Diverse Durham collection phages demonstrate complex BREX defense responses.

Bacteriophages (phages) outnumber bacteria ten-to-one and cause infections at a rate of 1025 per second. The ability of phages to reduce bacterial populations makes them attractive alternative antibacterials for use in combating the rise in antimicrobial resistance. This effort may be hindered due to bacterial defenses such as Bacteriophage Exclusion (BREX) that have arisen from the constant evolutionary battle between bacteria and phages. For phages to be widely accepted as therapeutics in Western medicine, more must be understood about bacteria-phage interactions and the outcomes of bacterial phage defense. Here, we present the annotated genomes of 12 novel bacteriophage species isolated from water sources in Durham, UK, during undergraduate practical classes. The collection includes diverse species from across known phylogenetic groups. Comparative analyses of two novel phages from the collection suggest they may be founding members of a new genus. Using this Durham phage collection, we determined that particular BREX defense systems were likely to confer a varied degree of resistance against an invading phage. We concluded that the number of BREX target motifs encoded in the phage genome was not proportional to the degree of susceptibility. IMPORTANCE Bacteriophages have long been the source of tools for biotechnology that are in everyday use in molecular biology research laboratories worldwide. Phages make attractive new targets for the development of novel antimicrobials. While the number of phage genome depositions has increased in recent years, the expected bacteriophage diversity remains underrepresented. Here we demonstrate how undergraduates can contribute to the identification of novel phages and that a single City in England can provide ample phage diversity and the opportunity to find novel technologies. Moreover, we demonstrate that the interactions and intricacies of the interplay between bacterial phage defense systems such as Bacteriophage Exclusion (BREX) and phages are more complex than originally thought. Further work will be required in the field before the dynamic interactions between phages and bacterial defense systems are fully understood and integrated with novel phage therapies.

Design, synthesis and evaluation of potent and selective inhibitors of mono-(ADP-ribosyl)transferases PARP10 and PARP14.

A series of diaryl ethers were designed and synthesized to discern the structure activity relationships against the two closely related mono-(ADP-ribosyl)transferases PARP10 and PARP14. Structure activity studies identified 8b as a sub-micromolar inhibitor of PARP10 with ∼15-fold selectivity over PARP14. In addition, 8k and 8m were discovered to have sub-micromolar potency against PARP14 and demonstrated moderate selectivity over PARP10. A crystal structure of the complex of PARP14 and 8b shows binding of the compound in a novel hydrophobic pocket and explains both potency and selectivity over other PARP family members. In addition, 8b, 8k and 8m also demonstrate selectivity over PARP1. Together, this study identified novel, potent and metabolically stable derivatives to use as chemical probes for these biologically interesting therapeutic targets.

Popping the medical education bubble before it forms: It's about dollars and sense.

Headlines have previously acknowledged the risk of a "bubble and crash" phenomenon in the physician workforce pipeline. A growing number of medical career dissatisfiers, including emotional and physical burnout, loss of autonomy and burdensome regulations, compound the longstanding fundamental issue of the prohibitive direct and opportunity costs associated with medical training. For U.S. medical education and, in turn, healthcare to remain robust and high-quality, creative solutions are needed to address the untenable physician debt-to-income ratios and to ensure not only that the quantity and quality of medical school aspirants remains favorable to the profession, but that the profession remains responsible to its future members. Creating fiscally healthy physicians is a societal imperative.

Cerebrospinal fluid untargeted metabolomic profiling of aneurysmal subarachnoid hemorrhage: an exploratory study.

INTRODUCTION: Despite advancements in medical and surgical therapies, clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH) continue to be poor. Currently, aSAH pathophysiology remains poorly understood. No aSAH biomarkers are commonly used in the clinical setting. This exploratory study used metabolomics profiling to identify global metabolic changes and metabolite predictors of long-term outcome using cerebrospinal fluid (CSF) samples of aSAH patients. METHODS AND METHODS: Gas chromatography time-of-flight mass spectrometry was applied to CSF samples collected from 15 consecutive high-grade aSAH patients (modified Fisher grade 3 or 4). Collected CSF samples were analyzed at two time points (admission and the anticipated vasospasm timeframe). Metabolite levels at both time points were compared and correlated with vasospasm status and Glasgow Outcome Scale (GOS) of patients at 1 year post-aSAH. Significance level was defined as p < 0.05 with false discovery rate correction for multiple comparisons. RESULTS: Of 97 metabolites identified, 16 metabolites, primarily free amino acids, significantly changed between the two time points. These changes were magnified in modified Fisher grade 4 compared with grade 3. Six metabolites (2-hydroxyglutarate, tryptophan, glycine, proline, isoleucine, and alanine) correlated with GOS at 1 year post-aSAH independent of vasospasm status. When predicting patients who had low disability (GOS 5 vs. GOS ≤4), 2-hydroxyglutarate had a sensitivity and specificity of 0.89 and 0.83 respectively. CONCLUSIONS: Our preliminary study suggests that specific metabolite changes occur in the brain during the course of aSAH and that quantification of specific CSF metabolites may be used to predict long-term outcome in patients with aSAH. This is the first study to implicate 2-hydroxyglutarate, a known marker of tissue hypoxia, in aSAH pathogenesis.

A Review of Cerebral Shunts, Current Technologies, and Future Endeavors.

Objective. The use of cerebrospinal shunts is the standard of care for hydrocephalus. However, shunts are extremely vulnerable to failure and lack noninvasive methods to monitor their viability. We review current shunt technologies and attempts to improve their function. Methods. A PubMed search was performed to find literature on shunts and shunt function. Company brochures and websites were also used. Results. Fixed and variable pressure valves from four major companies are discussed. Also reviewed are siphon resistive devices, intracranial pressure sensors, and recent attempts on the development of cerebrospinal fluid sensors, including a micromechanical flow sensor we have recently developed. Conclusions. While variable pressure valves and siphon resistive devices have both had considerable success in dealing with variable intracranial pressure, a more sophisticated, continuous monitoring system is needed to ensure shunt viability and patient safety. An integrated flow sensor may provide the ability to track fluid flow and determine shunt functionality.

Loss of Oncostatin M Signaling in Adipocytes Induces Insulin Resistance and Adipose Tissue Inflammation in Vivo.

Oncostatin M (OSM) is a multifunctional gp130 cytokine. Although OSM is produced in adipose tissue, it is not produced by adipocytes. OSM expression is significantly induced in adipose tissue from obese mice and humans. The OSM-specific receptor, OSM receptor ß (OSMR), is expressed in adipocytes, but its function remains largely unknown. To better understand the effects of OSM in adipose tissue, we knocked down Osmr expression in adipocytes in vitro using siRNA. In vivo, we generated a mouse line lacking Osmr in adiponectin-expressing cells (OSMR(FKO) mice). The effects of OSM on gene expression were also assessed in vitro and in vivo OSM exerts proinflammatory effects on cultured adipocytes that are partially rescued by Osmr knockdown. Osm expression is significantly increased in adipose tissue T cells of high fat-fed mice. In addition, adipocyte Osmr expression is increased following high fat feeding. OSMR(FKO) mice exhibit increased insulin resistance and adipose tissue inflammation and have increased lean mass, femoral length, and bone volume. Also, OSMR(FKO) mice exhibit increased expression of Osm, the T cell markers Cd4 and Cd8, and the macrophage markers F4/80 and Cd11c Interestingly, the same proinflammatory genes induced by OSM in adipocytes are induced in the adipose tissue of the OSMR(FKO) mouse, suggesting that increased expression of proinflammatory genes in adipose tissue arises both from adipocytes and other cell types. These findings suggest that adipocyte OSMR signaling is involved in the regulation of adipose tissue homeostasis and that, in obesity, OSMR ablation may exacerbate insulin resistance by promoting adipose tissue inflammation.

Injuries Associated with Subdural Hematoma: A Study of the National Trauma Data Bank.

Of 92030 patients with subdural hematoma (SDH) in the National Trauma Data Bank (NTDB), 55729 had fall mechanisms of injury (61%), while 36301 had other traumatic mechanisms (nonfall, 39%). For nonfall mechanisms, the three associated injuries with the highest incidence were: skull fractures (43.3%), rib/sternum injuries (25.0%), and thoracic organ injuries (24.0%). For fall mechanisms, the three associated injuries with the highest incidence were: skull fractures (19.0%), spinal injuries (7.1%), and upper extremity fractures (6.8%). Mortality was associated with age and most studied associated injuries (odds ratios ofup to 2.04). 'This study conveys an important clinical point: even though traditional teaching highlights the risk of noncontiguous spine fractures in patients with a known spine fracture, the risk of a noncontiguous spine fracture is higher when dealing with a patient with SDH. This is underscored by the fact that mortality is higher for SDH patients with other associated injuries.

CCL20 is elevated during obesity and differentially regulated by NF-κB subunits in pancreatic ß-cells.

Enhanced leukocytic infiltration into pancreatic islets contributes to inflammation-based diminutions in functional ß-cell mass. Insulitis (aka islet inflammation), which can be present in both T1DM and T2DM, is one factor influencing pancreatic ß-cell death and dysfunction. IL-1ß, an inflammatory mediator in both T1DM and T2DM, acutely (within 1h) induced expression of the CCL20 gene in rat and human islets and clonal ß-cell lines. Transcriptional induction of CCL20 required the p65 subunit of NF-κB to replace the p50 subunit at two functional κB sites within the CCL20 proximal gene promoter. The NF-κB p50 subunit prevents CCL20 gene expression during unstimulated conditions and overexpression of p50 reduces CCL20, but enhances cyclooxygenase-2 (COX-2), transcript accumulation after exposure to IL-1ß. We also identified differential recruitment of specific co-activator molecules to the CCL20 gene promoter, when compared with the CCL2 and COX2 genes, revealing distinct transcriptional requirements for individual NF-κB responsive genes. Moreover, IL-1ß, TNF-α and IFN-γ individually increased the expression of CCR6, the receptor for CCL20, on the surface of human neutrophils. We further found that the chemokine CCL20 is elevated in serum from both genetically obese db/db mice and in C57BL6/J mice fed a high-fat diet. Taken together, these results are consistent with a possible activation of the CCL20-CCR6 axis in diseases with inflammatory components. Thus, interfering with this signaling pathway, either at the level of NF-κB-mediated chemokine production, or downstream receptor activation, could be a potential therapeutic target to offset inflammation-associated tissue dysfunction in obesity and diabetes.

Primary spinal myxopapillary ependymoma in the pediatric population: a study from the Surveillance, Epidemiology, and End Results (SEER) database.

Primary spinal myxopapillary ependymomas (MPE) in children are extremely rare. We examined the patient demographics, treatment modalities, and the associated outcomes of children with MPE using the Surveillance, Epidemiology, and End Results (SEER) national cancer database to gain a better understanding of these tumors. The SEER database (1973-2012) was used to analyze patients 21 years of age and younger with histologically confirmed MPE localized to the spinal cord or cauda equina. We analyzed patient demographics, extent of surgical resection, and radiation treatment. Overall survival was calculated using the Kaplan-Meier method. Statistical significance was defined as p < 0.05, with all data analyzed in IBM SPSS Statistics 21. 122 pediatric patients met inclusion criteria. The median age was 16 years (range 0-21) with 63 % male and 87 % Caucasian. The mean follow-up time was 4.5 years (95 % CI 3.93-5.07). Overall survival at 5 and 10 years was 97 and 95 %, respectively. We found 37 % underwent gross-total resection (GTR), 36 % subtotal resection (STR), and 27 % biopsy only. Patients who received GTR alone (n = 37) had a statistically significant increase in overall survival compared to those who received STR plus adjuvant radiation (n = 20) (Χ2 = 5.9, p < 0.05). To our knowledge, this is the largest survival analysis of pediatric patients with MPE. Overall survival is excellent at the 5 and 10-year time points; however, GTR should be the goal of treatment when possible. For patients with MPE, future studies should focus on longer follow-up, the role of radiation, and the therapeutic approach at tumor recurrence.

Inactivation of C/ebp homologous protein-driven immune-metabolic interactions exacerbate obesity and adipose tissue leukocytosis.

Successful adaptation to periods of chronic caloric excess is a highly coordinated event that is critical to the survival and propagation of species. Transcription factor C/ebp homologous protein (Chop) is thought to be an important molecular mediator that integrates nutrient signals to endoplasmic reticulum (ER) stress and innate immune activation. Given that aberrant ER stress response is implicated in inducing metabolic inflammation and insulin resistance, we hypothesized that ER stress target gene Chop integrates immune and metabolic systems to adapt to chronic positive energy balance. Here we report that inactivation of Chop in mice fed a high fat diet led to significant increase in obesity caused by a reduction in energy expenditure without any change in food intake. Importantly, ablation of Chop does not induce metabolically healthy obesity, because Chop-deficient mice fed a high fat diet had increased hepatic steatosis with significantly higher insulin resistance. Quantification of adipose tissue leukocytosis revealed that elimination of Chop during obesity led to substantial increase in number of adipose tissue T and B lymphocytes. In addition, deficiency of Chop led to increase in total number of myeloid subpopulations like neutrophils and F4/80(+) adipose tissue macrophages without any alterations in the frequency of M1- or M2-like adipose tissue macrophages. Further investigation of inflammatory mechanisms revealed that ablation of Chop increases the sensitivity of macrophages to inflammasome-induced activation of IL-ß in macrophages. Our findings indicate that regulated expression of Chop during obesity is critical for adaptation to chronic caloric excess and maintenance of energy homeostasis via integration of metabolic and immune systems.

Fat in flames: influence of cytokines and pattern recognition receptors on adipocyte lipolysis.

Adipose tissue has the largest capacity to store energy in the body and provides energy through the release of free fatty acids during times of energy need. Different types of immune cells are recruited to adipose tissue under various physiological conditions, indicating that these cells contribute to the regulation of adipose tissue. One major pathway influenced by a number of immune cells is the release of free fatty acids through lipolysis during both physiological (e.g., cold stress) and pathophysiological processes (e.g., obesity, type 2 diabetes). Adipose tissue expansion during obesity leads to immune cell infiltration and adipose tissue remodeling, a homeostatic process that promotes inflammation in adipose tissue. The release of proinflammatory cytokines stimulates lipolysis and causes insulin resistance, leading to adipose tissue dysfunction and systemic disruptions of metabolism. This review focuses on the interactions of cytokines and other inflammatory molecules that regulate adipose tissue lipolysis during physiological and pathophysiological states.

Anaesthesia for deep brain stimulation: a review.

PURPOSE OF REVIEW: Deep brain stimulation (DBS) is a well tolerated and efficacious surgical treatment for movement disorders, chronic pain, psychiatric disorder, and a growing number of neurological disorders. Given that the brain targets are deep and small, accurate electrode placement is commonly accomplished by utilizing frame-based systems. DBS electrode placement is confirmed by microlectrode recordings and macrostimulation to optimize and verify target placement. With a reliance on electrophysiology, proper anaesthetic management is paramount to balance patient comfort without interfering with neurophysiology. RECENT FINDINGS: To achieve optimal pain control, generous amounts of local anaesthesia are instilled into the planned incision. During the opening and closing states, conscious sedation is the prevailing method of anaesthesia. The preferred agents are dexmedetomidine, propofol, and remifentanil, as they affect neurocognitive testing the least, and shorter acting. All the agents are turned off 15-30 min prior to microelectrode recording. Dexmedetomidine has gained popularity in DBS procedures, but has some considerations at higher doses. The addition of ketamine is helpful for pediatric cases. SUMMARY: DBS is a robust surgical treatment for a variety of neurological disorders. Appropriate anaesthetic agents that achieve patient comfort without interfering with electrophysiology are paramount.

Comparison of an anthropomorphic PRESAGE® dosimeter and radiochromic film with a commercial radiation treatment planning system for breast IMRT: a feasibility study.

This work presents a comparison of an anthropomorphic PRESAGE® dosimeter and radiochromic film measurements with a commercial treatment planning system to determine the feasibility of PRESAGE® for 3D dosimetry in breast IMRT. An anthropomorphic PRESAGE® phantom was created in the shape of a breast phantom. A five-field IMRT plan was generated with a commercially available treatment planning system and delivered to the PRESAGE® phantom. The anthropomorphic PRESAGE® was scanned with the Duke midsized optical CT scanner (DMOS-RPC) and the OD distribution was converted to dose. Comparisons were performed between the dose distribution calculated with the Pinnacle3 treatment planning system, PRESAGE®, and EBT2 film measurements. DVHs, gamma maps, and line profiles were used to evaluate the agreement. Gamma map comparisons showed that Pinnacle3 agreed with PRESAGE® as greater than 95% of comparison points for the PTV passed a ± 3%/± 3 mm criterion when the outer 8 mm of phantom data were discluded. Edge artifacts were observed in the optical CT reconstruction, from the surface to approximately 8 mm depth. These artifacts resulted in dose differences between Pinnacle3 and PRESAGE® of up to 5% between the surface and a depth of 8 mm and decreased with increasing depth in the phantom. Line profile comparisons between all three independent measurements yielded a maximum difference of 2% within the central 80% of the field width. For the breast IMRT plan studied, the Pinnacle3 calculations agreed with PRESAGE® measurements to within the ±3%/± 3 mm gamma criterion. This work demonstrates the feasibility of the PRESAGE® to be fashioned into anthropomorphic shape, and establishes the accuracy of Pinnacle3 for breast IMRT. Furthermore, these data have established the groundwork for future investigations into 3D dosimetry with more complex anthropomorphic phantoms.

Relative stopping power measurements to aid in the design of anthropomorphic phantoms for proton radiotherapy.

The delivery of accurate proton dose for clinical trials requires that the appropriate conversion function from Hounsfield unit (HU) to relative linear stopping power (RLSP) be used in proton treatment planning systems (TPS). One way of verifying that the TPS is calculating the correct dose is an end-to-end test using an anthropomorphic phantom containing tissue equivalent materials and dosimeters. Many of the phantoms in use for such end-to-end tests were originally designed using tissue-equivalent materials that had physical characteristics to match patient tissues when irradiated with megavoltage photon beams. The aim of this study was to measure the RLSP of materials used in the phantoms, as well as alternative materials to enable modifying phantoms for use at proton therapy centers. Samples of materials used and projected for use in the phantoms were measured and compared to the HU assigned by the treatment planning system. A percent difference in RLSP of 5% was used as the cutoff for materials deemed acceptable for use in proton therapy (i.e., proton equivalent). Until proper tissue-substitute materials are identified and incorporated, institutions that conduct end-to-end tests with the phantoms are instructed to override the TPS with the measured stopping powers we provide. To date, the RLSPs of 18 materials have been measured using a water phantom and/or multilayer ion chamber (MLIC). Nine materials were identified as acceptable for use in anthropomorphic phantoms. Some of the failing tissue substitute materials are still used in the current phantoms. Further investigation for additional appropriate tissue substitute materials in proton beams is ongoing. Until all anthropomorphic phantoms are constructed of appropriate materials, a unique HU-RLSP phantom has been developed to be used during site visits to verify the proton facility's treatment planning HU-RLSP calibration curve.

A Randomized, Double-Blind, Crossover Study to Investigate the Pharmacokinetics of Extended-Release Melatonin Compared to Immediate-Release Melatonin in Healthy Adults.

Exogenous melatonin can be helpful for treatment of some sleep disorders. However, immediate-release formulations are rapidly absorbed and cleared from the body making it difficult to provide coverage for an entire sleep period. Extended-release melatonin formulations can better mimic the naturally occurring melatonin profile and increase efficacy, but few studies have reported on their pharmacokinetics. To assess the pharmacokinetics of extended-release melatonin, we conducted a randomized, double-blind, crossover study of extended-release melatonin (4 mg) compared to immediate-release melatonin (4 mg) in 18 healthy adults, ages 18-65 years. Participants received immediate-release or extended-release melatonin in clinic after an 8 h fast, and blood samples were taken over a 10-h period. After a 7-day washout period, the same procedures were repeated with the melatonin form not previously received. Extended-release melatonin had a longer time to peak concentration (1.56 vs 0.6 h) and elimination half-life (1.63 vs 0.95 h) compared with immediate-release melatonin. Maximum concentration was lower for extended-release melatonin compared with immediate-release melatonin (7581 pg/mL vs 13120 pg/mL). Extended-release melatonin raised melatonin levels in as little as 15 min and sustained elevated melatonin levels (>300 pg/mL) for 6 h before falling below 50 pg/mL by 9 h. No clinically relevant adverse events were observed, and safety parameters remained within normal ranges for both formulations. The pharmacokinetic profile of this extended-release melatonin formulation suggests that it could be used for future efficacy studies of melatonin and sleep outcomes. This trial is registered at ClinicalTrials.gov, NCT04067791.

Subcutaneous and gonadal adipose tissue transcriptome differences in lean and obese female dogs.

Canine obesity leads to shortened life span and increased disease incidence. Adipose tissue depots are known to have unique metabolic and gene expression profiles in rodents and humans, but few comparisons of depot gene expression have been performed in the dog. Using microarray technology, our objective was to identify differentially expressed genes and enriched functional pathways between subcutaneous and gonadal adipose of lean and obese dogs to better understand the pathogenesis of obesity in the dog. Because no depot × body weight status interactions were identified in the microarray data, depot differences were the primary focus. A total of 946 and 703 transcripts were differentially expressed (FDR P < 0.05) between gonadal and subcutaneous adipose tissue in obese and lean dogs respectively. Of the adipose depot-specific differences in gene expression, 162 were present in both lean and obese dogs, with the majority (85%) expressed in the same direction. Both lean and obese dog gene lists had enrichment of the complement and coagulation cascade and systemic lupus erythematosus pathways. Obese dogs had enrichment of lysosome, extracellular matrix-receptor interaction, renin-angiotensin system and hematopoietic cell lineage pathways. Lean dogs had enrichment of glutathione metabolism and synthesis and degradation of ketone bodies. We have identified a core set of genes differentially expressed between subcutaneous and gonadal adipose tissue in dogs regardless of body weight. These genes contribute to depot-specific differences in immune function, extracellular matrix remodeling and lysosomal function and may contribute to the physiological differences noted between depots.

Decompressive hemicraniectomy for ischemic stroke in the pediatric population.

Adult patients with space-occupying hemispheric infarctions have a poor prognosis, with an associated fatality rate of 80%. Decompressive hemicraniectomy (DH) has been studied as a treatment option for patients with malignant cerebral infarction refractory to maximal medical therapy, with reasonable outcomes demonstrated in the adult population if the patient is decompressed within 48 h. However, there are no randomized controlled trials in the pediatric literature to make the same claims. In this study, we evaluated the current literature in regards to DH following malignant stroke in the pediatric population. We found that excellent recovery, with an acceptable quality of life, is possible, particularly in the pediatric patient. Our cohort suggests that pediatric intervention beyond the 48-h time interval may still lead to positive outcomes, unlike adult patients. Regardless, randomized controlled trials are needed to determine optimal timing of intervention following symptom onset, as well as to identify predictors for positive outcome in the pediatric population.

Resection of lateral temporal lobe arteriovenous malformations.

BACKGROUND: Cerebral arteriovenous malformations (AVMs) can be formidable lesions to treat. There are four modalities available for treatment: expectant management, radiosurgery, embolization, and microsurgery. In order to make a decision about treatment, the surgeon must consider the natural history of the lesion versus the rate of treated morbidity and mortality. Characteristics of temporal lobe AVMs such as their location, the potential for deep-seated arterial feeders and deep venous drainage, increase the risk of early clinical onset, hemorrhage, and overall morbidity and mortality (Fleetwood and Steinberg; Lancet 359:863-873, 3) and provide an additional challenge to surgeons attempting to remove the lesion while preserving eloquent local structures. METHODS: In this paper, we demonstrate our technique for the microsurgical resection of lateral temporal lobe AVMs. In order to maximize access to the lesion for safe resection, a large craniotomy is utilized, with the malformation separated from the MCA feeding arteries and underlying cortex, with care taken not to compromise en passage vessels. The entire nidus is resected and intraoperative angiography confirms appropriate resection. CONCLUSIONS: Microsurgical resection remains an important part of the treatment paradigm for temporal lobe AVMs. In appropriately selected patients, this can be done with minimal morbidity.

Higher intake of certain nutrients among older adults is associated with better cognitive function: an analysis of NHANES 2011-2014.

BACKGROUND: An increasing number of adults are over the age of 65, and there is concern about the increasing prevalence of age-associated cognitive decline and poor mental health status in older adults in the United States. Several nutrients are known to have important biological roles in brain health and neurological function, but many individuals fall short of recommended intake levels. The objective of this study was to examine the association between nutrient intake and cognitive function. We also explored whether nutrient intake was associated with depression. METHODS: This cross-sectional study was based on data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 and included participants ≥ 60 years of age who had reliable day 1 dietary recall data and either valid cognitive function data (n = 2713) or valid depression score data (n = 2943). The sample was stratified by gender, and cognitive functioning test (CFT) composite z-scores were analyzed by quartiles. Depression status was assessed using the Patient Health Questionnaire (PHQ-9). RESULTS: Higher intake and adequacy of a number of different nutrients from food were associated with higher cognitive function in both males and females. Nutrients that showed the most consistent associations with cognitive function across intake and adequacy analyses for food in both males and females were vitamin A, vitamin E, thiamin, riboflavin, vitamin B6, folate, magnesium, potassium, zinc, vitamin K, and lutein and zeaxanthin (p < 0.05 for all). These associations were positive with increasing intake and adequacy being associated with higher CFT composite z-scores. Analysis of nutrient intake and depression yielded results that differed by gender. In females, the nutrients that showed consistent inverse associations with depression scores across both intake and adequacy analyses for food were vitamin A, vitamin C, magnesium, vitamin K, potassium, and dietary fiber (p < 0.05 for all). In males, no significant associations between nutrient intake from food and depression scores were observed. CONCLUSIONS: Our findings suggest that older adults with sufficient intakes of certain essential nutrients have higher cognitive function. Future studies are needed to confirm whether a well-balanced diet and/or dietary supplements which emphasize these nutrients are effective for prevention of age-related declines in cognitive function and mood.

Awareness of inappropriate use related to antimicrobial resistance among medical doctors by country economic status: A systematic review.

BACKGROUND: Antimicrobial resistance (AMR) is promoted by inappropriate use and is a greater burden for low to middle income countries (LMIC) than high income countries (HIC). OBJECTIVE: This systematic review aimed to compare the awareness of inappropriate use related to AMR among medical doctors from LMIC and HIC using published knowledge, attitude and practice (KAP) studies. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, sequential systematic literature search of PubMed and Web of Science databases for articles published since inception up to June 1, 2022 for KAP studies involving medical doctors. Using fifteen KAP items related to promoting AMR, data on proportion of participants responding affirmatively was extracted and reported using means, ranges and 95% confidence intervals (CI). RESULTS: Forty-two studies met the inclusion criteria and involved 13,089 medical doctors from 11HIC and 21LMIC. All were cross-sectional studies, 71.4% involved non-probability sampling and 78.6% were of satisfactory quality. Knowledge items showed mean proportion of more medical doctors responding correctly. Similar affirmation trends were observed for attitude and prescribing practice items. Awareness appeared similar between medical doctors of the economic groups, except for a greater interest in training for LMIC (95.4%; 95%CI 93.0%, 97.9%) versus HIC (81.7%; 95%CI 65.6%, 97.9%). Countries with poor proportions were identified in both economic groups. CONCLUSION: For identified studies, trends suggest good awareness among medical doctors of the known inappropriate use and perceived threat of AMR, as well as prescribing practices to reduce the risk of AMR. Trends were similar across HIC and LMIC; however, countries with evidence of poor awareness exist in both economic groups.