Chemical evidence for the use of multiple psychotropic plants in a 1,000-year-old ritual bundle from South America.

Over several millennia, various native plant species in South America have been used for their healing and psychoactive properties. Chemical analysis of archaeological artifacts provides an opportunity to study the use of psychoactive plants in the past and to better understand ancient botanical knowledge systems. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to analyze organic residues from a ritual bundle, radiocarbon dated to approximately 1,000 C.E., recovered from archaeological excavations in a rock shelter located in the Lípez Altiplano of southwestern Bolivia. The site is located at an elevation of ∼3,900 m above sea level and contains evidence of intermittent human occupations during the last 4,000 years. Chemical traces of bufotenine, dimethyltryptamine, harmine, and cocaine, including its degradation product benzoylecgonine, were identified, suggesting that at least three plants containing these compounds were part of the shamanic paraphernalia dating back 1,000 years ago, the largest number of compounds recovered from a single artifact from this area of the world, to date. This is also a documented case of a ritual bundle containing both harmine and dimethyltryptamine, the two primary ingredients of ayahuasca. The presence of multiple plants that come from disparate and distant ecological areas in South America suggests that hallucinogenic plants moved across significant distances and that an intricate botanical knowledge was intrinsic to pre-Columbian ritual practices.

Introduction of Group Electronic Monitoring of Hand Hygiene on Inpatient Units: A Multicenter Cluster Randomized Quality Improvement Study.

BACKGROUND: The current approach to measuring hand hygiene (HH) relies on human auditors who capture <1% of HH opportunities and rapidly become recognized by staff, resulting in inflation in performance. Group electronic monitoring is a validated method of measuring HH adherence, but data demonstrating the clinical impact of this technology are lacking. METHODS: A stepped-wedge cluster randomized quality improvement study was performed on 26 inpatient medical and surgical units across 5 acute care hospitals in Ontario, Canada. The intervention involved daily HH reporting as measured by group electronic monitoring to guide unit-led improvement strategies. The primary outcome was monthly HH adherence (percentage) between baseline and intervention. Secondary outcomes included transmission of antibiotic-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and other healthcare-associated infections. RESULTS: After adjusting for the correlation within inpatient units and hospitals, there was a significant overall improvement in HH adherence associated with the intervention (incidence rate ratio [IRR], 1.73 [95% confidence interval {CI}, 1.47-1.99]; P < .0001). Monthly HH adherence relative to the intervention increased from 29% (1 395 450/4 544 144) to 37% (598 035/1 536 643) within 1 month, followed by consecutive incremental increases up to 53% (804 108/1 515 537) by 10 months (P < .0001). There was a trend toward reduced healthcare-associated transmission of MRSA (IRR, 0.74 [95% CI, .53-1.04]; P = .08). CONCLUSIONS: The introduction of a system for group electronic monitoring led to rapid, significant improvements in HH performance within a 2-year period. This method offers significant advantages over direct observation for measurement and improvement of HH.

Upregulation of pERK and c-JUN by γ-tocotrienol and not α-tocopherol are essential to the differential effect on apoptosis in prostate cancer cells.

BACKGROUND: α-tocopherol (AT) and γ-tocotrienol (GT3) are vitamin E isoforms considered to have potential chemopreventive properties. AT has been widely studied in vitro and in clinical trials with mixed results. The latest clinical study (SELECT trial) tested AT in prostate cancer patients, determined that AT provided no benefit, and could promote cancer. Conversely, GT3 has shown antineoplastic properties in several in vitro studies, with no clinical studies published to date. GT3 causes apoptosis via upregulation of the JNK pathway; however, inhibition results in a partial block of cell death. We compared side by side the mechanistic differences in these cells in response to AT and GT3. METHODS: The effects of GT3 and AT were studied on androgen sensitive LNCaP and androgen independent PC-3 prostate cancer cells. Their cytotoxic effects were analyzed via MTT and confirmed by metabolic assays measuring ATP. Cellular pathways were studied by immunoblot. Quantitative analysis and the determination of relationships between cell signaling events were analyzed for both agents tested. Non-cancerous prostate RWPE-1 cells were also included as a control. RESULTS: The RAF/RAS/ERK pathway was significantly activated by GT3 in LNCaP and PC-3 cells but not by AT. This activation is essential for the apoptotic affect by GT3 as demonstrated the complete inhibition of apoptosis by MEK1 inhibitor U0126. Phospho-c-JUN was upregulated by GT3 but not AT. No changes were observed on AKT for either agent, and no release of cytochrome c into the cytoplasm was detected. Caspases 9 and 3 were efficiently activated by GT3 on both cell lines irrespective of androgen sensitivity, but not in cells dosed with AT. Cell viability of non-cancerous RWPE-1 cells was affected neither by GT3 nor AT. CONCLUSIONS: c-JUN is a recognized master regulator of apoptosis as shown previously in prostate cancer. However, the mechanism of action of GT3 in these cells also include a significant activation of ERK which is essential for the apoptotic effect of GT3. The activation of both, ERK and c-JUN, is required for apoptosis and may suggest a relevant step in ensuring circumvention of mechanisms of resistance related to the constitutive activation of MEK1.

Germline De Novo Mutations in GNB1 Cause Severe Neurodevelopmental Disability, Hypotonia, and Seizures.

Whole-exome sequencing of 13 individuals with developmental delay commonly accompanied by abnormal muscle tone and seizures identified de novo missense mutations enriched within a sub-region of GNB1, a gene encoding the guanine nucleotide-binding protein subunit beta-1, Gß. These 13 individuals were identified among a base of 5,855 individuals recruited for various undiagnosed genetic disorders. The probability of observing 13 or more de novo mutations by chance among 5,855 individuals is very low (p = 7.1 × 10(-21)), implicating GNB1 as a genome-wide-significant disease-associated gene. The majority of these 13 mutations affect known Gß binding sites, which suggests that a likely disease mechanism is through the disruption of the protein interface required for Gα-Gßγ interaction (resulting in a constitutively active Gßγ) or through the disruption of residues relevant for interaction between Gßγ and certain downstream effectors (resulting in reduced interaction with the effectors). Strikingly, 8 of the 13 individuals recruited here for a neurodevelopmental disorder have a germline de novo GNB1 mutation that overlaps a set of five recurrent somatic tumor mutations for which recent functional studies demonstrated a gain-of-function effect due to constitutive activation of G protein downstream signaling cascades for some of the affected residues.

Carbon dynamics, net primary productivity and human-appropriated net primary productivity across a forest-cocoa farm landscape in West Africa.

Terrestrial net primary productivity (NPP) is an important metric of ecosystem functioning; however, there are little empirical data on the NPP of human-modified ecosystems, particularly smallholder, perennial crops like cocoa (Theobroma cacao), which are extensive across the tropics. Human-appropriated NPP (HANPP) is a measure of the proportion of a natural system's NPP that has either been reduced through land-use change or harvested directly and, previously, has been calculated to estimate the scale of the human impact on the biosphere. Additionally, human modification can create shifts in NPP allocation and decomposition, with concomitant impacts on the carbon cycle. This study presents the results of 3 years of intensive monitoring of forest and smallholder cocoa farms across disturbance, management intensity, distance from forest and farm age gradients. We measured among the highest reported NPP values in tropical forest, 17.57 ± 2.1 and 17.7 ± 1.6 Mg C ha-1  year-1 for intact and logged forest, respectively; however, the average NPP of cocoa farms was still higher, 18.8 ± 2.5 Mg C ha-1  year-1 , which we found was driven by cocoa pod production. We found a dramatic shift in litterfall residence times, where cocoa leaves decomposed more slowly than forest leaves and shade tree litterfall decomposed considerably faster, indicating significant changes in rates of nutrient cycling. The average HANPP value for all cocoa farms was 2.1 ± 1.1 Mg C ha-1  year-1 ; however, depending on the density of shade trees, it ranged from -4.6 to 5.2 Mg C ha-1  year-1 . Therefore, rather than being related to cocoa yield, HANPP was reduced by maintaining higher shade levels. Across our monitored farms, 18.9% of farm NPP was harvested (i.e., whole cocoa pods) and only 1.1% (i.e., cocoa beans) was removed from the system, suggesting that the scale of HANPP in smallholder cocoa agroforestry systems is relatively small.

A Cryptic Cause of Cardiac Arrest.

BACKGROUND: RIPPLY2-associated spondylocostal dysostosis is a rare disorder that leads to segmentation defects of the vertebrae. These vertebral defects can result in severe instability of the cervical spine, leading to cardiac arrest after only minor whiplash injury. CASE REPORT: We present the case of a healthy 7-year-old child who experienced an out-of-hospital cardiac arrest. He was reported to have profound respiratory distress and collapsed after going down a slide, without trauma. He was resuscitated in the field, and presented to the emergency department, where return of spontaneous circulation was achieved. Imaging of his cervical spine revealed multiple abnormalities. It was determined that a whiplash injury led to hypoxia and bradycardia due to the anatomic abnormalities of his cervical spine, resulting in cardiovascular collapse. He recovered fully and was later diagnosed with SCDO6, an autosomal recessive inherited disorder caused by a mutation in the RIPPLY2 gene. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Unfamiliarity of providers with this mechanism of cardiac arrest, and the rarity of the syndrome itself, make early recognition very difficult. Late diagnosis and lack of preventative measures, including immediate cervical spine stabilization, can lead to catastrophic outcomes. In patients with cardiac arrest of unclear etiology, early consideration of cervical spine immobilization and evaluation can be lifesaving.

De novo missense variants in HECW2 are associated with neurodevelopmental delay and hypotonia.

BACKGROUND: The causes of intellectual disability (ID) are diverse and de novo mutations are increasingly recognised to account for a significant proportion of ID. METHODS AND RESULTS: In this study, we performed whole exome sequencing on a large cohort of patients with ID or neurodevelopmental delay and identified four novel de novo predicted deleterious missense variants in HECW2 in six probands with ID/developmental delay and hypotonia. Other common features include seizures, strabismus, nystagmus, cortical visual impairment and dysmorphic facial features. HECW2 is an ubiquitin ligase that stabilises p73, a crucial mediator of neurodevelopment and neurogenesis. CONCLUSION: This study implicates pathogenic genetic variants in HECW2 as potential causes of neurodevelopmental disorders in humans.

Comparing a Statistical Model and Bayesian Approach to Establish the Design Space for the Coating of Ciprofloxacin HCl Beads at Different Scales of Production.

The primary objective of this study was to compare two methods for establishing a design space for critical process parameters that affect ethylcellulose film coating of multiparticulate beads and assess this design space validity across manufacturing scales. While there are many factors that can affect film coating, this study will focus on the effects processing conditions have on the quality and extent of film formation, as evaluated by their impact coating yield and drug release. Ciprofloxacin HCl layered beads were utilized as an active substrate core, ethylcellulose aqueous dispersion as a controlled release polymer, and triethyl citrate as a plasticizer. Thirty experiments were conducted using a central composite design to optimize the coating process and map the response surface to build a design space using either statistical least squares or a Bayesian approach. The response surface was fitted using a linear two-factor interaction model with spraying temperature, curing temperature, and curing time as significant model terms. The design spaces established by the two approaches were in close agreement with the statistical least squares approach being more conservative than the Bayesian approach. The design space established for the critical process parameters using small-scale batches was tested using scale-up batches and found to be scale-independent. The robustness of the design space was confirmed across scales and was successfully utilized to establish process signature for the coating process.

Urine and oral fluid drug testing in support of pain management.

In recent years, the abuse of opioid drugs has resulted in greater prevalence of addiction, overdose, and deaths attributable to opioid abuse. The epidemic of opioid abuse has prompted professional and government agencies to issue practice guidelines for prescribing opioids to manage chronic pain. An important tool available to providers is the drug test for use in the initial assessment of patients for possible opioid therapy, subsequent monitoring of compliance, and documentation of suspected aberrant drug behaviors. This review discusses the issues that most affect the clinical utility of drug testing in chronic pain management with opioid therapy. It focuses on the two most commonly used specimen matrices in drug testing: urine and oral fluid. The advantages and disadvantages of urine and oral fluid in the entire testing process, from specimen collection and analytical methodologies to result interpretation are reviewed. The analytical sensitivity and specificity limitations of immunoassays used for testing are examined in detail to draw attention to how these shortcomings can affect result interpretation and influence clinical decision-making in pain management. The need for specific identification and quantitative measurement of the drugs and metabolites present to investigate suspected aberrant drug behavior or unexpected positive results is analyzed. Also presented are recent developments in optimization of test menus and testing strategies, such as the modification of the standard screen and reflexed-confirmation testing model by eliminating some of the initial immunoassay-based tests and proceeding directly to definitive testing by mass spectrometry assays.

A Systematic Approach of Employing Quality by Design Principles: Risk Assessment and Design of Experiments to Demonstrate Process Understanding and Identify the Critical Process Parameters for Coating of the Ethylcellulose Pseudolatex Dispersion Using Non-Conventional Fluid Bed Process.

The goal of this study was to utilize risk assessment techniques and statistical design of experiments (DoE) to gain process understanding and to identify critical process parameters for the manufacture of controlled release multiparticulate beads using a novel disk-jet fluid bed technology. The material attributes and process parameters were systematically assessed using the Ishikawa fish bone diagram and failure mode and effect analysis (FMEA) risk assessment methods. The high risk attributes identified by the FMEA analysis were further explored using resolution V fractional factorial design. To gain an understanding of the processing parameters, a resolution V fractional factorial study was conducted. Using knowledge gained from the resolution V study, a resolution IV fractional factorial study was conducted; the purpose of this IV study was to identify the critical process parameters (CPP) that impact the critical quality attributes and understand the influence of these parameters on film formation. For both studies, the microclimate, atomization pressure, inlet air volume, product temperature (during spraying and curing), curing time, and percent solids in the coating solutions were studied. The responses evaluated were percent agglomeration, percent fines, percent yield, bead aspect ratio, median particle size diameter (d50), assay, and drug release rate. Pyrobuttons® were used to record real-time temperature and humidity changes in the fluid bed. The risk assessment methods and process analytical tools helped to understand the novel disk-jet technology and to systematically develop models of the coating process parameters like process efficiency and the extent of curing during the coating process.

Cross-scale feedbacks and scale mismatches as influences on cultural services and the resilience of protected areas.

Protected areas are a central strategy for achieving global conservation goals, but their continued existence depends heavily on maintaining sufficient social and political support to outweigh economic interests or other motives for land conversion. Thus, the resilience of protected areas can be considered a function of their perceived benefits to society. Nature-based tourism (NBT), a cultural ecosystem service, provides a key source of income to protected areas, facilitating a sustainable solution to conservation. The ability of tourism to generate income depends, however, on both the scales at which this cultural service is provided and the scales at which tourists respond to services on offer. This observation raises a set of location-, context-, and scale-related questions that need to be confronted before we can understand and value cultural service provision appropriately. We combine elements of resilience analysis with a systems ecology framework and apply this to NBT in protected areas to investigate cross-scale interactions and scale mismatches. We postulate that cross-scale effects can either have a positive effect on protected area resilience or lead to scale mismatches, depending on their interactions with cross-scale feedbacks. To demonstrate this, we compare spatial scales and nested levels of institutions to develop a typology of scale mismatches for common scenarios in NBT. In our new typology, the severity of a scale mismatch is expressed as the ratio of spatial scale to institutional level, producing 25 possible outcomes with differing consequences for system resilience. We predict that greater differences between interacting scales and levels, and greater magnitudes of cross-scale interactions, will lead to greater magnitudes of scale mismatch. Achieving a better understanding of feedbacks and mismatches, and finding ways of aligning spatial and institutional scales, will be critical for strengthening the resilience of protected areas that depend on NBT.

Understanding protected area resilience: a multi-scale, social-ecological approach.

Protected areas (PAs) remain central to the conservation of biodiversity. Classical PAs were conceived as areas that would be set aside to maintain a natural state with minimal human influence. However, global environmental change and growing cross-scale anthropogenic influences mean that PAs can no longer be thought of as ecological islands that function independently of the broader social-ecological system in which they are located. For PAs to be resilient (and to contribute to broader social-ecological resilience), they must be able to adapt to changing social and ecological conditions over time in a way that supports the long-term persistence of populations, communities, and ecosystems of conservation concern. We extend Ostrom's social-ecological systems framework to consider the long-term persistence of PAs, as a form of land use embedded in social-ecological systems, with important cross-scale feedbacks. Most notably, we highlight the cross-scale influences and feedbacks on PAs that exist from the local to the global scale, contextualizing PAs within multi-scale social-ecological functional landscapes. Such functional landscapes are integral to understand and manage individual PAs for long-term sustainability. We illustrate our conceptual contribution with three case studies that highlight cross-scale feedbacks and social-ecological interactions in the functioning of PAs and in relation to regional resilience. Our analysis suggests that while ecological, economic, and social processes are often directly relevant to PAs at finer scales, at broader scales, the dominant processes that shape and alter PA resilience are primarily social and economic.

Correlation analysis between cotinine hair concentrations from active smokers and nicotine intake and dependence.

OBJECTIVES: To determine cotinine levels in hair samples collected from smokers and estimate their relationship with nicotine intake and nicotine dependence class according to the Fagerström dependence questionnaire. DESIGN AND METHODS: Sixty-nine volunteers participated. They gave hair samples and answered questionnaires covering information related to smoking habits. Cotinine levels were determined by enzyme immunoassay after extraction from 20 mg of hair. Calibrators for the range 100 to 12,800 pg/mg were used. RESULTS: Mean cotinine concentration was 2070.9 pg/mg (range, 469.4-10,188.6 pg/mg). There were significant correlations between cotinine levels in hair and the questionnaire results (rs = 0.325, P = 0.018) and with the number of cigarettes smoked in a day (rs = 0.717, P < 0.001). Although the correlation between questionnaire results and the number of cigarettes smoked per day was significant (rs = 0.565, P < 0.01), it was weaker than the association between cotinine levels and number of cigarettes smoked. Cotinine levels were lower in the group that smoked from 1 to 5 cigarettes per day (1104.1 ng/mg) compared with the other groups. CONCLUSIONS: Cotinine levels were more highly correlated with nicotine exposure than with the Fagerström questionnaire scores. It was found that interference from exogenous sources of contamination, such as hair dyes, is a limitation to estimate nicotine intake from hair analysis.

Development of a new immunoassay for the detection of ethyl glucuronide (EtG) in meconium: validation with authentic specimens analyzed using LC-MS/MS. Preliminary results.

BACKGROUND: Ethyl glucuronide (EtG) measurement in neonatal meconium has emerged as a reliable marker to objectively assess prenatal exposure to maternal ethanol complementary to fatty acid ethyl ester (FAEEs) measurement. The detection of EtG in meconium is currently a lengthy, difficult and expensive process using liquid chromatography tandem mass spectrometry (LC-MS/MS) as the analytical procedure. An enzyme-linked immunosorbent assay (ELISA) for the identification of EtG in meconium was developed, validated and applied to authentic meconium specimens from newborns collected in Europe. METHODS: The ELISA procedure was calibrated using 0.45, 0.9, 1.35 and 1.8 nmol/g (100, 200 300 and 400 ng/g) standards. Meconium (0.25 g) was mixed thoroughly, with extraction buffer (pH 7.3; 0.5 mL). The tube was capped, sonicated, centrifuged and the supernatant was decanted. An aliquot of the extract (50 µL) was placed in the well of the microplate followed by enzyme conjugate (150 µL). The plate was incubated for 1 h, washed with deionized water, dried and substrate (200 µL) was added. After 30 min incubation, stop solution was added and the plate was read at 450 nm and 650 nm. Samples were also analyzed for EtG and FAEEs by validated LC-MS/MS assays. RESULTS: Using an EtG cut-off of 0.9 nmol/g for both ELISA screening test and confirmatory LC-MS/MS, immunoassay sensitivity was 100%; specificity 78%; positive-predictive value (PPV) 29% and negative-predictive value (NPV) 100%. CONCLUSIONS: The assay is proposed as a preliminary screening test for the meconium of newborns suspected of being born to mothers drinking alcohol during pregnancy.

Exploring the perceptual biases associated with believing and disbelieving in paranormal phenomena.

Ninety-five participants (32 believers, 30 disbelievers and 33 neutral believers in the paranormal) participated in an experiment comprising one visual and one auditory block of trials. Each block included one ESP, two degraded stimuli and one random trial. Each trial included 8 screens or epochs of "random" noise. Participants entered a guess if they perceived a stimulus or changed their mind about stimulus identity, rated guesses for confidence and made notes during each trial. Believers and disbelievers did not differ in the number of guesses made, or in their ability to detect degraded stimuli. Believers displayed a trend toward making faster guesses for some conditions and significantly higher confidence and more misidentifications concerning guesses than disbelievers. Guesses, misidentifications and faster response latencies were generally more likely in the visual than auditory conditions. ESP performance was no different from chance. ESP performance did not differ between belief groups or sensory modalities.

Patient-Centric Quality Standards.

To ensure the quality, safety and efficacy of medicinal products, it is necessary to develop and execute appropriate manufacturing process and product control strategies. Traditionally, product control strategies have focused on testing known quality attributes with limits derived from levels administered in preclinical and clinical studies with an associated statistical analysis to account for variability. However, not all quality attributes have impact to the patient and those with the potential to impact safety and efficacy may not be significant when dosed at patient-centric levels. Therefore, achieving patient-centricity is understanding patient relevance, which is defined as the level of impact that a quality attribute could have on safety and efficacy within the potential exposure range. A patient-centric quality standard (PCQS) is therefore a set of patient relevant attributes and their associated acceptance ranges to which a drug product should conform within the expected patient exposure range. This manuscript describes historical perspectives details the way to create and leverage a PCQS in a variety of pharmaceutical product modalities.

Recurrent HERV-H-mediated 3q13.2-q13.31 deletions cause a syndrome of hypotonia and motor, language, and cognitive delays.

We describe the molecular and clinical characterization of nine individuals with recurrent, 3.4-Mb, de novo deletions of 3q13.2-q13.31 detected by chromosomal microarray analysis. All individuals have hypotonia and language and motor delays; they variably express mild to moderate cognitive delays (8/9), abnormal behavior (7/9), and autism spectrum disorders (3/9). Common facial features include downslanting palpebral fissures with epicanthal folds, a slightly bulbous nose, and relative macrocephaly. Twenty-eight genes map to the deleted region, including four strong candidate genes, DRD3, ZBTB20, GAP43, and BOC, with important roles in neural and/or muscular development. Analysis of the breakpoint regions based on array data revealed directly oriented human endogenous retrovirus (HERV-H) elements of ~5 kb in size and of >95% DNA sequence identity flanking the deletion. Subsequent DNA sequencing revealed different deletion breakpoints and suggested nonallelic homologous recombination (NAHR) between HERV-H elements as a mechanism of deletion formation, analogous to HERV-I-flanked and NAHR-mediated AZFa deletions. We propose that similar HERV elements may also mediate other recurrent deletion and duplication events on a genome-wide scale. Observation of rare recurrent chromosomal events such as these deletions helps to further the understanding of mechanisms behind naturally occurring variation in the human genome and its contribution to genetic disease.

The World Neurosurgery Global Champions Program: First-Year Experience of a Model Initiative for Reducing Disparities in Global Neurosurgical Literature.

OBJECTIVE: Most surgical journals are published in English, representing a challenge for researchers from non-Anglophone countries. We describe the implementation, workflow, outcomes, and lessons learned from the WORLD NEUROSURGERY Global Champions Program (GCP), a novel journal-specific English language editing program for articles rejected because of poor English grammar or usage. METHODS: The GCP was advertised via the journal website and social media. Applicants were selected to be a reviewer for the GCP if they demonstrated English proficiency on writing samples supplied in their application. The demographics of GCP members and characteristics and outcomes of articles edited by the GCP during its first year were reviewed. Surveys of GCP members and authors who used the service were conducted. RESULTS: Twenty-one individuals became part of the GCP, representing 8 countries and 16 languages apart from English. A total of 380 manuscripts were peer reviewed by the editor-in-chief, who determined these manuscripts to have potentially worthwhile content but needed to be rejected due to poor language. The authors of these manuscripts were informed of the existence of this language assistance program. Forty-nine articles (12.9%) were edited by the GCP in 41.6 ± 22.8 days. Of 40 articles resubmitted to WORLD NEUROSURGERY, 24 (60.0%) were accepted. GCP members and authors understood the purpose and workflow of the program and recognized improvements in article quality and the probability of acceptance through their participation. CONCLUSIONS: The WORLD NEUROSURGERY Global Champions Program mitigated a critical barrier to publication in an English language journal for authors from non-Anglophone countries. This program promotes research equity by providing a free, largely medical student and trainee operated, English language editing service. This model or a similar service can be replicated by other journals.

Outbreak of extended-spectrum ß-lactamase-producing Klebsiella oxytoca infections associated with contaminated handwashing sinks(1).

Klebsiella oxytoca is primarily a health care-associated pathogen acquired from environmental sources. During October 2006-March 2011, a total of 66 patients in a hospital in Toronto, Ontario, Canada, acquired class A extended-spectrum ß-lactamase-producing K. oxytoca with 1 of 2 related pulsed-field gel electrophoresis patterns. New cases continued to occur despite reinforcement of infection control practices, prevalence screening, and contact precautions for colonized/infected patients. Cultures from handwashing sinks in the intensive care unit yielded K. oxytoca with identical pulsed-field gel electrophoresis patterns to cultures from the clinical cases. No infections occurred after implementation of sink cleaning 3×/day, sink drain modifications, and an antimicrobial stewardship program. In contrast, a cluster of 4 patients infected with K. oxytoca in a geographically distant medical ward without contaminated sinks was contained with implementation of active screening and contact precautions. Sinks should be considered potential reservoirs for clusters of infection caused by K. oxytoca.