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The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrials.gov: NCT04889209., Competing Interests: Declaration of interests R.L.A., C.D.I., C.M.P., D.S., R.P.C., M.E.D., A.E., H.M.E.S., R.E.R., M.B., A.C.K., T.M.B., D.D., R.N.C., J.I.A., S.C., J.A.Z., S.U.N., E.R.B., and D.J.P. report no competing interests. K.E.L. receives grant awards from Pfizer, Inc., COVID-19 vaccine research. L.A.J.’s institution receives grant funding from NIH and CDC for vaccine-related assessments, including those of COVID-19 vaccines. A.R.B. has grant funding from Pfizer, Janssen, Merck, and Cyanvac for non-COVID-19-related work and serves as a consultant for GSK and Janssen. C.A.R.'s institution has received funds to conduct clinical research from the National Institutes of Health, CDC, BioFire, Inc., Genentech, GSK, Janssen, MedImmune, Merck, Micron, Moderna, Novavax, PaxVax, Pfizer, Regeneron, and Sanofi-Pasteur. She is co-inventor of patented RSV vaccine technology, which has been licensed to Meissa Vaccines, Inc. J.M.M. has served as a consultant for Merck, Sharp, and Dohme for non-Covid-related work. C.J. receives funding from the Bill and Melinda Gates Foundation, NIH, and CDC, consults for Gilead and Abbvie, serves on a DSMB for MedPace, and receives royalties from UpToDate. M.J.M. has laboratory research and clinical trials contracts for vaccines or MAB versus SARS-CoV-2 with Lilly, Pfizer (exclusive of the current work), and Sanofi and personal fees for Scientific Advisory Board service from Merck, Meissa Vaccines, Inc., and Pfizer. R.C.B. receives funding for vaccine trials from Path Nipah and Pfizer. R.W.F. receives funding to perform clinical trials from Pfizer, Moderna, Astra Zeneca, and Emergent Health, and he serves on advisory boards for Johnson & Johnson, Merck, Sanofi Pasteur, and Seqirus. S.E. receives funding to her institution from Sanofi Pasteur for a non-COVID-19 vaccine study. K.M.N. holds a grant from Pfizer, without salary support, for a COVID-19 vaccine study and salary support from the National Institutes of Health (NIH) for work on multiple COVID-19 vaccine trials. D.S.S. is supported by grant awards from NIH/NIAID. P.C.R. and J.H.B. report a pending US patent application no. 63/025918 entitled “Coronavirus RNA vaccines and methods of use.” D.C.M. receives funding from NIH and Moderna for laboratory studies of COVID-19 vaccine antibody responses. M.S.S. receives funding from Moderna, Inc., and Ocugen. D.C.M. receives funding from Moderna, Inc., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Positron Emission Tomography is a non-disruptive and high-sensitive digital imaging technique which allows to measure in-vivo and non invasively the changes of metabolic and transport mechanisms in plants. When it comes to the early assessment of stress-induced alterations of plant functions, plant PET has the potential of a major breakthrough. The development of dedicated plant PET systems faces a series of technological and experimental difficulties, which make conventional clinical and preclinical PET systems not fully suitable to agronomy. First, the functional and metabolic mechanisms of plants depend on environmental conditions, which can be controlled during the experiment if the scanner is transported into the growing chamber. Second, plants need to be imaged vertically, thus requiring a proper Field Of View. Third, the transverse Field of View needs to adapt to the different plant shapes, according to the species and the experimental protocols. In this paper, we perform a simulation study, proposing a novel design of dedicated plant PET scanners specifically conceived to address these agronomic issues. We estimate their expected sensitivity, count rate performance and spatial resolution, and we identify these specific features, which need to be investigated when realizing a plant PET scanner. Finally, we propose a novel approach to the measurement and verification of the performance of plant PET systems, including the design of dedicated plant phantoms, in order to provide a standard evaluation procedure for this emerging digital imaging agronomic technology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Antonecchia, Bäcker, Cafolla, Ciardiello, Kühl, Pagnani, Wang, Wang, Zhou, D'Ascenzo, Gialanella, Pisante, Rose and Xie.)

Background: Effective therapies to combat coronavirus 2019 (COVID-19) are urgently needed. Hydroxychloroquine (HCQ) has in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the clinical benefit of HCQ in treating COVID-19 is unclear. Randomized controlled trials are needed to determine the safety and efficacy of HCQ for the treatment of hospitalized patients with COVID-19., Methods: We conducted a multicenter, double-blind randomized clinical trial of HCQ among patients hospitalized with laboratory-confirmed COVID-19. Subjects were randomized in a 1:1 ratio to HCQ or placebo for 5 days and followed for 30 days. The primary efficacy outcome was a severe disease progression composite end point (death, intensive care unit admission, mechanical ventilation, extracorporeal membrane oxygenation, and/or vasopressor use) at day 14., Results: A total of 128 patients were included in the intention-to-treat analysis. Baseline demographic, clinical, and laboratory characteristics were similar between the HCQ (n = 67) and placebo (n = 61) arms. At day 14, 11 (16.4%) subjects assigned to HCQ and 6 (9.8%) subjects assigned to placebo met the severe disease progression end point, but this did not achieve statistical significance ( P  = .350). There were no significant differences in COVID-19 clinical scores, number of oxygen-free days, SARS-CoV-2 clearance, or adverse events between HCQ and placebo. HCQ was associated with a slight increase in mean corrected QT interval, an increased D-dimer, and a trend toward an increased length of stay., Conclusions: In hospitalized patients with COVID-19, our data suggest that HCQ does not prevent severe outcomes or improve clinical scores. However, our conclusions are limited by a relatively small sample size, and larger randomized controlled trials or pooled analyses are needed., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Plant nucleotide-binding (NB) leucine-rich repeat (LRR) receptor (NLR) proteins function as intracellular immune receptors that perceive the presence of pathogen-derived virulence proteins (effectors) to induce immune responses. The 2 major types of plant NLRs that "sense" pathogen effectors differ in their N-terminal domains: these are Toll/interleukin-1 receptor resistance (TIR) domain-containing NLRs (TNLs) and coiled-coil (CC) domain-containing NLRs (CNLs). In many angiosperms, the RESISTANCE TO POWDERY MILDEW 8 (RPW8)-CC domain containing NLR (RNL) subclass of CNLs is encoded by 2 gene families, ACTIVATED DISEASE RESISTANCE 1 (ADR1) and N REQUIREMENT GENE 1 (NRG1), that act as "helper" NLRs during multiple sensor NLR-mediated immune responses. Despite their important role in sensor NLR-mediated immunity, knowledge of the specific, redundant, and synergistic functions of helper RNLs is limited. We demonstrate that the ADR1 and NRG1 families act in an unequally redundant manner in basal resistance, effector-triggered immunity (ETI) and regulation of defense gene expression. We define RNL redundancy in ETI conferred by some TNLs and in basal resistance against virulent pathogens. We demonstrate that, in Arabidopsis thaliana, the 2 RNL families contribute specific functions in ETI initiated by specific CNLs and TNLs. Time-resolved whole genome expression profiling revealed that RNLs and "classical" CNLs trigger similar transcriptome changes, suggesting that RNLs act like other CNLs to mediate ETI downstream of sensor NLR activation. Together, our genetic data confirm that RNLs contribute to basal resistance, are fully required for TNL signaling, and can also support defense activation during CNL-mediated ETI., Competing Interests: The authors have declared that no competing interests exist.

The formation of superconducting nanocomposites from preformed nanocrystals is still not well understood. Here, we examine the case of ZrO₂ nanocrystals in a YBa₂Cu₃O 7−x matrix. First we analyzed the preformed ZrO₂ nanocrystals via atomic pair distribution function analysis and found that the nanocrystals have a distorted tetragonal crystal structure. Second, we investigated the influence of various surface ligands attached to the ZrO₂ nanocrystals on the distribution of metal ions in the pyrolyzed matrix via secondary ion mass spectroscopy technique. The choice of stabilizing ligand is crucial in order to obtain good superconducting nanocomposite films with vortex pinning. Short, carboxylate based ligands lead to poor superconducting properties due to the inhomogeneity of metal content in the pyrolyzed matrix. Counter-intuitively, a phosphonate ligand with long chains does not disturb the growth of YBa₂Cu₃O 7−x . Even more surprisingly, bisphosphonate polymeric ligands provide good colloidal stability in solution but do not prevent coagulation in the final film, resulting in poor pinning. These results thus shed light on the various stages of the superconducting nanocomposite formation.

Bloodstream infection is a major contributor to morbidity and mortality in children on hemodialysis (HD). From January 2009 through April 2011, the incidence of access-related bloodstream infections (ARBs) in pediatric patients on HD at our hospital was 3.45/1000 patient days. Almost all of these children were receiving HD via central line catheters, and none were receiving HD via arteriovenous fistulas (AVFs). In an effort to reduce the rate of infection in children receiving HD at our institution, we introduced the Pediatric Fistula Initiative, a program to increase creation and use of AVFs in children. Thirty-three children on HD were observed, 9 of whom received AVFs during the study period. The incidence of ARBs decreased to 1.30/1000 patient days (P < .001) during the 24-month intervention period from May 2011 through May 2013., (© The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Designing novel or optimizing existing biodegradable polymers for biomedical applications requires numerous tests on the effect of substances on the degradation process. In the present work, polymer-modified electrolyte-insulator-semiconductor (PMEIS) sensors have been applied for monitoring an enzymatically catalyzed degradation of polymers for the first time. The thin films of biodegradable polymer poly(D,L-lactic acid) and enzyme lipase were used as a model system. During degradation, the sensors were read-out by means of impedance spectroscopy. In order to interpret the data obtained from impedance measurements, an electrical equivalent circuit model was developed. In addition, morphological investigations of the polymer surface have been performed by means of in situ atomic force microscopy. The sensor signal change, which reflects the progress of degradation, indicates an accelerated degradation in the presence of the enzyme compared to hydrolysis in neutral pH buffer media. The degradation rate increases with increasing enzyme concentration. The obtained results demonstrate the potential of PMEIS sensors as a very promising tool for in situ and real-time monitoring of degradation of polymers.

The semiconductor field-effect platform is a powerful tool for chemical and biological sensing with direct electrical readout. In this work, the field-effect capacitive electrolyte-insulator-semiconductor (EIS) structure - the simplest field-effect (bio-)chemical sensor - modified with citrate-capped gold nanoparticles (AuNPs) has been applied for a label-free electrostatic detection of charged molecules by their intrinsic molecular charge. The EIS sensor detects the charge changes in AuNP/molecule inorganic/organic hybrids induced by the molecular adsorption or binding events. The feasibility of the proposed detection scheme has been exemplarily demonstrated by realizing capacitive EIS sensors consisting of an Al-p-Si-SiO2-silane-AuNP structure for the label-free detection of positively charged cytochrome c and poly-d-lysine molecules as well as for monitoring the layer-by-layer formation of polyelectrolyte multilayers of poly(allylamine hydrochloride)/poly(sodium 4-styrene sulfonate), representing typical model examples of detecting small proteins and macromolecules and the consecutive adsorption of positively/negatively charged polyelectrolytes, respectively. For comparison, EIS sensors without AuNPs have been investigated, too. The adsorption of molecules on the surface of AuNPs has been verified via the X-ray photoelectron spectroscopy method. In addition, a theoretical model of the functioning of the capacitive field-effect EIS sensor functionalized with AuNP/charged-molecule hybrids has been discussed.

Objectives: Carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa are endemic in many medical centres. Because therapeutic options are limited, understanding the epidemiology and controlling the spread of these pathogens are of paramount importance., Methods: Isolates of K. pneumoniae, A. baumannii and P. aeruginosa were collected from 14 hospitals in New York City over a 3 month period in 2009, and analysed for the presence of genes encoding important carbapenemases. Comparisons were made with a similar study conducted in 2006. Demographic and infection control-related information from hospitals was collected., Results: Overall, 29% of K. pneumoniae possessed the carbapenemase KPC, significantly improved from the 38% observed in 2006 (P < 0.001). However, carbapenem resistance worsened in A. baumannii (mostly due to the emergence of strains with OXA-type carbapenemases) and P. aeruginosa. The decline in KPC-possessing K. pneumoniae was not uniformly observed in all of the hospitals. In a subset analysis of nine hospitals, those with a decreasing prevalence of bla(KPC) had shorter average lengths of stay., Conclusions: Measurable improvement has occurred in reducing the spread of KPC-possessing K. pneumoniae, and reducing the average length of stay may augment infection control efforts. However, the problem of carbapenem-resistant A. baumannii and P. aeruginosa lingers. New approaches, including respiratory isolation and environmental cleaning, need to be examined to control the spread of A. baumannii and P. aeruginosa.

We report the first case of recurrent intravascular-catheter-related bacteremia in a pediatric hemodialysis patient caused by Delftia acidovorans, previously called Comamonas acidovorans or Pseudomonas acidovorans. The patient had a history of multiple infections of central vascular catheters with other organisms, requiring courses of antibiotics and catheter replacements. Previously reported cases of D. acidovorans infections are reviewed. The isolate appeared to become resistant to cephalosporins after antibiotic treatment, but resistance could not be confirmed with additional testing. In vitro susceptibility testing for cephalosporins is not reliable for this organism.

Objectives: Multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa have become a global problem, often leaving the polymyxins as therapeutic agents of last resort. ACHN-490, a next-generation aminoglycoside with activity against a broad range of Gram-positive and Gram-negative pathogens, was examined against clinical isolates of A. baumannii and P. aeruginosa., Methods: The activity of aminoglycosides and ACHN-490 was determined against a contemporary collection of A. baumannii and P. aeruginosa. Selected aminoglycoside-resistant isolates were screened for the presence of genes encoding common aminoglycoside-modifying enzymes and methylases., Results: Resistance to the traditional aminoglycosides was common in the collection of A. baumannii. ACHN-490 possessed superior activity against these isolates, with an MIC(50) value of 8 mg/L. In P. aeruginosa, the activity of ACHN-490 was similar to that of amikacin (MIC(50) value of 8 mg/L for both agents). For both A. baumannii and P. aeruginosa, the MICs of ACHN-490 did not correlate with the presence of commonly encountered aminoglycoside-modifying enzymes., Conclusions: For A. baumannii, the MICs of ACHN-490 were lower than those of traditional aminoglycosides. For P. aeruginosa, the activity of ACHN-490 was similar to that of amikacin.

The detection of Enterobacteriaceae carrying the carbapenemase KPC has been problematic. Thirty isolates of KPC-possessing Escherichia coli were gathered from hospitals in New York City and Connecticut. The imipenem, meropenem, doripenem, and ertapenem MIC50 values were 4, 2, 1, and 4 μg/ml, respectively. Over half of the isolates belonged to a single ribotype. Using an ertapenem breakpoint of 0.25 μg/ml would efficiently detect these isolates.

Objectives: Reports of Enterobacteriaceae resistant to all commonly used antimicrobial agents, including β-lactams, fluoroquinolones and aminoglycosides, are increasing in hospitals worldwide. The activity of ACHN-490, a next-generation aminoglycoside, was examined against clinical isolates of Escherichia coli and Klebsiella pneumoniae from hospitals in New York City, an area where multidrug-resistant organisms are endemic., Methods: Unique patient isolates of E. coli and K. pneumoniae were gathered from 16 hospitals located in New York City in 2009 and underwent susceptibility testing to aminoglycosides and ACHN-490. Subsets of isolates were characterized by PCR for the presence of genes encoding aminoglycoside-modifying enzymes, ribosomal methylases and KPC-type carbapenemases., Results: Although most isolates of E. coli were susceptible to the aminoglycosides, the MIC(90) values of gentamicin, tobramycin and amikacin were 32, 8 and 4 mg/L, respectively. The MIC(90) of ACHN-490 was 1 mg/L. Multidrug resistance, including resistance to aminoglycosides and the presence of bla(KPC), was much more common in isolates of K. pneumoniae. However, the MIC(90) of ACHN-490 for K. pneumoniae was also 1 mg/L. The MICs of ACHN-490 did not correlate with the presence of commonly recovered aminoglycoside-modifying enzymes. Bactericidal activity was evident in most isolates at concentrations 4× the MIC., Conclusions: The novel aminoglycoside ACHN-490 retains activity against most isolates of E. coli and K. pneumoniae, including multidrug-resistant strains. Additional studies examining the roles of efflux systems and outer membrane permeability alterations are recommended in isolates with reduced susceptibility to this agent.

In this work, the reaction mechanism used in the preparation of fluorine-free superconducting YBa(2)Cu(3)O(7-delta) (YBCO) was investigated. To determine which precursor interactions are dominant, a comprehensive thermal analysis (thermogravimetric analysis-differential thermal analysis) study was performed. The results suggest that a three step reaction mechanism, with a predominant role for BaCO(3), is responsible for the conversion of the initial state to the superconducting phase. In the presence of CuO, the decarboxylation of BaCO(3) is kinetically favored with the formation of BaCuO(2) as a result. BaCuO(2) reacts with the remaining CuO to form a liquid which ultimately reacts with Y(2)O(3) in a last step to form YBCO. High temperature X-ray diffraction experiments confirm that these results are applicable for thin film synthesis prepared from an aqueous fluorine-free sol-gel precursor.

Periods of fasting are practiced worldwide on a cultural/religious background, and related mood-enhancing effects are postulated. We aimed to assess the effect of fasting on mood and to explore the interaction with neuroendocrine activation and leptin depletion in a controlled explorative study on consecutive inpatients (BMI < 35 kg/m2) of a nutritional ward. 36 subjects (38.9 +/- 7.0 years; 29 female, BMI 26.7 +/- 4.1 kg/m2) participated in an 8-day modified fast (300 kcal/day), 19 patients (38.1 +/- 5.9 years; 18 female, 23.5 +/- 4.1 kg/m2) received a mild low calorie diet. Measurements included daily ratings of mood (VAS), weight and levels of leptin and cortisol at four time-points of the 2-week study period. Weight loss was 4.8 +/- 1.2 and 1.6 +/- 0.9 kg in fasters and controls, respectively. Fasters showed a more pronounced decrease of leptin (58% vs. 20%; P < 0.001) and a 17% increase of cortisol levels (P < 0.001). Mood ratings increased significantly in the late phase of fasting (P < 0.01) but were not related to weight-loss, leptin-depletion or cortisol increase. Our findings suggest that fasting induces specific mood-enhancement. The physiological mediator appears to be neither leptin nor cortisol, the role of other mechanisms has to be further studied.

On the current discussion about efficacy and "point-specificity" of the needle therapy To improve the evidence base for acupuncture in pain treatment the German health insurance initiated the so called "Acupuncture randomised trials (ART)" and "German Acupuncture Trials" (GERAC) with a sample size of 300 (ART) and 1000 (GERAC) patients, providing a new dimension in acupuncture research. These studies have yielded data, which indicate that acupuncture is effective in the treatment of migraine, tension type headache, osteoarthritis of the knee and chronic low back pain. For the two latter indications acupuncture showed an even higher therapeutic response rate than conventional standard treatment. In migraine acupuncture showed an effect comparable to pharmacological treatment. The studies moreover indicate that the relevance of point-specific effects may have been overestimated concerning some indications. This article discusses the results of ART and GERAC, based on differentiating the mechanisms of action in acupuncture therapy. It is shown that the current data neither support the postulate of a "no-matter-where acupuncture" nor the irrefutability of the theorems of Chinese Medicine. Future studies will have to determine more precisely the mechanism by which the therapeutic effect of acupuncture is mediated. Furthermore, it will be necessary to find out more clearly in what diseases the location of needling represents the crucial part of the treatment and in what diseases rather different factors, like the intensity of stimulation or the doctor-patient interaction, are more relevant for the therapeutic effect. Research into acupuncture is still at the beginning. For this reason it should be avoided to draw premature and untenable conclusions from the current data.

Background: Alterations in the intestinal bacterial flora are believed to be contributing factors to many chronic inflammatory and degenerative diseases including rheumatic diseases. While microbiological fecal culture analysis is now increasingly used, little is known about the relationship of changes in intestinal flora, dietary patterns and clinical outcome in specific diseases. To clarify the role of microbiological culture analysis we aimed to evaluate whether in patients with rheumatoid arthritis (RA) or fibromyalgia (FM) a Mediterranean diet or an 8-day fasting period are associated with changes in fecal flora and whether changes in fecal flora are associated with clinical outcome., Methods: During a two-months-period 51 consecutive patients from an Integrative Medicine hospital department with an established diagnosis of RA (n = 16) or FM (n = 35) were included in the study. According to predefined clinical criteria and the subjects' choice the patients received a mostly vegetarian Mediterranean diet (n = 21; mean age 50.9 +/-13.3 y) or participated in an intermittent modified 8-day fasting therapy (n = 30; mean age 53.7 +/- 9.4 y). Quantitative aerob and anaerob bacterial flora, stool pH and concentrations of secretory immunoglobulin A (sIgA) were analysed from stool samples at the beginning, at the end of the 2-week hospital stay and at a 3-months follow-up. Clinical outcome was assessed with the DAS 28 for RA patients and with a disease severity rating scale in FM patients., Results: We found no significant changes in the fecal bacterial counts following the two dietary interventions within and between groups, nor were significant differences found in the analysis of sIgA and stool ph. Clinical improvement at the end of the hospital stay tended to be greater in fasting vs. non-fasting patients with RA (p = 0.09). Clinical outcome was not related to alterations in the intestinal flora., Conclusion: Neither Mediterranean diet nor fasting treatments affect the microbiologically assessed intestinal flora and sIgA levels in patients with RA and FM. The impact of dietary interventions on the human intestinal flora and the role of the fecal flora in rheumatic diseases have to be clarified with newer molecular analysis techniques. The potential benefit of fasting treatment in RA and FM should be further tested in randomised trials.

A basic principle in conventional pain therapy is that the treatment should be tailored to the pathological mechanism of the disease. This is based on the knowledge of the effector mechanisms of the applied treatment modalities. Although for acupuncture the mode of action still remains elusive in many parts, evidence about its mechanisms in pain treatment is growing. A better understanding of the hypalgesic effects of acupuncture might lead to a more differentiated and mechanism guided application. The aim of this article is to evaluate the scientific data about the neurobiological mechanisms of acupuncture in the treatment of pain. Data are critically evaluated regarding their relevance for clinical practice. Possible mechanisms are differentiated in local and systemic effects and the question of point specificity is discussed. Additionally a comprehensive hypothesis is set up for the long-term effects of acupuncture in the treatment of chronic pain. In this context acupuncture is considered as a mode of repetitive, nociceptive stimulation, which induces adaptive processes on different physiological levels leading to an improved ability of the nociceptive system to cope with painful stimuli.

The aim of the present study was to test the hypothesis that a creatine kinase/phosphocreatine system is involved in the regulation of K(ATP) channels in pancreatic beta-cells. The phosphocreatine concentration in isolated mouse islets clearly increased in parallel with the ATP/ADP ratio in response to a rise of the glucose concentration from 0.5 mM to 15 mM. The currents through K(ATP) channels expressed in oocytes of Xenopus laevis were inhibited by injection of phosphocreatine or ATP but not by phosphate or creatine alone. In inside-out patches of beta-cell membranes obtained from native beta-cells, phosphocreatine reduced the open probability of single K(ATP) channels in the presence of ADP but not in the absence of the nucleotide. These experiments suggest the existence of a K(ATP) channel-associated creatine kinase that phosphorylates ADP. The creatine kinase inhibitor iodoacetamide suppressed the glucose-induced oscillations of the cytoplasmic Ca(2+) concentration, [Ca(2+)](c). It is concluded that phosphocreatine serves as a shuttle for energy-rich phosphate from the mitochondria to the plasma membrane. The data provide a novel model for signal transduction to K(ATP) channels in pancreatic beta-cells.

Objectives: The aim of the study was to investigate the effects of acupuncture on the affective and sensory experience of pain in chronic pain patients. Furthermore, the study tried to estimate the therapeutical benefit of acupuncture in relation to the stage of chronic pain according to the Mainz pain staging system for chronic pain (MPSS)., Methods: Patients with chronic pain syndromes who received acupuncture treatment answered a standardized pain questionnaire before and after treatment. The questionnaire included the visual-analogue-scale for the intensity of pain, the pain perception scale for the assessment of affective and sensory components of pain perception, and addressed the patients to the three stages of chronic pain (MPSS)., Results: From April 1997 to October 1999, patients (n = 165) suffering from chronic headache and facial pain syndromes (23%), spine associated pain syndromes (48%) or other pain conditions (29%) were subsequently included. Treatment with acupuncture showed a more pronounced reduction of the affective assessment than of the sensory assessment of pain. These effects were particularly pronounced in patients assigned to stage 3 of chronic pain (MPSS)., Conclusions: Acupuncture in patients with high-stage chronic pain syndromes preferentially influences the affective dimension of pain perception. For the estimation of the overall clinical outcome of acupuncture treatment, a differentiation between affective and sensory components of pain is recommended.

We investigated the activation of the brain during anticipation of tactile stimuli by continuous cerebral blood flow velocity (CBFV) monitoring with bilateral transcranial Doppler sonography. A forced choice paradigm was performed where a first group of subjects (n=16) was expecting suprathreshold and a second group (n=19) was anticipating threshold tactile stimuli to the index finger after a cueing tone. During the anticipation of suprathreshold stimuli the CBFV always exhibited a significantly stronger increase in the right hemisphere than in the left, even when stimuli were anticipated at the right index finger. Conversely when stimuli at perception threshold were expected, the respective contralateral hemisphere showed a significantly stronger perfusion increase. These data show that preparatory activation of the brain during stimulus anticipation is dependant on the expected stimulus intensity.

Preparing for and processing of sensory stimuli are energy-requiring processes. We attempted to assess the relative contributions of these processes to increases in regional cerebral perfusion. Nineteen healthy right-handed subjects were examined while they were engaged in detecting tactile stimuli to the index finger 5 s after a cueing tone. Cerebral blood flow velocity (CBFV) modulations in the middle cerebral arteries (MCAs) were continuously measured by bilateral simultaneous transcranial Doppler ultrasonography. Tactile stimuli well above threshold per se did not produce a significant, relative CBFV increase in the contralateral MCA. However, when subjects were expecting a threshold tactile stimulus, there was a significant regional increase in CBFV in the hemisphere contralateral to the attended index finger for approximately 15 s, starting within the first seconds after the cueing. This increase was present even before the tactile stimulus was applied and also in sessions when the stimulus was omitted. We conclude that preparation of the cortex causes a stronger regional cerebral blood flow increase than the processing of the tactile stimulus itself.