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Background: Arterial hemodynamic parameters derived from reservoir-excess pressure analysis exhibit prognostic utility. Reservoir-excess pressure analysis may provide useful information about an influence of altered hemodynamics on target organ such as the kidneys. We determined whether the parameters derived from the reservoir-excess pressure analysis were associated with the reduction in estimated glomerular filtration rate in 542 older adults (69.4±7.9 years, 194 females) at baseline and after 3 years. Methods: Reservoir-excess pressure parameters, including reservoir pressure integral, excess pressure integral, systolic, and diastolic rate constants, were obtained by radial artery tonometry. Results: After 3 years, and in a group of 94 individuals (72.4±7.6 years, 26 females), there was an estimated glomerular filtration rate reduction of >5% per year (median reduction of 20.5% over 3 years). A multivariable logistic regression analysis revealed that higher baseline reservoir pressure integral was independently associated with a smaller reduction in estimated glomerular filtration rate after accounting for conventional cardiovascular risk factors and study centers (odds ratio: 0.660 [95% CIs, 0.494–0.883]; P =0.005). The association remained unchanged after further adjustments for potential confounders and baseline renal function (odds ratio: 0.528 [95% CIs, 0.351–0.794]; P =0.002). No other reservoir-excess pressure parameters exhibited associations with the reduction in renal function. Conclusions: This study demonstrates that baseline reservoir pressure integral was associated with the decline in renal function in older adults at 3-year follow-up, independently of conventional cardiovascular risk factors. This suggests that reservoir pressure integral may play a role in the functional decline of the kidneys.

The enterobacterial common antigen (ECA), a three-sugar repeat unit polysaccharide produced by Enterobacteriaceae family members, impacts bacterial outer membrane permeability, and its biosynthesis affects the glycan landscape of the organism. ECA synthesis impacts the production of other polysaccharides by reducing the availability of shared substrates, the most notable of which is the 55-carbon polyisoprenoid bactoprenyl phosphate (BP), which serves as a carrier for the production of numerous bacterial glycans including ECA, peptidoglycan, O-antigen, and more. Here, using a combination of in vitro enzymatic synthesis and liquid chromatography-mass spectrometry (LC-MS) analysis of bacterial lysates, we provide biochemical evidence for the effect on endogenous polyisoprenoid pools from cell culture that arises from glycan pathway disruption. In this work, we have cloned and expressed each gene involved in ECA repeat unit biosynthesis and reconstituted the pathway in vitro, providing LC-MS characterized standards for the investigation of cellular glycan-linked intermediates and BP. We then generated ECA deficient mutants in genes associated with production of the polysaccharide, which we suspected would accumulate materials identical to our standards. We found that indeed accumulated products from these cells were indistinguishable from our enzymatically prepared standards, and moreover we observed a concomitant decrease in cellular BP levels with each mutant. This work provides the first direct biochemical evidence for the sequestration of BP upon the genetic disruption of glycan biosynthesis pathways in bacteria. This work also provides methods for the direct assessment of both the ECA glycan, and a new understanding of the dynamic interdependence of the bacterial polysaccharide repertoire.

The protective surfaces of bacteria are comprised of polysaccharides and are involved in host invasion and colonization, host immune system evasion, as well as antibacterial resistance. A major barrier to our fundamental understanding of these complex surface polysaccharides lies in the tremendous diversity in glycan composition among bacterial species. The polyisoprenoid bactoprenyl phosphate (or undecaprenyl phosphate) is an essential lipid carrier necessary for early stages of glycopolymer assembly. Because of the ubiquity of bactoprenyl phosphate in these critical processes, molecular probes appended to this lipid carrier simplify identification of enzymatic roles during polysaccharide bioassembly. A limited number of these probes exist in the literature or have been assessed with such pathways, and the limits of their use are not currently known. Herein, we devise an efficient method for producing fluorescently modified bactoprenyl probes. We further expand our previous efforts utilizing 2-nitrileaniline, and additionally prepare nitrobenzoxadizol tagged bactoprenyl phosphate for the first time. We then assess enzyme promiscuity of these two probes utilizing four well characterized initiating phosphoglycosyltransferases: CPS2E (Streptococcus pneumoniae), WbaP (Salmonella enterica), WecA (Escherichia coli) and WecP (Aeromonas hydrophilia). Both probes serve as substrates for these enzymes and could be readily used to investigate a wide range of bacterial glycoassembly pathways. Interestingly, we have also identified unique solubility requirements for the nitrobenzoxadizol moiety for efficient enzymatic utilization that was not observed for the 2-nitrileaniline.

KEY POINTS The vasodilatory response to reactive hyperaemia is impaired with advancing age, but it is unclear whether this is because of an altered wall shear rate (WSR) stimulus or an altered flow-mediated dilatation (FMD) response. Using new technology that allows detailed WSR measurement, we assessed the WSR-FMD response in healthy older people. Our data show that older people have a markedly altered and diminished WSR response to reactive hyperaemia compared to young people, but reduced WSR alone does not fully explain reduced FMD. In young people, WSR appears to be coupled to FMD but, by age ∼65 years, the arterial vasodilatory response has begun to uncouple from the WSR stimulus. These findings point to the importance and utility of comprehensively characterizing the WSR-FMD response when using reactive hyperaemia to assess vascular function, as well as giving new insight into the age-related alteration in vascular function. ABSTRACT The vasodilatory response to reactive hyperaemia is impaired with age, but it is unknown whether this is because of an altered wall shear rate (WSR) stimulus or an altered flow-mediated dilatation (FMD) response to the WSR stimulus. Inherent difficulties in measuring blood flow velocity close to the arterial wall have prevented detailed assessment of the WSR-FMD response. Using an enhanced multigate spectral Doppler ultrasound system (ultrasound advanced open platform), we aimed to produce new data on the WSR-FMD relationship in healthy older adults. Sixty healthy people, comprising 28 young (27.5 ± 5.5 years) and 32 older (64.9 ± 3.7 years) individuals, underwent FMD assessment. Raw data were post-processed using custom-designed software to obtain WSR and diameter parameters. The data revealed that older people have a much altered and diminished WSR response to reactive hyperaemia compared to younger people [e.g. WSR peak: 622 (571-673) vs. 443 (396-491) 1/s in young and older respectively; P

Pancreatic ductal adenocarcinoma (PDAC) is characterized by KRAS- and autophagy-dependent tumorigenic growth. We determined the role of mutationally activated KRAS, found in ~95% of PDAC, in supporting autophagy. Surprisingly, acute KRAS suppression was associated with increased autophagic flux. Pharmacologic inhibition of ERK MAPK phenocopied the genetic silencing of KRAS and increased autophagic flux. We speculated that the loss of ERK-driven metabolic processes may induce compensatory mechanisms to increase autophagy. We then addressed whether ERK inhibition increased PDAC dependence on autophagy. Supporting this possibility, we found that cotreatment with the autophagy inhibitor chloroquine (CQ) synergistically enhanced ERK inhibitor-mediated anti-proliferative activity. Our findings, together with similar observations by others, provided the rationale for our initiation of Phase I/II clinical trials evaluating the combination of MEKi (binimetinib; NCT04132505) or ERKi (LY3214996; NCT04386057) with hydroxychloroquine (HCQ) in PDAC. Our ongoing studies are centered on developing additional combinations for targeting autophagy. First, we performed a CRISPR/Cas-9 mediated genetic loss-of-function screen in the presence of CQ to determine additional sensitizers as well as mediators of resistance to autophagy inhibition. Top sensitizers included multiple facilitators of the DNA damage response, mTOR pathway components, and genes involved in the upstream regulation of the autophagy pathway. Second, we determined that autophagic signaling is temporally regulated following RAS pathway inhibition and hypothesize that further dissection of this regulation will improve current anti-nutrient scavenging treatment strategies. We conclude that concurrent suppression of multiple metabolic processes, to block compensatory rebound activities, will be needed for effective PDAC treatment. Citation Format: Jonathan M. DeLiberty, Ryan Robb, Claire E. Gates, Noah L. Pieper, Runying Yang, Clint A. Stalnecker, Kirsten L. Bryant. Enhancing autophagy inhibition as a therapeutic strategy for pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B007.

The parameters derived from reservoir-excess pressure analysis have prognostic utility in several populations. However, evidence in type 2 diabetes (T2DM) remains scarce. We determined if these parameters were associated with T2DM and whether they would predict cardiovascular events in individuals with T2DM. We studied 306 people with T2DM with cardiovascular disease (CVD; DMCVD, 70.4±7.8 years), 348 people with T2DM but without CVD (diabetes mellitus, 67.7±8.4 years), and 178 people without T2DM or CVD (control group [CTRL], 67.2±8.9 years). Reservoir-excess pressure analysis–derived parameters, including reservoir pressure integral, peak reservoir pressure, excess pressure integral, systolic rate constant, and diastolic rate constant, were obtained by radial artery tonometry. Reservoir pressure integral was lower in DMCVD and diabetes mellitus than CTRL. Peak reservoir pressure was lower, and excess pressure integral was greater in DMCVD than diabetes mellitus and CTRL. Systolic rate constant was lower in a stepwise manner among groups (DMCVD< diabetes mellitus P

Introduction: Cerebral small vessel disease (SVD) is prevalent in the elderly population and is associated with increased risk of dementia, stroke and disability. Currently there are no clear targets or strategies for the treatment of cerebral SVD. We set out to identify modifiable vascular treatment targets. Patients and Methods: 112 participants with and without a history of CVD underwent macrovascular, microvascular and endothelial function tests and an MRI head scan. Results: Increased carotid intima media thickness and carotid-femoral pulse wave velocity were associated with cerebral WMH (β=1·1 p=0·001 and β=1·66, p

Few studies have investigated fathers’ roles in child care in Madagascar. This study explored the perceptions, attitudes, and practices regarding fathers’ involvement in child care using qualitative methods. Ten focus group discussions were conducted among parents of children aged 6–23 months; seven were among mothers, and three among fathers. In-depth semi-structured interviews (n = 8) were also conducted with key informants. Discussions and interviews were audio-recorded and the verbatim transcripts in Malagasy were translated into English. Data were analyzed using the thematic analysis approach. Provision of financial and material support as well as teaching and playing with the child were the main perceived roles of fathers. In practice, fathers spent their time alone with their children playing and holding them when the mother was unavailable. Busy schedules and separation due to work were major barriers to fathers’ involvement. Traditional gender roles for child care in which the mother is seen as primarily responsible for the child were salient across the data. Consequently, men involved in child care activities and their wives were often criticized by the community. Nevertheless, there was self-reported interest from both mothers and fathers in involving men more in child care. Interventions aimed to increase fathers’ involvement in child care may be more successful when they focus on shifting the community perceptions on the division of responsibilities between fathers and mothers.

Vascular endothelial cells lining the arteries are sensitive to wall shear stress (WSS) exerted by flowing blood. An important component of the pathophysiology of vascular diseases, WSS is commonly estimated by centerline ultrasound Doppler velocimetry (UDV). However, the accuracy of this method is uncertain. We have previously validated the use of a novel, ultrasound based, particle image velocimetry technique (echo PIV) to compute two-dimensional velocity vector fields, which can easily be converted into WSS data. We compared WSS data derived from UDV and echo PIV in the common carotid artery of 27 healthy participants. Compared with echo PIV, time-averaged WSS was lower using UDV (28 ± 35%). Echo PIV revealed that this was due to considerable spatio-temporal variation in the flow velocity profile, contrary to the assumption that flow is steady and the velocity profile is parabolic throughout the cardiac cycle. The largest WSS underestimation by UDV was found during peak-systole (118 ± 16%) and the smallest during mid-diastole (4.3 ± 46%). The UDV method underestimated WSS for the accelerating and decelerating systolic measurements (68 ± 30% and 24 ± 51%) whereas WSS was overestimated for end-diastolic measurements (−44 ± 55%). Our data show that UDV estimates of WSS provided limited and largely inaccurate information about WSS and that the complex spatio-temporal flow patterns do not fit well with traditional assumptions about blood flow in arteries. Echo PIV derived WSS provides detailed information about this important but poorly understood stimulus that influences vascular endothelial pathophysiology.

Carol, a teen forced into foster care, must learn how to navigate the path/road to postsecondary education. This case follows Carol’s matriculation through high school and the challenges she faces while trying to achieve her dream of going to college. Several challenges Carol encounters are discussed, such as her lack of higher education awareness, her need for tuition assistance, and aging out of foster care. The purpose of this case is to encourage future leaders to enhance opportunities for vulnerable populations, thus, it should be useful for students in education policy, educational administration, and higher education leadership.

Purpose Repeated cycles of endothelial ischemia–reperfusion injury and the resulting respiratory burst contribute to the irreversible pathophysiology of vascular diseases, and yet, the effects of ischemia reperfusion on vascular function, oxidative stress, and nitric oxide (NO) bioavailability have not been assessed simultaneously. Therefore, this study sought to examine the effects of prolonged forearm occlusion and subsequent reperfusion on NO-dependent brachial artery endothelial function. Methods Flow-mediated dilatation was measured at baseline and 15, 30, and 45 min after 20-min forearm occlusion in 14 healthy, but physically inactive middle-aged men (53.7 ± 1.2 years, BMI: 28.1 ± 0.1 kg m−2). Venous blood samples collected from the occluded arm were analyzed for NO metabolites and markers of oxidative stress. Results FMD was significantly depressed after the prolonged occlusion compared to baseline, with a significant reduction 15-min post-occlusion (6.6 ± 0.7 to 2.9 ± 0.4%, p

Wall shear rate (WSR) is an important stimulus for the brachial artery flow-mediated dilation (FMD) response. However, WSR estimation near the arterial wall by conventional Doppler is inherently difficult. To overcome this limitation, we utilized multigate Doppler to accurately determine the WSR stimulus near the vessel wall simultaneously with the FMD response using an integrated FMD system [Ultrasound Advanced Open Platform (ULA-OP)]. Using the system, we aimed to perform a detailed analysis of WSR-FMD response and establish novel WSR parameters in a healthy young population. Data from 33 young healthy individuals (27.5 ± 4.9 yr, 19 females) were analyzed. FMD was assessed with reactive hyperemia using ULA-OP. All acquired raw data were postprocessed using custom-designed software to obtain WSR and diameter parameters. The acquired velocity data revealed that nonparabolic flow profiles within the cardiac cycle and under different flow states, with heterogeneity between participants. We also identified seven WSR magnitude and four WSR time-course parameters. Among them, WSR area under the curve until its return to baseline was the strongest predictor of the absolute ( R2 = 0.25) and percent ( R2 = 0.31) diameter changes in response to reactive hyperemia. For the first time, we identified mono- and biphasic WSR stimulus patterns within our cohort that produced different magnitudes of FMD response [absolute diameter change: 0.24 ± 0.10 mm (monophasic) vs. 0.17 ± 0.09 mm (biphasic), P < 0.05]. We concluded that accurate and detailed measurement of the WSR stimulus is important to comprehensively understand the FMD response and that this advance in current FMD technology could be important to better understand vascular physiology and pathology. NEW & NOTEWORTHY An estimation of wall shear rate (WSR) near the arterial wall by conventional Doppler ultrasound is inherently difficult. Using a recently developed integrated flow-mediated dilation ultrasound system, we were able to accurately estimate WSR near the wall and identified a number of novel WSR variables that may prove to be useful in the measurement of endothelial function, an important biomarker of vascular physiology and disease.

Introduction: Inaccurate determination of arterial path-length by surface-distance (SD) measurement is an inherent source of error in calculating carotid-femoral pulse wave velocity (CFPWV). A recent development in calculating arterial path-length by a simple distance formula (DF) for CFPWV has been shown to not only remove intercentre measurement variability but also strengthen the association between CFPWV and traditional cardiovascular risk factors [1]. We determined whether the association of macro- and microvascular alterations with CFPWV derived from the distance formula (CFPWV-DF) would be stronger than that with CFPWV derived from the surface-distance measurement (CFPWV-SD). Methods: CFPWV-DF and CFPWV-SD were obtained from 489 older adults (67.2 ± 8.8 yrs, 154 F, 244 CVD). Macrovascular [carotid lumen diameter (LD), carotid inter-adventitial diameter (IAD), carotid intima-media thickness (IMT), carotid total plaque area, and ankle-brachial pressure index] and microvascular [reactive hyperaemia index and urinary albumin-creatinine ratio (UACR)] parameters were also obtained. Results: CFPWV-DF was significantly lower than CFPWV-SD (9.27 ± 2.38 vs 9.88 ± 2.55 m/s, p < 0.001), which resulted from a longer arterial path-length estimated by SD than DF (495.4 ± 44.8 vs 465.3 ± 20.6 mm, p < 0.001). The significant associations observed between CFPWV-SD and LD (r = 0.264), IAD (r = 0.303), and IMT (r = 0.165) were similarly observed between CFPWV-DF and LD (r = 0.253), IAD (r = 0.303), and IMT (r = 0.183, all p < 0.001). This was also the case with UACR (r = 0.163 and r = 0.141, both p = 0.001). Other parameters did not show any association in either CFPWV. Conclusion: The association of macro- and microvascular alterations with CFPWV-DF was not stronger than that with CFPWV-SD, suggesting that arterial path-length determination methods may not influence interactions between vascular biomarkers and CFPWV.

Aims/hypothesis Although cardiovascular disease is the biggest cause of death in people with diabetes, microvascular complications have a significant impact on quality of life and financial burden of the disease. Little is known about the progression of microvascular dysfunction in the early stages of type 2 diabetes before the occurrence of clinically apparent complications. We aimed to explore the determinants of endothelial-dependent and -independent microvascular function progression over a 3 year period, in people with and without both diabetes and few clinical microvascular complications. Methods Demographics were collected in 154 participants with type 2 diabetes and in a further 99 participants without type 2 diabetes. Skin microvascular endothelium-dependent response to iontophoresis of acetylcholine and endothelium-independent responses to sodium nitroprusside were measured using laser Doppler fluximetry. All assessments were repeated 3 years later. Results People with type 2 diabetes had impaired endothelial-dependent microvascular response compared with those without (AUC 93.9 [95% CI 88.1, 99.4] vs 111.9 [102.3, 121.4] arbitrary units [AU] × min, p p = 0.002). Mean microvascular function declined over 3 years in both groups to a similar degree (pinteraction 0.74 for response to acetylcholine and 0.69 for response to sodium nitroprusside). In those with diabetes, use of sulfonylurea was associated with greater decline (p = 0.022 after adjustment for co-prescriptions, change in HbA1c and weight), whereas improving glycaemic control was associated with less decline of endothelial-dependent microvascular function (p = 0.03). Otherwise, the determinants of microvascular decline were similar in those with and without diabetes. The principal determinant of change in microvascular function in the whole population was weight change over 3 years, such that those that lost ≥5% weight had very little decline in either endothelial-dependent or -independent function compared with those that were weight stable, whereas those who gained weight had a greater decline in function (change in endothelial-dependent function was 1.2 [95% CI −13.2, 15.7] AU × min in those who lost weight; −15.8 [−10.5, −21.0] AU × min in those with stable weight; and −37.8 [−19.4, −56.2] AU × min in those with weight gain; ptrend Conclusions/interpretation Over 3 years, physiological change in weight was the greatest predictor of change in microvascular function.

PURPOSE To provide updated recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. METHODS PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs published from August 1, 2014, through December 4, 2018. ASCO convened an Expert Panel to review the evidence and revise previous recommendations as needed. RESULTS The systematic review included 35 publications on VTE prophylaxis and treatment and 18 publications on VTE risk assessment. Two RCTs of direct oral anticoagulants (DOACs) for the treatment of VTE in patients with cancer reported that edoxaban and rivaroxaban are effective but are linked with a higher risk of bleeding compared with low-molecular-weight heparin (LMWH) in patients with GI and potentially genitourinary cancers. Two additional RCTs reported on DOACs for thromboprophylaxis in ambulatory patients with cancer at increased risk of VTE. RECOMMENDATIONS Changes to previous recommendations: Clinicians may offer thromboprophylaxis with apixaban, rivaroxaban, or LMWH to selected high-risk outpatients with cancer; rivaroxaban and edoxaban have been added as options for VTE treatment; patients with brain metastases are now addressed in the VTE treatment section; and the recommendation regarding long-term postoperative LMWH has been expanded. Re-affirmed recommendations: Most hospitalized patients with cancer and an acute medical condition require thromboprophylaxis throughout hospitalization. Thromboprophylaxis is not routinely recommended for all outpatients with cancer. Patients undergoing major cancer surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days. Patients with cancer should be periodically assessed for VTE risk, and oncology professionals should provide patient education about the signs and symptoms of VTE. Additional information is available at www.asco.org/supportive-care-guidelines .

Objectives: To examine physical activity (PA) levels, and how sociocultural factors, acculturation, self-efficacy and religion influence PA levels of Arab Muslim mothers of young children living in the United States. Design: Cross-sectional online survey. Participants and Setting: Arab Muslim mothers of young children (aged

Objectives The purpose of this paper is to describe the Black dentist workforce, the practice patterns of providers, and their contributions to oral health care for minority and underserved patients. Methods A national sample survey of underrepresented minority dentists was conducted in 2012 and received a 32.6 percent response rate for self-reported Black dentists. Data were weighted for selection and response bias to be nationally representative. Descriptive and multivariable statistics were computed to provide a workforce profile of Black dentists. National comparisons are provided from published data. Results Among all Black dentists (weighted n = 6,254), 76.6 percent self-identify as African-American, 13.2 percent as African, and 10.3 percent as Afro-Caribbean. The largest share of Black dentists are male, married, heterosexual, born in the United States and raised in a medium to large city. One third of Black dentists were the first in their family to graduate from college. Black dentists report higher average educational debt than all dental students, with graduates from International Dentist Programs having the greatest debt. Traditional practices (i.e., private practices) dominate, with 67.1 percent of Black dentists starting out in this setting and 73.5 percent currently in the setting. Black dentists care for a disproportionate share of Black patients, with an average patient mix that is 44.9 percent Black. Two in five Black dentists reported their patient pool is made up of more than 50 percent Black patients. Conclusions The underrepresentation for Black dentists is extraordinary, and the Black dentists that are in practice are shouldering a disproportionate share of dental care for minority and underserved communities.

Objectives The purpose of this article is to describe the American Indian/Alaska Native (AI/AN) dentist workforce, the general practice patterns of these providers, and their contributions to oral health care for AI/AN and underserved patients. Methods A national sample survey of underrepresented minority dentists was conducted in 2012 and received a 34 percent response rate for self-reported AI/AN dentists. Data were weighted for selection and response bias to be nationally representative. Descriptive and multivariable statistics were computed to provide a workforce profile. Comparisons to Census data and published information on dental students and dentists were used to examine practice patterns. Results The AI/AN dentist workforce (weighted n = 442) is very diverse with 55 reported individual tribal affiliations. Tribal heritage was provided by 95.7 percent of AI/AN dentists (n = 423), and of these, 93.9 percent (n = 400) reported an affiliation with only one tribe. The largest share of AI/AN dentists were born in the United States (98.2 percent, n = 434), married (75.6 percent, n = 333), and had dependent children under age 18 (52.0 percent, n = 222). Only 0.9 percent (n = 4) of AI/AN dentists spoke a traditional AI/AN language in patient care, while 10.6 percent (n = 46) were raised on tribal land or reservation. Initial practice in the Indian Health Service was reported by 15.8 percent of AI/AN dentists while 16.2 percent report currently practicing in a safety-net setting, and 42.0 percent report working in a practice that primarily serves underserved patients. Conclusions AI/AN dentists provide a disproportionate share of care for AI/AN populations, yet the number of AI/AN dentists would need to increase 7.4-fold in order to meet population parity.

The underrepresentation of Blacks, Hispanics or Latinos, and American Indians or Alaska Natives among dentists raises concerns about the diversity of the dental workforce, disparities in access to dental care and in oral health status, and social justice. We quantified the shortage of underrepresented minority dentists and examined these dentists’ practice patterns in relation to the characteristics of the communities they serve. The underrepresented minority dentist workforce is disproportionately smaller than, and unevenly distributed in relation to, minority populations in the United States. Members of minority groups represent larger shares of these dentists’ patient panels than of the populations in the communities where the dentists are located. Compared to counties with no underrepresented minority dentists, counties with one or more such dentists are more racially diverse and affluent but also have greater economic and social inequality. Current policy approaches to improve the diversity of the dental workforce are a critical first step, but more must be done to improve equity in dental health.

Background Data are limited on how feeding knowledge and practices relate to child undernutrition in the highlands of Madagascar. Objectives This study assessed maternal knowledge and practices of complementary feeding and their associations with anthropometrics of children aged 6–23 mo in the Vakinankaratra region of Madagascar. Methods Knowledge was assessed using WHO recommendations on child feeding, and WHO infant and young child feeding (IYCF) indicators were used to evaluate feeding practices. Child growth was measured as length-for-age, weight-for-age, and weight-for-length z-scores using the 2006 WHO growth standards. A z-score less than −2 was classified as child undernutrition. Logistic regression models were used to determine associations between independent variables and outcomes. Focus group discussions among mothers and in-depth interviews with key informants were conducted; barriers and facilitators of optimal feeding practices were identified using a thematic analysis approach. Results Maternal knowledge scores regarding child feeding averaged 6.4 of 11. Better knowledge scores were associated with higher odds of appropriate complementary feeding practices before and after covariate adjustments. The proportions of children achieving the minimum dietary diversity (35.8%), minimum acceptable diet (30.2%), and consuming meat, fish, and poultry (14.1%) were low. Only consumption of iron-rich foods was associated with lower odds of underweight (adjusted OR = 0.3; 95% CI: 0.1, 0.7; P, This study assessed linkages between maternal knowledge, complementary feeding practices, and child undernutrition in a highly agriculturally productive region in Madagascar.

OBJECTIVES: Complementary feeding practices in Madagascar are inadequate. The purpose of this study was to identify maternal barriers to and enablers of optimal child feeding practices in the Vakinankaratra region of Madagascar. METHODS: Seven focus group discussions with mothers (n = 46) who had a child aged 6–23 months and eight in-depth interviews were conducted with community health workers (6), a nurse (1), and a program field monitor (1) in Malagasy, the local language. Discussions were transcribed verbatim, then back-translated into English. The average length of the interviews was 50 minutes. The translated transcripts from the discussions and interviews were analyzed using NVivo v.12 and a thematic analysis approach was used. RESULTS: Poverty, lack of money, and limited food availability were mentioned by the mothers as obstacles to adequate complementary feeding practices. Lack of time because of work as well as heavy workload also were cited as problems. Mothers generally decide alone on what food to give to their infants, with little to no help from spouse or relatives. All mothers considered their children's health and giving them appropriate complementary foods as important. Another potential enabler was that mothers trust the community health workers and usually ask them for help and/or information on child feeding. The key informants confirmed all of the mothers’ responses. CONCLUSIONS: Interventions that aim to improve feeding practices in the Vakinankaratra region should address food insecurity and improve households’ income. Strengthening the local infrastructures with the community health workers appears to be important when aiming to reinforce appropriate feeding practices. FUNDING SOURCES: This study was funded by the Marilynn Thoma Chair in Human Sciences at Oklahoma State University.

OBJECTIVES: The Vakinankaratra region of Madagascar has the highest stunting rates of the country, yet it is one of most agriculturally productive regions. The purpose of this study was to assess maternal complementary feeding practices and their association with child growth. METHODS: Data from a cross-sectional study of 391 mothers and their infants aged 6–23 months were analyzed. The WHO infant and young child feeding (IYCF) indicators were used to assess complementary feeding practices. A questionnaire for collection of sociodemographic information and 24-hour dietary recall was translated and pre-tested before data collection. Child length and weight were converted to length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) using the 2006 WHO Growth Standards. Linear regression models were conducted while adjusting for survey design and confounding variables. RESULTS: Stunting (69.4%) and undernutrition (23.4%) rates were very high. The proportion of children achieving minimum dietary diversity (35.8%), minimum acceptable diet (30.2%) and consuming flesh foods (14.1%) were low. Higher dietary diversity score was associated with increased LAZ [β = 0.2, P

Produced as a tissue defence response to hypoxia and inflammation, growth differentiation factor-15 (GDF-15) is elevated in people receiving metformin treatment. To gain insight into the relationship of GDF-15 with metformin and major cardiovascular risk factors, we analysed the data from the SUMMIT cohort (n = 1438), a four-centre, nested, case-control study aimed at verifying whether biomarkers of atherosclerosis differ according to the presence of type 2 diabetes and cardiovascular disease. While in univariate analysis, major cardiovascular risk factors, with the exception of gender and cholesterol, increased similarly and linearly across GDF-15 quartiles, the independent variables associated with GDF-15, both in participants with and without diabetes, were age, plasma creatinine, N-terminal pro-brain natriuretic peptide, diuretic use, smoking exposure and glycated haemoglobin. In participants with diabetes, metformin treatment was associated with a 40% rise in GDF-15 level, which was independent of the other major factors, and largely explained their elevated GDF-15 levels. The relatively high GDF-15 bioavailability might partly explain the protective cardiovascular effects of metformin.

Flavonoid supplementation improves brachial artery flow-mediated dilation (FMD), but it is not known whether flavonoids protect against vascular dysfunction induced by ischemia-reperfusion (IR) injury and associated respiratory burst. In a randomized, double-blind, placebo-controlled, crossover study, we investigated whether 4 wk supplementation with freeze-dried Montmorency cherry (MC) attenuated suppression of FMD after IR induced by prolonged forearm occlusion. Twelve physically inactive overweight, middle-aged men (52.8 ± 5.8 yr, BMI: 28.1 ± 5.3 kg/m2) consumed MC (235 mg/day anthocyanins) or placebo capsules for 4 wk, with supplementation blocks separated by 4 wk washout. Before and after each supplementation block, FMD responses and plasma nitrate and nitrite ([[Formula: see text]]) concentrations were measured at baseline and 15, 30, and 45 min after prolonged (20 min) forearm occlusion. FMD response was significantly depressed by the prolonged occlusion ( P < 0.001). After a 45-min reperfusion, FMD was restored to baseline levels after MC (ΔFMD presupplementation: −30.5 ± 8.4%, postsupplementation: −0.6 ± 9.5%) but not placebo supplementation (ΔFMD presupplementation: −11.6 ± 10.6, postsupplementation: −25.4 ± 4.0%; condition × supplement interaction: P = 0.038). Plasma [[Formula: see text]] decreased after prolonged occlusion but recovered faster after MC compared with placebo (Δ45 min to baseline; MC: presupplementation: −15.3 ± 9.6, postsupplementation: −6.2 ± 8.1; Placebo: presupplementation: −16.3 ± 5.9, postsupplementation: −27.7 ± 11.1 nmol/l; condition × supplement × time interaction: P = 0.033). Plasma peroxiredoxin concentration ([Prx2]) was significantly higher after MC (presupplementation: 22.8 ± 1.4, postsupplementation: 28.0 ± 2.4 ng/ml, P = 0.029) but not after placebo supplementation (presupplementation: 22.1 ± 2.2, postsupplementation: 23.7 ± 1.5 ng/ml). In conclusion, 4 wk MC supplementation enhanced recovery of endothelium-dependent vasodilatation after IR, in parallel with faster recovery of plasma [[Formula: see text]], suggesting NO dependency. These protective effects seem to be related to increased plasma [Prx2], presumably conferring protection against the respiratory burst during reperfusion. NEW & NOTEWORTHY This is the first study to demonstrate that 4 wk of Montmorency cherry powder supplementation exerted protective effects on endothelium-dependent vasodilation after transient ischemia-reperfusion injury in overweight, physically inactive, nonmedicated, hypertensive middle-aged men. These effects seem to be due to increased nitric oxide availability, as evidenced by higher plasma nitrite concentration and peak arterial diameter during the flow-mediated dilation measurement. This may be a consequence of increased concentration of peroxiredoxin and other antioxidant systems and, hence, reduced reactive oxygen species exposure.

Most academic libraries offer numerous e-books alongside their print titles. Traditionally, print materials have been chosen by subject liaisons with input from departmental faculty, whereas e-books have been acquired en masse through large collection purchases, subscriptions, or PDA/DDA programs that include large numbers of discovery records. At Kraemer Family Library, the print budget is divided into subject areas using a formula that includes the number of students in a discipline, level of program (bachelor, master, or doctorate), number of faculty by discipline, and average cost of materials in a subject area. This budget breakdown is an attempt to balance the library’s collection so that it reflects the focus and emphasis of the curriculum being taught on campus. Beginning in 2012, the Kraemer Family Library at the University of Colorado Colorado Springs began participating in two PDA/DDA e-book programs. The library also began purchasing e-book packages that were either publisher or subject based. During this same time, the library continued to use a formula to allocate the library’s print budget. Because e-books were not purchased according to any allocation, and the library was beginning a process of weeding the print collection, an analysis of the effect of e-books on the overall collection was undertaken. The purpose of this analysis was to determine what metrics should be used to determine the impact of e-books on the overall collection and to analyze that data for overall impact on the collection.