Visible Light Imaging: Clinical Aspects with an Emphasis on Medical Photography-a HIMSS-SIIM Enterprise Imaging Community Whitepaper.

Photodocumentation is a subset of visible light imaging and is an important growing segment of enterprise imaging. Medical videography is another subset of visible light imaging that shares many of the challenges of photodocumentation. Medical photographs are used to document clinical conditions, support diagnosis, guide, and document procedures and to enable collaboration among colleagues. They also play a significant role in patient engagement and are a mechanism for patients to share information with their provider without the need for a clinical office visit. The content of medical photographs raises issues for acquisition, management, storage, and access. Medical photographs may contain protected health information, and these images benefit from the standardized, secure processes inherent in any enterprise imaging program. The ability to securely acquire images on mobile, and sometimes personally owned devices, is a necessity. In addition to containing protected health information, photograph content can be sensitive or gruesome or the images may be used for forensic purposes. These types of images require additional protections. Access to these images should be role-based and auditable. To properly identify photographs and to convey information about their acquisition parameters new metadata requirements and mechanisms for its association with the imaging files are evolving. Institutional policies need to be developed to define the organization's requirements for medical photography, including consent processes. Existing policies such as those defining the designated record set and legal health record should address the management of medical photography.

Variant Creutzfeldt-Jakob disease strain is identical in individuals of two PRNP codon 129 genotypes.

In 2004, a subclinical case of variant Creutzfeldt-Jakob disease in a PRNP 129 methionine/valine heterozygous individual infected via blood transfusion was reported, and we established that the spleen from this individual was infectious. Since host genetics is an important factor in strain modification, the identification of variant Creutzfeldt-Jakob disease infection in a PRNP 129 methionine/valine heterozygous individual has raised the possibility that the properties of the variant Creutzfeldt-Jakob disease agent could change after transmission to this different genetic background and concerns that this could lead to a more virulent strain of variant Creutzfeldt-Jakob disease. The variant Creutzfeldt-Jakob disease strain has to date been characterized only in methionine homozygous individuals, therefore to establish whether the strain characteristics of variant Creutzfeldt-Jakob disease had been modified by the host genotype, spleen material with prion protein deposition from a PRNP 129 methionine/valine individual was inoculated into a panel of wild-type mice. Three passages in mice were undertaken to allow stabilization of the strain characteristics following its passage into mice. In each passage, a combination of clinical signs, neuropathology (transmissible spongiform encephalopathy vacuolation and prion protein deposition) were analysed and biochemical analysis carried out. While some differences were observed at primary and first subpassage, following the second subpassage, strain characteristics in the methionine/valine individual were totally consistent with those of variant Creutzfeldt-Jakob disease transmitted to 129 methionine/methionine individuals thus demonstrated no alteration in strain properties were imposed by passage through the different host genotype. Thus we have demonstrated variant Creutzfeldt-Jakob disease strain properties are not affected by transmission through an individual with the PRNP methionine/valine codon 129 genotype and thus no alteration in virulence should be associated with the different host genotype.

Tapia syndrome: an unusual complication following posterior cervical spine surgery.

Tapia syndrome, a rare complication of posterior cervical surgery, characterised by concurrent paralyses of recurrent laryngeal branch of vagus and hypoglossal cranial nerves, occurred in a patient after posterior cervical foraminotomies for radiculopathy. We discuss hypothesised pathophysiology, and diagnostic, therapeutic and avoidance strategies in relevance to prone neurosurgical procedures.

10 Steps to Strategically Build and Implement your Enterprise Imaging System: HIMSS-SIIM Collaborative White Paper.

An enterprise imaging (EI) strategy is an organized plan to optimize the electronic health record (EHR) so that healthcare providers have intuitive and immediate access to all patient clinical images and their associated documentation, regardless of source. We describe ten steps recommended to achieve the goal of implementing EI for an institution. The first step is to define and access all images used for medical decision-making. Next, demonstrate how EI is a powerful strategy for enhancing patient and caregiver experience, improving population health, and reducing cost. Then, it is recommended that one must understand the specialties and their clinical workflow challenges as related to imaging. Step four is to create a strategy to improve quality of care and patient safety with EI. Step five demonstrates how EI can reduce costs. Then, show how EI can help enhance the patient experience. Step seven suggests how EI can enhance the work life of caregivers and step eight describes how to develop EI governance. Step nine describes the plan to implement an EI project, and finally, step 10, to understand cybersecurity from a patient safety perspective and to protect images from accidental and malicious intrusion.

Mechanical Characterization of Thermally Annealed Tablets Containing Polyethylene Oxide for Abuse Deterrence.

The abuse of prescription opioid drugs is a well-documented and very serious problem. One of the typical first steps an abuser will take is to manipulate a tablet into to a fine powder. To deter this behavior, formulators use crush-resistant technologies like polyethylene oxide (PEO). When heat-treated, PEO creates a hard, flexible tablet that cannot be easily ground down into a fine powder. We investigated the effects of PEO molecular weight (MW), annealing temperature, and annealing time on tablet compression deformation behavior and fracture resistance. These tests were designed to represent an abuser's attempt to smash and grind a tablet, respectively. Annealing temperatures above the melting point of PEO showed the most improvement in mechanical properties compared with that in unannealed tablets. The minimum annealing time was dependent on the polymer MW and annealing temperature. Tablets were manipulated using a coffee grinder, and the particle size of the resulting powders was measured. The particle size correlated well with fracture toughness, demonstrating that increasing fracture toughness increases the manipulation resistance of a PEO tablet.

Development of the Fray-Farthing-Chen Cambridge Process: Towards the Sustainable Production of Titanium and Its Alloys.

The Kroll process has been employed for titanium extraction since the 1950s. It is a labour and energy intensive multi-step semi-batch process. The post-extraction processes for making the raw titanium into alloys and products are also excessive, including multiple remelting steps. Invented in the late 1990s, the Fray-Farthing-Chen (FFC) Cambridge process extracts titanium from solid oxides at lower energy consumption via electrochemical reduction in molten salts. Its ability to produce alloys and powders, while retaining the cathode shape also promises energy and material efficient manufacturing. Focusing on titanium and its alloys, this article reviews the recent development of the FFC-Cambridge process in two aspects, (1) resource and process sustainability and (2) advanced post-extraction processing.

Considerations for Exchanging and Sharing Medical Images for Improved Collaboration and Patient Care: HIMSS-SIIM Collaborative White Paper.

The need for providers and patients to exchange and share imaging has never been more apparent, yet many organizations are only now, as a part of a larger enterprise imaging initiative, taking steps to streamline an important process that has historically been facilitated with the use of CDs or insecure methods of communication. This paper will provide an introduction to concepts and common-use cases for image exchange, outline challenges that have hindered adoption to date, and describe standards for image exchange that show increasing promise of being adopted by vendors and providers.

High Pressure-Temperature Phase Diagram of 1,1-Diamino-2,2-dinitroethylene (FOX-7).

The pressure-temperature (P-T) phase diagram of 1,1-diamino-2,2-dinitroethylene (FOX-7) was determined by in situ synchrotron infrared radiation spectroscopy with the resistively heated diamond anvil cell (DAC) technique. The stability of high-P-T FOX-7 polymorphs is established from ambient pressure up to 10 GPa and temperatures until decomposition. The phase diagram indicates two near isobaric phase boundaries at ∼2 GPa (α → I) and ∼5 GPa (I → II) that persists from 25 °C until the onset of decomposition at ∼300 °C. In addition, the ambient pressure, high-temperature α → ß phase transition (∼111 °C) lies along a steep boundary (∼100 °C/GPa) with a α-ß-δ triple point at ∼1 GPa and 300 °C. A 0.9 GPa isobaric temperature ramping measurement indicates a limited stability range for the γ-phase between 0.5 and 0.9 GPa and 180 and 260 °C, terminating in a ß-γ-δ triple point. With increasing pressure, the δ-phase exhibited a small negative dT/dP slope (up to ∼0.2 GPa) before turning over to a positive 70 °C/GPa slope, at higher pressures. The decomposition boundary (∼55 °C/GPa) was identified through the emergence of spectroscopic signatures of the characteristic decomposition products as well as trapped inclusions within the solid KBr pressure media.

Prion infectivity in the spleen of a PRNP heterozygous individual with subclinical variant Creutzfeldt-Jakob disease.

Blood transfusion has been identified as a source of human-to-human transmission of variant Creutzfeldt-Jakob disease. Three cases of variant Creutzfeldt-Jakob disease have been identified following red cell transfusions from donors who subsequently developed variant Creutzfeldt-Jakob disease and an asymptomatic red cell transfusion recipient, who did not die of variant Creutzfeldt-Jakob disease, has been identified with prion protein deposition in the spleen and a lymph node, but not the brain. This individual was heterozygous (MV) at codon 129 of the prion protein gene (PRNP), whereas all previous definite and probable cases of variant Creutzfeldt-Jakob disease have been methionine homozygotes (MM). A critical question for public health is whether the prion protein deposition reported in peripheral tissues from this MV individual correlates with infectivity. Additionally it is important to establish whether the PRNP codon 129 genotype has influenced the transmission characteristics of the infectious agent. Brain and spleen from the MV blood recipient were inoculated into murine strains that have consistently demonstrated transmission of the variant Creutzfeldt-Jakob disease agent. Mice were assessed for clinical and pathological signs of disease and transmission data were compared with other transmission studies in variant Creutzfeldt-Jakob disease, including those on the spleen and brain of the donor to the index case. Transmission of variant Creutzfeldt-Jakob disease was observed from the MV blood recipient spleen, but not from the brain, whereas there was transmission from both spleen and brain tissues from the red blood cell donor. Longer incubation times were observed for the blood donor spleen inoculum compared with the blood donor brain inoculum, suggesting lower titres of infectivity in the spleen. The distribution of vacuolar pathology and abnormal prion protein in infected mice were similar following inoculation with both donor and recipient spleen homogenates, providing initial evidence of similar transmission properties after propagation in PRNP codon 129 MV and MM individuals. These studies demonstrate that spleen tissue from a PRNP MV genotype individual can propagate the variant Creutzfeldt-Jakob disease agent and that the infectious agent can be present in the spleen without CNS involvement.

Polymorphism in paracetamol: evidence of additional forms IV and V at high pressure.

The structural phase stability of N-(4-hydroxyphenyl) acetamide (paracetamol) has been studied at ambient temperature up to 23 GPa using Raman spectroscopy. Spectral changes have provided further evidence for a highly kinetically driven Form I → II transition that occurs as a mixed phase from 4.8 to 6.5 GPa, and might complete as early as 7 GPa. Upon further compression to 8.1 GPa, a drastic shift in spectral signature was observed providing the first evidence for a previously undiscovered Form IV of paracetamol. Additional shifts in mode intensities were observed near 11 GPa indicating a potential restructuring of the hydrogen bonding network and/or structural modification to a potentially new Form V. Phase boundaries at 7 and 8 GPa were confirmed under hydrostatic conditions using Raman spectroscopy. Spectral changes indicate that the transition Form IV → V occurs near 11 GPa. Multiple ab initio harmonic frequency calculations at different levels of theory were performed with a B3LYP/6-31G** being used to provide a more robust mode assignment to our experimentally obtained Raman modes. High pressure X-ray diffraction (XRD) was performed up to 21 GPa, which provided further evidence for a highly kinetically driven Form I → II transition in agreement with our Raman measurements. In addition, the XRD provided further evidence for the existence of Form IV near 8 GPa and Form V near 11 GPa with Form V persisting up to 21 GPa.

Evaluation of the initiation of urine drug screens intended for use in transfer patients.

OBJECTIVE: The objective of this study was to determine if signs of clinical intoxication were present in patients who had transfer urine drug screens (UDS) performed and to determine the proportion of patients with UDS orders who were actually transferred to another facility. METHODS: Of all emergency department (ED) patient visits who had a transfer UDS ordered from November 19, 2011, to December 31, 2012, 54% of the population was randomly selected for review by 1 of 3 study investigators. For quality assurance, a random sample of 100 patient charts was independently reviewed by all 3 investigators to assure consistency in interpreting data. Demographics, clinical characteristics and history, disposition, and laboratory results were recorded. RESULTS: Of the 639 patients included in this study, only 18% were transferred to another psychiatric facility. Pediatric patients and those with presenting with suicidal ideation were more likely to be transferred to an outside facility. Thirty-six percent of the UDS were positive for at least one substance. Marijuana was the most common substance (23%), followed by cocaine (7%) and opiates (7%). There was no evidence that the UDS changed acute management decisions. CONCLUSIONS: Few (<6%) patients demonstrated any clinical characteristics that were consistent with an acute intoxication. Less than 20% of patients who had a transfer UDS were actually transferred to an outside facility corresponding with more than 80% not ordered appropriately according to the ED established guidelines. This number of inappropriate tests represented more than $152 000 of avoidable UDS cost during the study period.

Impact of Micro- and Nano-Plastics on Human Intestinal Organoid-Derived Epithelium.

The development of patient-derived intestinal organoids represents an invaluable model for simulating the native human intestinal epithelium. These stem cell-rich cultures outperform commonly used cell lines like Caco-2 and HT29-MTX in reflecting the cellular diversity of the native intestinal epithelium after differentiation. In our recent study examining the effects of polystyrene (PS), microplastics (MPs), and nanoplastics (NPs), widespread pollutants in our environment and food chain, on the human intestinal epithelium, these organoids have been instrumental in elucidating the absorption mechanisms and potential biological impacts of plastic particles. Building on previously established protocols in human intestinal organoid culture, we herein detail a streamlined protocol for the cultivation, differentiation, and generation of organoid-derived monolayers. This protocol is tailored to generate monolayers incorporating microfold cells (M cells), key for intestinal particle uptake but often absent in current in vitro models. We provide validated protocols for the characterization of MPs/NPs via scanning electron microscopy (SEM) for detailed imaging and their introduction to intestinal epithelial monolayer cells via confocal immunostaining. Additionally, protocols to test the impacts of MP/NP exposure on the functions of the intestinal barrier using transendothelial electrical resistance (TEER) measurements and assessing inflammatory responses using cytokine profiling are detailed. Overall, our protocols enable the generation of human intestinal organoid monolayers, complete with the option of including or excluding M cells, offering crucial techniques for observing particle uptake and identifying inflammatory responses in intestinal epithelial cells to advance our knowledge of the potential effects of plastic pollution on human gut health. These approaches are also amendable to the study of other gut-related chemical and biological exposures and physiological responses due to the robust nature of the systems. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Human intestinal organoid culture and generation of monolayers with and without M cells Support Protocol 1: Culture of L-WRN and production of WRN-conditioned medium Support Protocol 2: Neuronal cell culture and integration into intestinal epithelium Support Protocol 3: Immune cell culture and integration into intestinal epithelium Basic Protocol 2: Scanning electron microscopy: sample preparation and imaging Basic Protocol 3: Immunostaining and confocal imaging of MP/NP uptake in organoid-derived monolayers Basic Protocol 4: Assessment of intestinal barrier function via TEER measurements Basic Protocol 5: Cytokine profiling using ELISA post-MP/NP exposure.

Splice site SNPs of phospholipase PLCXD3 are significantly associated with variant and sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Variant Creutzfeldt-Jakob disease is an infectious, neurodegenerative, protein-misfolding disease, of the prion disease family, originally acquired through ingestion of meat products contaminated with bovine spongiform encephalopathy (BSE). Public health concern was increased by the discovery of human-to-human transmission via blood transfusion. This study has verified a novel genetic marker linked to disease risk. METHODS: SNP imputation and association testing indicated those genes that had significant linkage to disease risk and one gene was investigated further with Sanger resequencing. Results from variant Creutzfeldt-Jakob disease were compared with those from sporadic (idiopathic) Creutzfeldt-Jakob disease and published controls. RESULTS: The most significant disease risk, in addition to the prion protein gene, was for the phosphatidylinositol-specific phospholipase C, X domain containing 3 (PLCXD3) gene. Sanger resequencing of CJD patients across a region of PLCXD3 with known variants confirmed three SNPs associated with variant and sporadic CJD. CONCLUSIONS: These data provide the first highly significant confirmation of SNP allele frequencies for a novel CJD candidate gene providing new avenues for investigating these neurodegenerative prion diseases. The phospholipase PLCXD3 is primarily expressed in the brain and is associated with lipid catabolism and signal transduction.

Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties.

The biological determinants of the phenotypic variation in sporadic Creutzfeldt-Jakob disease (sCJD) are unknown. To categorize sCJD cases, the prion protein (PrP) codon 129 genotype and the biochemical characteristics of the disease-associated form of PrP (PrP(Sc)) can be combined to form six subgroups (MM1, MM2, MV1, MV2, VV1, and VV2). This classification largely correlates with the known variation in the clinical and pathological features of sCJD, with the MM1 and MV1 cases representing the "classic" phenotype of sCJD. To address how this classification relates to different strains of sCJD we have inoculated each subgroup of sCJD to a panel of mice expressing different forms of the human PRNP gene (129MM, 129VV, and 129MV). We have established that all subtypes are transmissible to at least one genotype of mouse, and both agent and host factors determine transmission efficiency and the form of PrP(Sc) deposited in the brain. Moreover, we have identified four distinct strains of sCJD using our in vivo strain typing panel.

Constant transmission properties of variant Creutzfeldt-Jakob disease in 5 countries.

Variant Creutzfeldt-Jakob disease (vCJD) has been reported in 12 countries. We hypothesized that a common strain of agent is responsible for all vCJD cases, regardless of geographic origin. To test this hypothesis, we inoculated strain-typing panels of wild-type mice with brain material from human vCJD case-patients from France, the Netherlands, Italy, and the United States. Mice were assessed for clinical disease, neuropathologic changes, and glycoform profile; results were compared with those for 2 reference vCJD cases from the United Kingdom. Transmission to mice occurred from each sample tested, and data were similar between non-UK and UK cases, with the exception of the ranking of mean clinical incubation times of mouse lines. These findings support the hypothesis that a single strain of infectious agent is responsible for all vCJD infections. However, differences in incubation times require further subpassage in mice to establish any true differences in strain properties between cases.

Functional properties of dopamine neurons and co-expression of vasoactive intestinal polypeptide in the dorsal raphe nucleus and ventro-lateral periaqueductal grey.

The dorsal raphe nucleus (DRN) and ventrolateral periaqueductal grey (vlPAG) regions contain populations of dopamine neurons, often considered to be a dorsal caudal extension of the A10 group [mostly found in the ventral tegmental area (VTA)]. Recent studies suggest they are involved in promoting wakefulness and mediate some of the antinociceptive and rewarding properties of opiates. However, little is known about their electrophysiological properties. To address this, we used Pitx3-GFP and tyrosine hydroxylase (TH)-GFP mice to carry out targeted whole-cell recordings from this population in acute brain slices. We found that DRN/vlPAG dopamine neurons have characteristics similar to most VTA dopamine neurons, but distinct from dorsal raphe serotonin neurons. They fire broad action potentials at a relatively slow, regular rate, exhibit a hyperpolarization-activated inward current and delayed repolarization, and show spike-frequency adaptation in response to prolonged depolarization. In addition, they receive fast excitatory and inhibitory synaptic inputs. Moreover, we found co-expression of vasoactive intestinal polypeptide in small, periaqueductal dopamine neurons, but generally not in larger, more ventral dopamine neurons.

Human embryonic stem cells rapidly take up and then clear exogenous human and animal prions in vitro.

Susceptibility to prion infection involves interplay between the prion strain and host genetics, but expression of the host-encoded cellular prion protein is a known prerequisite. Here we consider human embryonic stem cell (hESC) susceptibility by characterizing the genetics and expression of the normal cellular prion protein and by examining their response to acute prion exposure. Seven hESC lines were tested for their prion protein gene codon 129 genotype and this was found to broadly reflect that of the normal population. hESCs expressed prion protein mRNA, but only low levels of prion protein accumulated in self-renewing populations. Following undirected differentiation, up-regulation of prion protein expression occurred in each of the major embryonic lineages. Self-renewing populations of hESCs were challenged with infectious human and animal prions. The exposed cells rapidly and extensively took up this material, but when the infectious source was removed the level and extent of intracellular disease-associated prion protein fell rapidly. In the absence of a sufficiently sensitive test for prions to screen therapeutic cells, and given the continued use of poorly characterized human and animal bioproducts during hESC derivation and cultivation, the finding that hESCs rapidly take up and process abnormal prion protein is provocative and merits further investigation.

Inherited prion disease with 4-octapeptide repeat insertion: disease requires the interaction of multiple genetic risk factors.

Genetic factors are implicated in the aetiology of sporadic late-onset neurodegenerative diseases. Whether these genetic variants are predominantly common or rare, and how multiple genetic factors interact with each other to cause disease is poorly understood. Inherited prion diseases are highly heterogeneous and may be clinically mistaken for sporadic Creutzfeldt-Jakob disease because of a negative family history. Here we report our investigation of patients from the UK with four extra octapeptide repeats, which suggest that the risk of clinical disease is increased by a combination of the mutation and a susceptibility haplotype on the wild-type chromosome. The predominant clinical syndrome is a progressive cortical dementia with pyramidal signs, myoclonus and cerebellar abnormalities that closely resemble sporadic Creutzfeldt-Jakob disease. Autopsy shows perpendicular deposits of prion protein in the molecular layer of the cerebellum. Identity testing, PRNP microsatellite haplotyping and genealogical work confirm no cryptic close family relationships and suggests multiple progenitor disease haplotypes. All patients were homozygous for methionine at polymorphic codon 129. In addition, at a single nucleotide polymorphism upstream of PRNP thought to confer susceptibility to sporadic Creutzfeldt-Jakob disease (rs1029273), all patients were homozygous for the risk allele (combined P=5.9×10(-5)). The haplotype identified may also be a risk factor in other partially penetrant inherited prion diseases although it does not modify age of onset. Blood expression of PRNP in healthy individuals was modestly higher in carriers of the risk haplotype. These findings may provide a precedent for understanding apparently sporadic neurodegenerative diseases caused by rare high-risk mutations.

1,1-Diamino-2,2-dinitroethylene under high pressure-temperature.

The structural phase stability of 1,1-diamino-2,2-dinitroethylene (FOX-7) has been studied up to 10 GPa through isothermal compression at 100 °C and 200 °C using synchrotron mid- and far-infrared spectroscopy. During isothermal compression at 100 °C changes are observed in vibrational spectra with increase in pressure that are indicative of significant distortion to monoclinic α phase or a possible structural transformation to a high pressure α(') phase at 2.2 GPa and α(") phase at 6.1 GPa. At 200 °C, for the far- and mid-IR regimes, the similar changes were observed at 2.1 (2.0) GPa and 5.3 (5.5) GPa, respectively. The observed change is nearly isobaric, consistent with previously reported high pressure and room temperature values, up to the highest temperature of 200 °C reached in our experiments. Over the total P-T range investigated, up to ∼10 GPa and 200 °C, we observed no evidence of sample decomposition. The observed changes are partially reversible with only slight evidence of the high pressure distortion remaining upon complete decompression. Additional isobaric heating at 1.07 GPa was performed in the mid-IR regime, which clearly revealed an onset of decomposition at 360 °C. Further x-ray or neutron diffraction, which are needed to fully resolve the cause of observed changes above 2 and 5 GPa, are ongoing.

A polymorphism in the regulatory region of PRNP is associated with increased risk of sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rare transmissible neurodegenerative disorder. An important determinant for CJD risk and phenotype is the M129V polymorphism of the human prion protein gene (PRNP), but there are also other coding and non-coding polymorphisms inside this gene. METHODS: We tested whether three non-coding polymorphism located inside the PRNP regulatory region (C-101G, G310C and T385C) were associated with risk of CJD and with age at onset in a United Kingdom population-based sample of 131 sporadic CJD (sCJD) patients and 194 controls. RESULTS: We found no disease association for either PRNP C-101G or PRNP T385C. Although the crude analysis did not show a significant association between PRNP G310C and sCJD (OR: 1.5; 95%CI = 0.7 to 2.9), after adjusting by PRNP M129V genotype, it resulted that being a C allele carrier at PRNP G310C was significantly (p = 0.03) associated with a 2.4 fold increased risk of developing sCJD (95%CI = 1.1 to 5.4). Additionally, haplotypes carrying PRNP 310C coupled with PRNP 129M were significantly overrepresented in patients (p = 0.02) compared to controls. Cases of sCJD carrying a PRNP 310C allele presented at a younger age (on average 8.9 years younger than those without this allele), which was of statistical significance (p = 0.05). As expected, methionine and valine homozygosity at PRNP M129V increased significantly the risk of sCJD, alone and adjusted by PRNP G310C (OR MM/MV = 7.3; 95%CI 3.9 to 13.5 and OR VV/MV = 4.0; 95%CI 1.7 to 9.3). CONCLUSIONS: Our findings support the hypothesis that genetic variations in the PRNP promoter may have a role in the pathogenesis of sCJD.