Emphasizing responder speed or accuracy modulates but does not abolish the distractor-induced quitting effect in visual search.

When a highly salient distractor is present in a search array, it speeds target absent visual search and increases errors during target present visual search, suggesting lowered quitting thresholds (Moher in Psychol Sci 31(1):31-42, 2020). Missing a critical target in the presence of a highly salient distractor can have dire consequences in real-world search tasks where accurate target detection is crucial, such as baggage screening. As such, the current study examined whether emphasizing either accuracy or speed would eliminate the distractor-generated quitting threshold effect (QTE). Three blocks of a target detection search task which included a highly salient distractor on half of all trials were used. In one block, participants received no instructions or feedback regarding performance. In the remaining two blocks, they received instructions and trial-by-trial feedback that either emphasized response speed or response accuracy. Overall, the distractor lowered quitting thresholds, regardless of whether response speed or response accuracy was emphasized in a block of trials. However, the effect of the distractor on target misses was smaller when accuracy was emphasized. It, therefore, appears that while the distractor QTE is not easily eradicated by explicit instructions and feedback, it can be shifted. As such, future research should examine the applicability of these and similar strategies in real-world search scenarios.

Effect of nonsteroidal anti-inflammatory drugs on the inflammatory response of bovine endometrial epithelial cells in vitro.

Chronic postpartum uterine infection detrimentally affects subsequent fertility. Nonsteroidal anti-inflammatory drugs (NSAID) are used to alleviate pain and treat inflammatory conditions in transition dairy cows with varying success. To screen the efficacy of NSAID in the absence of animal experiments, we have established an in vitro model to study uterine inflammation. Inflammation was induced in cultured bovine endometrial epithelial cells by challenging cells with an inflammation cocktail: lipopolysaccharide and proinflammatory cytokines, interleukin-1ß (IL1ß) and tumor necrosis factor α (TNFα). Release of the inflammation markers, serum amyloid A (SAA) and α-1-acid glycoprotein (αAGP), was measured by ELISA. Concentration of these markers was used to indicate the effectiveness in dampening inflammation of 5 NSAID: meloxicam, flunixin meglumine, aspirin, ketoprofen, and tolfenamic acid. Three NSAID, meloxicam, flunixin meglumine, and tolfenamic acid, were successful at dampening the release of SAA and αAGP into cell-culture supernatant, and the corresponding treated cells were selected for down-stream mRNA expression analysis. Expression of 192 genes involved in regulation of inflammatory pathways were investigated using Nanostring. Of the genes investigated, 81 were above the mRNA expression-analysis threshold criteria and were included in expression analysis. All SAA genes investigated (SAA2, SAA3, M-SAA3.2) were upregulated in response to the inflammation cocktail, relative to mRNA expression in control cells; however, AGP mRNA expression was below the expression analysis threshold and was, therefore, excluded from analysis. Treatment with NSAID downregulated genes involved in regulating chemokine signaling (e.g., CXCL2, CXCR4, CXCL5, and CXCL16) and genes that regulate the eicosanoid pathway (e.g., LTA4H, PTGS2, PLA2G4A, and PTGDS). Of the 5 NSAID investigated, meloxicam, flunixin meglumine, and tolfenamic acid are recommended for further investigation into treatment of postpartum uterine inflammation. The results from this study confirm the immunomodulatory properties of the endometrial epithelium in response to inflammatory stimuli and suggest that NSAID may be beneficial in alleviating uterine inflammation.

Medullary and cortical thick ascending limb: similarities and differences.

The thick ascending limb of the loop of Henle (TAL) is the first segment of the distal nephron, extending through the whole outer medulla and cortex, two regions with different composition of the peritubular environment. The TAL plays a critical role in the control of NaCl, water, acid, and divalent cation homeostasis, as illustrated by the consequences of the various monogenic diseases that affect the TAL. It delivers tubular fluid to the distal convoluted tubule and thereby affects the function of the downstream tubular segments. The TAL is commonly considered as a whole. However, many structural and functional differences exist between its medullary and cortical parts. The present review summarizes the available data regarding the similarities and differences between the medullary and cortical parts of the TAL. Both subsegments reabsorb NaCl and have high Na+-K+-ATPase activity and negligible water permeability; however, they express distinct isoforms of the Na+-K+-2Cl- cotransporter at the apical membrane. Ammonia and bicarbonate are mostly reabsorbed in the medullary TAL, whereas Ca2+ and Mg2+ are mostly reabsorbed in the cortical TAL. The peptidic hormone receptors controlling transport in the TAL are not homogeneously expressed along the cortical and medullary TAL. Besides this axial heterogeneity, structural and functional differences are also apparent between species, which underscores the link between properties and role of the TAL under various environments.

Age-Related Blood Pressure Sensitivity to Aldosterone in Blacks and Whites.

Aldosterone sensitivity, defined as the magnitude of the association of plasma aldosterone concentration with blood pressure (BP), seems to be a function of plasma volume. It increases as plasma renin activity decreases, and it is more significant in blacks but less so in whites. Age is a strong determinant of BP, and an increase in aldosterone sensitivity could contribute to the increase in BP. In the present study, we tested the hypothesis that aldosterone sensitivity increases with age. We used observational data collected from normotensive blacks and whites enrolled in a prospective cohort study. They were studied as children (248 blacks/357 whites) and again as young adults (74 blacks/125 whites) over an age range of 7 to 39 years. A varying-coefficient regression analysis was used to explore the influences of aldosterone on systolic BP. After controlling for body mass index, race, and sex, both plasma renin activity and plasma aldosterone concentration were lower in blacks, and their levels declined with age (P<0.001). In blacks, plasma aldosterone concentration decreased 0.25 ng/dL per year; in whites, plasma aldosterone concentration decreased 0.18 per year. Aldosterone's effect on BP, characterized by a smooth function of age, intensified as age increased, especially in blacks (P<0.01), suggesting an increased aldosterone sensitivity with age. In comparison to blacks, age-related changes in aldosterone sensitivity in whites were not statistically significant. These findings extend the rationale for targeting aldosterone in the treatment of hypertension, especially in blacks.

Removal of percutaneous endoscopic gastrostomy tubes in adults using the "cut and push" method: A systematic review.

BACKGROUND: PEG tubes are inserted for long term enteral feeding and may need to be removed at some point post insertion. A recognized method to remove the PEG is the cut and push method (CP). Some studies have suggested that CP is safe whilst others have reported complications and death. Subsequently the use of CP is not uniform but, if safe, could provide a cost effective, minimally invasive, alternative to gastroscopy. The aim of this study was to locate and critically appraise all publications relevant to CP in adult patients using a systematic approach. METHOD: Systematic searching of electronic databases Embase, Medline and Cinahl, using keywords in title and abstracts. Exclusions were: non-human, under 18 years of age, English language. Time limits were not applied. Preliminary searching gave 538 hits that were then hand reviewed for relevance. Selected studies were critically appraised and data summarized into tables for use in the review. RESULTS: 27 records were included in the review spanning from 1990-2014. A total of 21 case reports detailing complications in 24 individuals, including 5 deaths. There were 5 cohort studies and 1 case report detailing the safe use of CP, with 3 complications. Cases totalled 373 with 27 complications (7%). Most common complication was gastrointestinal obstruction, usually occurring in the first 6 months post CP. A history of bowel surgery was evident in some cases where obstruction occurred. The majority of cohort studies reported the use of assessment criteria to exclude those at risk of obstruction and reported low complication rates. CONCLUSIONS: The quality and quantity of the evidence on CP is insufficient to make recommendations for clinical practice. Further research is needed to evaluate the effectiveness of CP.

Mice haploinsufficient for Map2k7, a gene involved in neurodevelopment and risk for schizophrenia, show impaired attention, a vigilance decrement deficit and unstable cognitive processing in an attentional task: impact of minocycline.

RATIONALE: Members of the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein (MAP) kinases, and the upstream kinase MKK7, have all been strongly linked with synaptic plasticity and with the development of the neocortex. However, the impact of disruption of this pathway on cognitive function is unclear. OBJECTIVE: In the current study, we test the hypothesis that reduced MKK7 expression is sufficient to cause cognitive impairment. METHODS: Attentional function in mice haploinsufficient for Map2k7 (Map2k7 +/- mice) was investigated using the five-choice serial reaction time task (5-CSRTT). RESULTS: Once stable performance had been achieved, Map2k7 +/- mice showed a distinctive attentional deficit, in the form of an increased number of missed responses, accompanied by a more pronounced decrement in performance over time and elevated intra-individual reaction time variability. When performance was reassessed after administration of minocycline-a tetracycline antibiotic currently showing promise for the improvement of attentional deficits in patients with schizophrenia-signs of improvement in attentional performance were detected. CONCLUSIONS: Overall, Map2k7 haploinsufficiency causes a distinctive pattern of cognitive impairment strongly suggestive of an inability to sustain attention, in accordance with those seen in psychiatric patients carrying out similar tasks. This may be important for understanding the mechanisms of cognitive dysfunction in clinical populations and highlights the possibility of treating some of these deficits with minocycline.

Invited Article: A precise instrument to determine the Planck constant, and the future kilogram.

A precise instrument, called a watt balance, compares mechanical power measured in terms of the meter, the second, and the kilogram to electrical power measured in terms of the volt and the ohm. A direct link between mechanical action and the Planck constant is established by the practical realization of the electrical units derived from the Josephson and the quantum Hall effects. We describe in this paper the fourth-generation watt balance at the National Institute of Standards and Technology (NIST), and report our initial determination of the Planck constant obtained from data taken in late 2015 and the beginning of 2016. A comprehensive analysis of the data and the associated uncertainties led to the SI value of the Planck constant, h = 6.626 069 83(22) × 10(-34) J s. The relative standard uncertainty associated with this result is 34 × 10(-9).

Crohn's Disease and Gynecologic Manifestations in Young Women.

STUDY OBJECTIVE: The purpose of this study was to describe the reproductive and gynecological concerns of young women with Crohn's disease. DESIGN, SETTING, AND PARTICIPANTS: Retrospective chart review of young women with Crohn's disease and gynecologic concerns at a large, urban tertiary children's hospital. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Documentation of abnormal bleeding, pelvic pain, genital fistula, ulcer, or abscess. RESULTS: Most of the patients (85.7%) had menstrual concerns reported as abnormal bleeding patterns or chronic pelvic pain. Genital complaints (fistula, ulcer, or abscess) were present in 75% of patients who ultimately required immune modulators or antibiotics to control their Crohn's disease. Genital complaints were present in only 1 of 3 patients who did not have a history of immune modulator use for Crohn's disease related flare. CONCLUSION: There is a paucity of information available on gynecological concerns occurring in patients with Crohn's disease. Providers should be aware of gynecological manifestations that might appear concurrently with Crohn's colitis, including vulvovaginal pain, vulvar infections, rectovaginal or rectovestibular fistulas, pelvic pain, and menstrual irregularities.

Association of Circulating Renin and Aldosterone With Osteocalcin and Bone Mineral Density in African Ancestry Families.

Hypertension is associated with accelerated bone loss, and the renin-angiotensin-aldosterone system is a key regulator of blood pressure. Although components of this system are expressed in human bone cells, studies in humans are sparse. Thus, we studied the association of circulating renin and aldosterone with osteocalcin and bone mineral density. We recruited 373 African ancestry family members without regard to health status from 6 probands (mean family size: 62 and relative pairs: 1687). Participants underwent a clinical examination, dual-energy x-ray absorptiometry, and quantitative computed tomographic scans. Renin activity, aldosterone concentration, and osteocalcin were measured in fasting blood samples. Aldosterone/renin ratio was calculated as aldosterone concentration/renin activity. All models were analyzed using pedigree-based variance components methods. Full models included adjustment for age, sex, body composition, comorbidities, lifestyle factors, blood pressure, and antihypertensive medication. Higher renin activity was significantly associated with lower total osteocalcin and with higher trabecular bone mineral density (both P<0.01). There were also significant genetic correlations between renin activity and whole-body bone mineral density. There were no associations with aldosterone concentration in any model and results for aldosterone/renin ratio were similar to those for renin activity. This is the first study to report a significant association between renin activity and a marker of bone turnover and bone mineral density in generally healthy individuals. Also, there is evidence for significant genetic pleiotropy and, thus, there may be a shared biological mechanism underlying both the renin-angiotensin-aldosterone system and bone metabolism that is independent of hypertension.

Bridging classical and quantum mechanics.

Using a watt balance and a frequency comb, a mass-energy equivalence is derived. The watt balance compares mechanical power measured in terms of the meter, the second, and the kilogram to electrical power measured in terms of the volt and the ohm. A direct link between mechanical action and the Planck constant is established by the practical realization of the electrical units derived from the Josephson and the quantum Hall effects. By using frequency combs to measure velocities and acceleration of gravity, the unit of mass can be realized from a set of three defining constants: the Planck constant h, the speed of light c, and the hyperfine splitting frequency of 133Cs.

Triamterene Enhances the Blood Pressure Lowering Effect of Hydrochlorothiazide in Patients with Hypertension.

BACKGROUND: Triamterene, because of its potassium-sparing properties, is frequently used in combination with hydrochlorothiazide (HCTZ) to treat patients with hypertension. By inhibiting the epithelial sodium channel (ENaC) in the cortical collecting duct, triamterene reduces potassium secretion, thus reducing the risk of hypokalemia. Whether triamterene has an independent effect on blood pressure (BP) has not been well studied. OBJECTIVE: To determine if triamterene provides an effect to further lower BP in patients treated with HCTZ. DESIGN: We conducted an observational study using electronic medical record data from the Indiana Network for Patient Care. Participants were 17,291 patients with the diagnosis of hypertension between 2004 and 2012. MAIN MEASURES: BP was the primary outcome. We compared the BP between patients who were taking HCTZ, with and without triamterene, either alone or in combination with other antihypertensive medications, by using a propensity score analysis. For each medication combination, we estimated the propensity score (i.e., probability) of a patient receiving triamterene using a logistic regression model. Patients with similar propensity scores were stratified into subclasses and BP was compared between those taking triamterene or not within each subclass; the effect of triamterene was then assessed by combining BP differences estimated from all subclasses. KEY RESULTS: The mean systolic BP in the triamterene + HCTZ group was 3.8 mmHg lower than in the HCTZ only group (p < 0.0001); systolic BP was similarly lower for patients taking triamterene with other medication combinations. Systolic BP reduction was consistently observed for different medication combinations. The range of systolic BP reduction was between 1 and 4 mm Hg, depending on the concurrently used medications. CONCLUSIONS: In the present study, triamterene was found to enhance the effect of HCTZ to lower BP. In addition to its potassium-sparing action, triamterene's ability to lower BP should also be considered.

Miniature wireless recording and stimulation system for rodent behavioural testing.

OBJECTIVE: Elucidation of neural activity underpinning rodent behaviour has traditionally been hampered by the use of tethered systems and human involvement. Furthermore the combination of deep-brain stimulation (DBS) and various neural recording modalities can lead to complex and time-consuming laboratory setups. For studies of this type, novel tools are required to drive forward this research. APPROACH: A miniature wireless system weighing 8.5 g (including battery) was developed for rodent use that combined multichannel DBS and local-field potential (LFP) recordings. Its performance was verified in a working memory task that involved 4-channel fronto-hippocampal LFP recording and bilateral constant-current fimbria-fornix DBS. The system was synchronised with video-tracking for extraction of LFP at discrete task phases, and DBS was activated intermittently at discrete phases of the task. MAIN RESULTS: In addition to having a fast set-up time, the system could reliably transmit continuous LFP at over 8 hours across 3-5 m distances. During the working memory task, LFP pertaining to discrete task phases was extracted and compared with well-known neural correlates of active exploratory behaviour in rodents. DBS could be wirelessly activated/deactivated at any part of the experiment during EEG recording and transmission, allowing for a seamless integration of this modality. SIGNIFICANCE: The wireless system combines a small size with a level of robustness and versatility that can greatly simplify rodent behavioural experiments involving EEG recording and DBS. Designed for versatility and simplicity, the small size and low-cost of the system and its receiver allow for enhanced portability, fast experimental setup times, and pave the way for integration with more complex behaviour.

Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1.

Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal-PFC connectivity. Altered hippocampal-PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1-PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity.

Case series of four-factor prothrombin complex concentrate for warfarin reversal before heart transplantation.

OBJECTIVE: Describe the experience of using 4-factor prothrombin complex concentrate (PCC4) in patients with a ventricular assist device (VAD) scheduled for imminent heart transplant who are receiving warfarin. METHODS: We are reporting a clinical case series describing 4 patients with VADs treated with PCC4 for anticoagulation reversal before heart transplantation. Data collection was performed via retrospective medical chart review from March 27, 2014, to July 20, 2014. RESULTS: Average time to anticoagulation reversal was 2.45 hours and average volume of PCC4 injection was 86 mL. No patient experienced a thromboembolic event or a decrease in hemoglobin indicative of a bleeding event. Average volume of packed red blood cells, platelets, and fresh frozen plasma (FFP) patients received was 2,325 mL. Patient 1 experienced a hypersensitivity reaction and patient 2 experienced thrombocytopenia postoperatively. The average acquisition cost was $3,824 and the average retail price was $7,143 per complete dose. CONCLUSIONS: PCC4 contributed to efficient reduction of International Normalized Ratio (INR) before surgery. PCC4 requires less volume than FFP for similar INR reductions. PCC4 was a beneficial agent in our patients with VADs; however, a cost-benefit analysis is needed to evaluate the future utility of PCC4.

Nurse-led educational interventions on cancer pain outcomes for oncology outpatients: a systematic review.

BACKGROUND: Cancer pain management is still unsatisfactory, although some effective guidelines exist. Educational interventions are reported to be useful in pain relief for oncology outpatients. AIM: The aims of this systematic review were to evaluate the effects of nurse-led educational interventions on improving cancer pain outcomes for oncology patients, and to establish an effective cancer pain protocol for clinical nursing practice in China. METHODS: A three-step search strategy was utilized. Eight databases were searched using the standards provided by the Joanna Briggs Institute that guided article selection, critical appraisal, data collection and data synthesis. RESULTS: A total of 1093 studies were identified through a literature search. Only six studies complied with the inclusion criteria and were found to be methodologically sound. In general, the included studies indicated positive results pertaining to patient's knowledge and attitudes towards analgesics and cancer pain management and decreased pain intensity. Studies reported minimal effects of intervention on anxiety, depression, satisfaction regarding cancer pain management and patient's quality of life. CONCLUSIONS: Educational interventions were reported as effective methods to improve cancer pain outcomes. Analysis of the six included studies demonstrated the overall positive effects of nurse-led educational interventions for improving cancer pain management. IMPLICATIONS FOR NURSING AND HEALTH POLICY: The results suggest that an effective cancer pain protocol for improving cancer pain management can be established in China.

Associations between menarche-related genetic variants and pubertal growth in male and female adolescents.

PURPOSE: Previous studies have identified novel genetic variants associated with age at menarche in females of European descent. The pubertal growth effects of these variants have not been carefully evaluated in non-European descent groups. We aimed to examine the effects of 31 newly identified menarche-related single-nucleotide polymorphisms (SNPs) on growth outcomes in African-American (AA) and European-American (EA) children in a prospective cohort. METHODS: We analyzed longitudinal data collected from 263 AAs and 338 EAs enrolled between ages 5 and 17 years; the subjects were followed semiannually for an average of 6 years. The associations between the SNPs and growth-related outcomes, including weight, height, and body mass index (BMI), were examined using mixed-effect models. RESULTS: Longitudinal analyses revealed that 4 (near or in genes VGLL3, PEX2, CA10, and SKOR2) of the 14 menarche-only-related SNPs were associated with changes in weight and BMI in EA and AA (p ≤ .0032), but none of them was associated with changes in height. Of the eight menarche-timing and BMI-related SNPs, none was associated with changes in height, but three (in or near genes NEGR1, ETV5, and FTO) were associated with more rapid increases in weight and/or BMI in EA (p ≤ .0059). Among the nine menarche-timing and height-related SNPs, four (in or near genes ZBTB38, LOC728666, TBX2, and CABLES) were associated with changes in weight or height in EA and AA (p ≤ .0042). CONCLUSIONS: Genetic variants related to age at menarche were found to be associated with various growth parameters in healthy adolescents. The identified associations were often race and sex specific.

The effect of body mass index on blood pressure varies by race among obese children.

OBJECTIVE: Previous studies have shown that the effect of adiposity on blood pressure (BP) intensifies as children become increasingly obese. Black children tend to have greater body mass index (BMI) and higher BP than age-matched white children. It is unclear whether the BP effects of BMI are race-specific among black and white children, and data on obese Hispanic children are sparse. We compared the BP effect of BMI in obese white, black, and Hispanic children. METHODS: We examined the medical records of children enrolled in a pediatric obesity clinic. Height, weight, BP, and fasting insulin were assessed as part of routine clinical care. The concurrent effects of age and BMI on BP percentile values were examined using semiparametric regression, which allows the accommodation of nonlinear effects. RESULTS: The study included 873 children (338 male; 354 black, 447 white, 72 Hispanic; 11.7±3.5 years, BMI 36.2±8.5 kg/m2). While BMI Z-scores were similar among the groups, systolic BP (SBP) was higher in black children and Hispanic children (white: 107 mm Hg; black: 112 mm Hg; Hispanic: 112 mm Hg; p=0.0001). Age, sex, and height-adjusted SBP percentiles were significantly different among the three groups (white: 50; black: 59; Hispanic: 59; p=0.0006). In children of the same age, BP was higher at any given BMI in black children and Hispanic children. CONCLUSIONS: Among children referred for treatment of obesity, black children and Hispanic children are at a greater risk for having elevated BP when compared to white children of similar age and BMI.