Electronic health records (EHR) are becoming more common because of the federal EHR incentive programme, which is also promoting electronic health information exchange (HIE). To determine whether consumers' attitudes toward EHR and HIE are associated with experience with doctors using EHR, a nationwide random-digit-dial survey was conducted in December 2011. Of 1603 eligible people contacted, 1000 (63%) participated. Most believed EHR and HIE would improve healthcare quality (66% and 79%, respectively). Respondents whose doctor had an EHR were more likely to believe that these technologies would improve quality (for EHR, OR 2.3; for HIE, OR 1.7). However, experience with physicians using EHR was not associated with privacy concerns. Consumers whose physicians use EHR were more likely to believe that EHR and HIE will improve healthcare when compared to others. However, experience with a physician using an EHR had no relationship with privacy concerns.
Electronic health records; health information exchange; health information technology; privacy and security; public attitudes and perceptions
Alcohol tolerance is observed as a diminished response to a given dose as a function of repeated administrations of the drug. Research has consistently shown that heavier drinkers display reduced reactions to alcohol (i.e., tolerance) compared with lighter drinkers. However, the majority of this work has focused primarily on measures of motor performance, whereas the development of tolerance to alcohol’s impairing effects on cognitive processes, such as inhibitory mechanisms of behavioral control, remains relatively unexplored.
The purpose of the present study was to examine the relationship between drinking habits and the degree to which alcohol affects drinkers’ inhibitory control and motor coordination.
Fifty-two non-dependent drinkers reported their recent drinking patterns. Their inhibitory control and motor coordination were measured in response to placebo and 0.65 g/kg alcohol.
Alcohol significantly impaired inhibitory control and motor coordination compared with placebo. Moreover, greater quantity and frequency of recent consumption predicted less alcohol impairment of motor coordination. However, there was no relationship between recent drinking habits and the degree of impairment of inhibitory control.
These findings suggest that tolerance to the disinhibiting effects of alcohol might not readily develop as a result of recent, heavy drinking.
Alcohol; Tolerance; Inhibitory control; Motor coordination
There are several U.S. FDA-cleared molecular respiratory virus panels available today, each with advantages and disadvantages. This study compares four multiplex panels, the BioFire Diagnostics FilmArray RP (respiratory panel), the GenMark Dx eSensor RVP (respiratory viral panel), the Luminex xTAG RVPv1, and the Luminex xTAG RVP fast. Three hundred specimens (200 retrospective and 100 consecutive) were tested using all four platforms to determine performance characteristics. The overall sensitivity and specificity, respectively, and 95% confidence interval (CI; in parentheses) for each panel were as follows: FilmArray RP, 84.5% (79.2, 88.6) and 100% (96.2, 100); eSensor RVP, 98.3% (95.5, 99.5) and 99.2% (95.4, 100); xTAG RVPv1, 92.7% (88.5, 95.4) and 99.8% (96.0, 100); and xTAG RVP fast, 84.4% (78.5, 88.9) and 99.9% (96.1, 100). The sensitivity of each assay fluctuated by viral target, with the greatest discrepancies noted for adenovirus and influenza virus B detection. Hands-on time and time to result were recorded and ease of use was assessed to generate a complete profile of each assay.
Constructed wetland systems are used to reduce pollutants and pathogens in wastewater effluent, but comparatively little is known about pathogen transport through natural wetland habitats. Fecal protozoans, including Cryptosporidium parvum, Giardia lamblia, and Toxoplasma gondii, are waterborne pathogens of humans and animals, which are carried by surface waters from land-based sources into coastal waters. This study evaluated key factors of coastal wetlands for the reduction of protozoal parasites in surface waters using settling column and recirculating mesocosm tank experiments. Settling column experiments evaluated the effects of salinity, temperature, and water type (“pure” versus “environmental”) on the vertical settling velocities of C. parvum, G. lamblia, and T. gondii surrogates, with salinity and water type found to significantly affect settling of the parasites. The mesocosm tank experiments evaluated the effects of salinity, flow rate, and vegetation parameters on parasite and surrogate counts, with increased salinity and the presence of vegetation found to be significant factors for removal of parasites in a unidirectional transport wetland system. Overall, this study highlights the importance of water type, salinity, and vegetation parameters for pathogen transport within wetland systems, with implications for wetland management, restoration efforts, and coastal water quality.
Cyanobacteria (also called blue-green algae) are ubiquitous in aquatic environments. Some species produce potent toxins that can sicken or kill people, domestic animals, and wildlife. Dogs are particularly vulnerable to cyanotoxin poisoning because of their tendency to swim in and drink contaminated water during algal blooms or to ingestalgal mats.. Here, we summarize reports of suspected or confirmed canine cyanotoxin poisonings in the U.S. from three sources: (1) The Harmful Algal Bloom-related Illness Surveillance System (HABISS) of the National Center for Environmental Health (NCEH), Centers for Disease Control and Prevention (CDC); (2) Retrospective case files from a large, regional veterinary hospital in California; and (3) Publicly available scientific and medical manuscripts; written media; and web-based reports from pet owners, veterinarians, and other individuals. We identified 231 discreet cyanobacteria harmful algal bloom (cyanoHAB) events and 368 cases of cyanotoxinpoisoning associated with dogs throughout the U.S. between the late 1920s and 2012. The canine cyanotoxin poisoning events reviewed here likely represent a small fraction of cases that occur throughout the U.S. each year.
anatoxin; dog; canine; cyanotoxin; hepatotoxin; microcystin; neurotoxin poisoning; cyanobacteria; blue-green algae
Research has linked adolescent romantic and sexual activities to depressive symptoms. The current study examines whether such activities are uniquely linked to depressive symptoms versus symptoms of other disorders (including anxiety, externalizing, and eating disorders), and whether co-occurring symptoms more precisely account for the association between depressive symptoms and romantic involvement.
Early adolescent girls (N = 83; mean age = 13.45) participated in baseline and 1-year follow up data collection.
Romantic (i.e., dating and sexual) activities were longitudinally related to numerous types of symptoms. The association between depressive symptoms and romantic variables remained when considering co-occurring symptoms. Girls with more comorbid disorders reported more romantic activities.
Results suggest that the maladaptive consequences and precipitants of adolescent romantic activities extend beyond depression, but also imply that this association is not secondary to comorbid symptoms. Future work should clarify causal pathways.
adolescence; romantic involvement; sexual activity; depression; specificity
The S4 transmembrane segment in voltage-gated ion channels, a highly basic α helix, responds to changes in membrane potential and induces channel opening. Earlier work by others indicates that the S4 segment interacts with lipids in plasma membrane, but its mechanism is unclear. Working with synthetic tryptophan-labeled S4 peptides, we characterized binding of autonomous S4 to lipid membranes. The binding free energy (5.2 ± 0.2 kcal/mol) of the peptide-lipid interaction was estimated from the apparent dissociation constants, determined from the changes in anisotropy of tryptophan fluorescence induced by addition of lipid vesicles with 30 mol% phosphatidylglycerol. The results are in good agreement with the prediction based on the Wimley-White hydrophobicity scale for interfacial (IF) binding of an alpha-helical peptide to the lipid bilayer (6.98 kcal/mol). High salt inhibited the interaction, thus indicating that the peptide/membrane interaction has both electrostatic and non-electrostatic components. Furthermore, the synthetic S4 corresponding to the Shaker potassium channel was found to spontaneously penetrate into the negatively charged lipid membrane to a depth of about 9 Å. Our results revealed important biophysical parameters that influence the interaction of S4 with the membrane: they include fluidity, surface charge, and surface pressure of the membrane, and the α helicity and regular spacing of basic amino-acid residues in the S4 sequence.
Potassium channel; voltage sensor domain; S4; fluorescence spectroscopy; resonance energy transfer; small unilamellar vesicles
Using retrospective (n = 200) and prospective (n = 150) nasopharyngeal specimens, we evaluated the Nanosphere Verigene RV+ and the Focus Diagnostics Simplexa Flu A/B & RSV tests. Overall, RV+ demonstrated sensitivities and specificities of 96.6% and 100% for influenza A virus, 100% and 99.7% for influenza B virus, and 100% and 100% for respiratory syncytial virus (RSV), while the Simplexa test sensitivities and specificities were 82.8 and 99.7%, 76.2 and 100%, and 94.6 and 100%, respectively.
The risk of disease transmission from waterborne protozoa is often dependent on the origin (e.g., domestic animals versus wildlife), overall parasite load in contaminated waterways, and parasite genotype, with infections being linked to runoff or direct deposition of domestic animal and wildlife feces. Fecal samples collected from domestic animals and wildlife along the central California coast were screened to (i) compare the prevalence and associated risk factors for fecal shedding of Cryptosporidium and Giardia species parasites, (ii) evaluate the relative importance of animal host groups that contribute to pathogen loading in coastal ecosystems, and (iii) characterize zoonotic and host-specific genotypes. Overall, 6% of fecal samples tested during 2007 to 2010 were positive for Cryptosporidium oocysts and 15% were positive for Giardia cysts. Animal host group and age class were significantly associated with detection of Cryptosporidium and Giardia parasites in animal feces. Fecal loading analysis revealed that infected beef cattle potentially contribute the greatest parasite load relative to other host groups, followed by wild canids. Beef cattle, however, shed host-specific, minimally zoonotic Cryptosporidium and Giardia duodenalis genotypes, whereas wild canids shed potentially zoonotic genotypes, including G. duodenalis assemblages A and B. Given that the parasite genotypes detected in cattle were not zoonotic, the public health risk posed by protozoan parasite shedding in cattle feces may be lower than that posed by other animals, such as wild canids, that routinely shed zoonotic genotypes.
Pulsed-field gel electrophoresis (PFGE) was used to type 128 Streptococcus infantarius subsp. coli isolates from sea otters and mussels. Six SmaI PFGE groups were detected, with one predominant group representing 57% of the isolates collected over a wide geographic region. Several sea otter and mussel isolates were highly related, suggesting that an environmental infection source is possible.
A two and a half year old spayed female Miniature Australian Shepherd presented to a Montana veterinary clinic with acute onset of anorexia, vomiting and depression. Two days prior, the dog was exposed to an algal bloom in a community lake. Within h, the animal became lethargic and anorexic, and progressed to severe depression and vomiting. A complete blood count and serum chemistry panel suggested acute hepatitis, and a severe coagulopathy was noted clinically. Feces from the affected dog were positive for the cyanobacterial biotoxin, microcystin-LA (217 ppb). The dog was hospitalized for eight days. Supportive therapy consisted of fluids, mucosal protectants, vitamins, antibiotics, and nutritional supplements. On day five of hospitalization, a bile acid sequestrant, cholestyramine, was administered orally. Rapid clinical improvement was noted within 48 h of initiating oral cholestyramine therapy. At 17 days post-exposure the dog was clinically normal, and remained clinically normal at re-check, one year post-exposure. To our knowledge, this is the first report of successful treatment of canine cyanobacterial (microcystin) toxicosis. Untreated microcystin intoxication is commonly fatal, and can result in significant liver damage in surviving animals. The clinical success of this case suggests that oral administration of cholestyramine, in combination with supportive therapy, could significantly reduce hospitalization time, cost-of-care and mortality for microcystin-poisoned animals.
acute hepatitis; blue-green algae; cholestyramine; cyanobacteria; hepatotoxin; microsystin; poisoning; silibinin
The Cancer Support Community (CSC) provides psychosocial support to people facing cancer in community settings. The purpose of this study was to evaluate the compatibility, effectiveness, and fidelity of the Situation–Choices–Objectives–People–Evaluation–Decisions (SCOPED) question-listing intervention at three CSC sites. Between August 2008 and August 2011, the Program Director at each CSC site implemented question-listing, while measuring patient distress, anxiety, and self-efficacy before and after each intervention. We analyzed the quantitative results using unadjusted statistical tests and reviewed qualitative comments by patients and the case notes of Program Directors to assess compatibility and fidelity. Program Directors implemented question-listing with 77 blood cancer patients. Patients reported decreased distress (p = 0.009) and anxiety (p = 0.005) and increased self-efficacy (p < 0.001). Patients and Program Directors endorsed the intervention as compatible with CSC’s mission and approach and feasible to implement with high fidelity. CSC effectively translated SCOPED question-listing into practice in the context of its community-based psychosocial support services at three sites.
Visit preparation; Coaching; Shared decision making; Patient participation; Professional–patient relations; Questioning; SCOPED
Despite strong medical evidence and policy initiatives supporting the use of daily interruption of sedation in mechanically ventilated patients, compliance remains suboptimal. We sought to identify new barriers to daily interruption of sedation.
Materials and Methods
We conducted 5 focus groups of intensive care unit (ICU) physicians, nurses, and respiratory therapists over a two-month period to identify attitudes, barriers, and motivations to perform a daily interruption of sedation. Each focus group was audiotaped and the transcripts analyzed using qualitative methods to identify recurrent themes.
There was wide consensus on the importance of daily interruptions of sedation, however practitioners usually performed sedation interruption for 1 of 5 distinct reasons: minimizing the dose of sedation, performing a neurologic exam, facilitating ventilator weaning, reducing ICU length of stay, and assessing patient pain. Participants rarely espoused more than one main reason, and there was no shared understanding of why one might do a DIS. This lack of shared understanding led to different patients being selected and diverse approaches to carrying out the DIS.
Despite apparent consensus, lack of shared understanding of the rationale for an intervention may lead to divergent practice patterns and failure to implement standardized, evidence-based practice.
Interdisciplinary Communication; Conscious Sedation; Intensive Care; Mechanical Ventilators
Nontuberculous mycobacteria are increasingly associated with cutaneous infections after cosmetic procedures. Fractionated CO2 resurfacing, a widely used technique for photorejuvenation, has been associated with a more favorable side effect profile than alternative procedures. We describe 2 cases of nontuberculous mycobacterial infection after treatment with a fractionated CO2 laser at a private clinic. Densely distributed erythematous papules and pustules developed within the treated area within 2 weeks of the laser procedure. Diagnosis was confirmed by histologic analysis and culture. Both infections responded to a 4-month course of a multidrug regimen. An environmental investigation of the clinic was performed, but no source of infection was found. The case isolates differed from each other and from isolates obtained from the clinic, suggesting that the infection was acquired by postprocedure exposure. Papules and pustules after fractionated CO2 resurfacing should raise the suspicion of nontuberculous mycobacterial infection.
tuberculosis and other mycobacteria; nontuberculous mycobacterial infection; nontuberculous mycobacteria; NTM; Mycobacterium chelonae; Mycobacterium abscessus; bacteria; fractionated CO2 laser resurfacing; cosmetic techniques
Aircraft carriers, electrical power grids, and wildland firefighting, though seemingly different, are exemplars of high reliability organizations (HROs) - organizations that have the potential for catastrophic failure yet engage in nearly error-free performance. HROs commit to safety at the highest level and adopt a special approach to its pursuit. High reliability organizing has been studied and discussed for some time in other industries and is receiving increasing attention in health care, particularly in high-risk settings like the intensive care unit (ICU). The essence of high reliability organizing is a set of principles that enable organizations to focus attention on emergent problems and to deploy the right set of resources to address those problems. HROs behave in ways that sometimes seem counterintuitive - they do not try to hide failures but rather celebrate them as windows into the health of the system, they seek out problems, they avoid focusing on just one aspect of work and are able to see how all the parts of work fit together, they expect unexpected events and develop the capability to manage them, and they defer decision making to local frontline experts who are empowered to solve problems. Given the complexity of patient care in the ICU, the potential for medical error, and the particular sensitivity of critically ill patients to harm, high reliability organizing principles hold promise for improving ICU patient care.
Fecal pathogen contamination of watersheds worldwide is increasingly recognized, and natural wetlands may have an important role in mitigating fecal pathogen pollution flowing downstream. Given that waterborne protozoa, such as Cryptosporidium and Giardia, are transported within surface waters, this study evaluated associations between fecal protozoa and various wetland-specific and environmental risk factors. This study focused on three distinct coastal California wetlands: (i) a tidally influenced slough bordered by urban and agricultural areas, (ii) a seasonal wetland adjacent to a dairy, and (iii) a constructed wetland that receives agricultural runoff. Wetland type, seasonality, rainfall, and various water quality parameters were evaluated using longitudinal Poisson regression to model effects on concentrations of protozoa and indicator bacteria (Escherichia coli and total coliform). Among wetland types, the dairy wetland exhibited the highest protozoal and bacterial concentrations, and despite significant reductions in microbe concentrations, the wetland could still be seen to influence water quality in the downstream tidal wetland. Additionally, recent rainfall events were associated with higher protozoal and bacterial counts in wetland water samples across all wetland types. Notably, detection of E. coli concentrations greater than a 400 most probable number (MPN) per 100 ml was associated with higher Cryptosporidium oocyst and Giardia cyst concentrations. These findings show that natural wetlands draining agricultural and livestock operation runoff into human-utilized waterways should be considered potential sources of pathogens and that wetlands can be instrumental in reducing pathogen loads to downstream waters.
A patient with systemic cytomegalovirus (CMV), including chorioretinitis, received localized and systemic ganciclovir, systemic cidofovir analog, and localized foscarnet. Mutations conferring ganciclovir and cidofovir resistance were detected in CMV from the aqueous fluid but not in CMV from plasma. Quantifying CMV from aqueous fluid was valuable for monitoring the clinical response and predicting resistance.
We investigated whether omega-3 fatty acid intake and erythrocyte membrane omega-3 fatty acid levels are associated with conversion to type 1 diabetes in children with islet autoimmunity (IA).
The Diabetes Autoimmunity Study in the Young is following children at increased genetic risk for type 1 diabetes for the development of persistent IA, as defined as being positive for glutamic acid decarboxylase 65, i, or insulin autoantibodies on two consecutive visits, and then for the development of type 1 diabetes, as diagnosed by a physician. One hundred and sixty-seven children with persistent IA were followed for a mean of 4.8 yr, and 45 of these developed type 1 diabetes at a mean age of 8.7 yr. Erythrocyte membrane fatty acids (as a percent of total lipid) and dietary fatty acid intake (estimated via food frequency questionnaire) were analyzed as time-varying covariates in proportional hazards survival analysis, with follow-up time starting at detection of the first autoantibody.
Neither dietary intake of omega-3 fatty acids nor omega-6 fatty acids were associated with conversion to type 1 diabetes, adjusting for human leukocyte antigen (HLA)-DR, family history of type 1 diabetes, age at first IA positivity, maternal age, maternal education, and maternal ethnicity. Adjusting for HLA-DR, family history of type 1 diabetes and age at first IA positivity, omega-3 and omega-6 fatty acid levels of erythrocyte membranes were not associated with conversion to type 1 diabetes.
In this observational study, omega-3 fatty acid intake and status are not associated with conversion to type 1 diabetes in children with IA.
dietary intake; IA; omega-3 fatty acids; type 1 diabetes mellitus
Because the ability to flexibly experience and appropriately express emotions across a range of developmentally relevant contexts is crucial to adaptive functioning, we examined how adolescent attachment security may be related to more functional emotional behavior during a relationship promoting interaction task. Data were collected from 74 early adolescent girls (Mean age 13.45 years; SD = 0.68; 89% Caucasian) and their primary caregiver. Results indicated that, regardless of the parent’s interaction behavior and the level of stress in the parent-adolescent relationship, greater adolescent security was associated with more positive and less negative behavioral displays, including greater positivity, greater coherence of verbal content and affect, less embarrassment, and less emotional dysregulation in response to a situational demand for establishing intimacy with the parent. Implications for encouraging and fostering adolescents’ capacity to respond to interpersonal contexts in ways that promote the relationship are discussed.
adolescence; attachment; security; intimacy; parent-adolescent interaction
The study evaluated how spiritual and religious functioning (SRF), alcohol-related problems, and psychiatric symptoms change over the course of treatment and follow-up. Problem drinkers (n = 55, including 39 males and 16 females) in outpatient treatment were administered questionnaires at pretreatment, post-treatment, and follow up, which assessed two aspects of SRF (religious well-being and existential well-being), two aspects of alcohol misuse (severity and consequences), and two aspects of psychiatric symptoms (depression and anxiety). Significant improvements in SRF, psychiatric symptoms and alcohol misuse were observed from pretreatment to follow-up. Although SRF scores were significantly correlated with psychiatric symptoms at all three time points, improvement in the former did not predict improvement in the latter. When measured at the same time points, SRF scores were not correlated with the measures of alcohol misuse. However, improvement in SRF (specifically in existential well-being) over the course of treatment was predictive of improvement in the alcohol misuse measures at follow-up. These results suggest that the association between SRF, emotional problems, and alcohol misuse is complex. They further suggest that patients who improve spiritual functioning over the course of treatment are more likely to experience improvement in drinking behavior and alcohol-related problems after treatment has ended.
Alcohol; Spirituality; Psychiatric; Psychotherapy
The nutrient amino acid transporter (NAT) subfamily is the largest subdivision of the sodium neurotransmitter symporter family (SNF; also known as SLC6; HUGO). There are seven members of the NAT population in the African malaria mosquito Anopheles gambiae, two of which, AgNAT6 and AgNAT8, preferably transport indole- and phenyl-branched substrates, respectively. The relative expression and distribution of these aromatic NATs were examined with transporter-specific antibodies in Xenopus oocytes and mosquito larval alimentary canal, representing heterologous and tissue expression systems, respectively. NAT-specific aromatic-substrate-induced currents strongly corresponded with specific accumulation of both transporters in the plasma membrane of oocytes. Immunolabeling revealed elevated expressions of both transporters in specific regions of the larval alimentary canal, including salivary glands, cardia, gastric caeca, posterior midgut and Malpighian tubules. Differences in relative expression densities and spatial distribution of the transporters were prominent in virtually all of these regions, suggesting unique profiles of the aromatic amino acid absorption. For the first time reversal of the location of a transporter between apical and basal membranes was identified in posterior and anterior epithelial domains corresponding with secretory and absorptive epithelial functions, respectively. Both aromatic NATs formed putative homodimers in the larval gut whereas functional monomers were overexpressed heterologously in Xenopus oocytes. The results unequivocally suggest functional synergy between substrate-specific AgNAT6 and AgNAT8 in intracellular absorption of aromatic amino acids. More broadly, they suggest that the specific selectivity, regional expression and polarized membrane docking of NATs represent key adaptive traits shaping functional patterns of essential amino acid absorption in the metazoan alimentary canal and other tissues.
insect; mosquito; essential amino acid; nutrient amino acid transporter; NAT; co-transporter; phenylalanine; tryptophan; monoamine neurotransmitter; malaria; Anopheles gambiae
The Cepheid Xpert MTB/RIF research-use-only (RUO) assay and a laboratory-developed test (LDT) targeting IS6110 were evaluated and compared to mycobacterial culture as the gold standard. The performance characteristics of both molecular assays were determined by using 112 specimens from 90 patients, including 89 pulmonary specimens and 23 extrapulmonary specimens. Of the specimens tested, 37 (33%) were culture positive for the Mycobacterium tuberculosis complex; 29 were pulmonary, and 8 were extrapulmonary. Of these culture-positive specimens, 83% of the pulmonary specimens and 50% of the extrapulmonary specimens were smear positive. There was complete concordance between the smear-positive culture-positive specimens, independent of the anatomical site (100% sensitivity). The sensitivity of the MTB/RIF RUO assay for smear-negative specimens was 60% for pulmonary and 75% for extrapulmonary specimens, while the IS6110 LDT sensitivities were 40% and 0%, respectively. There was also complete concordance among the culture-negative specimens tested. Both assays showed 95% specificity, with four culture-negative specimens testing as positive. A review of patient records indicated that there was a high likelihood of the presence of M. tuberculosis complex DNA in the false-positive specimens. Biosafety analysis was performed and showed an acceptable reduction in organism viability using the processing methods described above. Both molecular assays are suitable for the detection of M. tuberculosis isolates in smear-positive pulmonary and extrapulmonary specimens, while the sensitivity of the detection of M. tuberculosis isolates in smear-negative specimens was variable.
We performed a retrospective (n = 121) and prospective (n = 305) verification of the Cepheid Xpert Flu assay to determine its performance characteristics. The overall sensitivity and specificity were 93% and 100%, respectively. Nasopharyngeal specimen sensitivities were 100% for seasonal influenza A/H1 virus and influenza A/H3 virus, 90% for influenza A/2009/H1N1 virus, and 95% for influenza B virus.
Fragment-based lead design (FBLD) has been used to identify new metal-binding groups for metalloenzyme inhibitors. When screened at 1 mM, a chelator fragment library (CFL-1.1) of 96 compounds produced hit rates ranging from 29–43% for five matrix metalloproteases (MMPs), 24% for anthrax lethal factor (LF), 49% for 5-lipoxygenase (5-LO), and 60% for tyrosinase (TY). The ligand efficiencies (LE) of the fragment hits are excellent, in the range of 0.4–0.8 kcal/mol. The MMP enzymes all generally elicit the same chelators as hits from CFL-1.1; however, the chelator fragments that inhibit structurally unrelated metalloenzymes (LF, 5-LO, TY) vary considerably. To develop more advanced hits, one hit from CFL-1.1, 8-hydroxyquinoline, was elaborated at four different positions around the ring system to generate new fragments. 8-Hydroxyquinoline fragments substituted at either the 5- or 7-positions gave potent hits against MMP-2, with IC50 values in the low micromolar range. The 8-hydroxyquinoline represents a promising, new chelator scaffold for the development of MMP inhibitors that was discovered by use of a metalloprotein-focused chelator fragment library.
In this observational study, we compared erythrocyte membrane fatty acids in infants consuming formula supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA) with those consuming other types of milks. In 110 infants who were participants in a cohort study of otherwise healthy children at risk for developing type 1 diabetes, erythrocytes were collected at approximately 9 months of age, and fatty acid content was measured as a percent of total lipids. Parents reported the type of milk the infants consumed in the month of and prior to erythrocyte collection – infant formula supplemented with ARA and DHA (supplemented formula), formula with no ARA and DHA supplements (non-supplemented formula), breast-milk, or non-supplemented formula plus breast-milk. Membrane DHA (4.42 versus 1.79, p < 0.001) and omega-3 fatty acid (5.81 versus 3.43, p < 0.001) levels were higher in infants consuming supplemented versus non-supplemented formula. Omega-6 fatty acids were lower in infants consuming supplemented versus non-supplemented formula (26.32 versus 29.68, p = 0.023); ARA did not differ between groups. Infants given supplemented formula had higher DHA (4.42 versus 2.81, p < 0.001) and omega-3 fatty acids (5.81 versus 4.45, p = 0.008) than infants drinking breast-milk. In infants whose mothers did not receive any dietary advice, use of supplemented formula is associated with higher omega-3 and lower omega-6 fatty acid status.
Arachidonic Acid; Docosahexaenoic Acid; Breastfeeding; Infant Feeding; Infant Formula; Infant Feeding Behavior