Motion-compensated diffusion encoding in multi-shot human brain acquisitions: Insights using high-performance gradients.

PURPOSE: To evaluate the utility of up to second-order motion-compensated diffusion encoding in multi-shot human brain acquisitions. METHODS: Experiments were performed with high-performance gradients using three forms of diffusion encoding motion-compensated through different orders: conventional zeroth-order-compensated pulsed gradients (PG), first-order-compensated gradients (MC1), and second-order-compensated gradients (MC2). Single-shot acquisitions were conducted to correlate the order of motion compensation with resultant phase variability. Then, multi-shot acquisitions were performed at varying interleaving factors. Multi-shot images were reconstructed using three levels of shot-to-shot phase correction: no correction, channel-wise phase correction based on FID navigation, and correction based on explicit phase mapping (MUSE). RESULTS: In single-shot acquisitions, MC2 diffusion encoding most effectively suppressed phase variability and sensitivity to brain pulsation, yielding residual variations of about 10° and of low spatial order. Consequently, multi-shot MC2 images were largely satisfactory without phase correction and consistently improved with the navigator correction, which yielded repeatable high-quality images; contrarily, PG and MC1 images were inadequately corrected using the navigator approach. With respect to MUSE reconstructions, the MC2 navigator-corrected images were in close agreement for a standard interleaving factor and considerably more reliable for higher interleaving factors, for which MUSE images were corrupted. Finally, owing to the advanced gradient hardware, the relative SNR penalty of motion-compensated diffusion sensitization was substantially more tolerable than that faced previously. CONCLUSION: Second-order motion-compensated diffusion encoding mitigates and simplifies shot-to-shot phase variability in the human brain, rendering the multi-shot acquisition strategy an effective means to circumvent limitations of retrospective phase correction methods.

Mindfulness meditation use in chronic pain treatment in rural Australia: Pitfalls and potential - A case report.

Mindfulness is a state of awareness characterized by open and non-judgmental recognition of thoughts and sensations and an ability to resist the usual wandering of an individual's attention. Usually achieved by meditation, mindfulness is recognized as a treatment for chronic pain. Evidence, thus far, has been characterized by poor quality trials and mixed results, but a growing body of research is further investigating its effectiveness. Despite inconclusive evidence, the inherent difficulties of mindfulness research, and problems of accessibility in rural settings, mindfulness meditation is an emerging treatment strategy for many chronic pain patients. This report presents the case of a patient admitted to a rural hospital in New South Wales, whose quality of life was severely impacted by chronic pain.

Highly differentiated genomic properties underpin the different cell walls of Poaceae and eudicots.

Plant cell walls of Poaceae and eudicots differ substantially, both in the content and composition of their components. However, the genomic and genetic basis underlying these differences is not fully resolved. In this research, we analyzed multiple genomic properties of 150 cell wall gene families across 169 angiosperm genomes. The properties analyzed include gene presence/absence, copy number, synteny, occurrence of tandem gene clusters, and phylogenetic gene diversity. Results revealed a profound genomic differentiation of cell wall genes between Poaceae and eudicots, often associated with the cell wall diversity between these plant groups. For example, overall patterns of gene copy number variation and synteny were clearly divergent between Poaceae and eudicot species. Moreover, differential Poaceae-eudicot copy number and genomic contexts were observed for all the genes within the BEL1-like HOMEODOMAIN 6 regulatory pathway, which respectively induces and represses secondary cell wall synthesis in Poaceae and eudicots. Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. All these patterns are discussed in detail in this study, along with their evolutionary and biological relevance for cell wall (genomic) diversification between Poaceae and eudicots.

Synteny Identifies Reliable Orthologs for Phylogenomics and Comparative Genomics of the Brassicaceae.

Large genomic data sets are becoming the new normal in phylogenetic research, but the identification of true orthologous genes and the exclusion of problematic paralogs is still challenging when applying commonly used sequencing methods such as target enrichment. Here, we compared conventional ortholog detection using OrthoFinder with ortholog detection through genomic synteny in a data set of 11 representative diploid Brassicaceae whole-genome sequences spanning the entire phylogenetic space. Then, we evaluated the resulting gene sets regarding gene number, functional annotation, and gene and species tree resolution. Finally, we used the syntenic gene sets for comparative genomics and ancestral genome analysis. The use of synteny resulted in considerably more orthologs and also allowed us to reliably identify paralogs. Surprisingly, we did not detect notable differences between species trees reconstructed from syntenic orthologs when compared with other gene sets, including the Angiosperms353 set and a Brassicaceae-specific target enrichment gene set. However, the synteny data set comprised a multitude of gene functions, strongly suggesting that this method of marker selection for phylogenomics is suitable for studies that value downstream gene function analysis, gene interaction, and network studies. Finally, we present the first ancestral genome reconstruction for the Core Brassicaceae which predating the Brassicaceae lineage diversification ∼25 million years ago.

Evaluating diffusion dispersion across an extended range of b-values and frequencies: Exploiting gap-filled OGSE shapes, strong gradients, and spiral readouts.

PURPOSE: To address the long echo times and relatively weak diffusion sensitization that typically limit oscillating gradient spin-echo (OGSE) experiments, an OGSE implementation combining spiral readouts, gap-filled oscillating gradient shapes providing stronger diffusion encoding, and a high-performance gradient system is developed here and utilized to investigate the tradeoff between b-value and maximum OGSE frequency in measurements of diffusion dispersion (i.e., the frequency dependence of diffusivity) in the in vivo human brain. In addition, to assess the effects of the marginal flow sensitivity introduced by these OGSE waveforms, flow-compensated variants are devised for experimental comparison. METHODS: Using DTI sequences, OGSE acquisitions were performed on three volunteers at b-values of 300, 500, and 1000 s/mm2 and frequencies up to 125, 100, and 75 Hz, respectively; scans were performed for gap-filled oscillating gradient shapes with and without flow sensitivity. Pulsed gradient spin-echo DTI acquisitions were also performed at each b-value. Upon reconstruction, mean diffusivity (MD) maps and maps of the diffusion dispersion rate were computed. RESULTS: The power law diffusion dispersion model was found to fit best to MD measurements acquired at b = 1000 s/mm2 despite the associated reduction of the spectral range; this observation was consistent with Monte Carlo simulations. Furthermore, diffusion dispersion rates without flow sensitivity were slightly higher than flow-sensitive measurements. CONCLUSION: The presented OGSE implementation provided an improved depiction of diffusion dispersion and demonstrated the advantages of measuring dispersion at higher b-values rather than higher frequencies within the regimes employed in this study.

A new P450 involved in the furanocoumarin pathway underlies a recent case of convergent evolution.

Furanocoumarins are phytoalexins often cited as an example to illustrate the arms race between plants and herbivorous insects. They are distributed in a limited number of phylogenetically distant plant lineages, but synthesized through a similar pathway, which raised the question of a unique or multiple emergence in higher plants. The furanocoumarin pathway was investigated in the fig tree (Ficus carica, Moraceae). Transcriptomic and metabolomic approaches led to the identification of CYP76F112, a cytochrome P450 catalyzing an original reaction. CYP76F112 emergence was inquired using phylogenetics combined with in silico modeling and site-directed mutagenesis. CYP76F112 was found to convert demethylsuberosin into marmesin with a very high affinity. This atypical cyclization reaction represents a key step within the polyphenol biosynthesis pathway. CYP76F112 evolutionary patterns suggests that the marmesin synthase activity appeared recently in the Moraceae family, through a lineage-specific expansion and diversification. The characterization of CYP76F112 as the first known marmesin synthase opens new prospects for the use of the furanocoumarin pathway. It also supports the multiple acquisition of furanocoumarin in angiosperms by convergent evolution, and opens new perspectives regarding the ability of cytochromes P450 to evolve new functions related to plant adaptation to their environment.

Insights into Oncogenesis from Circadian Timing in Cancer Stem Cells.

Cancer and circadian rhythms are linked in several ways, through immunomodulatory, neuroendocrine, and metabolic pathways. The circadian timing system consists of interacting circadian clocks in organs throughout the body that contain cells endowed with self-sustaining molecular circadian oscillations. Circadian rhythms are spontaneously generated by specific transcription and translation feedback cycles. Cancer cells emerging from these rhythmic tissues are subjected to daily physiological rhythms imposed by the circadian system, and some transformed cells have their own intrinsic circadian clocks. The role of these circadian clock cells in cancer prevention and oncogenesis remains to be fully explored. Nevertheless, evidence suggests that new cancers are fostered by degradation of the circadian system's rhythmic properties. In contrast, circadian clocks within cancer cells might aid in their survival if they provide benefits such as an ability to synchronize with daily nutrient availability or circadian rhythms in immune cell activity. Here, we address new evidence challenging the simplicity of carcinogenesis models that depend solely on the importance of minimized cancer risk provided by well-aligned and robust circadian clocks in the body. The biology of cancer stem cells and the benefits they may receive from their own rhythmic and non-rhythmic expressions of core circadian clock genes are examined with a focus on gliomas and liver cancer stem cells, along with possibilities for timed medical interventions.

Improved gradient waveforms for oscillating gradient spin-echo (OGSE) diffusion tensor imaging.

The dependence of the diffusion tensor on frequency is of great interest in studies of tissue microstructure because it reveals restrictions to the Brownian motion of water molecules caused by cell membranes. Oscillating gradient spin-echo (OGSE) sequences can sample this dependence with gradient shapes for which the power spectrum of the zeroth moment is focused at a target frequency. In order to maintain the total spectral power (ie the b-value), oscillating gradient amplitudes must grow with the frequency squared. For this reason, OGSE applications on clinical MRI scanners are limited to low frequencies, for which it is difficult to obtain a narrow frequency bandwidth of the gradient moment in a useful echo time. In particular, the commonly used pair of single-period trapezoidal-cosine pulses separated by a half-period produces significant side lobes away from the target frequency. To mitigate this effect, improved OGSE waveforms are proposed, which reduce the gap between the two gradient pulses to the minimum duration required for the refocusing RF pulse. Additionally, a slight deviation from the periodicity of the waveforms is proposed in order to permit using the maximum slew rate of the gradient system for all lobes of trapezoidal waveforms while maintaining advantageous spectral properties, which is not the case for the currently used OGSE sequences. Numerical calculations validate these changes, showing that both modifications significantly narrow the gradient moment power spectrum and increase the contribution of its main lobe to the b-value, thus improving the specificity of the measurement. The utility of the new shapes is demonstrated by diffusion tensor measurements of human white matter in vivo over the range of 30-75 Hz with a b-value of nearly 1000 s/mm2 , using a high-performance gradient insert. However, the improvement should increase the sampling precision of OGSE experiments for all gradient systems.

Genomic Blocks in Aethionema arabicum Support Arabideae as Next Diverging Clade in Brassicaceae.

The tribe Aethionemeae is sister to all other crucifers, making it a crucial group for unraveling genome evolution and phylogenetic relationships within the crown group Brassicaceae. In this study, we extend the analysis of Brassicaceae genomic blocks (GBs) to Aethionema whereby we identified unique block boundaries shared only with the tribe Arabideae. This was achieved using bioinformatic methods to analyze synteny between the recently updated genome sequence of Aethionema arabicum and other high-quality Brassicaceae genome sequences. We show that compared to the largely conserved genomic structure of most non-polyploid Brassicaceae lineages, GBs are highly rearranged in Aethionema. Furthermore, we detected similarities between the genomes of Aethionema and Arabis alpina, in which also a high number of genomic rearrangements compared to those of other Brassicaceae was found. These similarities suggest that tribe Arabideae, a clade showing conflicting phylogenetic position between studies, may have diverged before diversification of the other major lineages, and highlight the potential of synteny information for phylogenetic inference.

Relative Strength of Common Directing Groups in Palladium-Catalyzed Aromatic C-H Activation.

Efficient functionalization of C-H bonds can be achieved using transition metal catalysts, such as Pd(OAc)2. To better control the regioselectivity in these reactions, some functional groups on the substrate may be used as directing groups, guiding the reactivity to an ortho position. Herein, we describe a methodology to score the relative strength of such directing groups in palladium-catalyzed aromatic C-H activation. The results have been collected into a scale that serves to predict the regioselectivity on molecules with multiple competing directing groups. We demonstrate that this scale yields accurate predictions on over a hundred examples, taken from the literature. In addition to the regioselectivity prediction on complex molecules, the knowledge of the relative strengths of directing groups can also be used to work with new combinations of functionalities, exploring uncharted chemical space.

NATO Military Medical Exercise Vigorous Warrior 2017.

Our intent in presenting this information is to increase the awareness of the Special Operations Forces (SOF) medical community and the overall international medical/military communities about the North Atlantic Treaty Organization (NATO) military medicine's premiere Vigorous Warrior Exercises organized by NATO Centre of Excellence for Military Medicine (MILMED COE). The Vigorous Warrior medical exercise series is conducted biennially, with four successful iterations since 2011. These international medical exercises engage military medical elements that enhance NATO capabilities and ensure that new NATO medical concepts are being exercised and tested across the full capability-requirement spectrum. The primary aims of these exercises are to provide NATO and partner nations a multipurpose platform to collectively train their medical forces and personnel; test and experiment new concepts and doctrines; medically evaluate national or multinational medical treatment facilities in accordance with NATO doctrine; produce medical lessons identified and lessons learned; and provide the participants with multinational experience to enhance the provision of health care in NATO operations. These exercises directly strengthen partnerships, improve military medical interoperability, and demonstrate the Alliance's commitment to improving international military collaboration. More than 1,000 medical personnel from 26 NATO and partner nations successfully conducted the joint, multilevel, multinational, medical live exercise Vigorous Warrior 2017 (VW17) throughout three locations in Germany during 4-22 September 2017. This article details the highly successful VW17 and paves the way for a very bright future for the Alliance's military medicine as well as a Vigorous Warrior 2019.

EpiNATO-2: Enhancing Situational Awareness and Overall Force Health Protection While Deployed in the Combined Joint NATO Environment: Describing the Identified 2016 Q Fever Outbreak in Kosovo Force (KFOR).

EpiNATO-2 is the only interoperable health surveillance system that is defined in North Atlantic Treaty Organization (NATO) doctrine. It was first implemented in the Kosovo Force and European Union Training Mission Mali in 2013. EpiNATO-2 is mandated for use during all NATO operations. Its coverage has steadily increased and now includes all NATO Joint and Component Command Operations and several non-NATO operations. The system monitors morbidity predominately for Role 1 sites by using weekly reports from the medics and other medical providers. The reports for all sites in theater are sent to the Combined Joint Medical (CJMED), which consolidates and submits them to NATO Deployment Health Surveillance Capability (DHSC), the satellite branch of NATO Centre of Excellence for Military Medicine (MILMED COE), for analysis and feedback. Although EpiNATO-2 will likely have a number of overlaps with most nations' disease and nonbattle injury trackers, a distinguishing characteristic is that it has specific categories for classifying more clinical activity. Sustaining the quality of data collection is paramount and achieved through contemporaneous analysis and feedback that are disseminated via CJMED to all providers. This enhances situational awareness about evolving trends in health issues across the deployed force and is intended to provide information for action and medical decision-making and force health protection assurance at the local and theater levels. The awareness imparted by this article can add to the Special Operations Forces (SOF) medics' tool kit to ensure success for the SOF medic and SOF community while deployed or collaborating with NATO and NATO partner nation militaries at any level in theater.

Improving Communication Between Surgery and Critical Care Teams: Beyond the Handover.

BACKGROUND: Structured communication tools for postoperative surgical handover to the intensive care unit (ICU) have shown promise, yet little work has addressed ongoing daily communication between the surgery and ICU teams thereafter. OBJECTIVES: Evaluation of a novel, 2-part communication intervention between surgery and ICU teams focused on postoperative handover and ongoing daily communication. METHODS: A mixed-methods, pre- and postintervention survey study was conducted in a closed quaternary medical-surgical ICU. Study participants (N = 112) included ICU physicians, nurses, allied health professionals, and physicians on the surgical team. The intervention consisted of a handover checklist completed postoperatively on arrival in the ICU and a 5-item communication tool completed daily by the surgical team. RESULTS: Satisfaction improved significantly in the following areas: postoperative handover communication (P < .001), daily communication (P = .001), understanding the postoperative plan (P < .001), initiation of deep vein thrombosis prophylaxis (P = .008), initiation of feeding (P = .009), and daily primary resident contact (P = .008). No significant improvement was seen in communication regarding disposition or overall improvement in patient safety risk from communication errors. CONCLUSIONS: A simple handover checklist improved health care practitioner satisfaction with communication during postoperative handover to the ICU. Concise daily communication tools are an appropriate option for improving ongoing communication between surgeons and the ICU team thereafter.

TPA-023 attenuates subchronic phencyclidine-induced declarative and reversal learning deficits via GABAA receptor agonist mechanism: possible therapeutic target for cognitive deficit in schizophrenia.

GABAergic drugs are of interest for the treatment of anxiety, depression, bipolar disorder, pain, cognitive impairment associated with schizophrenia (CIAS), and other neuropsychiatric disorders. Some evidence suggests that TPA-023, (7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b] pyridazine), a GABAA α2,3 subtype-selective GABAA partial agonist and α1/5 antagonist, and the neurosteroid, pregnenolone sulfate, a GABAA antagonist, may improve CIAS in pilot clinical trials. The goal of this study was to investigate the effect of TPA-023 in mice after acute or subchronic (sc) treatment with the N-methyl-D-aspartate receptor (NMDAR) antagonist, phencyclidine (PCP), on novel object recognition (NOR), reversal learning (RL), and locomotor activity (LMA) in rodents. Acute TPA-023 significantly reversed scPCP-induced NOR and RL deficits. Co-administration of sub-effective dose (SED) TPA-023 with SEDs of the atypical antipsychotic drug, lurasidone, significantly potentiated the effect of TPA-023 in reversing the scPCP-induced NOR deficit. Further, scTPA-023 co-administration significantly prevented scPCP-induced NOR deficit for 5 weeks. Also, administration of TPA-023 for 7 days following scPCP reversed the NOR deficit for 1 week. However, TPA-023 did not blunt acute PCP-induced hyperactivity, suggesting lack of efficacy as a treatment for psychosis. Systemic TPA-023 significantly blocked lurasidone-induced increases in cortical acetylcholine, dopamine, and glutamate without affecting increases in norepinephrine and with minimal effect on basal release of these neurotransmitters. TPA-023 significantly inhibited PCP-induced cortical and striatal dopamine, serotonin, norepinephrine, and glutamate efflux. These results suggest that TPA-023 and other GABAA agonists may be of benefit to treat CIAS.

A Meta-Analysis Characterizing Stem-Like Gene Expression in the Suprachiasmatic Nucleus and Its Circadian Clock.

Cells expressing proteins characteristic of stem cells and progenitor cells are present in the suprachiasmatic nucleus (SCN) of the adult mammalian hypothalamus. Any relationship between this distinctive feature and the master circadian clock of the SCN is unclear. Considering the lack of obvious neurogenesis in the adult SCN relative to the hippocampus and other structures that provide neurons and glia, it is possible that the SCN has partially differentiated cells that can provide neural circuit plasticity rather than ongoing neurogenesis. To test this possibility, available databases and publications were explored to identify highly expressed genes in the mouse SCN that also have known or suspected roles in cell differentiation, maintenance of stem-like states, or cell-cell interactions found in adult and embryonic stem cells and cancer stem cells. The SCN was found to have numerous genes associated with stem cell maintenance and increased motility from which we selected 25 of the most relevant genes. Over ninety percent of these stem-like genes were expressed at higher levels in the SCN than in other brain areas. Further analysis of this gene set could provide a greater understanding of how adjustments in cell contacts alter period and phase relationships of circadian rhythms. Circadian timing and its role in cancer, sleep, and metabolic disorders are likely influenced by genes selected in this study.

RP5063, an atypical antipsychotic drug with a unique pharmacologic profile, improves declarative memory and psychosis in mouse models of schizophrenia.

Various types of atypical antipsychotic drugs (AAPDs) modestly improve the cognitive impairment associated with schizophrenia (CIAS). RP5063 is an AAPD with a diverse and unique pharmacology, including partial agonism at dopamine (DA) D2, D3, D4, serotonin (5-HT)1A, and 5-HT2A receptors (Rs), full agonism at α4ß2 nicotinic acetylcholine (ACh)R (nAChR), and antagonism at 5-HT2B, 5-HT6, and 5-HT7Rs. Most atypical APDs are 5-HT2A inverse agonists. The efficacy of RP5063 in mouse models of psychosis and episodic memory were studied. RP5063 blocked acute phencyclidine (PCP)-as well as amphetamine-induced hyperactivity, indicating antipsychotic activity. Acute administration of RP5063 significantly reversed subchronic (sc)PCP-induced impairment in novel object recognition (NOR), a measure of episodic memory, but not reversal learning, a measure of executive function. Co-administration of a sub-effective dose (SED) of RP5063 with SEDs of a 5-HT7R antagonist, a 5-HT1BR antagonist, a 5-HT2AR inverse agonist, or an α4ß2 nAChR agonist, restored the ability of RP5063 to ameliorate the NOR deficit in scPCP mice. Pre-treatment with a 5-HT1AR, a D4R, antagonist, but not an α4ß2 nAChR antagonist, blocked the ameliorating effect of RP5063. Further, co-administration of scRP5063 prior to each dose of PCP prevented the effect of PCP to produce a deficit in NOR for one week. RP5063, given to scPCP-treated mice for one week restored NOR for one week only. Acute administration of RP5063 significantly increased cortical DA efflux, which may be critical to some of its cognitive enhancing properties. These results indicate that RP5063, by itself, or as an adjunctive treatment has a multifaceted basis for improving some cognitive deficits associated with schizophrenia.

Developmental Control and Plasticity of Fruit and Seed Dimorphism in Aethionema arabicum.

Understanding how plants cope with changing habitats is a timely and important topic in plant research. Phenotypic plasticity describes the capability of a genotype to produce different phenotypes when exposed to different environmental conditions. In contrast, the constant production of a set of distinct phenotypes by one genotype mediates bet hedging, a strategy that reduces the temporal variance in fitness at the expense of a lowered arithmetic mean fitness. Both phenomena are thought to represent important adaptation strategies to unstable environments. However, little is known about the underlying mechanisms of these phenomena, partly due to the lack of suitable model systems. We used phylogenetic and comparative analyses of fruit and seed anatomy, biomechanics, physiology, and environmental responses to study fruit and seed heteromorphism, a typical morphological basis of a bet-hedging strategy of plants, in the annual Brassicaceae species Aethionema arabicum Our results indicate that heteromorphism evolved twice within the Aethionemeae, including once for the monophyletic annual Aethionema clade. The dimorphism of Ae. arabicum is associated with several anatomic, biomechanical, gene expression, and physiological differences between the fruit and seed morphs. However, fruit ratios and numbers change in response to different environmental conditions. Therefore, the life-history strategy of Ae. arabicum appears to be a blend of bet hedging and plasticity. Together with the available genomic resources, our results pave the way to use this species in future studies intended to unravel the molecular control of heteromorphism and plasticity.

Comparison of the Nanopulse Lithotripter to the Holmium Laser: Stone Fragmentation Efficiency and Impact on Flexible Ureteroscope Deflection and Flow.

INTRODUCTION: The Nanopulse Lithotripter (NPL; Lithotech Medical, Israel) is a novel intracorporeal device that uses a nanosecond duration electrical discharge through a reusable flexible coaxial probe to endoscopically fragment urinary stones. This device was compared with a holmium laser lithotripsy (HoL) with regard to stone fragmentation efficiency (SFE) and its impact on flexible ureteroscope (URS) deflection and flow of irrigation. METHODS: Using a custom bench model, a 6 mm BegoStone cylindrical phantom (mixture 5:2) was confined under 0.9% saline atop sequential mesh sieves. The SFE of two NPL probe sizes (2.0F, 3.6F) and two HoL fibers (200, 365 µm) was evaluated using concordant settings of 1 J and 5 Hz. URS deflection and irrigation flow with NPL probes in the working channel were tested in five new fourth generation flexible URS and compared with other adjunct endourologic instruments. RESULTS: The 2.0F NPL showed improved SFE compared with the 200 µm laser (86 mg/min vs 52 mg/min, p = 0.014) as did the 3.6F NPL vs the 365 µm laser (173 mg/min vs 80 mg/min, p = 0.05). The NPL created more 1 to 2 mm fragments; the laser created more dust. URS deflection reduced by 3.75° with the 2.0 NPL probe. URS irrigation flow reduced from 36.5 to 6.3 mL/min with the 2.0F NPL probe. CONCLUSION: NPL shows improved SFE compared with HoL. Flow with the 2.0F probe is akin to a stone basket. NPL offers an effective alternative to HoL.

Serotonin (5-HT)1A receptor agonism and 5-HT7 receptor antagonism ameliorate the subchronic phencyclidine-induced deficit in executive functioning in mice.

RATIONALE: Reversal learning (RL), a type of executive function, dependent on prefrontal cortical function, is impaired in rodents by subchronic (sc) treatment with the N-methyl-D-aspartate receptor antagonist, phencyclidine (PCP), a widely studied model of cognitive impairment in schizophrenia (CIS). OBJECTIVE: The principal objective of this study was to determine the ability of serotonin (5-HT)1A partial agonism and 5-HT7 receptor antagonism to improve RL in scPCP-treated mice. METHODS: Male C57BL/6J mice were trained on an operant RL (ORL) task, then received PCP, 10 mg/kg, or saline, bid, for 7 days, followed by a 7-day washout period. RESULTS: scPCP significantly diminished the percent correct responding, increased total incorrect trials, and total incorrect responses, in the reversal phase performance of the ORL task. Pre-treatment with the selective 5-HT1A partial agonist, tandospirone, or the selective 5-HT7 antagonist, SB269970, but not the 5-HT7 agonist, AS 19, reversed the scPCP-induced deficit in RL. Pre-treatment with atypical antipsychotic drug lurasidone, which is a 5-HT1A partial agonist and 5-HT7 antagonist, as well as a 5-HT2A and dopamine (D)2 antagonist, also reversed RL deficit in the scPCP-treated mice. Furthermore, the selective 5-HT1A antagonist, WAY100635, blocked the ability of lurasidone to reverse the scPCP-induced RL deficit. CONCLUSIONS: These results indicate that 5-HT7 antagonism and 5-HT1A partial agonism contribute to restoration of RL in scPCP-treated mice. It is suggested that these two mechanisms are effective in restoring RL by decreasing excessive GABAergic inhibition of cortical pyramidal neurons following withdrawal of scPCP treatment.