Explore the vast range of titles available.

Rationale A novel group of designer drugs containing benzylpiperazine (BZP) and/or trifluoromethylphenylpiperazine (TFMPP) have been available worldwide for more than a decade; however, their effects on human brain function have not been extensively described. Objectives In a double-blind, placebo-controlled crossover study, the acute effects of BZP and TFMPP (alone and in combination) on the neural networks involved in executive function were investigated using an event-related Stroop functional magnetic resonance imaging (fMRI) paradigm. Methods Thirteen healthy participants aged 18–40 years undertook the Stroop task 90 min after taking an oral dose of either BZP (200 mg), TFMPP (either 50 or 60 mg), BZP + TFMPP (100 + 30 mg) or placebo. A change in activity in neural regions reflects an increase in local demand for oxygen, due to an increase in neuronal activity. Results Relative to placebo, an increase in neural activation was observed in the dorsal striatum following BZP, and in the thalamus following TFMPP, when performing the Stroop task. Conclusion These data suggest that additional compensatory resources were recruited to maintain performance during the Stroop task. When BZP and TFMPP were administered together, both the dorsal striatum and thalamus were activated. However, the combination of BZP/TFMPP attenuated activation in the caudate, possibly due to TFMPP’s indirect effects on dopamine release via 5HT 2C receptors.

Rationale A novel group of designer drugs containing benzylpiperazine (BZP) and/or trifluoromethylphenylpiperazine (TFMPP) have been available worldwide for more than a decade; however, their effects on human brain function have not been extensively described. Objectives In a double-blind, placebo-controlled crossover study, the acute effects of BZP and TFMPP (alone and in combination) on the neural networks involved in executive function were investigated using an event-related Stroop functional magnetic resonance imaging (fMRI) paradigm. Methods Thirteen healthy participants aged 18-40 years undertook the Stroop task 90 min after taking an oral dose of either BZP (200 mg), TFMPP (either 50 or 60 mg), BZP + TFMPP (100 + 30 mg) or placebo. A change in activity in neural regions reflects an increase in local demand for oxygen, due to an increase in neuronal activity. Results Relative to placebo, an increase in neural activation was observed in the dorsal striatum following BZP, and in the thalamus following TFMPP, when performing the Stroop task. Conclusion These data suggest that additional compensatory resources were recruited to maintain performance during the Stroop task. When BZP and TFMPP were administered together, both the dorsal striatum and thalamus were activated. However, the combination of BZP/TFMPP attenuated activation in the caudate, possibly due to TFMPP's indirect effects on dopamine release via 5HT.sub.2C receptors.

A novel group of designer drugs containing benzylpiperazine (BZP) and/or trifluoromethylphenylpiperazine (TFMPP) have been available worldwide for more than a decade; however, their effects on human brain function have not been extensively described. In a double-blind, placebo-controlled crossover study, the acute effects of BZP and TFMPP (alone and in combination) on the neural networks involved in executive function were investigated using an event-related Stroop functional magnetic resonance imaging (fMRI) paradigm. Thirteen healthy participants aged 18-40 years undertook the Stroop task 90 min after taking an oral dose of either BZP (200 mg), TFMPP (either 50 or 60 mg), BZP + TFMPP (100 + 30 mg) or placebo. A change in activity in neural regions reflects an increase in local demand for oxygen, due to an increase in neuronal activity. Relative to placebo, an increase in neural activation was observed in the dorsal striatum following BZP, and in the thalamus following TFMPP, when performing the Stroop task. These data suggest that additional compensatory resources were recruited to maintain performance during the Stroop task. When BZP and TFMPP were administered together, both the dorsal striatum and thalamus were activated. However, the combination of BZP/TFMPP attenuated activation in the caudate, possibly due to TFMPP's indirect effects on dopamine release via 5HT.sub.2C receptors.

We investigate a recent suggestion that the spatial distribution of earthquake hypocenters makes a fractal set with a structure and fractal dimensionality close to those of the backbone of critical percolation clusters, by analyzing four different sets of data for the hypocenter distributions and calculating the dynamical properties of the geometrical distribution such as the spectral dimension \\(d_s\\). We find that the value of \\(d_s\\) is consistent with that of the backbone, thus supporting further the identification of the hypocenter distribution as having the structure of the percolation backbone.

The immunological surveillance factors controlling vulnerability of the female reproductive tract (FRT) to sexually transmitted viral infections are not well understood. Interferon-epsilon (IFNɛ) is a distinct, immunoregulatory type-I IFN that is constitutively expressed by FRT epithelium and is not induced by pathogens like other antiviral IFNs α, β and λ. We show the necessity of IFNɛ for Zika Virus (ZIKV) protection by: increased susceptibility of IFNɛ -/- mice; their “rescue” by intravaginal recombinant IFNɛ treatment and blockade of protective endogenous IFNɛ by neutralising antibody. Complementary studies in human FRT cell lines showed IFNɛ had potent anti-ZIKV activity, associated with transcriptome responses similar to IFNλ but lacking the proinflammatory gene signature of IFNα. IFNɛ activated STAT1/2 pathways similar to IFNα and λ that were inhibited by ZIKV-encoded non-structural (NS) proteins, but not if IFNε exposure preceded infection. This scenario is provided by the constitutive expression of endogenous IFNε. However, the IFNɛ expression was not inhibited by ZIKV NS proteins despite their ability to antagonise the expression of IFNβ or λ. Thus, the constitutive expression of IFNɛ provides cellular resistance to viral strategies of antagonism and maximises the antiviral activity of the FRT. These results show that the unique spatiotemporal properties of IFNε provides an innate immune surveillance network in the FRT that is a significant barrier to viral infection with important implications for prevention and therapy.

An energy input is often required to promote chemical reactions. Although heat is commonly applied to overcome activation barriers in such processes, other forms of energy can also be utilized to unlock chemical potential. Light, electricity and mechanical force can facilitate chemical transformations, and these strategies can also benefit from technological advancements in reactor design and the integration of flow processes. Although these approaches have been investigated since the 19th century, they are enjoying a resurgence and now find mainstream and diverse synthetic applications. Improvements have generally coincided with conceptual and technological developments, and this Review showcases recent advances aligned with themes spanning photoredox catalysis, mechanochemistry, electrosynthesis and synthesis in static electric fields and in flow. This Review highlights recent conceptual and/or technological advances in photoredox catalysis, organic electrosynthesis, electrostatic chemistry and synthesis in static electric fields, mechanochemistry and synthesis in flow.

(SOURCES by Population: Department of City Planning, from census figures Ferries: City Department of Transportation Crime: New York Police Department Cab fare: Taxi and Limousine Commission Parking ticket: City Department of Finance Subways: New York City Transit Baby names, obesity: City Department of Health Roman Catholics: The Official Catholic Directory Cosmetic procedure: Dr. Debra Jaliman, dermatologist on Fifth Avenue Poll data: The New York Times Poll Schools: City Department of Education Water tunnel: City Department of Environmental Protection Mosques: Louis Abdellatif Cristillo, Columbia University Films: Mayors Office of Film, Theater and Broadcasting Cable: Harriet Novet, vice president, Time Warner Cable of New York City Wedding dance: Kameleon Orchestra CBGB: Hilly Kristal, owner Film Forum: Karen Cooper, director, Film Forum Pornography, Broadway shows: Times Square Business Improvement District Letters to The New York Times: Thomas Feyer, letters editor Weather: Stephen Fybish, weather historian Phrase: Jeffrey McQuain, author of Coined by God Yankees: Forbes magazine Marathon: New York Road Runners Club Tourists: NYC & Company Cafes: Department of Consumer Affairs Building permits, sidewalk sheds: City Department of Buildings Fashion: Bill Cunningham, street fashion photographer, The New York Times Restaurants, cuisine: Kris Ensminger, compiler, Good Eating column Nathans: International Federation of Competitive Eating Brownstone: The Corcoran Group Brooklyn Hotels: PKF Consulting Trump buildings: The Trump Organization)

Certain clinical indications and treatments such as the use of rasburicase in cancer therapy and 8-aminoquinolines for Plasmodium vivax malaria treatment would benefit from a point-of-care test for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Three studies were conducted to evaluate the performance of one such test: the STANDARD ™ G6PD Test (SD BIOSENSOR, South Korea). First, biological interference on the test performance was evaluated in specimens with common blood disorders, including high white blood cell (WBC) counts. Second, the test precision on fingerstick specimens was evaluated against five individuals of each, deficient, intermediate, and normal G6PD activity status. Third, clinical performance of the test was evaluated at three point-of-care settings in the United States. The test performed equivalently to the reference assay in specimens with common blood disorders. High WBC count blood samples resulted in overestimation of G6PD activity in both the reference assay and the STANDARD G6PD Test. The STANDARD G6PD Test showed good precision on multiple fingerstick specimens from the same individual. The same G6PD threshold values (U/g Hb) were applied for a semiquantitative interpretation for fingerstick- and venous-derived results. The sensitivity/specificity values (95% confidence intervals) for the test for G6PD deficiency were 100 (92.3–100.0)/97 (95.2–98.2) and 100 (95.7–100.0)/97.4 (95.7–98.5) for venous and capillary specimens, respectively. The same values for females with intermediate (> 30% to ≤ 70%) G6PD activity were 94.1 (71.3–99.9)/88.2 (83.9–91.7) and 82.4 (56.6–96.2)/87.6(83.3–91.2) for venous and capillary specimens, respectively. The STANDARD G6PD Test enables point-of-care testing for G6PD deficiency.

Despite the large number of promising neuroprotective agents identified in experimental traumatic brain injury (TBI) studies, none has yet shown meaningful improvements in long-term outcome in clinical trials. To develop recommendations and guidelines for pre-clinical testing of pharmacological or biological therapies for TBI, the Moody Project for Translational Traumatic Brain Injury Research hosted a symposium attended by investigators with extensive experience in pre-clinical TBI testing. The symposium participants discussed issues related to pre-clinical TBI testing including experimental models, therapy and outcome selection, study design, data analysis, and dissemination. Consensus recommendations included the creation of a manual of standard operating procedures with sufficiently detailed descriptions of modeling and outcome measurement procedures to permit replication. The importance of the selection of clinically relevant outcome variables, especially related to behavior testing, was noted. Considering the heterogeneous nature of human TBI, evidence of therapeutic efficacy in multiple, diverse (e.g., diffuse vs. focused) rodent models and a species with a gyrencephalic brain prior to clinical testing was encouraged. Basing drug doses, times, and routes of administration on pharmacokinetic and pharmacodynamic data in the test species was recommended. Symposium participants agreed that the publication of negative results would reduce costly and unnecessary duplication of unsuccessful experiments. Although some of the recommendations are more relevant to multi-center, multi-investigator collaborations, most are applicable to pre-clinical therapy testing in general. The goal of these consensus guidelines is to increase the likelihood that therapies that improve outcomes in pre-clinical studies will also improve outcomes in TBI patients.

There is urgent need for new drug regimens that more rapidly cure tuberculosis (TB). Existing TB drugs and regimens vary in treatment-shortening activity, but the molecular basis of these differences is unclear, and no existing assay directly quantifies the ability of a drug or regimen to shorten treatment. Here, we show that drugs historically classified as sterilizing and non-sterilizing have distinct impacts on a fundamental aspect of Mycobacterium tuberculosis physiology: ribosomal RNA (rRNA) synthesis. In culture, in mice, and in human studies, measurement of precursor rRNA reveals that sterilizing drugs and highly effective drug regimens profoundly suppress M. tuberculosis rRNA synthesis, whereas non-sterilizing drugs and weaker regimens do not. The rRNA synthesis ratio provides a readout of drug effect that is orthogonal to traditional measures of bacterial burden. We propose that this metric of drug activity may accelerate the development of shorter TB regimens. It is unclear why different antibiotics vary in their ability to shorten treatment of tuberculosis. Here, the authors show that a measure based on ribosomal RNA synthesis in Mycobacterium tuberculosis correlates with treatment shortening in culture, in mice and in human studies.