Publications by authors named "Janice Baker"

22 Publications

  • Page 1 of 1

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior.

Genet Med 2021 Mar 3. Epub 2021 Mar 3.

Division of Medical Genetics, Nemours/A.I. DuPont Hospital for Children, Wilmington, DE, USA.

Purpose: We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis.

Methods: We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes.

Results: These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes.

Conclusion: These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.
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http://dx.doi.org/10.1038/s41436-021-01114-zDOI Listing
March 2021

Expanding the phenotype of Wiedemann-Steiner syndrome: Craniovertebral junction anomalies.

Am J Med Genet A 2020 12 11;182(12):2877-2886. Epub 2020 Oct 11.

Medical Genetics Unit, Meyer Children's University Hospital, Florence, Italy.

Wiedemann-Steiner syndrome (WDSTS) is a rare autosomal dominant condition caused by heterozygous loss of function variants in the KMT2A (MLL) gene, encoding a lysine N-methyltransferase that mediates a histone methylation pattern specific for epigenetic transcriptional activation. WDSTS is characterized by a distinctive facial phenotype, hypertrichosis, short stature, developmental delay, intellectual disability, congenital malformations, and skeletal anomalies. Recently, a few patients have been reported having abnormal skeletal development of the cervical spine. Here we describe 11 such individuals, all with KMT2A de novo loss-of-function variants: 10 showed craniovertebral junction anomalies, while an 11th patient had a cervical abnormality in C7. By evaluating clinical and diagnostic imaging data we characterized these anomalies, which consist primarily of fused cervical vertebrae, C1 and C2 abnormalities, small foramen magnum and Chiari malformation type I. Craniovertebral anomalies in WDSTS patients have been largely disregarded so far, but the increasing number of reports suggests that they may be an intrinsic feature of this syndrome. Specific investigation strategies should be considered for early identification and prevention of craniovertebral junction complications in WDSTS patients.
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http://dx.doi.org/10.1002/ajmg.a.61859DOI Listing
December 2020

Genotype-phenotype correlation at codon 1740 of SETD2.

Am J Med Genet A 2020 09 24;182(9):2037-2048. Epub 2020 Jul 24.

Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.

The SET domain containing 2, histone lysine methyltransferase encoded by SETD2 is a dual-function methyltransferase for histones and microtubules and plays an important role for transcriptional regulation, genomic stability, and cytoskeletal functions. Specifically, SETD2 is associated with trimethylation of histone H3 at lysine 36 (H3K36me3) and methylation of α-tubulin at lysine 40. Heterozygous loss of function and missense variants have previously been described with Luscan-Lumish syndrome (LLS), which is characterized by overgrowth, neurodevelopmental features, and absence of overt congenital anomalies. We have identified 15 individuals with de novo variants in codon 1740 of SETD2 whose features differ from those with LLS. Group 1 consists of 12 individuals with heterozygous variant c.5218C>T p.(Arg1740Trp) and Group 2 consists of 3 individuals with heterozygous variant c.5219G>A p.(Arg1740Gln). The phenotype of Group 1 includes microcephaly, profound intellectual disability, congenital anomalies affecting several organ systems, and similar facial features. Individuals in Group 2 had moderate to severe intellectual disability, low normal head circumference, and absence of additional major congenital anomalies. While LLS is likely due to loss of function of SETD2, the clinical features seen in individuals with variants affecting codon 1740 are more severe suggesting an alternative mechanism, such as gain of function, effects on epigenetic regulation, or posttranslational modification of the cytoskeleton. Our report is a prime example of different mutations in the same gene causing diverging phenotypes and the features observed in Group 1 suggest a new clinically recognizable syndrome uniquely associated with the heterozygous variant c.5218C>T p.(Arg1740Trp) in SETD2.
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http://dx.doi.org/10.1002/ajmg.a.61724DOI Listing
September 2020

The variability of SMARCA4-related Coffin-Siris syndrome: Do nonsense candidate variants add to milder phenotypes?

Am J Med Genet A 2020 09 20;182(9):2058-2067. Epub 2020 Jul 20.

Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, Virginia, USA.

SMARCA4 encodes a central ATPase subunit in the BRG1-/BRM-associated factors (BAF) or polybromo-associated BAF (PBAF) complex in humans, which is responsible in part for chromatin remodeling and transcriptional regulation. Variants in this and other genes encoding BAF/PBAF complexes have been implicated in Coffin-Siris Syndrome, a multiple congenital anomaly syndrome classically characterized by learning and developmental differences, coarse facial features, hypertrichosis, and underdevelopment of the fifth digits/nails of the hands and feet. Individuals with SMARCA4 variants have been previously reported and appear to display a variable phenotype. We describe here a cohort of 15 unrelated individuals with SMARCA4 variants from the Coffin-Siris syndrome/BAF pathway disorders registry who further display variability in severity and degrees of learning impairment and health issues. Within this cohort, we also report two individuals with novel nonsense variants who appear to have a phenotype of milder learning/behavioral differences and no organ-system involvement.
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http://dx.doi.org/10.1002/ajmg.a.61732DOI Listing
September 2020

Rise in the incidence of abusive head trauma during the COVID-19 pandemic.

Arch Dis Child 2021 03 2;106(3):e14. Epub 2020 Jul 2.

Department of Radiology, Great Ormond Street Hospital For Children NHS Foundation Trust, London, UK

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http://dx.doi.org/10.1136/archdischild-2020-319872DOI Listing
March 2021

Body Temperature Responses During Phases of Work in Human Remains Detection Dogs Undergoing a Simulated Deployment.

Animals (Basel) 2020 Apr 13;10(4). Epub 2020 Apr 13.

Department of Animal Science Food & Nutrition, Southern Illinois University, Carbondale, IL 62901, USA.

Body temperature responses were recorded during phases of work (waiting-to-work in close proximity to search site, active work in a search site, and post-work recovery crated in vehicle) in human remains detection dogs during search training. State or federally certified human remains detection dogs ( = 8) completed eight iterations of searching across multiple novel search environments to detect numerous scent sources including partial and complete, buried, hidden, or fully visible human remains. Internal temperature (Tgi) of the body was measured continuously using an ingestible thermistor in the gastrointestinal tract. Mean total phase times were: waiting-to-work: 9.17 min (±2.27); active work: 8:58 min (±2:49); and post-work recovery: 24:04 min (±10.59). Tgi was impacted by phase of work ( < 0.001) with a small increase during active work, with mean peak temperature 39.4 °C (±0.34 °C) during that period. Tgi continued to increase for a mean of 6:37 (±6:04) min into the post-work recovery phase in the handler's vehicle with a mean peak Tgi of 39.66 °C (±0.41 °C). No significant increase in temperature was measured during the waiting-to-work phase, suggesting behaviors typical of anticipation of work did not appear to contribute to overall body temperature increase during the waiting-to-work recovery cycle. Continued increase of gastrointestinal body temperature several minutes after cessation of exercise indicates that risk of heat injury does not immediately stop when the dog stops exercising, although none of the dogs in this study reached clinically concerning body temperatures or displayed any behavioral signs suggestive of pending heat injury. More work is needed to better understand the impact of vehicle crating on post-work recovery temperatures in dogs.
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http://dx.doi.org/10.3390/ani10040673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222851PMC
April 2020

Refining the phenotype associated with GNB1 mutations: Clinical data on 18 newly identified patients and review of the literature.

Am J Med Genet A 2018 11 8;176(11):2259-2275. Epub 2018 Sep 8.

Carle Physician Group, Urbana, Illinois.

De novo germline mutations in GNB1 have been associated with a neurodevelopmental phenotype. To date, 28 patients with variants classified as pathogenic have been reported. We add 18 patients with de novo mutations to this cohort, including a patient with mosaicism for a GNB1 mutation who presented with a milder phenotype. Consistent with previous reports, developmental delay in these patients was moderate to severe, and more than half of the patients were non-ambulatory and nonverbal. The most observed substitution affects the p.Ile80 residue encoded in exon 6, with 28% of patients carrying a variant at this residue. Dystonia and growth delay were observed more frequently in patients carrying variants in this residue, suggesting a potential genotype-phenotype correlation. In the new cohort of 18 patients, 50% of males had genitourinary anomalies and 61% of patients had gastrointestinal anomalies, suggesting a possible association of these findings with variants in GNB1. In addition, cutaneous mastocytosis, reported once before in a patient with a GNB1 variant, was observed in three additional patients, providing further evidence for an association to GNB1. We will review clinical and molecular data of these new cases and all previously reported cases to further define the phenotype and establish possible genotype-phenotype correlations.
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http://dx.doi.org/10.1002/ajmg.a.40472DOI Listing
November 2018

Trauma Management of Military Working Dogs.

Mil Med 2018 09;183(suppl_2):180-189

Joint Trauma System, 3698 Chambers Pass, Joint Base San Antonio, Fort Sam Houston, TX.

There are about 2,500 war and military service dogs in service, with about 700 serving at any given time overseas. Military Working Dogs (MWDs) are critical assets for military police, special operations units, and others operating in today's combat environment. The expectation, given the significant combat multiplier impact of these dogs and the intense bond between the handler and dog, is that injured working dogs will receive the same level of care as any injured U.S. military personnel. Veterinary care is available at multiple locations throughout theater, and the veterinary healthcare team is the MWD's primary provider. Yet, human healthcare providers (HCPs) may be the only medical personnel available to MWDs that are gravely ill or injured. As most HCPs are unfamiliar with medical care of dogs, the Joint Trauma System published a Clinical Practice Guideline (CPG), a set of detailed clinical guidelines for managing life-threatening problems of MWDs encountered in combat operations. The CPG is available at the JTS website. This article is covers the most common urgent MWD care challenges HCPs may face.
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http://dx.doi.org/10.1093/milmed/usy119DOI Listing
September 2018

Causes of Death in Military Working Dogs During Operation Iraqi Freedom and Operation Enduring Freedom, 2001-2013.

Mil Med 2018 09;183(9-10):e467-e474

US Army Institute of Surgical Research, 3698 Chambers Pass, JBSA-Fort Sam Houston, TX.

Background: Military working dogs (MWDs) are a major asset in the theater of operations. Their unique abilities make them ideal for tasks such as tracking, patrol, and scent detection. MWDs deployed to a war zone are exposed to harsh environments and battlefield dangers that increase their risk of disease, injuries, and death. Although canines have been used extensively in Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF), no published studies have reported detailed causes of death among MWDs deployed to these conflicts.

Materials And Methods: Potential cases were defined as U.S. military-owned MWDs that died while deployed in Iraq (OIF) or Afghanistan (OEF) from January 1, 2001 through December 31, 2013 and identified from both official sources and unofficial sources, that is, online searches. Cases included in this study were limited to MWDs with data on cause of death obtained by abstraction from official veterinary treatment records (VTRs) from the Department of Defense Military Working Dog Veterinary Service, Joint Base San Antonio-Lackland Air Force Base, San Antonio, Texas, and Special Operations Forces units.

Results: We identified 92 MWDs that died while deployed to OEF/OIF from 2001 through 2013 and had cause of death information from official VTRs. For both OEF and OIF, the most common training program was Multi-Purpose Canine (36.5% and 51.7%, respectively), followed by Improvised Explosive Detector Dog for OEF (34.9%) and Patrol Explosive Detector Dog for OIF (34.5%). Injuries were the primary cause of death for 77.2% of the MWDs for which we had cause of death data. The most frequent external injuries were gunshot wounds (GSW) (31.5%), explosion or blast (26.1%), and heat stress (9.8%). The proportion of deaths due to GSW was similar for OEF and OIF (30.2% vs. and 34.5%, respectively). However, a greater proportion of MWDs died from explosions during OEF than during OIF (30.2% vs. 17.2%, respectively). Diseases were the cause of death in 23.0% of the MWDs. The most common diseases were gastric dilation and volvulus (GDV, n = 3), pleuritis (n = 2), and sepsis (n = 3). Two deaths were associated with anesthesia-related medical procedures. A total of 8.7% of cases were missing cause of death, 8.7% were missing age, 32.6% of cases were missing data on necropsy, and 14.1% were missing data on final disposition of the body. Other variables of interest including number of deployments and duration of training had a very high proportion of missing values and thus could not be analyzed.

Conclusions: Our study is the most comprehensive to date that reports causes of death of MWDs deployed to OIF and OEF. However, limitations in the available data lessen the potential of our results to inform improvements in training and point of injury medical care. Better documentation in VTRs and systematic data collection into an official MWD trauma registry could lead to improved training and facilitate further development and evaluation of guidelines to improve care of wounded MWDs in future conflicts.
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http://dx.doi.org/10.1093/milmed/usx235DOI Listing
September 2018

Best practice recommendations for prehospital veterinary care of dogs and cats.

J Vet Emerg Crit Care (San Antonio) 2016 Mar-Apr;26(2):166-233

The Veterinary Specialty Hospital of the Carolinas, Cary, NC, 27518.

Objective: To examine available evidence on prehospital care in human and veterinary trauma and emergency medicine and develop best practice guidelines for use by both paramedical and nonparamedical personnel in the approach to the prehospital care of dogs and cats.

Design: Systematic evaluation of the literature gathered via medical databases searches of Medline, CAB abstracts, and Google Scholar.

Synthesis: From a review and systematic evaluation of the available evidence, consensus guidelines on the approach to prehospital care of dogs and cats in 18 scenarios were developed.

Conclusions: Due to the lack of current evidence in the veterinary prehospital arena, best practice guidelines were developed as an initial platform. Recommendations were based on a review of pertinent human and available veterinary literature as well as a consensus of the authors' professional opinions. It is anticipated that evidence-based additions will be made in the future.
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http://dx.doi.org/10.1111/vec.12455DOI Listing
November 2016

POGZ truncating alleles cause syndromic intellectual disability.

Genome Med 2016 Jan 6;8(1). Epub 2016 Jan 6.

Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, 77030, USA.

Background: Large-scale cohort-based whole exome sequencing of individuals with neurodevelopmental disorders (NDDs) has identified numerous novel candidate disease genes; however, detailed phenotypic information is often lacking in such studies. De novo mutations in pogo transposable element with zinc finger domain (POGZ) have been identified in six independent and diverse cohorts of individuals with NDDs ranging from autism spectrum disorder to developmental delay.

Methods: Whole exome sequencing was performed on five unrelated individuals. Sanger sequencing was used to validate variants and segregate mutations with the phenotype in available family members.

Results: We identified heterozygous truncating mutations in POGZ in five unrelated individuals, which were confirmed to be de novo or not present in available parental samples. Careful review of the phenotypes revealed shared features that included developmental delay, intellectual disability, hypotonia, behavioral abnormalities, and similar facial characteristics. Variable features included short stature, microcephaly, strabismus and hearing loss.

Conclusions: While POGZ has been associated with neurodevelopmental disorders in large cohort studies, our data suggest that loss of function variants in POGZ lead to an identifiable syndrome of NDD with specific phenotypic traits. This study exemplifies the era of human reverse clinical genomics ushered in by large disease-directed cohort studies; first defining a new syndrome molecularly and, only subsequently, phenotypically.
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http://dx.doi.org/10.1186/s13073-015-0253-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702300PMC
January 2016

SCAI welcomes the rest of the cath lab team.

Catheter Cardiovasc Interv 2015 Oct;86(4):609-10

2015-2016 President of SCAI, Geisinger Medical Center, Danville, PA.

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http://dx.doi.org/10.1002/ccd.26156DOI Listing
October 2015

Review of Canine Deaths While in Service in US Civilian Law Enforcement (2002-2012).

J Spec Oper Med 2014 ;14(4):86-91

Background: Working dogs have been proven effective in multiple military and law enforcement applications. Similar to their human counterparts, understanding mortality while still in service can help improve treatment of injuries, and improve equipment and training, to potentially reduce deaths. This is a retrospective study to characterize mortality of working dogs used in civilian law enforcement.

Methods: Reported causes of death were gathered from two working dog and law enforcement officer memorial websites.

Results: Of the 867 civilian law enforcement dogs reported to these memorial websites from 2002 to 2012 with reported causes of death while in service, the deaths of 318 were categorized as traumatic. The leading reported causes of traumatic death or euthanasia include trauma as a result of a vehicle strike, 25.8% (n=82); heatstroke, 24.8% (n=79); and penetrating ballistic trauma, 23.0% (n=73).

Conclusion: Although the information gathered was from online sources, this study casts some light on the risks that civilian law enforcement dogs undergo as part of the tasks to which they are assigned. These data underscore the need for a comprehensive database for this specialized population of working dogs to provide the robust, reliable data needed to develop prevention and treatment strategies for this valuable resource.
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July 2016

Gunshot wounds in military working dogs in Operation Enduring Freedom and Operation Iraqi Freedom: 29 cases (2003-2009).

J Vet Emerg Crit Care (San Antonio) 2013 Jan-Feb;23(1):47-52

Joint Special Operations Command, Ft Bragg, NC, USA.

Objective: To describe the patient population, injuries, and treatment received on the battlefield, and ultimate outcome of U.S. military working dogs that incurred gunshot wound (GSW) injury in Operation Enduring Freedom (Afghanistan) or Operation Iraqi Freedom (Iraq).

Design: Retrospective study between January 2003 and December 2009.

Animals: Twenty-nine military working dogs from the U.S. military with confirmed GSW injuries incurred in combat in Operation Enduring Freedom or Operation Iraqi Freedom.

Interventions: None.

Measurements And Main Results: Clinical data from battlefield treatment, which includes care from the point of injury through arrival to, but not including, a designated veterinary treatment facility. Twenty-nine dogs were injured between 2003 and 2009. All but one of the injuries were from high caliber, high velocity weapons. Of the 29 injured dogs, 11 survived the injuries and 18 died (38% survival rate). Of the dogs that died, all but 1 died from catastrophic nonsurvivable injuries before treatment or evacuation could be instituted. The thorax was the most common site of injury (50%) followed by extremity wounds (46%). The leading cause of death from GSWs was from thoracic wounds, followed by head wounds. Dogs with extremity wounds as their only injury were most likely to survive, and dogs with multiple injuries were least likely to survive. All surviving dogs received treatment at the point of injury by military medics and dog handlers consistent with Tactical Combat Casualty Care guidelines for combat injuries in human service members. Of the 11 that survived, all dogs returned to full duty with subsequent deployment to combat zones. Location of wounds and injury severity at the time of presentation to veterinary care was not correlated with length of time until return to duty.
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http://dx.doi.org/10.1111/j.1476-4431.2012.00823.xDOI Listing
July 2013

The effects of environmental extremes on working dogs: a collaborative initiative.

US Army Med Dep J 2013 Jan-Mar:22-7

Naval Warfare Development Group, Dam Neck, VA, USA.

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March 2013

Rethinking Heat Injury in the SOF Multipurpose Canine: A Critical Review.

J Spec Oper Med 2012 ;12(2):8-15

Heat injury is a significant concern of the Special Operations Forces Multipurpose Canine (SOF MPC). The unique athletic abilities and working environment of the SOF MPC differ from that of companion dogs or even conventional military working dogs. This should be considered in the prevention, diagnosis, and treatment of heat injury of the SOF MPC. A critical review of the literature on canine heat injury as it pertains to working dogs demonstrates limited scientific evidence on best practices for immediate clinical management of heat injury in SOF MPCs. A majority of management guidelines for heat injury in veterinary reference books and journals are based on review articles or professional opinion of the author vs. evidence from original research. In addition, guidelines are written primarily for companion animal populations vs. SOF MPCs and focus on measures to be undertaken in a clinical setting vs. point of injury. The phenomenon of ?circular referencing? is also prevalent in the heat injury literature. Current guidelines supported by review articles and textbooks often provide no citation or cite other review articles for clinical standards such as normal temperature ranges, treatment methods, and recurrence of heat injury. This ?circular referencing? phenomenon misrepresents anecdotal evidence and professional opinion as scientifically validated, reinforcing concepts and recommendations that are not truly supported by the evidence. Further study is needed to fully understand heat injury in SOF MPCs and how this applies to prevention, diagnosis and treatment guidelines. In order to provide SOF canine programs with best clinical advice and care, SOF Veterinarians must make clinical judgments based on evaluation of the most accurate and valid information possible. Clinical guidelines are fluid and should be reviewed regularly for relevance to the defined population in question. Clinical Guidelines should also be utilized as guiding principles in conjunction with clinical judgment vs. dictate a clinical protocol. SOF veterinarians as the veterinary support asset to SOF MPC programs should be clinically competent as well as versed in evidence based medicine practices to provide the cutting edge clinical support that is required to keep SOF MPCs operating in modern warfare environments.
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April 2016

Overview of combat trauma in military working dogs in Iraq and Afghanistan.

US Army Med Dep J 2009 Jan-Mar:33-7

Joint Special Operations Command, Fort Bragg, NC, USA.

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April 2010

Overview of combat trauma in military working dogs in Iraq and Afghanistan.

J Spec Oper Med 2009 ;9(2):105-8

Joint Special Operations Command, Fort Bragg, North Carolina, USA.

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September 2010

Are patients in labor satisfied with PCEA?

Nursing 2006 Jun;36(6):18-9

Women and Infants Service at Banner Thunderbird Medical Center in Glendale, Ariz., USA.

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http://dx.doi.org/10.1097/00152193-200606000-00015DOI Listing
June 2006

Evidence for Increased Thermostability of Bacillus cereus Enterotoxin in Milk.

J Food Prot 1995 Apr;58(4):443-445

Department of Food Science, University of Guelph, Guelph, Ontario, N1G 2W1, Canada.

A commercially available kit for the detection of Bacillus cereus diarrhegenic enterotoxin (TECRA BDE Visual Immunoassay) was used to evaluate the heat stability of the toxin in milk and cell-free culture supernatant. The immunological activity of the toxin was approximately four times more stable in milk.
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http://dx.doi.org/10.4315/0362-028X-58.4.443DOI Listing
April 1995

Predictive Modeling of Psychrotrophic Bacillus cereus.

J Food Prot 1993 Aug;56(8):684-688

Department of Food Science, University of Guelph, Guelph, Ontario, Canada N1G 2WI.

Response surface analysis was used to determine the effects and interactions of water activity (0.965 to 0.995), pH (5.8 to 8.0), temperature (6 to 38°C), glucose concentration (0 to 1.8%), and starch concentration (0 to 0.625%) on the growth of and toxin production by a psychrotrophic strain of Bacillus cereus in brain heart infusion broth. Growth was measured by monitoring optical density and plate counts, toxin production was assayed by an immunological method (BCET-RPLA toxin assay) and cytotoxicity with Vero and HEp-2 cells. Regressions were performed using response surface techniques, on Growth, LnGrowth, RPLA, LnRPLA, Vero, LnVero, and HEp-2; quadratic predictive equations for growth and toxin production were obtained. The results indicate the factors that had the greatest influence on both growth and toxin production were water activity and temperature. Predicted values obtained from the model were in good agreement with experimental values.
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http://dx.doi.org/10.4315/0362-028X-56.8.684DOI Listing
August 1993