.

Leukemia inhibitory factor participates in the expansion of neural stem/progenitors after perinatal hypoxia/ischemia.

Subsequent to perinatal hypoxia/ischemia there is an increase in the number of neural stem/progenitor cells (NSP) within the subventricular zone (SVZ). Gene expression analyses have implicated Notch signaling in the expansion of these tripotential cells but there are limited data as to which signals are stimulating Notch activation. There is evidence that the leukemia inhibitory factor receptor (LIFR)/gp130 receptor heterodimer induces Notch1 to maintain NSP populations during normal development. LIF and ciliary neurotrophic factor (CNTF) bind to these receptor components and they coordinate injury responses in the CNS. Therefore, the aim of these studies was to investigate whether CNTF and/or leukemia inhibitory factor (LIF) participate in NSP expansion in the rat SVZ after hypoxia/ischemia (H/I) as well as to characterize the downstream events that regulate NSP numbers. We report that LIF mRNA is induced 48 h post-insult by 13-fold but that it returns almost to baseline by 72 h. Commensurate with increased LIF expression there is a corresponding increase in phosphorylated Stat-3 within the SVZ. Modeling the changes that occur in vivo, we show that LIF induces Stat-3 phosphorylation in neurospheres to enhance Delta-like-1 and Notch1 expression as well as to increase Notch1 activation. LIF also expands neurosphere number and size in vitro. Whereas CNTF can mimic the effects of LIF in vitro, CNTF expression in the SVZ was unchanged during recovery from H/I. Cumulatively, these data implicate LIF and not CNTF in the expansion of NSPs in the rat SVZ after perinatal brain injury. As both LIF expression and the endogenous regenerative response after brain injury are time-delimited, these findings provide insights into strategies to expand the endogenous pool of NSPs to repopulate the damaged brain.

Hypoxia/ischemia expands the regenerative capacity of progenitors in the perinatal subventricular zone.

Neurons and oligodendrocyte progenitors are highly sensitive to perinatal hypoxic-ischemic injury. As accumulating evidence suggests that many insults to the human infant occur in utero, and preventing brain damage to infants in utero will prove difficult, there is strong rationale to pursue regenerative strategies to reduce the morbidity associated with developmental brain injuries. The purpose of this study was to determine whether a hypoxic-ischemic insult stimulates the neural stem/progenitor cells in the subventricular zone to generate new neurons and oligodendrocytes. Hypoxia-ischemia was induced using the Vannucci rat model on postnatal day-6 pups. Injections of 5'-bromo-2'-deoxyuridine to label cells undergoing DNA synthesis after hypoxia-ischemia revealed that there is a robust proliferative response within the subventricular zone of the injured hemisphere that continues for at least 1 week after the hypoxic-ischemic episode. Using the neurosphere assay to quantify the number of neural stem/progenitor cells in the subventricular zone, we find that there are twice as many neural stem/progenitor cells in the affected dorsolateral subventricular zone at 1 week of recovery and that these cells generate larger spheres in response to growth factors compared with controls. Precursors from the injured hemisphere generate three times as many neurons in vitro and more than twice as many oligodendroglia compared with controls. Hypoxia-ischemia also increases neurogenesis in vivo. Doublecortin positive cells with migratory profiles were observed streaming from the ipsilateral subventricular zone to the striatum and neocortex, whereas, few doublecortin positive cells were found in the contralateral hemisphere after hypoxia-ischemia. These observations provide evidence that the somatic neural progenitors of the subventricular zone participate in the production of new brain cells lost after hypoxia-ischemia.

Glutamate enhances survival and proliferation of neural progenitors derived from the subventricular zone.

Extracellular glutamate levels increase as a consequence of perinatal hypoxia/ischemia, causing the death of neurons and oligodendrocytes. Precursors in the subventricular zone (SVZ) also die following perinatal hypoxia/ischemia; therefore we hypothesized that glutamate would stimulate the death of neural precursors. Here we demonstrate using calcium imaging that SVZ derived neural stem/progenitor cells respond to both ionotropic and metabotropic excitatory amino acids. Therefore, we tested the effects of high levels of glutamate receptor agonists on the proliferation, survival, and differentiation of SVZ derived neural stem/progenitor cells in vitro. We show that high levels of glutamate, up to 1 mM, are not toxic to neural precursor cultures. In fact, stimulation of either the kainate receptor or group 2 metabotropic glutamate receptors (group 2 mGluR) reduces basal levels of apoptosis and increases neural precursor proliferation. Furthermore, group 2 mGluR activation expands the number of multipotent progenitor cells present in these cultures while maintaining equivalent mature cell production. We conclude that the glutamate released following perinatal hypoxia/ischemia may act to acutely promote the proliferation of multipotent precursors in the subventricular zone.

Pro-regenerative properties of cytokine-activated astrocytes.

The prevailing view of the astrocytic response to injury is that reactive astrocytes impede the regenerative process by forming scar tissue. As the levels of many cytokines dramatically increase following CNS insult and as this increase in cytokine expression precedes the production of the glial scar, a long-standing view has been that cytokines diminish neuronal survival and regeneration by stimulating the formation of astrogliotic scar tissue. However, there is a wealth of data indicating that cytokines "activate" astrocytes, and that cytokine-stimulated astrocytes can promote the recovery of CNS function. Supporting evidence demonstrates that cytokine-activated astrocytes produce energy substrates and trophic factors for neurons and oligodendrocytes, act as free radical and excess glutamate scavengers, actively restore the blood-brain barrier, promote neovascularization, restore CNS ionic homeostasis, promote remyelination and also stimulate neurogenesis from neural stem cells. Accordingly, a re-assessment of cytokine-activated astrocytes is necessary. Here, we review studies that promote the thesis that cytokines elicit potent neuroprotective and regenerative responses from astrocytes.

Perinatal hypoxia-ischemia induces apoptotic and excitotoxic death of periventricular white matter oligodendrocyte progenitors.

Hypoxia-ischemia (HI) is a leading cause of white matter damage, a major contributor to cerebral palsy in premature infants. Preferential white matter damage is believed to result from vulnerability of the immature oligodendrocyte (the pro-OL) to factors elevated during ischemic damage, such as oxygen free radicals and glutamate. In order to determine whether pro-OLs undergo apoptotic death after HI, we analyzed periventricular white matter OLs in P7 rats 4, 12 and 24 h after HI to analyze the time course and mode of cell death. DNA fragmentation was seen at 12 and 24 h of recovery after HI, representing a 17-fold increase over control. In addition, caspase-3 activation was found in NG2+ pro-OLs at 12 h. Electron-microscopic analysis of cell death in the white matter revealed a transition from early necrotic deaths to hybrid cell deaths to classical apoptosis between 4 and 24 h of recovery from HI. The delayed time course of apoptosis in pro-OLs supports the feasibility of interventions to improve clinical outcomes for newborns surviving birth asphyxia.

Hypoxia/ischemia depletes the rat perinatal subventricular zone of oligodendrocyte progenitors and neural stem cells.

Cerebral hypoxia/ischemia of the newborn has a frequency of 4/1,000 births and remains a major cause of cerebral palsy, epilepsy, and mental retardation. Despite progress in understanding the pathogenesis of hypoxic-ischemic injury, the data are incomplete regarding the mechanisms leading to permanent brain injury. Here we tested the hypothesis that cerebral hypoxia/ischemia damages stem/progenitor cells in the subventricular zone (SVZ), resulting in a permanent depletion of oligodendrocytes. We used a widely accepted rat model and examined animals at recovery intervals ranging from 4 h to 3 weeks. Within hours after the hypoxic-ischemic insult 20% of the total cells were deleted from the SVZ. The residual damaged cells appeared necrotic. During 48 h of recovery deaths accumulated; however, these later deaths were predominantly apoptotic. Many apoptotic SVZ cells stained with a marker for immature oligodendrocytes. At 3 weeks survival, the SVZ was smaller and markedly less cellular, and it contained less than 1/4 the normal complement of neural stem cells. The corresponding subcortical white matter was dysmyelinated, relatively devoid of oligodendrocytes and enriched in astrocytes. We conclude that neural stem cells and oligodendrocyte progenitors in the SVZ are vulnerable to hypoxia/ischemia. Consequently, the developmental production of oligodendrocytes is compromised and regeneration of damaged white matter oligodendrocytes does not occur resulting in failed regeneration of CNS myelin in periventricular loci. The resulting dysgenesis of the brain that occurs subsequent to perinatal hypoxic/ischemic injury may contribute to the cognitive and motor dysfunction that results from asphyxia of the newborn.

The FLT3 tyrosine kinase receptor inhibits neural stem/progenitor cell proliferation and collaborates with NGF to promote neuronal survival.

The FLT3 receptor tyrosine kinase (FLT3) was originally identified on hematopoietic stem cells (HSCs) and its ligand (FL) induces HSC proliferation. As stem cells originating from various tissues are more similar than once thought, the goal of this study was to determine whether neural stem cells express FLT3 and proliferate in response to FL. In fact, a subset of neural stem/progenitor cells does express FLT3, but contrary to our expectations, FL inhibited EGF and FGF-2 stimulated proliferation. Since FLT3 is expressed weakly by proliferative neuroepithelia but strongly by subsets of neurons in the CNS and PNS, we tested its ability to support neuronal survival. FL synergized with NGF to promote the survival of cultured DRG neurons, although it lacked any neurotrophic activity alone. We conclude that FL serves as an adjunct trophic factor in the nervous system, which differs from its role in the hematopoietic system.

Expression of the anaphylatoxin C5a receptor in the oligodendrocyte lineage.

Expression of the C5a receptor in the central nervous system has been demonstrated on microglia, astrocytes and neurons. In the present study, we demonstrate C5aR expression in vitro by rat and murine O2-A progenitor cells and oligodendrocytes. We also observed that in vitro differentiation of O2-A progenitors into mature oligodendrocytes is accompanied by down-regulation of C5aR mRNA expression. These results suggest that the C5aR may be a marker for oligodendroglial differentiation and play a role in oligodendrocyte function.

IL-6-type cytokines enhance epidermal growth factor-stimulated astrocyte proliferation.

Proliferating astrocytes are frequently observed in diseased and injured brains. These newly generated astrocytes are necessary to reestablish the barriers that isolate the CNS from the rest of the body; however, they also create a matrix that inhibits regeneration and remyelination. Therefore, it is important to understand the mechanisms that enable a terminally differentiated astrocyte to reenter the cell cycle. Ciliary neurotrophic factor (CNTF), interleukin-6 (IL-6), transforming growth factor-alpha (TGF-alpha), and fibroblastic growth factor-2 (FGF-2) are four cytokines that are rapidly elevated in damaged neural tissue. These cytokines also have been implicated in glial scar formation. We sought to determine whether IL-6 and CNTF stimulate astroglial proliferation alone or in combination with other mitogens. Intraparenchymal CNTF modestly increased the number of proliferating cell nuclear antigen (PCNA) and glial fibrillary acidic protein (GFAP) double positive astrocytes when introduced by stereotactic injection into the adult rat brain. When applied directly to highly enriched rat forebrain astrocyte cultures, neither CNTF nor IL-6-stimulated DNA synthesis. Therefore, they are not astroglial mitogens. However, both cytokines synergized with epidermal growth factor (EGF), increasing its mitogenicity by approximately twofold. Astrocytes that had been "aged" for at least 3 weeks in vitro became refractory to EGF; however, when these "aged" astrocytes were pretreated with either IL-6 or CNTF for as little as 2 h, they became competent to reenter the cell cycle upon exposure to EGF. These data suggest that IL-6 type cytokines, likely by activating STAT family transcription factors, induce the expression of signaling molecules that endow resting astrocytes with the competence to respond to mitogens and to reenter the cell cycle.

Tools for integrating women's health into medical education: clinical cases and concept mapping.

The authors describe two teaching tools, case-based learning and concept mapping, and how they support cross-disciplinary, multidisciplinary, and interdisciplinary learning, use a biopsychosocial model, and promote the integration of sex- and gender-based science into the medical curriculum. The process of case development at MCP Hahnemann University (MCPHU) is outlined in detail for a specific case. That case, which integrates three different components of women's health, is then presented in full. The authors then provide an example of a concept map dealing with women and alcohol use; the map defines current knowledge and serves as a blueprint for developing curricular goals and learning objectives for the topic. Properly constructed concept maps and cases help teach patient-centered approaches to problem solving, address sex- and gender-based differences in disease as well as in pathophysiology and pharmacology, integrate psychosocial issues-such as family dynamics, environmental stressors, access to health care, effective gender-based communication between patient and provider, and cultural variations-along with biomedical ones, and encourage a multidisciplinary approach to patient care. The authors maintain that these tools might be used to transform medical education by making it more integrated and interdisciplinary.

Ceramide-coated balloon catheters limit neointimal hyperplasia after stretch injury in carotid arteries.

Neointimal hyperplasia at the site of surgical intervention is a common and deleterious complication of surgery for cardiovascular diseases. We hypothesized that direct delivery of a cell-permeable growth-arresting lipid via the balloon tip of an embolectomy catheter would limit neointimal hyperplasia after stretch injury. We have previously demonstrated that sphingolipid-derived ceramide arrested the growth of smooth muscle cell pericytes in vitro. Here, we show that ceramide-coated balloon catheters significantly reduced neointimal hyperplasia induced by balloon angioplasty in rabbit carotid arteries in vivo. This ceramide treatment decreased the number of vascular smooth muscle cells entering the cell cycle without inducing apoptosis. In situ autoradiographic studies demonstrated that inflating the balloon catheter forced cell-permeable ceramide into the intimal and medial layers of the artery. Intercalation of ceramide into vascular smooth muscle cells correlated with rapid inhibition of trauma-associated phosphorylation of extracellular signal-regulated kinase and protein kinase B. These studies demonstrate the utility of cell-permeable ceramide as a novel therapy for reducing neointimal hyperplasia after balloon angioplasty.