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Mays AC, Moustafa F, Worley M, Waltonen JD, D'Agostino R.
JAMA Otolaryngol Head Neck Surg. 2014 Dec 1;140(12):1198-206.
PMID: 25321077
Identifying high-risk patients in the preoperative period can allow physicians to optimize nutritional status early for better outcomes after head and neck cancer resections.
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Izawa KP, Watanabe S, Brubaker PH, Tochimoto S, Hirano Y, Matsushima S, Suzuki T, Oka K, Saito T, Omori Y, Suzuki K, Osada N, Omiya K, Shimizu H, Akashi YJ.
Medicine (Baltimore). 2014 Dec ;93(29):e306.
PMID: 25546676
This study aimed to determine the relation between the regression slope relating minute ventilation to carbon dioxide output (V˙E/V˙CO2 slope) and maximum phonation time (MPT), and the MPT required to attain a threshold value for V˙E/V˙CO2 slope of ≤34 in chronic heart failure (CHF) patients.This cross-sectional study enrolled 115 CHF patients (mean age, 54.5 years; men, 84.9%). V˙E/V˙CO2 slope was assessed during cardiopulmonary exercise testing (CPX). Thereafter, patients were divided into 2 groups according to exercise capacity: V˙E/V˙CO2 slope ≤34 (V˙E/V˙CO2 ≤34 group, n = 81) and V˙E/V˙CO2 slope >34 (V˙E/V˙CO2 >34 group, n = 34). For MPT measurements, all patients produced a sustained vowel/a:/ for as long as possible during respiratory effort from the seated position.All subjects showed significant negative correlation between V˙E/V˙CO2 slope and MPT (r = -0.51, P < 0.001). After adjustment for clinical characteristics, MPT was significantly higher in the V˙E/V˙CO2 ≤34 group vs V˙E/V˙CO2 >34 group (21.4 ± 6.4 vs 17.4 ± 4.3 s, F = 7.4, P = 0.007). The appropriate MPT cut-off value for identifying a V˙E/V˙CO2 slope ≤34 was 18.12 seconds.An MPT value of 18.12 seconds may be a useful target value for identifying CHF patients with a V˙E/V˙CO2 slope ≤34 and for risk management in these patients.
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Zhao Y, Li Q, Katzenellenbogen BS, Lau LF, Taylor RN, Bagchi IC, Bagchi MK.
Mol Endocrinol. 2014 Dec ;28(12):1934-47.
PMID: 25321413
Endometriosis is a prevalent gynecological disorder in which endometrial tissue proliferates in extrauterine sites, such as the peritoneal cavity, eventually giving rise to painful, invasive lesions. Dysregulated estradiol (E) signaling has been implicated in this condition. However, the molecular mechanisms that operate downstream of E in the ectopic endometrial tissue are unknown. To investigate these mechanisms, we used a mouse model of endometriosis. Endometrial tissue from donor mice was surgically transplanted on the peritoneal surface of immunocompetent syngeneic recipient mice, leading to the establishment of cystic endometriosis-like lesions. Our studies revealed that treatment with E led to an approximately 3-fold increase in the lesion size within a week of transplantation. E also caused a concomitant stimulation in the expression of connective tissue growth factor/Cyr61/Nov (CCN1), a secreted cysteine-rich matricellular protein, in the lesions. Interestingly, CCN1 is highly expressed in human ectopic endometriotic lesions. To address its role in endometriosis, endometrial tissue from Ccn1-null donor mice was transplanted in wild-type recipient mice. The resulting ectopic lesions were reduced up to 75% in size compared with wild-type lesions due to diminished cell proliferation and cyst formation. Notably, loss of CCN1 also disrupted the development of vascular networks in the ectopic lesions and reduced the expression of several angiogenic factors, such as vascular endothelial growth factor-A and vascular endothelial growth factor-C. These results suggest that CCN1, acting downstream of E, critically controls cell proliferation and neovascularization, which support the growth and survival of endometriotic tissue at ectopic sites. Blockade of CCN1 signaling during the early stages of lesion establishment may provide a therapeutic avenue to control endometriosis.
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Zaitlen N, Pasaniuc B, Sankararaman S, Bhatia G, Zhang J, Gusev A, Young T, Tandon A, Pollack S, Vilhjálmsson BJ, Assimes TL, Berndt SI, Blot WJ, Chanock S, Franceschini N, Goodman PG, He J, Hennis AJ, Hsing A, Ingles SA, Isaacs W, Kittles RA, Klein EA, Lange LA, Nemesure B, Patterson N, Reich D, Rybicki BA, Stanford JL, Stevens VL, Strom SS, Whitsel EA, Witte JS, Xu J, Haiman C, Wilson JG, Kooperberg C, Stram D, Reiner AP, Tang H, Price AL.
Nat Genet. 2014 Dec ;46(12):1356-62.
PMID: 25383972
Despite recent progress on estimating the heritability explained by genotyped SNPs (h(2)g), a large gap between h(2)g and estimates of total narrow-sense heritability (h(2)) remains. Explanations for this gap include rare variants or upward bias in family-based estimates of h(2) due to shared environment or epistasis. We estimate h(2) from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (h(2)γ). We show that h(2)γ = 2FSTCθ(1 - θ)h(2), where FSTC measures frequency differences between populations at causal loci and θ is the genome-wide ancestry proportion. Our approach is not susceptible to biases caused by epistasis or shared environment. We applied this approach to the analysis of 13 phenotypes in 21,497 African-American individuals from 3 cohorts. For height and body mass index (BMI), we obtained h(2) estimates of 0.55 ± 0.09 and 0.23 ± 0.06, respectively, which are larger than estimates of h(2)g in these and other data but smaller than family-based estimates of h(2).
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Freedman BI, Robinson TW.
Nat Rev Nephrol. 2014 Dec ;10(12):677-8.
PMID: 25266211
A new population-based study of a Norwegian registry containing data on more than 5 million individuals has confirmed the existence of powerful familial clustering of complex aetiologies of end-stage renal disease. Novel strategies for identifying additional nephropathy risk genes will benefit from such large familial registries.
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Strowd RE, Swett K, Harmon M, Carter AF, Pop-Vicas A, Chan M, Tatter SB, Ellis T, Blevins M, High K, Lesser GJ.
Neuro Oncol. 2014 Dec ;16(12):1639-44.
PMID: 24714522
Patients with central nervous system (CNS) malignancies represent an "at-risk" population for contracting influenza, particularly if they are receiving ongoing chemotherapy, radiation, and/or glucocorticoid treatment. The Centers for Disease Control endorses vaccination for these patients, although data are not available to indicate whether they mount an immunologic response adequate to achieve clinical protection.
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Nader MA, Balster RL, Henningfield JE.
Neuropharmacology. 2014 Dec ;87():4-8.
PMID: 24859612
Clinical findings suggest that the most promising strategy for cocaine addiction is a combination of indirect-acting monoamine agonists with some form of behavioral intervention. This approach can be traced back to preclinical research, some of which was conducted by William L. Woolverton. The goal of this brief review is to provide readers with an appreciation for the experimental breadth involving both behavior and pharmacology that encompassed Woolverton's amazing career, from the evaluation of abuse liability of drugs to the use of complex behavioral contingencies to better model the human condition. We begin with Woolverton's research using simple and complex schedules of reinforcement to evaluate abuse liability and how that has impacted current animal models. We also discuss his use of cocaine vs. food choice schedules of reinforcement as a model to evaluate potential medications for treating cocaine use disorders. Woolverton concluded that drug taking behavior was not "impulsive" and "out of control" as has often been proposed, but rather directly determined by the environmental contingencies and the context of its availability, providing a nuanced understanding of drug-behavior interactions. This article is part of the Special Issue entitled 'CNS Stimulants'
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Chew EY, Davis MD, Danis RP, Lovato JF, Perdue LH, Greven C, Genuth S, Goff DC, Leiter LA, Ismail-Beigi F, Ambrosius WT, .
Ophthalmology. 2014 Dec ;121(12):2443-51.
PMID: 25172198
To report additional ocular outcomes of intensive treatment of hyperglycemia, blood pressure, and dyslipidemia in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study.
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Boada MD, Martin TJ, Peters CM, Hayashida K, Harris MH, Houle TT, Boyden ES, Eisenach JC, Ririe DG.
Pain. 2014 Dec ;155(12):2646-55.
PMID: 25267211
Fast-conducting myelinated high-threshold mechanoreceptors (AHTMR) are largely thought to transmit acute nociception from the periphery. However, their roles in normal withdrawal and in nerve injury-induced hyperalgesia are less well accepted. Modulation of this subpopulation of peripheral neurons would help define their roles in withdrawal behaviors. The optically active proton pump, ArchT, was placed in an adeno-associated virus-type 8 viral vector with the CAG promoter and was administered by intrathecal injection resulting in expression in myelinated neurons. Optical inhibition of peripheral neurons at the soma and transcutaneously was possible in the neurons expressing ArchT, but not in neurons from control animals. Receptive field characteristics and electrophysiology determined that inhibition was neuronal subtype-specific with only AHTMR neurons being inhibited. One week after nerve injury the AHTMR are hyperexcitable, but can still be inhibited at the soma and transcutaneously. Withdrawal thresholds to mechanical stimuli in normal and in hyperalgesic nerve-injured animals also were increased by transcutaneous light to the affected hindpaw. This suggests that AHTMR neurons play a role not only in threshold-related withdrawal behavior in the normal animal, but also in sensitized states after nerve injury. This is the first time this subpopulation of neurons has been reversibly modulated to test their contribution to withdrawal-related behaviors before and after nerve injury. This technique may prove useful to define the role of selective neuronal populations in different pain states.
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Nahman-Averbuch H, Martucci KT, Granovsky Y, Weissman-Fogel I, Yarnitsky D, Coghill RC.
Pain. 2014 Dec ;155(12):2491-501.
PMID: 25047783
The role of endogenous analgesic mechanisms has largely been viewed in the context of gain modulation during nociceptive processing. However, these analgesic mechanisms may play critical roles in the extraction and subsequent utilization of information related to spatial and temporal features of nociceptive input. To date, it remains unknown if spatial and temporal filtering of nociceptive information is supported by similar analgesic mechanisms. To address this question, human volunteers were recruited to assess brain activation with functional magnetic resonance imaging during conditioned pain modulation (CPM) and offset analgesia (OA). CPM provides one paradigm for assessing spatial filtering of nociceptive information while OA provides a paradigm for assessing temporal filtering of nociceptive information. CPM and OA both produced statistically significant reductions in pain intensity. However, the magnitude of pain reduction elicited by CPM was not correlated with that elicited by OA across different individuals. Different patterns of brain activation were consistent with the psychophysical findings. CPM elicited widespread reductions in regions engaged in nociceptive processing such as the thalamus, insula, and secondary somatosensory cortex. OA produced reduced activity in the primary somatosensory cortex but was associated with greater activation in the anterior insula, dorsolateral prefrontal cortex, intraparietal sulcus, and inferior parietal lobule relative to CPM. In the brain stem, CPM consistently produced reductions in activity, while OA produced increases in activity. Conjunction analysis confirmed that CPM-related activity did not overlap with that of OA. Thus, dissociable mechanisms support inhibitory processes engaged during spatial vs temporal filtering of nociceptive information.
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Helzer EG, Furr RM, Hawkins A, Barranti M, Blackie LE, Fleeson W.
Pers Soc Psychol Bull. 2014 Dec ;40(12):1698-710.
PMID: 25326476
This study tested for inter-judge agreement on moral character. A sample of students and community members rated their own moral character using a measure that tapped six moral character traits. Friends, family members, and/or acquaintances rated these targets on the same traits. Self/other and inter-informant agreement was found at the trait level for both a general character factor and for residual variance explained by individual moral character traits, as well as at the individual level (judges agreed on targets' "moral character profiles"). Observed inter-judge agreement constitutes evidence for the existence of moral character, and raises questions about the nature of moral character traits.
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Cho M, Henry EM, Lewis DR, Wu G, Muday GK, Spalding EP.
Plant Physiol. 2014 Dec ;166(4):2091-9.
PMID: 25324509
Polar transport of the hormone auxin through tissues and organs depends on membrane proteins, including some B-subgroup members of the ATP-binding cassette (ABC) transporter family. The messenger RNA level of at least one B-subgroup ABCB gene in Arabidopsis (Arabidopsis thaliana), ABCB19, increases upon treatment with the anion channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), possibly to compensate for an inhibitory effect of the drug on ABCB19 activity. Consistent with this hypothesis, NPPB blocked ion channel activity associated with ABCB19 expressed in human embryonic kidney cells as measured by patch-clamp electrophysiology. NPPB inhibited polar auxin transport through Arabidopsis seedling roots similarly to abcb19 mutations. NPPB also inhibited shootward auxin transport, which depends on the related ABCB4 protein. NPPB substantially decreased ABCB4 and ABCB19 protein levels when cycloheximide concomitantly inhibited new protein synthesis, indicating that blockage by NPPB enhances the degradation of ABCB transporters. Impairing the principal auxin transport streams in roots with NPPB caused aberrant patterns of auxin signaling reporters in root apices. Formation of the auxin-signaling gradient across the tips of gravity-stimulated roots, and its developmental consequence (gravitropism), were inhibited by micromolar concentrations of NPPB that did not affect growth rate. These results identify ion channel activity of ABCB19 that is blocked by NPPB, a compound that can now be considered an inhibitor of polar auxin transport with a defined molecular target.
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Sanz L, Fernández-Marcos M, Modrego A, Lewis DR, Muday GK, Pollmann S, Dueñas M, Santos-Buelga C, Lorenzo O.
Plant Physiol. 2014 Dec ;166(4):1972-84.
PMID: 25315603
Nitric oxide (NO) is a unique reactive nitrogen molecule with an array of signaling functions that modulates plant developmental processes and stress responses. To explore the mechanisms by which NO modulates root development, we used a pharmacological approach and NO-deficient mutants to unravel the role of NO in establishing auxin distribution patterns necessary for stem cell niche homeostasis. Using the NO synthase inhibitor and Arabidopsis (Arabidopsis thaliana) NO biosynthesis mutants (nitric oxide-associated1 [noa1], nitrate reductase1 [nia1] and nia2, and nia1 nia2 noa1), we show that depletion of NO in noa1 reduces primary root elongation and increases flavonol accumulation consistent with elevated reactive oxygen species levels. The elevated flavonols are required for the growth effect, because the transparent testa4 mutation reverses the noa1 mutant root elongation phenotype. In addition, noa1 and nia1 nia2 noa1 NO-deficient mutant roots display small root meristems with abnormal divisions. Concomitantly, auxin biosynthesis, transport, and signaling are perturbed. We further show that NO accumulates in cortex/endodermis stem cells and their precursor cells. In endodermal and cortical cells, the noa1 mutant acts synergistically to the effect of the wuschel-related homeobox5 mutation on the proximal meristem, suggesting that NO could play an important role in regulating stem cell decisions, which has been reported in animals.
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Ferreira de Sá DS, Schulz A, Streit FE, Turner JD, Oitzl MS, Blumenthal TD, Schächinger H.
Psychoneuroendocrinology. 2014 Dec ;50():311-20.
PMID: 25265284
Stress glucocorticoids and insulin are important endocrine regulators of energy homeostasis, but little is known about their central interaction on the reward-related processing of food cues. According to a balanced group design, healthy food deprived men received either 40IU intranasal insulin (n=13), 30mg oral cortisol (n=12), both (n=15), or placebo (n=14). Acoustic startle responsiveness was assessed during presentation of food and non-food pictures. Cortisol enhanced startle responsiveness during visual presentation of "high glycemic" food pictures, but not during presentation of neutral and pleasant non-food pictures. Insulin had no effect. Based on the "frustrative nonreward" model these results suggest that the reward value of high glycemic food items is specifically increased by cortisol.
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Zeineh NS, Bachman TN, El-Haddad H, Champion HC.
Pulm Circ. 2014 Dec ;4(4):612-8.
PMID: 25610597
The inotropic effects of prostacyclins in chronic pulmonary arterial hypertension (PAH) are unclear and may be important in directing patient management in the acute setting. We sought to study the effects of an acute intravenous (IV) infusion of iloprost on right ventricular (RV) contractility in a rat model of chronic PAH. Rats were treated with monocrotaline, 60 mg/kg intraperitoneally, to induce PAH. Six weeks later, baseline hemodynamic assessment was performed with pressure-volume and Doppler flow measurements. In one group of animals, measurements were repeated 10-15 minutes after IV infusion of a fixed dose of iloprost (20 μg/kg). A separate group of rats underwent dose-response assessment. RV contractility and RV-pulmonary artery coupling were assessed by the end-systolic pressure-volume relationship (ESPVR) and end-systolic elastance/effective arterial elastance (Ees/Ea). RV cardiomyocytes were isolated, and intracellular cAMP (cyclic adenosine monophosphate) concentration was measured with a cAMP-specific enzyme immunoassay kit. Animals had evidence of PAH and RV hypertrophy. Right ventricle/(left ventricle + septum) weight was 0.40 ± 0.03. RV systolic pressure (RVSP) was 39.83 ± 1.62 mmHg. Administration of iloprost demonstrated an increase in the slope of the ESPVR from 0.29 ± 0.02 to 0.42 ± 0.05 (P < .05). Ees/Ea increased from 0.63 ± 0.07 to 0.82 ± 0.06 (P < .05). The RV contractility index (max dP/dt normalized for instantaneous pressure) increased from 94.11 to 114.5/s (P < .05), as did the RV ejection fraction, from 48.0% to 52.5% (P < .05). This study suggests a positive inotropic effect of iloprost on a rat model of chronic PAH.
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Waugh CE, Lemus MG, Gotlib IH.
Soc Cogn Affect Neurosci. 2014 Dec ;9(12):2001-9.
PMID: 24493835
Evidence is accruing that people can maintain their emotional states, but how they do it and which brain regions are responsible still remains unclear. We examined whether people maintain emotional states 'actively', with explicit elaboration of the emotion, or 'passively', without elaboration. Twenty-four participants completed an emotion maintenance task in which they either maintained the emotional intensity from the first picture of a pair to compare to that of the second picture ('maintain' condition), or only rated their emotional response to the second picture ('non-maintain' condition). Supporting the 'active' maintenance hypothesis, when maintaining vs not maintaining emotion, participants exhibited increased height and width of activation in the dorsal medial frontal cortex (MFC) and lateral prefrontal cortex, regions associated with explicit emotion generation and manipulation of contents in working memory, respectively. Supporting the 'passive' maintenance hypothesis, however, when viewing negative emotional pictures (vs neutral pictures) that were not explicitly maintained, participants exhibited greater duration of activity in the rostral MFC, a region associated with implicit emotion generation. Supported by behavioral findings, this evidence that people maintain emotional states both naturally in the rMFC and strategically in the dMFC may be critical for understanding normal as well as disordered emotion regulation.
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Tamam C, Poehling GG.
Sports Med Arthrosc. 2014 Dec ;22(4):219-22.
PMID: 25370877
In recent years, development of computer graphics and haptic feedback technology enabled the use of virtual reality. Virtual reality provides the opportunity to combine 3D visual imagery with interactivity, visual, and tactile realism. Robotic-assisted orthopedic surgery is defined as the use of computers and robotic technology to assist the orthopedist in providing musculoskeletal care, in which machine has the capability of precision and accuracy. Robotic-assisted orthopedic surgery is used in simulating diagnosis, preoperative and intraoperative planning, and actual surgery. One of the main areas for computer-assisted surgical applications is unicompartmental or bicompartmental knee arthroplasty, in which the clinical efficacy is improved by providing enhanced component positioning with dynamic ligament balancing.
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Lord AS, Langefeld CD, Sekar P, Moomaw CJ, Badjatia N, Vashkevich A, Rosand J, Osborne J, Woo D, Elkind MS.
Stroke. 2014 Dec ;45(12):3535-42.
PMID: 25316275
Risk factors for infections after intracerebral hemorrhage (ICH) and their association with outcomes are unknown. We hypothesized there are predictors of poststroke infection and infections drive worse outcomes.
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Gorbachinsky I, Sherertz R, Russell G, Krane LS, Hodges SJ.
Ther Adv Urol. 2014 Dec ;6(6):224-9.
PMID: 25435916
Vulvovaginitis has a known association with urinary tract infections (UTIs) in girls. We hypothesize that vulvovaginitis is a major contributor to UTIs in prepubertal girls by increasing periurethral colonization with uropathogens.
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Huang JW, Xie MK, Zhang Y, Wei GJ, Li X, Li HB, Wang JH, Zhu WD, Li C, Xu YM, Song LJ.
Urology. 2014 Dec ;84(6):1499-505.
PMID: 25306480
To evaluate the effect of reconstruction of penile urethra with the 3-dimensional (3-D) porous bladder acellular matrix (BAM) in a rabbit model.
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