Non-canonical odor coding in the mosquito.

Aedes aegypti mosquitoes are a persistent human foe, transmitting arboviruses including dengue when they feed on human blood. Mosquitoes are intensely attracted to body odor and carbon dioxide, which they detect using ionotropic chemosensory receptors encoded by three large multi-gene families. Genetic mutations that disrupt the olfactory system have modest effects on human attraction, suggesting redundancy in odor coding. The canonical view is that olfactory sensory neurons each express a single chemosensory receptor that defines its ligand selectivity. We discovered that Ae. aegypti uses a different organizational principle, with many neurons co-expressing multiple chemosensory receptor genes. In vivo electrophysiology demonstrates that the broad ligand-sensitivity of mosquito olfactory neurons depends on this non-canonical co-expression. The redundancy afforded by an olfactory system in which neurons co-express multiple chemosensory receptors may increase the robustness of the mosquito olfactory system and explain our long-standing inability to disrupt the detection of humans by mosquitoes.

How many kinases are druggable? A review of our current understanding.

There are over 500 human kinases ranging from very well-studied to almost completely ignored. Kinases are tractable and implicated in many diseases, making them ideal targets for medicinal chemistry campaigns, but is it possible to discover a drug for each individual kinase? For every human kinase, we gathered data on their citation count, availability of chemical probes, approved and investigational drugs, PDB structures, and biochemical and cellular assays. Analysis of these factors highlights which kinase groups have a wealth of information available, and which groups still have room for progress. The data suggest a disproportionate focus on the more well characterized kinases while much of the kinome remains comparatively understudied. It is noteworthy that tool compounds for understudied kinases have already been developed, and there is still untapped potential for further development in this chemical space. Finally, this review discusses many of the different strategies employed to generate selectivity between kinases. Given the large volume of information available and the progress made over the past 20 years when it comes to drugging kinases, we believe it is possible to develop a tool compound for every human kinase. We hope this review will prove to be both a useful resource as well as inspire the discovery of a tool for every kinase.

What does degeneration at the cervicothoracic junction tell us? A kinematic MRI study of 93 individuals.

PURPOSE: Current decision-making in multilevel cervical fusion weighs the potential to protect adjacent levels and reduce reoperation risk by crossing the cervicothoracic junction (C7/T1) against increased operative time and risk of complication. Careful planning is required, and the planned distal and adjacent levels should be assessed for degenerative disc disease (DDD). This study assessed whether DDD at the cervicothoracic junction was associated with DDD, disc height, translational motion, or angular variation in the adjacent superior (C6/C7) or inferior (T1/T2) levels. METHODS: This study retrospectively analyzed 93 cases with kinematic MRI. Cases were randomly selected from a database with inclusion criteria being no prior spine surgery and images having sufficient quality for analysis. DDD was assessed using Pfirrmann classification. Vertebral body bone marrow lesions were assessed using Modic changes. Disc height was measured at the mid-disc in neutral and extension. Translational motion and angular variation were calculated by assessing translational or angular motion segment integrity respectively in flexion and extension. Statistical associations were assessed with scatterplots and Kendall's tau. RESULTS: DDD at C7/T1 was positively associated with DDD at C6/C7 (tau = 0.53, p < 0.01) and T1/T2 (tau = 0.58, p < 0.01), with greater disc height in neutral position at T1/T2 (tau = 0.22, p < 0.01), and with greater disc height in extended position at C7/T1 (tau = 0.17, p = 0.04) and at T1/T2 (tau = 0.21, p < 0.01). DDD at C7/T1 was negatively associated with angular variation at C6/C7 (tau = - 0.23, p < 0.01). No association was appreciated between DDD at C7/T1 and translational motion. CONCLUSION: The association of DDD at the cervicothoracic junction with DDD at the adjacent levels emphasizes the necessity for careful selection of the distal level in multilevel fusion in the distal cervical spine.

Neuromodulation in Beta-Band Power Between Movement Execution and Inhibition in the Human Hippocampus.

INTRODUCTION: The hippocampus is thought to be involved in movement, but its precise role in movement execution and inhibition has not been well studied. Previous work with direct neural recordings has found beta-band (13-30 Hz) modulation in both movement execution and inhibition throughout the motor system, but the role of beta-band modulation in the hippocampus during movement inhibition is not well understood. Here, we perform a Go/No-Go reaching task in ten patients with medically refractory epilepsy to study human hippocampal beta-power changes during movement. MATERIALS AND METHODS: Ten epilepsy patients (5 female; ages 21-46) were implanted with intracranial depth electrodes for seizure monitoring and localization. Local field potentials were sampled at 2000 Hz during a Go/No-Go movement task. Comparison of beta-band power between Go and No-Go conditions was conducted using Wilcoxon signed-rank hypothesis testing for each patient. Sub-analyses were conducted to assess differences in the anterior vs posterior contacts, ipsilateral vs contralateral contacts, and male vs female beta-power values. RESULTS: Eight out of ten patients showed significant beta-power decreases during the Go movement response (p < 0.05) compared to baseline. Eight out of ten patients also showed significant beta-power increases in the No-Go condition, occurring in the absence of movement. No significant differences were noted between ipsilateral vs contralateral contacts nor in anterior vs posterior hippocampal contacts. Female participants had a higher task success rate than males and had significantly greater beta-power increases in the No-Go condition (p < 0.001). CONCLUSION: These findings indicate that increases in hippocampal beta power are associated with movement inhibition. To the best of our knowledge, this study is the first to report this phenomenon in the human hippocampus. The beta band may represent a state-change signal involved in motor processing. Future focus on the beta band in understanding human motor and impulse control will be vital.

Does qSOFA score predict ICU admission and outcomes in patients with obstructed infected ureteral stones?

INTRODUCTION: Obstructing stones with infection represent a true urologic emergency requiring prompt decompression. Historically the systemic inflammatory response syndrome (SIRS) criteria has been used to predict outcomes in patients with sepsis. The quick Sequential Organ Failure Assessment (qSOFA) score has been proposed as a prognostic factor in patients with acute pyelononephritis associated with nephrolithiasis. However there has been limited application of qSOFA to patients undergoing ureteral stenting with obstructive pyelonephritis. The purpose of this study was to evaluate the predictive value of the qSOFA score for postoperative outcomes following renal decompression in this patient population. MATERIALS AND METHODS: A retrospective review was conducted at three medical centers within one academic institution to identify patients with obstructive pyelonephritis secondary to ureteral stones. All patients underwent emergent ureteral stent placement for decompression. The primary outcome was the predictive value of preoperative qSOFA score ≥ 2 for intensive care unit (ICU) admission postoperatively. Univariate analysis and multivariate regression analysis were performed to identify factors associated with postoperative outcomes, with p < 0.05 considered significant. RESULTS: Of the 289 patients who had ureteral stents placed, 147 patients met inclusion criteria. Twenty-four (16.3%) patients required ICU admission and there were 3 (2%) mortalities, all of these within the ICU admission group. The sensitivity and specificity of the qSOFA score ≥ 2 for ICU admission was 70.8% and 79.5% respectively which outperformed SIRS criteria, which had a sensitivity and specificity of 100% and 33.6% respectively. CONCLUSION: A preoperative qSOFA score ≥ 2 was a significant predictor for postoperative ICU admission in patients undergoing ureteral stent placement for obstructive pyelonephritis. The qSOFA score can be used to determine which patients will require ICU admission.

Mechanism of Ti-Catalyzed Oxidative Nitrene Transfer in [2 + 2 + 1] Pyrrole Synthesis from Alkynes and Azobenzene.

A combined computational and experimental study on the mechanism of Ti-catalyzed formal [2 + 2 + 1] pyrrole synthesis from alkynes and aryl diazenes is reported. This reaction proceeds through a formally TiII/TiIV redox catalytic cycle as determined by natural bond orbital (NBO) and intrinsic bond orbital (IBO) analysis. Kinetic analysis of the reaction of internal alkynes with azobenzene reveals a complex equilibrium involving Ti═NPh monomer/dimer equilibrium and Ti═NPh + alkyne [2 + 2] cycloaddition equilibrium along with azobenzene and pyridine inhibition equilibria prior to rate-determining second alkyne insertion. Computations support this kinetic analysis, provide insights into the structure of the active species in catalysis and the roles of solvent, and provide a new mechanism for regeneration of the Ti imido catalyst via disproportionation. Reductive elimination from a 6-membered azatitanacyclohexadiene species to generate pyrrole-bound TiII is surprisingly facile and occurs through a unique electrocyclic reductive elimination pathway similar to a Nazarov cyclization. The resulting TiII species are stabilized through backbonding into the π* of the pyrrole framework, although solvent effects also significantly stabilize free TiII species that are required for pyrrole loss and catalytic turnover. Further computational and kinetic analysis reveals that in complex reactions with unysmmetric alkynes the resulting pyrrole regioselectivity is driven primarily by steric effects for terminal alkynes and inductive effects for internal alkynes.

Ta(CNDipp)6 : An Isocyanide Analogue of Hexacarbonyltantalum(0).

Hexakis(2,6-diisopropylphenylisocyanide)tantalum is the first isocyanide analogue of the highly unstable Ta(CO)6 and represents the only well-defined zerovalent tantalum complex to be prepared by conventional laboratory methods. Two prior examples of homoleptic Ta0 complexes are known, Ta(benzene)2 and Ta(dmpe)3 , dmpe=1,2-bis(dimethylphosphano)ethane, but these have only been accessed via ligand co-condensation with tantalum vapor in a sophisticated metal-atom reactor. Consistent with its 17-electron nature, Ta(CNDipp)6 undergoes facile one-electron oxidation, reduction, or disproportionation reactions. In this sense, it qualitatively resembles V(CO)6 , the only paramagnetic homoleptic metal carbonyl isolable under ambient conditions.

Ti-Catalyzed Multicomponent Oxidative Carboamination of Alkynes with Alkenes and Diazenes.

The inter- or intramolecular oxidative carboamination of alkynes catalyzed by [py2TiCl2NPh]2 is reported. These multicomponent reactions couple alkenes, alkynes and diazenes to form either α,ß-unsaturated imines or α-(iminomethyl)cyclopropanes via a TiII/TiIV redox cycle. Each of these products is formed from a common azatitanacyclohexene intermediate that undergoes either ß-H elimination or α,γ-coupling, wherein the selectivity is under substrate control.

Altered expression of Raet1e, a major histocompatibility complex class 1-like molecule, underlies the atherosclerosis modifier locus Ath11 10b.

RATIONALE: Quantitative trait locus mapping of an intercross between C57.Apoe⁻/⁻ and FVB.Apoe⁻/⁻ mice revealed an atherosclerosis locus controlling aortic root lesion area on proximal chromosome 10, Ath11. In a previous work, subcongenic analysis showed Ath11 to be complex with proximal (10a) and distal (10b) regions. OBJECTIVE: To identify the causative genetic variation underlying the atherosclerosis modifier locus Ath11 10b. METHODS AND RESULTS: We now report subcongenic J, which narrows the 10b region to 5 genes, Myb, Hbs1L, Aldh8a1, Sgk1, and Raet1e. Sequence analysis of these genes revealed no amino acid coding differences between the parental strains. However, comparing aortic expression of these genes between F1.Apoe⁻/⁻ Chr10SubJ((B/F)) and F1.Apoe⁻/⁻ Chr10SubJ((F/F)) uncovered a consistent difference only for Raet1e, with decreased, virtually background, expression associated with increased atherosclerosis in the latter. The key role of Raet1e was confirmed by showing that transgene-induced aortic overexpression of Raet1e in F1.Apoe⁻/⁻ Chr10SubJ((F/F)) mice decreased atherosclerosis. Promoter reporter constructs comparing C57 and FVB sequences identified an FVB mutation in the core of the major aortic transcription start site abrogating activity. CONCLUSIONS: This nonbiased approach has revealed Raet1e, a major histocompatibility complex class 1-like molecule expressed in lesional aortic endothelial cells and macrophage-rich regions, as a novel atherosclerosis gene and represents one of the few successes of the quantitative trait locus strategy in complex diseases.

Primary somatosensory cortex organization for engineering artificial somatosensation.

Somatosensory deficits from stroke, spinal cord injury, or other neurologic damage can lead to a significant degree of functional impairment. The primary (SI) and secondary (SII) somatosensory cortices encode information in a medial to lateral organization. SI is generally organized topographically, with more discrete cortical representations of specific body regions. SII regions corresponding to anatomical areas are less discrete and may represent a more functional rather than topographic organization. Human somatosensory research continues to map cortical areas of sensory processing with efforts primarily focused on hand and upper extremity information in SI. However, research into SII and other body regions is lacking. In this review, we synthesize the current state of knowledge regarding the cortical organization of human somatosensation and discuss potential applications for brain computer interface. In addition to accurate individualized mapping of cortical somatosensation, further research is required to uncover the neurophysiological mechanisms of how somatosensory information is encoded in the cortex.

Beta-band power classification of go/no-go arm-reaching responses in the human hippocampus.

Objective.Can we classify movement execution and inhibition from hippocampal oscillations during arm-reaching tasks? Traditionally associated with memory encoding, spatial navigation, and motor sequence consolidation, the hippocampus has come under scrutiny for its potential role in movement processing. Stereotactic electroencephalography (SEEG) has provided a unique opportunity to study the neurophysiology of the human hippocampus during motor tasks. In this study, we assess the accuracy of discriminant functions, in combination with principal component analysis (PCA), in classifying between 'Go' and 'No-go' trials in a Go/No-go arm-reaching task.Approach.Our approach centers on capturing the modulation of beta-band (13-30 Hz) power from multiple SEEG contacts in the hippocampus and minimizing the dimensional complexity of channels and frequency bins. This study utilizes SEEG data from the human hippocampus of 10 participants diagnosed with epilepsy. Spectral power was computed during a 'center-out' Go/No-go arm-reaching task, where participants reached or withheld their hand based on a colored cue. PCA was used to reduce data dimension and isolate the highest-variance components within the beta band. The Silhouette score was employed to measure the quality of clustering between 'Go' and 'No-go' trials. The accuracy of five different discriminant functions was evaluated using cross-validation.Main results.The Diagonal-Quadratic model performed best of the 5 classification models, exhibiting the lowest error rate in all participants (median: 9.91%, average: 14.67%). PCA showed that the first two principal components collectively accounted for 54.83% of the total variance explained on average across all participants, ranging from 36.92% to 81.25% among participants.Significance.This study shows that PCA paired with a Diagonal-Quadratic model can be an effective method for classifying between Go/No-go trials from beta-band power in the hippocampus during arm-reaching responses. This emphasizes the significance of hippocampal beta-power modulation in motor control, unveiling its potential implications for brain-computer interface applications.

Beta-band power modulation in the human amygdala differentiates between go/no-go responses in an arm-reaching task.

Objective. Traditionally known for its involvement in emotional processing, the amygdala's involvement in motor control remains relatively unexplored, with sparse investigations into the neural mechanisms governing amygdaloid motor movement and inhibition. This study aimed to characterize the amygdaloid beta-band (13-30 Hz) power between 'Go' and 'No-go' trials of an arm-reaching task.Approach. Ten participants with drug-resistant epilepsy implanted with stereoelectroencephalographic (SEEG) electrodes in the amygdala were enrolled in this study. SEEG data was recorded throughout discrete phases of a direct reach Go/No-go task, during which participants reached a touchscreen monitor or withheld movement based on a colored cue. Multitaper power analysis along with Wilcoxon signed-rank and Yates-correctedZtests were used to assess significant modulations of beta power between the Response and fixation (baseline) phases in the 'Go' and 'No-go' conditions.Main results. In the 'Go' condition, nine out of the ten participants showed a significant decrease in relative beta-band power during the Response phase (p⩽ 0.0499). In the 'No-go' condition, eight out of the ten participants presented a statistically significant increase in relative beta-band power during the response phase (p⩽ 0.0494). Four out of the eight participants with electrodes in the contralateral hemisphere and seven out of the eight participants with electrodes in the ipsilateral hemisphere presented significant modulation in beta-band power in both the 'Go' and 'No-go' conditions. At the group level, no significant differences were found between the contralateral and ipsilateral sides or between genders.Significance.This study reports beta-band power modulation in the human amygdala during voluntary movement in the setting of motor execution and inhibition. This finding supplements prior research in various brain regions associating beta-band power with motor control. The distinct beta-power modulation observed between these response conditions suggests involvement of amygdaloid oscillations in differentiating between motor inhibition and execution.

Stereotactic Frame-Based Electrode Insertion: The Accuracy of Increasingly Oblique Insertion Angles.

AIM: To investigate the relationship between planned drill approach angle and angular deviation of the stereotactically placed intracranial electrode tips. MATERIAL AND METHODS: Stereotactic electrode implantation was performed in 13 patients with drug resistant epilepsy. A total of 136 electrodes were included in our analysis. Stereotactic targets were planned on pre-operative magnetic resonance imaging (MRI) scans and implantation was carried out using a Cosman-Roberts-Wells stereotactic frame with the Ad-Tech drill guide and electrodes. Post implant electrode angles in the axial, coronal, and sagittal planes were determined from post-operative computerized tomography (CT) scans and compared with planned angles using Bland-Altman plots and linear regression. RESULTS: Qualitative assessment of correlation plots between planned and actual angles demonstrated a linear relationship for axial, coronal, and sagittal planes, with no overt angular deflection for any magnitude of the planned angle. CONCLUSION: The accuracy of CRW frame-based electrode placement using the Ad-Tech drill guide and electrodes is not significantly affected by the magnitude of the planning angle. Based on our results, oblique electrode insertion is a safe and accurate procedure.

Understanding the human conflict processing network: A review of the literature on direct neural recordings during performance of a modified stroop task.

The Stroop Task is a well-known neuropsychological task developed to investigate conflict processing in the human brain. Our group has utilized direct intracranial neural recordings in various brain regions during performance of a modified color-word Stroop Task to gain a mechanistic understanding of non-emotional human conflict processing. The purpose of this review article is to: 1) synthesize our own studies into a model of human conflict processing, 2) review the current literature on the Stroop Task and other conflict tasks to put our research in context, and 3) describe how these studies define a network in conflict processing. The figures presented are reprinted from our prior publications and key publications referenced in the manuscript. We summarize all studies to date that employ invasive intracranial recordings in humans during performance of conflict-inducing tasks. For our own studies, we analyzed local field potentials (LFPs) from patients with implanted stereotactic electroencephalography (SEEG) electrodes, and we observed intracortical oscillation patterns as well as intercortical temporal relationships in the hippocampus, amygdala, and orbitofrontal cortex (OFC) during the cue-processing phase of a modified Stroop Task. Our findings suggest that non-emotional human conflict processing involves modulation across multiple frequency bands within and between brain structures.

Similar Risk of Kidney Failure among Patients with Blinding Diseases Who Receive Ranibizumab, Aflibercept, and Bevacizumab: An Observational Health Data Sciences and Informatics Network Study.

PURPOSE: To characterize the incidence of kidney failure associated with intravitreal anti-VEGF exposure; and compare the risk of kidney failure in patients treated with ranibizumab, aflibercept, or bevacizumab. DESIGN: Retrospective cohort study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network. SUBJECTS: Subjects aged ≥ 18 years with ≥ 3 monthly intravitreal anti-VEGF medications for a blinding disease (diabetic retinopathy, diabetic macular edema, exudative age-related macular degeneration, or retinal vein occlusion). METHODS: The standardized incidence proportions and rates of kidney failure while on treatment with anti-VEGF were calculated. For each comparison (e.g., aflibercept versus ranibizumab), patients from each group were matched 1:1 using propensity scores. Cox proportional hazards models were used to estimate the risk of kidney failure while on treatment. A random effects meta-analysis was performed to combine each database's hazard ratio (HR) estimate into a single network-wide estimate. MAIN OUTCOME MEASURES: Incidence of kidney failure while on anti-VEGF treatment, and time from cohort entry to kidney failure. RESULTS: Of the 6.1 million patients with blinding diseases, 37 189 who received ranibizumab, 39 447 aflibercept, and 163 611 bevacizumab were included; the total treatment exposure time was 161 724 person-years. The average standardized incidence proportion of kidney failure was 678 per 100 000 persons (range, 0-2389), and incidence rate 742 per 100 000 person-years (range, 0-2661). The meta-analysis HR of kidney failure comparing aflibercept with ranibizumab was 1.01 (95% confidence interval [CI], 0.70-1.47; P = 0.45), ranibizumab with bevacizumab 0.95 (95% CI, 0.68-1.32; P = 0.62), and aflibercept with bevacizumab 0.95 (95% CI, 0.65-1.39; P = 0.60). CONCLUSIONS: There was no substantially different relative risk of kidney failure between those who received ranibizumab, bevacizumab, or aflibercept. Practicing ophthalmologists and nephrologists should be aware of the risk of kidney failure among patients receiving intravitreal anti-VEGF medications and that there is little empirical evidence to preferentially choose among the specific intravitreal anti-VEGF agents. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Evaluating Changes to the Modified K-Line Using Kinematic MRIs.

STUDY DESIGN: Retrospective cross-sectional review of a large database. OBJECTIVE: Little is known regarding extension K-lines for treatment of cervical myelopathy. Therefore, this study seeks to examine differences between K-lines drawn in neutral and extension. SUMMARY OF BACKGROUND DATA: The modified K-line is a radiological tool used in surgical planning of the cervical spine. As posterior cervical decompression and fusion often results in patients being fused in a more lordotic position than the preoperative neutral radiograph, a K-line measured in the extension position may offer better utility for these patients. MATERIALS AND METHODS: Total of 97 patients were selected with T2-weighted, upright cervical magnetic resonance imaging taken in neutral and extension. For each patient, the K-line was drawn at the mid-sagittal position for both neutral and extension. The distance from the most posterior portion of each disk (between C2 and C7) to the K-line was measured in neutral and extension and the difference was calculated. Paired t test was used to assess significant differences. RESULTS: Across all levels between C2 and C7 there was an increase in the distance between the dorsal aspect of the disk and K-line when comparing neutral and extension radiographs. The average change in difference (extension minus neutral) at each cervical spinal level was 0.9 mm (C2-C3), 2.5 mm (C3-C4), 2.6 mm (C4-C5), 2.0 mm (C5-C6), and 0.9 mm (C6-C7). A paired t test showed that the K-line increase from neutral to extension was statistically significant across all disk levels ( P <0.001). CONCLUSION: When positioned in extension, patients experience a significant increase in distance from the dorsal aspect of a disk to the K-line compared to when positioned in neutral, especially between C3 and C6. This is clinically relevant for surgeons considering a posterior cervical decompression and fusion in patients with a negative modified K-line on preoperative magnetic resonance imaging, as these patients may have enough cervical cord drift back when fused in an extended position, maximizing likelihood of improving postoperative DSM functional outcomes.

A review of neurophysiological effects and efficiency of waveform parameters in deep brain stimulation.

Neurostimulation has diverse clinical applications and potential as a treatment for medically refractory movement disorders, epilepsy, and other neurological disorders. However, the parameters used to program electrodes-polarity, pulse width, amplitude, and frequency-and how they are adjusted have remained largely untouched since the 1970 s. This review summarizes the state-of-the-art in Deep Brain Stimulation (DBS) and highlights the need for further research to uncover the physiological mechanisms of neurostimulation. We focus on studies that reveal the potential for clinicians to use waveform parameters to selectively stimulate neural tissue for therapeutic benefit, while avoiding activating tissue associated with adverse effects. DBS uses cathodic monophasic rectangular pulses with passive recharging in clinical practice to treat neurological conditions such as Parkinson's Disease. However, research has shown that stimulation efficiency can be improved, and side effects reduced, through modulating parameters and adding novel waveform properties. These developments can prolong implantable pulse generator lifespan, reducing costs and surgery-associated risks. Waveform parameters can stimulate neurons based on axon orientation and intrinsic structural properties, providing clinicians with more precise targeting of neural pathways. These findings could expand the spectrum of diseases treatable with neuromodulation and improve patient outcomes.

Discovery of a Potent and Selective Naphthyridine-Based Chemical Probe for Casein Kinase 2.

Naphthyridine-based inhibitors were synthesized to yield a potent and cell-active inhibitor of casein kinase 2 (CK2). Compound 2 selectively inhibits CK2α and CK2α' when profiled broadly, thereby making it an exquisitely selective chemical probe for CK2. A negative control that is structurally related but lacks a key hinge-binding nitrogen (7) was designed on the basis of structural studies. Compound 7 does not bind CK2α or CK2α' in cells and demonstrates excellent kinome-wide selectivity. Differential anticancer activity was observed when compound 2 was profiled alongside a structurally distinct CK2 chemical probe: SGC-CK2-1. This naphthyridine-based chemical probe (2) represents one of the best available small molecule tools with which to interrogate biology mediated by CK2.

Osteoporosis Prevention and Treatment: The Risk of Comorbid Cardiovascular Events in Postmenopausal Women.

Treatment modalities used for the management of postmenopausal osteoporosis have come under increased scrutiny more recently due to the elevated risk of cardiovascular disease (CVD) among this patient population. A review of the literature found that postmenopausal women with osteoporosis were at an increased risk of experiencing cardiovascular events such as myocardial infarction. This increased CVD risk among postmenopausal women with osteoporosis has been linked to the use of calcium supplements. It has also been linked to the presence of sclerostin, a wingless-type mouse mammary virus-integration site pathway, which is currently being used as a target for some osteoporosis medications. Research efforts have demonstrated that the prevention and treatment of osteoporosis, especially among postmenopausal women, need to be carefully designed to prevent and reduce the risk of CVD events. As such, the most effective regimens should be tailored to each patient, ensuring that the benefits of certain treatments, such as selective estrogen receptor modulators and calcium supplementation, outweigh the potential health risks, especially CVD event risk among postmenopausal women.

Theta low-gamma phase amplitude coupling in the human orbitofrontal cortex increases during a conflict-processing task.

Objective. The human orbitofrontal cortex (OFC) is involved in automatic response inhibition and conflict processing, but the mechanism of frequency-specific power changes that control these functions is unknown. Theta and gamma activity have been independently observed in the OFC during conflict processing, while theta-gamma interactions in other brain areas have been noted primarily in studies of memory. Within the OFC, it is possible that theta-gamma phase amplitude coupling (PAC) drives conflict processing. This study aims to characterize the coupled relationship between theta and gamma frequency bands in the OFC during conflict processing using a modified Stroop task.Approach. Eight epilepsy patients implanted with OFC stereotactic electroencephalography electrodes participated in a color-word modified Stroop task. PAC between theta phase and gamma amplitude was assessed to determine the timing and magnitude of neural oscillatory changes. Group analysis was conducted using a non-parametric cluster-permutationt-test on coherence values.Main results.Theta-low gamma (LG) PAC significantly increased in five out of eight patients during successful trials of the incongruent condition compared with the congruent condition. Significant increases in theta-LG PAC were most prominent during cue processing 200-800 ms after cue presentation. On group analysis, trial-averaged mean theta-LG PAC was statistically significantly greater in the incongruent condition compared to the congruent condition (p< 0.001, Cohen'sd= 0.51).Significance.For the first time, we report that OFC theta phase and LG amplitude coupling increases during conflict resolution. Given the delayed onset after cue presentation, OFC theta-LG PAC may contribute to conflict processing after conflict detection and before motor response. This explanation follows the hypothesis that global theta waves modulate local gamma signals. Understanding this relationship within the OFC will help further elucidate the neural mechanisms of human conflict resolution.