Overriding water table control on managed peatland greenhouse gas emissions.

Global peatlands store more carbon than is naturally present in the atmosphere1,2. However, many peatlands are under pressure from drainage-based agriculture, plantation development and fire, with the equivalent of around 3 per cent of all anthropogenic greenhouse gases emitted from drained peatland3-5. Efforts to curb such emissions are intensifying through the conservation of undrained peatlands and re-wetting of drained systems6. Here we report eddy covariance data for carbon dioxide from 16 locations and static chamber measurements for methane from 41 locations in the UK and Ireland. We combine these with published data from sites across all major peatland biomes. We find that the mean annual effective water table depth (WTDe; that is, the average depth of the aerated peat layer) overrides all other ecosystem- and management-related controls on greenhouse gas fluxes. We estimate that every 10 centimetres of reduction in WTDe could reduce the net warming impact of CO2 and CH4 emissions (100-year global warming potentials) by the equivalent of at least 3 tonnes of CO2 per hectare per year, until WTDe is less than 30 centimetres. Raising water levels further would continue to have a net cooling effect until WTDe is within 10 centimetres of the surface. Our results suggest that greenhouse gas emissions from peatlands drained for agriculture could be greatly reduced without necessarily halting their productive use. Halving WTDe in all drained agricultural peatlands, for example, could reduce emissions by the equivalent of over 1 per cent of global anthropogenic emissions.

PET Imaging of Differentiated Thyroid Cancer with TSHR-Targeted [89Zr]Zr-TR1402.

Thyroid cancer is the most common endocrine cancer, with differentiated thyroid cancers (DTCs) accounting for 95% of diagnoses. While most DTC patients are diagnosed and treated with radioiodine (RAI), up to 20% of DTC patients become RAI refractory (RAI-R). RAI-R patients have significantly reduced survival rates compared to patients who remain RAI-avid. This study explores [89Zr]Zr-TR1402 as a thyroid-stimulating hormone receptor (TSHR)-targeted PET radiopharmaceutical for DTC. [89Zr]Zr-TR1402 was synthesized with a molar activity of 25.9 MBq/nmol by conjugating recombinant human TSH (rhTSH) analogue TR1402 to chelator p-SCN-Bn-deferoxamine (DFO) in a molar ratio of 3:1 (DFO/TR1402) and radiolabeling with 89Zr (t1/2 = 78.4 h, ß+ = 22.7%). As TSHR is absent in commonly available DTC-derived cell lines, TSHR was reintroduced via stable transduction by delivering a lentivirus containing the full-length coding region of the human TSHR gene. Receptor-mediated uptake of [89Zr]Zr-TR1402 was evaluated in vitro in stably transduced TSHR+ and wild-type TSHR- DTC cell lines. In vivo PET imaging was performed on Days 1-3 postinjection in male and female athymic nude mice bearing TSHR+ and TSHR- xenografts, along with ex vivo biodistribution on Day 3 postinjection. In vitro uptake of 1 nM [89Zr]Zr-TR1402 was significantly higher in TSHR+ THJ529T (P < 0.0001) and FTC133 (P < 0.01) cells than in TSHR- THJ529T and FTC133 cells. This uptake was shown to be specific in both TSHR+ THJ529T (P < 0.0001) and TSHR+ FTC133 (P < 0.0001) cells by blocking uptake with 250 nm DFO-TR1402. In vivo PET imaging showed accumulation of [89Zr]Zr-TR1402 in TSHR+ tumors, which was the highest on Day 1. In the male FTC133 xenograft model, ex vivo biodistribution confirmed a significant difference (P < 0.001) in uptake between FTC133+ (1.3 ± 0.1%ID/g) and FTC133- (0.8 ± 0.1%ID/g) tumors. A significant difference (P < 0.05) in uptake was also seen in the male THJ529T xenograft model between THJ529T+ (1.8 ± 0.6%ID/g) and THJ529T- (0.8 ± 0.4%ID/g) tumors. The in vitro and in vivo accumulation of [89Zr]Zr-TR1402 in TSHR-expressing DTC cell lines support the continued preclinical optimization of this approach.

Rapid, Accurate Classification of Single Emitters in Various Conditions and Environments for Blinking-Based Multiplexing.

Although single-molecule imaging is widely applied in biology and materials science, most studies are limited by their reliance on spectrally distinct fluorescent probes. We recently introduced blinking-based multiplexing (BBM), a simple approach to differentiate spectrally overlapped single emitters based solely on their intrinsic blinking dynamics. The original proof-of-concept study implemented two methods for emitter classification: an empirically derived metric and a deep learning algorithm, both of which have significant drawbacks. Here, a multinomial logistic regression (LR) classification is applied to rhodamine 6G (R6G) and CdSe/ZnS quantum dots (QDs) in various experimental conditions (i.e., excitation power and bin time) and environments (i.e., glass versus polymer). We demonstrate that LR analysis is rapid and generalizable, and classification accuracies of 95% are routinely observed, even within a complex polymer environment where multiple factors contribute to blinking heterogeneity. In doing so, this study (1) reveals the experimental conditions (i.e., Pexc = 1.2 µW and tbin = 10 ms) that optimize BBM for QD and R6G and (2) demonstrates that BBM via multinomial LR can accurately classify both emitter and environment, opening the door to new opportunities in single-molecule imaging.

Breaking Binaries: The Critical Need for Feminist Bioethics in Pediatric Gender-Affirming Care.

This commentary responds to Moti Gorin's article "What Is the Aim of Pediatric 'Gender-Affirming' Care?" We argue that Gorin's case against pediatric gender-affirming care rests upon numerous false conceptual binaries: female/male, public/private, objective/subjective, and medically necessary/elective. Drawing on feminist bioethics, we show how such dichotomous thinking is both inaccurate and marginalizing of gender minorities.

Blinking characteristics of organic fluorophores for blink-based multiplexing.

Single-molecule fluorescence experiments have transformed our understanding of complex materials and biological systems. Whether single molecules are used to report on their nano-environment or provide for localization, understanding their blinking dynamics (i.e., stochastic fluctuations in emission intensity under continuous illumination) is paramount. We recently demonstrated another use for blinking dynamics called blink-based multiplexing (BBM), where individual emitters are classified using a single excitation laser based on blinking dynamics, rather than color. This study elucidates the structure-activity relationships governing BBM performance in a series of model rhodamine, BODIPY, and anthraquinone fluorophores that undergo different photo-physical and-chemical processes during blinking. Change point detection and multinomial logistic regression analyses show that BBM can leverage spectral fluctuations, electron and proton transfer kinetics, as well as photostability for molecular classification-even within the context of a shared blinking mechanism. In doing so, we demonstrate two- and three-color BBM with ≥ 93% accuracy using spectrally-overlapped fluorophores.

Thyroid-stimulating hormone receptor (TSHR) as a target for imaging differentiated thyroid cancer.

BACKGROUND: Of the half a million cases of thyroid cancer diagnosed annually, 95% are differentiated thyroid cancers. Although clinical guidelines recommend surgical resection followed by radioactive iodine ablation, loss of sodium-iodine symporter expression causes up to 20% of differentiated thyroid cancers to become radioactive iodine refractory. For patients with radioactive iodine refractory disease, there is an urgent need for new diagnostic and therapeutic approaches. We evaluated the thyroid-stimulating hormone receptor as a potential target for imaging of differentiated thyroid cancer. METHODS: We immunostained tissue microarrays containing 52 Hurthle cell carcinomas to confirm thyroid-stimulating hormone receptor expression. We radiolabeled chelator deferoxamine conjugated to recombinant human thyroid-stimulating hormone analog superagonist TR1402 with 89Zr (t1/2 = 78.4 h, ß+ =22.7%) to produce [89Zr]Zr-TR1402. We performed in vitro uptake assays in high-thyroid-stimulating hormone receptor and low-thyroid-stimulating hormone receptor-expressing THJ529T and FTC133 thyroid cancer cell lines. We performed in vivo positron emission tomography/computed tomography and biodistribution studies in male athymic nude mice bearing thyroid-stimulating hormone receptor-positive THJ529T tumors. RESULTS: Immunohistochemical analysis revealed 62% of patients (27 primary and 5 recurrent) were thyroid-stimulating hormone receptor membranous immunostain positive. In vitro uptake of 1nM [89Zr]Zr-TR1402 was 38 ± 17% bound/mg in thyroid-stimulating hormone receptor-positive THJ529T thyroid cancer cell lines compared to 3.2 ± 0.5 in the low-expressing cell line (P < .01), with a similar difference seen in FTC133 cell lines (P < .0001). In vivo and biodistribution studies showed uptake of [89Zr]Zr-TR1402 in thyroid-stimulating hormone receptor-expressing tumors, with a mean percentage of injected dose/g of 1.9 ± 0.4 at 3 days post-injection. CONCLUSION: Our observation of thyroid-stimulating hormone receptor expression in tissue microarrays and [89Zr]Zr-TR1402 accumulation in thyroid-stimulating hormone receptor-positive thyroid cancer cells and tumors suggests thyroid-stimulating hormone receptor is a promising target for imaging of differentiated thyroid cancer.

Network meta-analysis: What is its purpose in Orthopaedic literature?

Systematic reviews, of level-I primary literature, are the gold standard for the formation of Clinical Practice Guidelines in Orthopaedic Surgery. When systematic reviews have multiple groups of data, meta-analyses can be conducted to analyse the direct comparison of the data points (pairwise meta-analysis). Over recent years, statisticians have created a new statistical model called network meta-analyses that can be applied to systematic reviews. network meta-analyses allow for comparison of different treatment outcomes that may or may not have been directly assessed through level-I primary studies. network meta-analyses are appearing more and more in Orthopaedic Surgery literature; therefore, in this article, we discuss what a Network Meta-analysis is and its application in Orthopaedics.

The presence of person-centered language in orthopedic-related amputation research: a cross-sectional analysis.

CONTEXT: Amputations are routine in orthopedics, specifically during trauma and when patients have recurrent surgical site infections. When undergoing amputations, patients must combat the psychosocial factors associated with the loss of an extremity, including stigmatization. OBJECTIVES: This study analyzes the presence of person-centered language (PCL) within amputation-related orthopedic publications in the top orthopedic journals. METHODS: We conducted a cross-sectional analysis with a database search on February 14, 2021 utilizing PubMed. Utilizing a previously published search string, we isolated studies that were published in the top 20 orthopedic journals based on the Google h5-index. In addition to the top 20 orthopedic journals, we included the top two hand and foot & ankle journals in our search to incorporate more amputation literature. Our search yielded 687 returns. The sample was then randomized, and the first 300 studies that fit our inclusion criteria were examined for prespecified non-PCL terminology. RESULTS: Our results show that 157 (52.2%) studies were adherent to PCL according to the American Medical Association's Manual of Style 10th Edition (AMAMS). Of the 143 (47.7%) studies that were not adherent to PCL, 51 studies (35.7%) had more than one type of non-PCL language. The term "amputee," which is being labeled as identity-first language (IFL), was found in 101 articles (33.7%). Further investigation found that 73.3% (74/101) of the studies containing IFL were found to have other non-PCL terms. Of the other studies in the sample, non-PCL was found 34.7% (88/199) of the time. This analysis was done due to the discrepancies in stigmatization of the term "amputee." No statistical association was found between adherence to PCL and study characteristics. CONCLUSIONS: Our findings show that amputation literature within the top orthopedic journals has limited adherence to PCL. Additionally, the use of the term "amputee," which is widely accepted by the amputation community, resulted in a greater rate of non-PCL terminology within orthopedic amputation literature. Efforts should be implemented within orthopedics to avoid the use of stigmatizing language, regarding individuals that underwent amputations, to minimize psychosocial stressors.

Cemented vs Uncemented hemiarthroplasties for femoral neck fractures: An overlapping systematic review and evidence appraisal.

BACKGROUND: The purpose of our study is to assess the methodology of overlapping systematic reviews related to cemented vs uncemented hip hemiarthroplasties for the treatment of femoral neck fractures to find the study with the best evidence. Also, we assess the gaps in methodology and information to help with direction of future studies. METHODS: A systematic search was conducted in September 2022 using Pubmed, Embase, and Cochrane Library. Clinical outcome data and characteristics of each study were extracted to see which treatment had better favorability. The outcomes and characteristics extracted from each study includes, first author, search date, publication journal and date, number of studies included, databases, level of evidence, software used, subgroup analyses that were conducted, and heterogeneity with the use of I2 statistics Methodological quality information was extracted from each study using four different methodologic scores (Oxford Levels of Evidence; Assessment of Multiple Systematic Reviews (AMSTAR); Quality of reporting of meta-analyses (QUROM); Oxman and Guyatt. After that, the Jadad decision algorithm was used to identify which studies in our sample contained the best available evidence. Finally, overlap of each systematic review was assessed using Corrected Covered Area (CCA) to look at redundancy and research waste among the systematic reviews published on the topic. RESULTS: After screening, 12 studies were included in our sample. For the Oxford Levels of Evidence, we found that all the studies were Level I evidence. For the QUORUM assessment, we had 1 study with the highest score of 18. Additionally, we did the Oxman and Guyatt assessment, where we found 4 studies with a maximum score of 6. Finally, we did an AMSTAR assessment and found 2 studies with a score of 9. After conducting the methodological scores; the authors determined that Li. L et al 2021 had the highest quality. In addition, it was found that the CCA found among the primary studies in each systematic review calculated to .22. Any CCA above .15 is considered "very high overlap". CONCLUSIONS: The best available evidence suggests that Cemented HAs are better at preventing Prosthesis-related complications. Conversely, the best evidence also suggests that Cemented HA also results in longer operative time and increased intraoperative blood loss. When conducting future systematic reviews related to the topic, we ask that authors restrict conducting another systematic review until new evidence emerges so as not to confuse the clinical decision-making of physicians.

The impacts of prescribed moorland burning on water colour and dissolved organic carbon: a critical synthesis.

Discolouration of natural surface waters due to the humic component of dissolved organic carbon (DOC) is a costly problem for water supply companies. This paper reviews what is known about the impacts of prescribed moorland vegetation burning on water colour. Relevant research has taken place at three scales: laboratory experiments on peat cores, plot scale sampling of soil waters and catchment scale sampling of stream waters. While laboratory studies suggest burning increases colour production, the evidence from catchment and plot studies is contradictory. Plot studies suggest colour production may decrease or remain unchanged following burning although there is evidence for some transient changes. Catchment studies suggest prescribed moorland burning causes stream water colour to increase, although in most cases the evidence is not clear cut since most studies could not clearly disentangle the effects of burning from those of vegetation cover. The differences in findings between plot and catchment studies may be explained by: i) the short-term nature of some studies which do not measure long-term response and recovery times to burning; ii) the lack of colour measurements from shallow soil depths which contribute more to streamflow than soil water from deeper in the peat; and iii) the possibility of hydrological interactions occurring between different experimental plots at some sites. Additionally, the increase in recent patch burning in some catchments that has been statistically attributed by some authors to increases in stream water colour cannot be reconciled with theoretical calculations. When dilution with waters derived from other parts of the catchment are taken into account, large values of colour have to be theoretically derived from those recently burnt areas that occupy a small proportion of the catchment area in order to balance the change in stream water colour observed in recent years. Therefore, much further process-based work is required to properly investigate whether prescribed vegetation burning is a direct driver of enhanced colour and DOC in upland streams, rivers and lakes.

Blinking-Based Multiplexing: A New Approach for Differentiating Spectrally Overlapped Emitters.

Multicolor single-molecule imaging is widely applied to answer questions in biology and materials science. However, most studies rely on spectrally distinct fluorescent probes or time-intensive sequential imaging strategies to multiplex. Here, we introduce blinking-based multiplexing (BBM), a simple approach to differentiate spectrally overlapped emitters based solely on their intrinsic blinking dynamics. The blinking dynamics of hundreds of rhodamine 6G and CdSe/ZnS quantum dots on glass are obtained using the same acquisition settings and analyzed with a change point detection algorithm. Although substantial blinking heterogeneity is observed, the analysis yields a blinking metric with 93.5% classification accuracy. We further show that BBM with up to 96.6% accuracy is achieved by using a deep learning algorithm for classification. This proof-of-concept study demonstrates that a single emitter can be accurately classified based on its intrinsic blinking dynamics and without the need to probe its spectral color.

A randomized feasibility study evaluating temozolomide circadian medicine in patients with glioma.

Background: Gliomas are the most common primary brain tumor in adults. Current treatments involve surgery, radiation, and temozolomide (TMZ) chemotherapy; however, prognosis remains poor and new approaches are required. Circadian medicine aims to maximize treatment efficacy and/or minimize toxicity by timed delivery of medications in accordance with the daily rhythms of the patient. We published a retrospective study showing greater anti-tumor efficacy for the morning, relative to the evening, administration of TMZ in patients with glioblastoma. We conducted this prospective randomized trial to determine the feasibility, and potential clinical impact, of TMZ chronotherapy in patients with gliomas (NCT02781792). Methods: Adult patients with gliomas (WHO grade II-IV) were enrolled prior to initiation of monthly TMZ therapy and were randomized to receive TMZ either in the morning (AM) before 10 am or in the evening (PM) after 8 pm. Pill diaries were recorded to measure compliance and FACT-Br quality of life (QoL) surveys were completed throughout treatment. Study compliance, adverse events (AE), and overall survival were compared between the two arms. Results: A total of 35 evaluable patients, including 21 with GBM, were analyzed (18 AM patients and 17 PM patients). Compliance data demonstrated the feasibility of timed TMZ dosing. There were no significant differences in AEs, QoL, or survival between the arms. Conclusions: Chronotherapy with TMZ is feasible. A larger study is needed to validate the effect of chronotherapy on clinical efficacy.

Novel Tracers and Radionuclides in PET Imaging.

The use of PET imaging agents in oncology, cardiovascular disease, and neurodegenerative disease shows the power of this technique in evaluating the molecular and biological characteristics of numerous diseases. These agents provide crucial information for designing therapeutic strategies for individual patients. Novel PET tracers are in continual development and many have potential use in clinical and research settings. This article discusses the potential applications of tracers in diagnostics, the biological characteristics of diseases, the ability to provide prognostic indicators, and using this information to guide treatment strategies including monitoring treatment efficacy in real time to improve outcomes and survival.

Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study.

BACKGROUND: Chronotherapy is an innovative approach to improving survival through timed delivery of anti-cancer treatments according to patient daily rhythms. Temozolomide (TMZ) is a standard-of-care chemotherapeutic agent for glioblastoma (GBM). Whether timing of TMZ administration affects GBM patient outcome has not previously been studied. We sought to evaluate maintenance TMZ chronotherapy on GBM patient survival. METHODS: This retrospective study reviewed patients with newly diagnosed GBM from January 1, 2010 to December 31, 2018 at Washington University School of Medicine who had surgery, chemoradiation, and were prescribed TMZ to be taken in the morning or evening. The Kaplan-Meier method and Cox regression model were used for overall survival (OS) analyses. The propensity score method accounted for potential observational study biases. The restricted mean survival time (RMST) method was performed where the proportional hazard assumption was violated. RESULTS: We analyzed 166 eligible GBM patients with a median follow-up of 5.07 years. Patients taking morning TMZ exhibited longer OS compared to evening (median OS, 95% confidence interval [CI] = 1.43, 1.12-1.92 vs 1.13, 0.84-1.58 years) with a significant year 1 RMST difference (-0.09, 95% CI: -0.16 to -0.018). Among MGMT-methylated patients, median OS was 6 months longer for AM patients with significant RMST differences at years 1 (-0.13, 95% CI = -0.24 to -0.019) to 2.5 (-0.43, 95% CI = -0.84 to -0.028). Superiority of morning TMZ at years 1, 2, and 5 (all P < .05) among all patients was supported by RMST difference regression after adjusting for confounders. CONCLUSIONS: Our study presents preliminary evidence for the benefit of TMZ chronotherapy to GBM patient survival. This impact is more pronounced in MGMT-methylated patients.

Prevalence of Deep Surgical Site Infection After Repair of Periarticular Knee Fractures: A Systematic Review and Meta-analysis.

Importance: Surgical management of periarticular knee fractures can be challenging, and adverse outcomes may be severe. Recent literature indicates that the rate of periarticular knee surgical site infection (SSI) may range from 2% to 88% depending on the fracture site. Objective: To examine the prevalence of deep SSI and the rate of septic arthritis after surgical repair of fractures around the knee. Data Sources: The electronic databases MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from their inception to July 1, 2018. Study Selection: Eligible studies had to specifically report deep SSI rates and include fractures in the distal femur, patella, tibial plateau, or proximal tibia. Risk factors that were associated with increased the risk of deep SSI were also examined. Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were extracted by multiple investigators. Comprehensive Meta-Analysis software was used for the pooling of data, using either random-effects or fixed-effects models, with respect to the degree of statistical heterogeneity present. Data analyses were conducted in October 2019. Main Outcomes and Measures: The primary outcome was overall prevalence of deep SSI after periarticular knee fracture repair. The secondary outcomes were the overall prevalence of septic arthritis, risk factors associated with deep SSI, and the most commonly cultured bacteria specimens found periarticular knee infections. Results: Of 6928 articles screened, 117 articles met inclusion criteria and were included in analysis. Among 11 432 patients included in analysis, 653 patients (5.7%) experienced deep SSIs, most commonly among patients with proximal tibia fractures (56 of 872 patients [6.4%]). Among studies that included information on septic arthritis, 38 of 1567 patients (2.4%) experienced septic arthritis. The 2 most commonly reported bacteria were methicillin-resistant Staphylococcus aureus, found in 67 SSIs, and methicillin-susceptible S aureus, found in 53 SSIs. Sixty-two studies (53.0%) in the sample received a Coleman Methodological Score of poor (<50 points). Conclusions and Relevance: Deep SSIs occurred in nearly 6% of periarticular knee fracture repairs, and 2.4% of SSIs were associated with septic arthritis. Surgeons managing these injuries should be vigilant when wounds are not pristine. Efforts should be made to elevate the quality of research conducted not only in this subject but also in orthopedic surgery as a whole.

Pressure-volume analysis as a method for quantifying simultaneous drug (amrinone) effects on arterial load and contractile state in vivo.

Pressure-volume relation analysis was used to independently quantify changes in ventricular contractile performance and vascular loading in intact anesthetized dogs before and after a single bolus of intravenous amrinone. Ventricular systolic property changes were characterized by the end-systolic elastance (Ees = slope of the end-systolic pressure-volume relation) and arterial properties by the effective arterial elastance (Ea = end-systolic pressure/stroke volume ratio). Pressure-volume data were obtained by the conductance catheter technique with loading varied by transient inferior vena cava occlusion. Amrinone induced a 27% increase in ejection fraction at 10 min (from 44% to 56%) as a result of both a significant rise in contractility (mean Ees 4 +/- 2 to 6 +/- 3 mm Hg/ml, p less than 0.001) and simultaneous reduction in arterial loading (Ea reduction from 6 +/- 2 mm Hg/ml to 5 mm Hg/ml, p less than 0.001). Over the subsequent 30 min, Ea revealed a significant recovery toward baseline, whereas Ees was less altered. Mean percent changes (% delta) in both variables were linearly correlated: % delta Ea = -1.6 x % delta Ees + 3.1, r = 0.96, p less than 0.001. In addition to separating ventricular from vascular property changes, the pressure-volume coupling framework was used to predict net pump performance (ejection fraction). Model predictions showed good agreement with experimental data. Thus, pressure-volume relations can be used to separately quantitate simultaneous changes in ventricular and vascular loading properties in vivo produced by pharmacologic agents with complex actions. Use of this approach in drug testing in humans should simplify data interpretation regarding mechanisms of action in specific clinical settings.

Cocaine-induced reduction of glucose utilization in human brain. A study using positron emission tomography and [fluorine 18]-fluorodeoxyglucose.

We examined the effects of cocaine hydrochloride (40 mg intravenously) on regional cerebral metabolic rates for glucose and on subjective self-reports of eight polydrug abusers in a double-blind, placebo-controlled, crossover study. The regional cerebral metabolic rate for glucose was measured by the [fluorine 18]-fluorodeoxyglucose method, using positron emission tomography. With eyes covered, subjects listened to a tape that presented white noise, "beep" prompts, and questions about subjective effects of cocaine or saline. Cocaine produced euphoria and reduced glucose utilization globally (mean reduction, 14%). Twenty-six of 29 brain regions (all neocortical areas, basal ganglia, portions of the hippocampal formation, thalamus, and midbrain) showed significant decrements (5% to 26%) in the regional cerebral metabolic rate for glucose. No significant effects of cocaine were observed in the pons, the cerebellar cortex, or the vermis. Right-greater-than-left hemispheric asymmetry of regional cerebral metabolic rates for glucose occurred in the lateral thalamus. The findings demonstrate that reduced cerebral metabolism is associated with cocaine-induced euphoria.

Cerebral glucose utilization in polysubstance abuse.

Regional cerebral glucose metabolism in subjects with histories of polysubstance abuse was compared to that in control subjects who were drawn from the same community. The substance abuse group showed lower absolute metabolic rates for glucose in lateral occipital gyrus and higher normalized metabolic rates in temporal and frontal areas, including orbitofrontal cortex. It is suggested that some patterns of brain function associated with polysubstance abuse may represent consequences of drug exposure, or they could reflect pre-existing differences that may be relevant to the etiology and maintenance of polysubstance abuse.

Buprenorphine reduces cerebral glucose metabolism in polydrug abusers.

Buprenorphine is a mixed opioid agonist-antagonist, which acts as a partial mu agonist and a kappa antagonist. The present study evaluated the acute effects of buprenorphine on cerebral glucose metabolism (CMRglc) in six human substance abusers using a double-blind, placebo-controlled, counterbalanced, crossover design. Each subject participated in two positron emission tomographic (PET) studies, 1 week apart, following the injection of buprenorphine (1 mg, intramuscularly) and placebo. Buprenorphine significantly reduced CMRglc and the regional cerebral metabolic rate for glucose (rCMRglc) by up to 32% in all but three of 22 bilateral and in 4 midline regions (p < .05). No region showed an increase in rCMRglc. Buprenorphine also produced miosis, respiratory depression, and subjective ratings of euphoria and sedation in comparison to placebo (p < .05). These observations extend previous findings of reduced CMRglc following acute treatment with morphine and other nonopioid euphorigenic drugs.