Measuring access to food banks and food pantries: A scoping review of spatial analysis approaches.

Food banks and food pantries are crucial in supporting access to food and addressing food insecurity for millions of people. This scoping review identified eighteen articles that applied spatial analysis approaches to measure access to food banks and food pantries. The review summarizes the methods and primary findings of these studies, and examines how these address different dimensions of food access. Findings suggest that the majority of studies measured the accessibility and availability dimensions of food access, and two addressed accommodation. Through a discussion of these studies' methods and broader literature on food environments, we highlight opportunities to integrate advanced geospatial and mixed methods to support an empirically grounded and broader understanding of food bank and pantry access in future research. This will yield a more holistic picture of food environments and provide practical implications for site selection, resource allocation, and food assistance operations.

Assessing changes in food pantry access after extreme events.

Food pantries play a growing role in supporting households facing or at risk of food insecurity in the United States. They also support emergency response and recovery following disasters and extreme weather events. Although food pantries are often placed in close proximity to communities with the highest rates of poverty and risk of food insecurity, access to these facilities can be disrupted during and after extreme events. Decreased access to food pantries following disasters can be particularly problematic as the need for these services is also likely to grow after such events. Despite the vast body of research on food retail access and food environments, relatively little research has utilized spatial analysis to understand food pantry access, particularly after extreme events. Using Geographic Information Systems (GIS), we characterize changes in access to food pantries following flooding events in Harris County, Texas-a highly populated and flood prone region with high levels of food insecurity and poverty. Specifically, our study models disruptions in road networks due to flooding and assesses the impacts of these disruptions on proximity to food pantries. The results reveal that much of Harris County sees only small increases in travel distance to food pantries due to extreme flooding, but some areas may be unable to access food pantries at all. This research highlights the potential and some of the limits of private food assistance networks to support emergency response efforts.

Business recovery from disasters: Lessons from natural hazards and the COVID-19 pandemic.

This paper compares economic recovery in the COVID-19 pandemic with other types of disasters, at the scale of businesses. As countries around the world struggle to emerge from the pandemic, studies of business impact and recovery have proliferated; however, pandemic research is often undertaken without the benefit of insights from long-standing research on past large-scale disruptive events, such as floods, storms, and earthquakes. This paper builds synergies between established knowledge on business recovery in disasters and emerging insights from the COVID-19 pandemic. It first proposes a disaster event taxonomy that allows the pandemic to be compared with natural hazard events from the perspective of economic disruption. The paper then identifies five key lessons on business recovery from disasters and compares them to empirical findings from the COVID-19 pandemic. For synthesis, a conceptual framework on business recovery is developed to support policy-makers to anticipate business recovery needs in economically disruptive events, including disasters. Findings from the pandemic largely resonate with those from disasters. Recovery tends to be more difficult for small businesses, those vulnerable to supply chain problems, those facing disrupted markets, and locally-oriented businesses in heavily impacted neighborhoods. Disaster assistance that is fast and less restrictive provides more effective support for business recovery. Some differences emerge, however: substantial business disruption in the pandemic derived from changes in demand due to regulatory measures as well as consumer behaviour; businesses in high-income neighborhoods and central business districts were especially affected; and traditional forms of financial assistance may need to be reconsidered.

Primary Care Providers' Perspectives on Prescribing Antidepressant Medication to Latino Immigrant Patients: A Preliminary Study.

Latinos in the United States are less likely to take antidepressants than non-Latino whites, and more likely to prefer depression treatment in primary care. This preliminary study comprised focus groups (2) with primary care providers (12) serving uninsured immigrant Latinos regarding their experiences prescribing and counseling patients about antidepressants. Barriers and challenges included health literacy, language barriers, and illiteracy; perceived stigma; patients' concerns about addiction, polypharmacy, and adverse effects; time constraints of office visits; and difficulty discussing comorbid posttraumatic stress disorder. Messages providers try to share with patients included allowing time for medications to work, taking medications daily as prescribed, mechanisms of action, weighing risks versus benefits, and flexible options for treatment. Providers' recommendations for improving this process included better low-literacy, culturally appropriate written materials with pictures or videos discussing depression. More research is needed to understand patients' and providers' needs in optimizing counseling about antidepressants, particularly regarding underserved and at-risk US populations.

Treatment of depression and PTSD in primary care clinics serving uninsured low-income mostly Latina/o immigrants: A naturalistic prospective evaluation.

OBJECTIVES: Uninsured immigrants to the United States are psychologically vulnerable due to limited access to mental health services. Latina/o immigrants from Central and South America are further at risk due to high levels of trauma exposure, both in their country of origin and their adopted country. Effective behavioral interventions in primary care are needed to address this services gap for common trauma-related mental disorders, including depression and posttraumatic stress disorder (PTSD). A naturalistic prospective study compared depression and PTSD outcomes for uninsured primary care patients, mostly Latina/o immigrants, in clinics with distinct models for integrating behavioral health services. One clinic had a collaborative care program, that is, a multicomponent, system-level intervention with the goals of facilitating increased screening, improving diagnostic accuracy, increasing uptake of evidence-based treatment, and utilizing measurement-based treatment to target. The other had colocated services, with an on-site therapist. METHOD: One hundred thirty-eight patients with presumptive depression were interviewed at baseline. Follow-up data were collected 8 months later. Care received between the two assessments was ascertained by chart review. RESULTS: There was a significant decrease in depression symptoms regardless of clinic. Factors associated with improved depression outcomes included absence of comorbid PTSD and lack of additional trauma exposures. Although there was overall improvement in PTSD, there was significantly more improvement in the collaborative care clinic. CONCLUSIONS: Results suggest that both models were effective for depression and PTSD; however, the collaborative care model had added benefits for those patients with PTSD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Knowledge and Preferences Regarding Antidepressant Medication Among Depressed Latino Patients in Primary Care.

US Latinos are less likely to utilize mental health services than non-Latino whites and to take antidepressant medications. This mixed-method study followed a subset (N = 28) of a research sample of depressed Latino immigrant primary care patients, who took depression medication, with a telephone interview to study their knowledge about and experiences with antidepressant medications. Most (82%) reported taking medication for 2 months or more, and 75% reported feeling better, whereas more than half reported side effects. Most (61%) agreed that antidepressants are generally safe and helpful in treating depression (68%); however, many believed they could be addictive (39%). Fifty percent of patients who discontinued their medication did not inform their providers. Twelve of the 28 patients also participated in focus groups about interactions with providers and made suggestions for conveying information about antidepressants. Patients suggested videos as a format to disseminate medication information because they do not require written comprehension. Other patient recommendations are presented.

Assessing health literacy and oral health: preliminary results of a multi-site investigation.

OBJECTIVES: To introduce a multi-site assessment of oral health literacy and to describe preliminary analyses of the relationships between health literacy and selected oral health outcomes within the context of a comprehensive conceptual model. METHODS: Data for this analysis came from the Multi-Site Oral Health Literacy Research Study (MOHLRS), a federally funded investigation of health literacy and oral health. MOHLRS consisted of a broad survey, including several health literacy assessments, and measures of attitudes, knowledge, and other factors. The survey was administered to 922 initial care-seeking adult patients presenting to university-based dental clinics in California and Maryland. For this descriptive analysis, confidence filling out forms, word recognition, and reading comprehension comprised the health literacy assessments. Dental visits, oral health functioning, and dental self-efficacy were the outcomes. RESULTS: Overall, up to 21% of participants reported having difficulties with practical health literacy tasks. After controlling for sociodemographic confounders, no health literacy assessment was associated with dental visits or dental caries self-efficacy. However, confidence filling out forms and word recognition were each associated with oral health functioning and periodontal disease self-efficacy. CONCLUSIONS: Our analysis showed that dental school patients exhibit a range of health literacy abilities. It also revealed that the relationship between health literacy and oral health is not straightforward, depending on patient characteristics and the unique circumstances of the encounter. We anticipate future analyses of MOHLRS data will answer questions about the role that health literacy and various mediating factors play in explaining oral health disparities.

Whole blood measurement of histone modifications linked to the epigenetic regulation of gene expression.

Rapid progress is being made to understand the regulatory mechanisms that underlie the epigenetic control of gene expression through histone modification. It is now recognized that this plays a major role in normal development and disease. This unit describes the application of flow cytometry to the study of epigenetic mechanisms by combining labeling of individual histone modifications and phenotypic markers, and it also discusses practical issues to optimize staining. The focus is on normal blood and samples from leukemia patients, but it can also be applied to cells grown in tissue culture.

The study of epigenetic mechanisms based on the analysis of histone modification patterns by flow cytometry.

Epigenetic regulation of genes involved in cell growth, survival, or differentiation through histone modifications is an important determinant of cancer development and outcome. The basic science of epigenetics uses analytical tools that, although powerful, are not well suited to the analysis of heterogeneous cell populations found in human cancers, or for monitoring the effects of drugs designed to modulate epigenetic mechanisms in patients. To address this, we selected three clinically relevant histone marks (H3K27me3, H3K9ac, and H3K9me2), modulated their expression levels by in vitro treatments to generate high and low expressing control cells, and tested the relative sensitivity of candidate antibodies to detect the differences in expression levels by flow cytoametry using a range of sample preparation techniques. We identified monoclonal antibodies to all three histone marks that were suitable for flow cytoametry. Staining intensities were reduced with increasing formaldehyde concentration, and were not affected by ionic strength or by alcohol treatment. A protocol suitable for clinical samples was then developed, to allow combined labeling of histone marks and surface antigens while preserving light scatter signals. This was applied to normal donor blood, and to samples obtained from 25 patients with leukemia (predominantly acute myeloid leukemia). Significant cellular heterogeneity in H3K9ac and H3K27me3 staining was seen in normal peripheral blood, but the patterns were very similar between individual donors. In contrast, H3K27me3 in particular showed considerable inter-patient heterogeneity in the leukemia cell populations. Although further refinements are likely needed to fully optimize sample staining protocols, "flow epigenetics" appears to be technically feasible, and to have potential both in basic research, and in clinical application.

A collaborative mental health research agenda in a community of poor and underserved Latinos.

The goal of this project was to engage community members and grassroots organizations in a discussion regarding perceived mental health needs and priorities of the population of underserved Latinos in Montgomery County, Maryland. Community-based participatory research was used to establish structures for participation and to design studies that effectively address local mental health needs. Four focus groups with 30 Latino lay health promoters and 20 key informant interviews were conducted to ascertain communal mental health needs and priorities. The main issues that emerged included mental health stigma, consequences of immigration-related stress, violence and alcoholism, and concerns about psychotropic medications. Ideas to address these issues and foster wellness through research were generated during a community-based workshop that included consumers, primary care and mental health clinicians, researchers, and representatives of local organizations and federal agencies. The product of this process was an implementable mental health research agenda, which is presented and discussed.

Defining the contribution of AMP-activated protein kinase (AMPK) and protein kinase C (PKC) in regulation of glucose uptake by metformin in skeletal muscle cells.

The importance of AMP-activated protein kinase (AMPK) and protein kinase C (PKC) as effectors of metformin (Met) action on glucose uptake (GU) in skeletal muscle cells was investigated. GU in L6 myotubes was stimulated 2-fold following 16 h of Met treatment and acutely enhanced by insulin in an additive fashion. Insulin-stimulated GU was sensitive to PI3K inhibition, whereas that induced by Met was not. Met and its related biguanide, phenformin, stimulated AMPK activation/phosphorylation to a level comparable with that induced by the AMPK activator, 5-amino-1-ß-d-ribofuranosyl-imidazole-4-carboxamide (AICAR). However, the increase in GU elicited by AICAR was significantly lower than that induced by either biguanide. Expression of a constitutively active AMPK mimicked the effects of AICAR on GU, whereas a dominant interfering AMPK or shRNA silencing of AMPK prevented AICAR-stimulated GU and Met-induced AMPK signaling but only repressed biguanide-stimulated GU by ∼20%. Consistent with this, analysis of GU in muscle cells from α1(-/-)/α2(-/-) AMPK-deficient mice revealed a significant retention of Met-stimulated GU, being reduced by ∼35% compared with that of wild type cells. Atypical PKCs (aPKCs) have been implicated in Met-stimulated GU, and in line with this, Met and phenformin induced activation/phosphorylation of aPKC in L6 myotubes. However, although cellular depletion of aPKC (>90%) led to loss in biguanide-induced aPKC phosphorylation, it had no effect on Met-stimulated GU, whereas inhibitors targeting novel/conventional PKCs caused a significant reduction in biguanide-induced GU. Our findings indicate that although Met activates AMPK, a significant component of Met-stimulated GU in muscle cells is mediated via an AMPK-independent mechanism that involves novel/conventional PKCs.

Chronic effects of palmitate overload on nutrient-induced insulin secretion and autocrine signalling in pancreatic MIN6 beta cells.

BACKGROUND: Sustained exposure of pancreatic ß cells to an increase in saturated fatty acids induces pleiotropic effects on ß-cell function, including a reduction in stimulus-induced insulin secretion. The objective of this study was to investigate the effects of chronic over supply of palmitate upon glucose- and amino acid-stimulated insulin secretion (GSIS and AASIS, respectively) and autocrine-dependent insulin signalling with particular focus on the importance of ceramide, ERK and CaMKII signalling. PRINCIPAL FINDINGS: GSIS and AASIS were both stimulated by >7-fold resulting in autocrine-dependent activation of protein kinase B (PKB, also known as Akt). Insulin release was dependent upon nutrient-induced activation of calcium/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinase (ERK) as their pharmacological inhibition suppressed GSIS/AASIS significantly. Chronic (48 h, 0.4 mM) palmitate treatment blunted glucose/AA-induced activation of CaMKII and ERK and caused a concomitant reduction (~75%) in GSIS/AASIS and autocrine-dependent activation of PKB. This inhibition could not be attributed to enhanced mitochondrial fatty acid uptake/oxidation or ceramide synthesis, which were unaffected by palmitate. In contrast, diacylglycerol synthesis was elevated suggesting increased palmitate esterification rather than oxidation may contribute to impaired stimulus-secretion coupling. Consistent with this, 2-bromopalmitate, a non-oxidisable palmitate analogue, inhibited GSIS as effectively as palmitate. CONCLUSIONS: Our results exclude changes in ceramide content or mitochondrial fatty acid handling as factors initiating palmitate-induced defects in insulin release from MIN6 ß cells, but suggest that reduced CaMKII and ERK activation associated with palmitate overload may contribute to impaired stimulus-induced insulin secretion.

Incidence and US costs of corticosteroid-associated adverse events: a systematic literature review.

OBJECTIVE: The objective of this systematic literature review was to evaluate the incidences and risks for adverse events (AEs) associated with oral and parenteral corticosteroids. An assessment was performed to estimate the costs of such AEs. METHODS: A systematic review of literature published from 2007 to 2009 was conducted to identify the incidence rates and risk ratios of corticosteroid-related AEs. The review protocol was developed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The literature search was expanded to include additional search terms for psychiatric conditions, infections, and peptic ulcers. Costs obtained from a separate narrative literature review were applied to AEs likely to affect third-party payers in the United States. RESULTS: A total of 357 publications were identified from the primary (n = 323) and secondary (n = 34) searches. Of these, 310 were excluded because they did not evaluate AEs related to corticosteroids, were an excluded publication type, or for other reasons. A final list of 47 studies were used for data extraction. Across patient populations, the most frequently reported corticosteroid-associated AEs were psychiatric events, infections, gastric conditions, and fractures. Corticosteroid-associated AEs reported to occur at an incidence >30% were sleep disturbances, lipodystrophy, adrenal suppression, metabolic syndrome, weight gain, and hypertension. Vertebral fractures were reported at an incidence of 21% to 30%. Dose-response relationships were documented for fractures, acute myocardial infarction, hypertension, and peptic ulcer. The costs of managing AEs that may occur with corticosteroids can be substantial. The literature reported 1-year per-patient costs of up to $26,471.80 for nonfatal myocardial infarction, and per-event costs as high as $18,357.90 for fracture. The findings from the present review should be interpreted cautiously due to several limitations, including the retrospective design of most of the studies identified, risk for confounding due to underlying disease activity or patient population, and the relatively small number of studies that reported each AE association. As this cost analysis was preliminary, a comprehensive pharmacoeconomic analysis should be undertaken to confirm the findings. CONCLUSION: Based on the findings from this review, systemic corticosteroids are a common cause of AEs that may be costly to payers.

The Childhood Asthma Control Test: retrospective determination and clinical validation of a cut point to identify children with very poorly controlled asthma.

BACKGROUND: The Childhood Asthma Control Test (C-ACT) has demonstrated validity in classifying children aged 4 to 11 years as having either "well-controlled" or "not well-controlled" asthma. However, new asthma management guidelines distinguish 3 levels of asthma control. OBJECTIVE: We sought to determine a second cut point on the C-ACT to identify children with "very poorly controlled" asthma. METHODS: Binomial logistic regression was performed on data from 671 children. The specialist's rating of control was the criterion measure. Specialists' severity ratings, specialists' assessment of therapy, and FEV(1) percent predicted were used to assess the clinical validity of the cut point. RESULTS: A cut point of 12 was selected because it correctly classified the highest percentage of participants (66.3%) as having "very poorly controlled" (vs "not well controlled") asthma and demonstrated high specificity (89.8%) and moderate positive predictive value (69.1%). Children scoring 12 or less versus 13 to 19 had lower mean FEV(1) percent predicted (79.8% vs 92.6%, P = .0002) and were more frequently stepped up in therapy (72.9% vs 53.6%, P = .0131) and rated as having severe asthma (13.6% vs 4.5%, P = .0005). One month later, significant differences in C-ACT scores and lung function between these 2 groups persisted. The mean C-ACT score of participants classified as "very poorly controlled" was significantly lower than that of participants classified as "not well-controlled" (17.2 vs 20.3, respectively; P = .0001). CONCLUSION: A second cut point of 12 or less on the C-ACT identifies children with the lowest level of control, who are at risk for poorer outcomes, and is conceptually consistent with the classification of "very poorly controlled" asthma adopted by asthma management guidelines.

Economic efficiency of genetic screening to inform the use of abacavir sulfate in the treatment of HIV.

BACKGROUND: Abacavir sulfate (abacavir) is associated with a hypersensitivity reaction (HSR) that affects 5-8% of patients. While serious complications are rare, failure to identify it, or abacavir re-challenge following HSR, can be fatal. Genetic screening for HLA-B*5701 can identify patients who are likely to experience an HSR and reduces the incidence of the reaction. OBJECTIVE: We assessed the intrinsic and practical value, from the US healthcare system perspective, of prospective HLA-B*5701 screening among a population of antiretroviral-naive patients without elevated risk factors for cardiovascular disease, plasma HIV RNA >100,000 copies/mL, or pre-existing renal insufficiency. METHODS: Two approaches were used to evaluate the costs and benefits of prospective screening. First, the efficiency of HLA-B*5701 screening compared with no screening prior to abacavir initiation (intrinsic value of screening) was evaluated using a 60-day decision-tree model. Next, the practical value of screening was assessed using a lifetime discrete-event simulation model that compared HLA-B*5701 screening prior to abacavir use versus initiation with a tenofovir-containing regimen. Screening-effectiveness parameters were taken from an open-label trial that incorporated screening prior to abacavir initiation and other published studies. Treatment efficacy was derived from clinical trials. Modelling assumptions, costs ($US, year 2007 values) and other parameters were derived from published sources, primary data analysis and expert opinion. Multiple one-way sensitivity and scenario analyses were performed to assess parameter uncertainty. The primary outcome measure for the short-term screening versus no screening analysis was cost per patient. For the long-term analysis, outcomes were presented as QALYs. Costs and effects were discounted at 3% per year. RESULTS: Over the first 60 days of treatment, prospective screening prior to abacavir initiation cost an additional $US17 per patient and avoided 537 HSRs per 10,000 patients. The per-patient cost of screening was sensitive to the cost of the genetic test, HSR costs and screening performance. In the lifetime model, screening-informed abacavir use was more effective and less costly than initiation with a tenofovir-containing regimen in the base case and in sensitivity analyses. CONCLUSIONS: Our results suggest that prospective HLA-B*5701 screening prior to abacavir initiation produces cost savings and should become a standard component of HIV care.

A study of HIV provider attitudes toward HLA-B 5701 testing in the United States.

Screening for HLA-B 5701 reduces the risk of developing an abacavir hypersensitivity reaction (ABC HSR) and is recommended in all patients before initiating highly active antiretroviral therapy (HAART) with abacavir. Between September 2007 and March 2008 we conducted a study of the attitudes and practice patterns of HIV providers in the United States to identify barriers to HLA-B 5701 testing in clinical practice. Study participants who completed an educational program could receive HLA-B 5701 test kits for use in their clinical practice. Surveys were administered before and after the educational program. A total of 477 HIV providers registered to participate in the survey, and 134 providers tested a total of 874 HIV-infected subjects, of which 6% (49/874) were HLA-B 5701 positive. Of 433 providers who completed the preeducation survey, 97% indicated that the test provided clinical value and 77% anticipated barriers to testing, with cost/reimbursement the most frequently cited. Among 202 providers who completed the posteducation survey, perceptions of the test's value remained largely unchanged while the proportion of providers who anticipated or encountered barriers to testing decreased. Of providers who used HLA-B 5701 test kits, 86% (115/134) found it "very easy" or "easy" to obtain test results, 95% (127/134) found it "very easy" or "easy" to interpret results, and 89% (119/134) indicated that they planned to continue HLA-B 5701 testing after the study. The results of this study suggest that HLA-B 5701 testing is easy to use in clinical practice and is a valuable tool to help reduce the risk of developing ABC HSR.

The minimally important difference of the Asthma Control Test.

BACKGROUND: The Asthma Control Test (ACT) has been well validated, but a minimally important difference (MID) has not been established. OBJECTIVE: We sought to identify an MID for the ACT. METHODS: Data come from 4 independent samples of adult asthmatic patients. Distributional methods for determining the MID included 0.5 SD, 1 SEM, and 2 SEM. Anchor-based methods assessed the relationship of differences in ACT scores to (1) self-reported asthma severity, (2) asthma episode frequency in the past 4 weeks, (3) physician ratings of asthma control, (4) physician recommendation of a change in therapy, (5) FEV(1), (6) the risk over the next 12 months of excess short-acting beta-agonist use and exacerbations, and (7) patient-defined changes in asthma course over 3 months. RESULTS: Four thousand one hundred eighteen patients completed the ACT. The 0.5 SD criterion for MID ranged from 2.03 to 2.45 points (mean, 2.2 points). The 1 SEM criterion ranged from 1.77 to 2.05 points (mean, 1.88 points), and the 2 SEM criterion ranged from 3.55 to 4.10 points (mean, 3.75 points). Differences in mean ACT scores across patient groups differing on criterion measures ranged from 1.06 to 5.28 points (mean, 3.1 points). Predictive analyses showed that a difference of 3 points on the ACT was associated with a subsequent 76% increased risk (95% CI, 73% to 79%) of excess short-acting beta-agonist use and a 33% increased risk (95% CI, 31% to 35%) of exacerbations. CONCLUSION: The data support an MID for the ACT of 3 points.

Benefits, risk, and uncertainty: preferences of antiretroviral-naïve African Americans for HIV treatments.

While African Americans in the United States are disproportionately affected by HIV, they are less likely to take antiretroviral therapies. Different first-line antiretroviral therapies are associated with short-term and long-term adverse event (AE) risks. We estimated the willingness of antiretroviral-naïve, HIV-positive African Americans to accept risks of acute AEs with known outcomes and long-term AEs with uncertain outcomes in exchange for virologic suppression. We estimated the relative importance of short-term and long-term AE risks. Two hundred thirty-five subjects were recruited through eight clinics in the United States. One hundred fifty-eight subjects met study inclusion criteria. One hundred fifty-three subjects completed a series of choice-format conjoint trade-off tasks. In each task, subjects were asked to choose between two hypothetical treatments with varying levels of virologic failure, risks of hypersensitivity reaction, decreases in bone mineral density (BMD), and renal impairment, and outcome uncertainty associated with the risks of decreased BMD and renal impairment. Attributes were expressed as probabilities of occurrence. We calculated the relative importance of each AE and the level of risk subjects would accept to reduce the risk of virologic failure. Subjects indicated that short-term AEs with relatively certain outcomes are preferred to long-term AEs with uncertain outcomes. Subjects were strongly averse to the risk of decreased BMD that could not be treated successfully or when the outcome was uncertain and to the risk of renal impairment that could not be treated successfully. Subjects were willing to accept increased risks of AEs in exchange for lower risk of virologic failure.

Modulating serine palmitoyl transferase (SPT) expression and activity unveils a crucial role in lipid-induced insulin resistance in rat skeletal muscle cells.

Saturated fatty acids, such as palmitate, promote accumulation of ceramide, which impairs activation and signalling of PKB (protein kinase B; also known as Akt) to important end points such as glucose transport. SPT (serine palmitoyl transferase) is a key enzyme regulating ceramide synthesis from palmitate and represents a potential molecular target in curbing lipid-induced insulin resistance. In the present study we explore the effects of palmitate upon insulin action in L6 muscle cells in which SPT expression/activity has been decreased by shRNA (small-hairpin RNA) or sustained incubation with myriocin, an SPT inhibitor. Incubation of L6 myotubes with palmitate (for 16 h) increases intramyocellular ceramide and reduces insulin-stimulated PKB activation and glucose uptake. PKB inhibition was not associated with impaired IRS (insulin receptor substrate) signalling and was ameliorated by short-term treatment with myriocin. Silencing SPT expression (approximately 90%) by shRNA or chronic cell incubation with myriocin (for 7 days) markedly suppressed SPT activity and palmitate-driven ceramide synthesis; however, challenging these muscle cells with palmitate still inhibited the hormonal activation of PKB. This inhibition was associated with reduced IRS1/p85-PI3K (phosphoinositide 3-kinase) coupling that arises from diverting palmitate towards greater DAG (diacylglycerol) synthesis, which elevates IRS1 serine phosphorylation via activation of DAG-sensitive PKCs (protein kinase Cs). Treatment of SPT-shRNA cells or those treated chronically with myriocin with PKC inhibitors antagonized palmitate-induced loss in insulin signalling. The findings of the present study indicate that SPT plays a crucial role in desensitizing muscle cells to insulin in response to incubation with palmitate. While short-term inhibition of SPT ameliorates palmitate/ceramide-induced insulin resistance, sustained loss/reduction in SPT expression/activity promotes greater partitioning of palmitate towards DAG synthesis, which impacts negatively upon IRS1-directed insulin signalling.

Estado epiléptico y encefalopatía por Shigella flexneri: reporte de un caso / Status epilepticus and encephalopathy caused by Shigelle fIexneri: case report

Es reconocido que la shigellosis produce una variedad de complicaciones intestinales y extraintestinales, siendo la encefalopatía y las crisis epilépticas manifestaciones frecuentes del compromiso cerebral. Estas manifestaciones pueden anteceder la aparición de diarrea disentérica. Se presenta a continuación un caso inusual de shigellosis en un paciente de 2 años que presentó encefalopatia y estado epiléptico febril aislándose Shigella flexneri del coprocultivo. Esta condición se presentó en ausencia de causas metabólicas o intestinales que explicaran el cuadro clinico.Conclusión: La encefalopatía por Shigella ha de considerarse en el diagnóstico diferencial de todo paciente que acude a emergencia con cuadro de diarrea y crisis epilépticas febriles. El cuadro neurológico puede anteceder a las manifestaciones gastrointestinales y sistémicas. La presencia de encefalopatía prolongada y estado epiléptico son hallazgos anormales que sugieren una forma severa de shigellosis y potencialmente letal.

It is recognized that shigellosis produces a wide range of intestinal and extra-intestinal complications, being seizures and encephalopathy frequent neurologic symptoms. These symptoms may appear prior to dysenteric diarrhea. An unusual case of shigellosis is reported of a two-year-old patient who presented with febril e status epilepticus and encephalopathy and who had Shigella flexneri in his stool. He presented no other metabolic or intestinal disturbances to explain his symptoms. Conclusion: Shigella-induced encephalopathy has to be considered in the differential diagnosis of patients who present to the emergency room with diarrhea, and febrile seizures. Neurologic symptoms may appear before de onset of dysentery. Asevere and potentially lethal form of shigellosis must be considered in patients with prolonged encephalopathy and status epilepticus.