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Background: Workplace violence (WPV) presents challenges in intensive care units (ICUs) calling for reliable prediction of violence. This narrative review aimed to identify and evaluate risk assessment tools from acute care settings which are or might be used to predict violent behavior in adult ICU patients focusing on their performance and clinical utility., Methods: A screening of PubMed, Scopus and Google Scholar was conducted to identify risk scores used in the acute care setting such as emergency departments, hospitals and ICUs. Risk factors, predictive validity of scores and their relevance to the ICU setting were evaluated., Results: 24 studies were included. Two studies reported the use in general ICU populations, while eight studies were conducted in psychiatric ICUs and 14 studies implemented the use of risk tools in emergency departments or general wards. Ten risk scores were identified using 30 different variables. Those could be categorized into patient demographics, behavior, history of violence, mental status and other items such as sleep disturbances. The Broset Violence Checklist (BVC) was the most commonly used risk score. It showed moderate predictive accuracy in psychiatric settings including psychiatric ICUs, but limited validation for general ICUs. The overall evidence level was low with serious risk of bias. Other tools demonstrated varying sensitivity and specificity but lacked validation in ICUs., Implications for Clinical Practice: ICU nurses and physicians are often subjected to violence. There is little evidence on scores to predict patients' behavior. Most assessments come from outside the ICU, but may be promising in critical care., Conclusion: This review underscores the need for the development of violence risk assessment tools tailored to the ICU, as the challenges with violent ICU patients differ from other populations. New predictive models must be developed including factors associated with patients' violent behavior in ICUs as compiled in this review., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Declaration of interests We declare no competing interests relating to the content of the manuscript. ÖY reports honoraria from Biogen. HHH reports grants from Moderna to the University of Basel; and he reports personal consulting fees from AlCuris, Allovir, Moderna, VeraTX, and Roche, and personal honoraria from VeraTX, Takeda, Biotest, and Gilead. UFischer reports research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, Medtronic, Stryker, Penumbra, Rapid medical, Phenox, and Boehringer Ingelheim; consulting fees from Medtronic, Stryker, CSL Behring (fees paid to institution); has membership in a data safety monitoring board for the TITAN trial, IN EXTREMIS trial, LATE-MT trial, Rapid Puls Trial; has membership in the Clinical Event Committee of the COATING Trial (Phenox) and membership in the advisory board for CLS Behring, Acthera, Alexion/Portola, Boehringer Ingelheim (all fees paid to institution); is president of the Swiss Neurological Society.

Ligand activation of the aryl hydrocarbon receptor (AHR) accelerates keratinocyte differentiation and the formation of the epidermal permeability barrier. Several classes of lipids, including ceramides, are critical to the epidermal permeability barrier. In normal human epidermal keratinocytes, the AHR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin, increased RNA levels of ceramide metabolism and transport genes: uridine diphosphate glucose ceramide glucosyltransferase (UGCG), ABCA12, GBA1, and SMPD1. Levels of abundant skin ceramides were also increased by 2,3,7,8-tetrachlorodibenzo-p-dioxin. These included the metabolites synthesized by UGCG, glucosylceramides, and acyl glucosylceramides. Chromatin immunoprecipitation-sequence analysis and luciferase reporter assays identified UGCG as a direct AHR target. The AHR antagonist, GNF351, inhibited the 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated RNA and transcriptional increases. Tapinarof, an AHR ligand approved for the treatment of psoriasis, increased UGCG RNA, protein, and its lipid metabolites hexosylceramides as well as increased the RNA expression of ABCA12, GBA1, and SMPD1. In Ahr-null mice, Ugcg RNA and hexosylceramides were lower than those in the wild type. These results indicate that the AHR regulates the expression of UGCG, a ceramide-metabolizing enzyme required for ceramide trafficking, keratinocyte differentiation, and epidermal permeability barrier formation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Phase-contrast MRI of CSF and spinal cord dynamics has evolved among diseases caused by altered CSF volume (spontaneous intracranial hypotension, normal pressure hydrocephalus) and by altered CSF space (degenerative cervical myelopathy (DCM), Chiari malformation). While CSF seems to be an obvious target for possible diagnostic use, craniocaudal spinal cord motion analysis offers the benefit of fast and reliable assessments. It is driven by volume shifts between the intracranial and the intraspinal compartments (Monro-Kellie hypothesis). Despite promising initial reports, comparison of spinal cord motion data across different centers is challenged by reports of varying value, raising questions about the validity of the findings., Objective: To systematically investigate inter-center differences between phase-contrast MRI data., Methods: Age- and gender matched, retrospective, pooled-data analysis across two centers: cardiac-gated, sagittal phase-contrast MRI of the cervical spinal cord (segments C2/C3 to C7/T1) including healthy participants and DCM patients; comparison and analysis of different MRI sequences and processing techniques (manual versus fully automated)., Results: A genuine craniocaudal spinal cord motion pattern and an increased focal spinal cord motion among DCM patients were depicted by both MRI sequences (p < 0.01). Higher time-resolution resolved steeper and larger peaks, causing inter-center differences (p < 0.01). Comparison of different processing methods showed a high level of rating reliability (ICC > 0.86 at segments C2/C3 to C6/C7)., Discussion: Craniocaudal spinal cord motion is a genuine finding. Differences between values were attributed to time-resolution of the MRI sequences. Automated processing confers the benefit of unbiased and consistent analysis, while data did not reveal any superiority., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To develop reproducible 3-dimensional measurements for quantification of the distal radioulnar joint (DRUJ) morphology. We hypothesized that automated 3-dimensional measurement of the ulnar variance (UV) and the sigmoid notch (SN) angle would be comparable to those of the reference standard while overcoming some drawbacks of conventional 2-dimensional measurements., Methods: Radiological data of healthy forearm bones (radiographs and computed tomography) of 53 adult subjects were included in the study. Automated measurements were developed for assessment of the SN morphology based on 3-dimensional landmarks, incorporating subject-specific estimation of cartilage surface orientation. A common anatomical reference was defined among the different imaging modalities and a comparison of the SN angle and UV measurements was performed in radiographs, computed tomography scans, and 3-dimensional models. Finally, the 3-dimensional UV measurements were evaluated in an experimental setup using 3-dimensional printed bone models., Results: The automated 3-dimensional measurements of SN subtypes showed a notably larger notch radius (18.9 mm) for negative SN angles compared with positive SN angles in subjects (16.9 mm). Similar UV measurements were obtained in healthy DRUJ morphologies, with a high correlation between radiographs and 3-dimensional measurements for the SN angle (0.77) and UV (0.85). In the experimental setup with pathological radial inclinations, UV was on average 1.13 mm larger in the radiographs compared with the 3-dimensional measurements, and 1.30 mm larger in the cases with pathological palmar tilts. Furthermore, UV radiograph measurements on the modified palmar tilt deviated from the 3-dimensional measurements., Conclusions: The developed 3-dimensional automated measurements were able to quantify morphological differences among sigmoid notch subtypes and were comparable to those of the reference standard., Clinical Relevance: The developed methods do not depend on the forearm position or orientation of the distal radius and can be used for 3-dimensional quantification of DRUJ pathologies in 3-dimensional surgical planning., (Copyright © 2020 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: Meniscus allograft transplantation is a valuable surgical option for post-meniscectomy syndrome. For best results, the selected allograft should be as similar as possible to the original meniscus. Three-dimensional meniscus sizing could be a new approach to improve the accuracy of meniscus matching. The contralateral anatomy might therefore be a suitable reconstruction template. The purpose of this study was to compare the three-dimensional shape of the right and left menisci by bi-planar segmentation of magnetic resonance imaging (MRI) scans., Methods: Three-dimensional surface models of healthy menisci were created based on 40 bilateral MRI scans. Manual segmentation was performed on the MRI data in sagittal and coronal planes. For side-to-side comparison, each left meniscus model was mirrored and then superimposed to its corresponding right meniscus model. Differences between the meniscus pairs were assessed by width, length, height and surface distances. Inter-reader reliability, as well as accuracy of bi-planar segmentation was assessed by two different readers., Results: The meniscus pairs were not significantly different in terms of width, length and height (P = at least 0.138). Side difference of mean surface distances was 0.76 mm (±0.13 standard deviation (SD)) for medial and 0.78 mm (±0.15 SD) for lateral menisci. Inter-reader reliability was good to excellent (0.828-0.987)., Conclusion: The three-dimensional shapes of the left and right menisci are very similar. Therefore, the contralateral meniscus can be used as a template for three-dimensional meniscus allograft sizing. Three-dimensional meniscus segmentation and sizing can be performed accurately by combination of sagittal and coronal planes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Activation of the transcription factor, AHR, in normal human epidermal keratinocytes increased AHR binding in the gene regions of the glucose transporter, SLC2A1, and the glycolytic enzyme, ENO1. This increased chromatin binding corresponded with AHR-dependent decreases in levels of SLC2A1 and ENO1 mRNA, protein, and activities. Studies of the ENO1 promoter showed activation of the AHR decreases the transcription of ENO1. Glycolysis was lowered by activation of the AHR as measured by decreases in glucose uptake and the production of pyruvate and lactate. Levels of ATP were also decreased. Downregulation of glucose metabolism, either by activation of the AHR, inhibition of glycolysis, inhibition of glucose transport, or inhibition of enolase, increased SIRT1 protein levels in normal human epidermal keratinocytes and the immortalized keratinocyte cell line, N/TERT-1. This increase in SIRT1 was abrogated by the addition of exogenous pyruvate. Moreover, keratinocyte differentiation in response to downregulation of glycolysis, either by activation of the AHR, inhibition of glucose transport, or inhibition of enolase, was dependent on SIRT1. These results indicate that regulation of glycolysis controls keratinocyte differentiation, and that activation of the AHR, by lowering the expression of SLC2A1 and ENO1, can determine this fate., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The antimicrobial peptide α-defensin has recently been introduced as a potential 'single' biomarker with a high sensitivity and specificity for the preoperative diagnosis of periprosthetic joint infections (PJIs). However, most studies assessed the benefits of the test with exclusion of patients with rheumatic diseases. We aimed to evaluate the α-defensin test in a cohort study without exclusion of people with inflammatory diseases., Methods: Between June 2016 and June 2017, we prospectively included cases with a suspected PJI and an available lateral flow test α-defensin (Synovasure ® ) in synovial fluid. We compared the test result to the diagnostic criteria for PJIs published by an International Consensus Group in 2013., Results: We included 109 cases (49 hips, 60 knees) in which preoperative α-defensin tests had been performed. Among these, 20 PJIs (16 hips, four knees) were diagnosed. Preoperative α-defensin tests were positive in 25 cases (22.9%) with a test sensitivity and specificity of 90% and 92.1% (95% CI 68.3%-98.8% and 84.5%-96.8%, respectively), and a high negative predictive value of 97.6% (95% CI 91.7%-99.4%). We interpreted seven α-defensin tests as false positive, mainly in cases with inflammatory rheumatic diseases, including crystal deposition diseases., Conclusions: A negative synovial α-defensin test can reliably rule out a PJI. However, the test can be false positive in conjunction with an underlying non-infectious inflammatory disease. We therefore propose to use the α-defensin test only in combination with Musculoskeletal Infection Society criteria and assessment for crystals in synovial aspirates., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

In cultures of normal human epidermal keratinocytes (NHEKs), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces the expression of the epidermal growth factor receptor ligands transforming growth factor-α (TGF-α) and epiregulin (EREG). TCDD also down-regulates EGF receptors (EGFR), suggesting that decreases in signaling contribute to the effects of TCDD. In this study, we treated post-confluent NHEKs with 10 nM TCDD and assessed its effects on EGFR binding, EGFR ligand secretion, basal ERK activity, and proliferation. TCDD caused time-dependent deceases in [(125)I]-EGF binding to levels 78% of basal cell values at 72 h. Amphiregulin (AREG) levels increased with time in culture in basal and TCDD-treated cells, while TGF-α and epiregulin (EREG) secretion were stimulated by TCDD. Inhibiting EGFR ligand release with the metalloproteinase inhibitor batimastat prevented EGFR down-regulation and neutralizing antibodies for AREG and EREG relieved receptor down-regulation. In contrast, neutralizing TGF-α intensified EGFR down-regulation. Treating NHEKs with AREG or TGF-α caused rapid internalization of receptors with TGF-α promoting recycling within 90 min. EREG had limited effects on rapid internalization or recycling. TCDD treatment increased ERK activity, a response reduced by batimastat and the neutralization of all three ligands indicating that the EGFR and its ligands maintain ERK activity. All three EGFR ligands were required for the maintenance of total cell number in basal and TCDD-treated cultures. The EGFR inhibitor PD1530305 blocked basal and TCDD-induced increases in the number of cells labeled by 5-ethynyl-2'-deoxyuridine, identifying an EGFR-dependent pool of proliferating cells that is larger in TCDD-treated cultures. Overall, these data indicate that TCDD-induced EGFR down-regulation in NHEKs is caused by AREG, TGF-α, and EREG, while TGF-α enhances receptor recycling to maintain a pool of EGFR at the cell surface. These receptors are required for ERK activity, maintenance of total cell number, and stimulating the proliferation of a small subset cells., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Myoclonus is the second most common involuntary non-epileptic movement in intensive care units following tremor-like gestures. Although there are several types of myoclonus, they remain underappreciated, and their diagnostic and prognostic associations are largely ignored. This review discusses clinical, electrophysiological, neuroanatomical, and neuroimaging characteristics of different types of myoclonus in critically ill adults along with their prognostic impact and treatment options. Myoclonus is characterized by a sudden, brief, and sometimes repetitive muscle contraction of body parts, or a brief and sudden cessation of tonic muscle innervation followed by a rapid recovery of tonus. Myoclonus can resemble physiologic and other pathologic involuntary movements. Neurologic injuries, anesthetics, and muscle relaxants interfere with the typical appearance of myoclonus. Identifying "real myoclonus" and determining the neuroanatomical origin are important, as treatment responses depend on the involved neuroanatomical structures. The identification of the type of myoclonus, the involved neuroanatomical structures, and the associated illnesses is essential to direct treatment. In conclusion, the combined clinical, electrophysiological, and neuroradiological examination reliably uncovers the neuroanatomical sources and the pathophysiology of myoclonus. Recognizing cortical myoclonus is critical, as it is treatable and may progress to generalized convulsive seizures or status epilepticus., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objectives: To confirm the previously identified EEG characteristics for HSV encephalitis and to determine the diagnostic and predictive value of electroencephalography (EEG) features for etiology and outcome of acute encephalitis in adults. In addition, we sought to investigate their independence from possible clinical confounders., Methods: This study was performed in the Intensive Care Units of two academic tertiary care centers. From 1997 to 2011, all consecutive patients with acute encephalitis who received one or more EEGs were included. Examination of the diagnostic and predictive value of EEG patterns regarding etiology, clinical conditions, and survival was performed. The main outcome measure was in-hospital death., Results: Of 103 patients with encephalitis, EEGs were performed in 76 within a median of 1 day (inter quartile range 0.5-3) after admission. Mortality was 19.7%. Higher proportions of periodic discharges (PDs) (p=0.029) and focal slowing (p=0.017) were detected in Herpes Simplex virus (HSV) encephalitis as compared to non-HSV encephalitis, while clinical characteristics did not differ. Normal EEG remained the strongest association with a low relative risk for death in multivariable analyses (RR<0.001, p<0.001) adjusting for confounders as coma, global cerebral edema and mechanical ventilation. None of the patients with a normal EEG had a GCS of 15., Conclusions: Normal EEG predicted survival independently from possible confounders, highlighting the prognostic value of EEG in evaluating patients with encephalitis. EEG revealed higher proportions of PDs along with focal slowing in HSV encephalitis as compared to other etiologies., Significance: EEG significantly adds to clinical, diagnostic and prognostic information in patients with acute encephalitis., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: Triphasic waves (TWs) are a frequent electroencephalography (EEG) finding in encephalopathy, yet their origin and prognostic significance are not well understood. The aim of this study was to determine the clinical and EEG characteristics in encephalopathic patients with TWs. We hypothesized that specific EEG characteristics are predictive of outcome., Methods: Consecutive adult encephalopathic patients with TWs on EEG and neuroimaging were included. EEG analysis included semiquantitative evaluation of TWs, background activity, and EEG reactivity. The study endpoint was death., Results: Over a nine-year period, 105 patients with TWs were included. Common abnormalities on neuroimaging were white matter lesions (60%) and cerebral atrophy (59%). Pathologic conditions included infections (56%), renal (50%) and liver insufficiency (12%), and respiratory failure (20%). Mortality was 20%. Absent EEG background reactivity and respiratory failure were independently associated with death (OR 3.73, 95%CI 1.08-12.80, p=0.037 and OR 6.47, 95%CI 1.98-21.12, p=0.02)., Conclusions: These results suggest that TWs are a marker of structural brain disease coupled with toxic-metabolic perturbations, and that etiologies or underlying pathologies were not predictive for outcome while non-reactive EEG was independently associated with death., Significance: In contrast to clinical, EEG and neuroimaging findings, non-reactive EEG patterns predicted death in encephalopathic patients with TWs., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

The Toxic Equivalency Factor (TEF) approach is a methodology that assigns relative toxicity values to structurally related chemicals in comparison to a reference chemical. For the polychlorinated dibenzo-p-dioxins (PCDDs), the reference is the most potent congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Here, we critically review the literature on the effects of a weak PCDD, 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (OCDD), and describe the uncertainties of assigning its TEF. PCDDs, including OCDD, are less potent in human cell models compared to the rat models from which the TEF are estimated. This lack of concordance is even more pronounced with the weaker congeners such as OCDD. Furthermore, OCDD is also likely to compete with TCDD for binding to cytochrome P4501A2 (CYP1A2), effectively decreasing the hepatic tissue/fat ratio of TCDD. Overall, the predictive value of TEFs would be improved by incorporating into this number the relative sensitivity of human cell responses compared to rodent responses, by determining the toxicological effects of altering the tissue distribution of dioxin-like compounds through competition for CYP-binding sites, and by understanding the mechanism of cancer causation of any dioxin and whether this mechanism is conserved in humans and at equivalent doses.

Cytochrome p450 1B1 (CYP1B1) has been shown to be important in the bioactivation of 7,12-dimethylbenz[a]anthracene (DMBA) to an adrenal toxin in rats. We investigated the effects of diet and stage of estrous cycle on CYP1B1 expression in rat adrenal glands and on DMBA metabolism by rat adrenal and hepatic microsomes. Female Sprague-Dawley (SD) rats were placed on either standard soy-containing NIH-31 rat chow or soy- and alfalfa-free 5K96 diet from postnatal day (PND) 21 until sacrifice at PND50+/-5. Stage of estrous at sacrifice was assessed by vaginal cytology and confirmed by histological examination of the vagina. Dietary soy at the level present in NIH-31 diet did not affect serum estrogen and progesterone levels. Immunohistochemical analysis confirmed that CYP1B1 was exclusively expressed in the zona fasciculata and zona reticularis in adrenal cortex, which are the regions vulnerable to DMBA-induced adrenal necrosis. Adrenal CYP1B1 protein expression, 3H-DMBA depletion, and formation of DMBA-3,4-, and -8,9-dihydrodiols by adrenal microsomes were greater in animals fed 5K96 diet, and the stage of the estrous cycle affected these parameters only in the soy-free 5K96 diet. In hepatic microsomes, the formation of DMBA-3,4-dihydrodiol, 7-hydroxy- and 12-hydroxy-DMBA were lower in animals fed NIH-31 diet than in those fed 5K96 diet. Thus, dietary soy and the estrous cycle appear to regulate adrenal CYP1B1 expression and DMBA metabolism by both adrenal and hepatic microsomes. The use of different basal diets containing variable levels of soy components may affect certain toxicity assessments.

Human cytochrome P450 (P450) 1B1 was expressed in Escherichia coli at a level of 200 nmol/liter culture using a pCW vector by removal of codons 2-4 and modification of the nucleotide sequence of the resulting N-terminal seven codons; a similar level of expression was found with a bicistronic construct that also expressed human NADPH-P450 reductase. P450 1B1 was purified (from the monocistronic system) to electrophoretic homogeneity and a specific content of 9.2 nmol P450/mg protein using DEAE, CM, and hydroxylapatite chromatography. The absolute spectra showed a considerable fraction of high-spin iron and little cytochrome P420. The catalytic activity of the purified enzyme was considerably enhanced in the presence of cholate. Both reconstituted P450 1B1 and the bacterial membranes prepared from the bicistronic vector system had similar7-ethoxyresorufin O-deethylation activities; as expected, 17beta-estradiol was hydroxylated primarily at the 4-position. The ability of human P450 1B1 to activate several heterocyclic amines and polycyclic hydrocarbon dihydrodiols was confirmed with reconstituted P450 1B1 and the P450 1B1 membranes in which NADPH-P450 reductase was coexpressed., (Copyright 1998 Academic Press.)

Since 1990, an epidemic of diphtheria has spread throughout the newly independent states of the former Soviet Union, and by 1995 a total of 47 808 cases were reported. During the early stages of the epidemic, adequate control measures were not taken and vaccine was in short supply; possible contributing factors to the spread of the epidemic are the presence of highly susceptible child and adult populations, socioeconomic instability, population movement, and a deteriorating health infrastructure. Although WHO views the epidemic as an International public-health emergency and, together with UNICEF and the International Red Cross, has formulated a strategy to combat the epidemic, the necessary funds have not been made fully available. Current vaccination recommendations also need to be reviewed to ensure that population immunity will be adequate to prevent any resurgence of diphtheria in Europe and North America.

We have developed a biologically bounded marginal effect model for use in risk assessment of human exposure to receptor-mediated nongenotoxic carcinogens. Schematically this model can be reduced to four components: CI, the absence of an observable biological response; CII, observable biochemical responses but no observable pathology; CIII, observable pathology; and CIV, both observable pathology and lethality. The inflection point in the marginal response curve between CI and CII is defined as the biologically evaluated scientifically tested no observable effect level (BESTNOEL). We demonstrate the utility of this approach by applying it to the well-studied nongenotoxic carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Using a well-developed mechanistic understanding of the initial interactions of TCDD with the cell, we justify the selection of the minimal effective dose for CYP1A1 mRNA induction as the BESTNOEL. With allowance for variation in human sensitivity to TCDD, the BESTNOEL is assigned a human liver tissue burden of approximately 0.25-25 ppt and an allowable daily intake level in the range of 15-1500 fg/kg/day. In the future, the BESTNOEL can help establish a lower boundary for acceptable extrapolation when using either statistical or biologically based attributable risk models.

From January, 1988, to March, 1989, a widespread outbreak (118 cases) of poliomyelitis type 1 occurred in Oman. Incidence of paralytic disease was highest in children younger than 2 years (87/100,000) despite an immunisation programme that recently had raised coverage with 3 doses of oral poliovirus vaccine (OPV) among 12-month-old children from 67% to 87%. We did a case-control study (70 case-patients, 692 age-matched controls) to estimate the clinical efficacy of OPV, assessed the immunogenicity of OPV and extent of poliovirus spread by serology, retrospectively evaluated the cold chain and vaccine potency, and sought the origin of the outbreak strain by genomic sequencing. 3 doses of OPV reduced the risk of paralysis by 91%; vaccine failures could not be explained by failures in the cold chain nor on suboptimum vaccine potency. Cases and controls had virtually identical type 1 neutralising antibody profiles, suggesting that poliovirus type 1 circulation was widespread. Genomic sequencing indicated that the outbreak strain had been recently imported from South Asia and was distinguishable from isolates indigenous to the Middle East. Accumulation of enough children to sustain the outbreak seems to have been due to previous success of the immunisation programme in reducing spread of endemic strains, suboptimum efficacy of OPV, and delay in completing the primary immunisation series until 7 months of age. Additionally, the estimated attack rate of infection among children aged 9-23 months exceeded 25% in some regions, suggesting that a substantial proportion of fully vaccinated children had been involved in the chain of transmission.

Strains of Saccharomyces cerevisiae deleted in the NADPH-cytochrome P450 reductase gene by transplacement are 200-fold more sensitive to ketoconazole, an inhibitor of the cytochrome P450 lanosterol 14 alpha-demethylase. Resistance is restored through complementation by the plasmid-borne wild type gene from either S. cerevisiae or Candida tropicalis. Neither Southern hybridization nor Western immunoblot techniques provided evidence for a second NADPH-cytochrome P450 reductase gene, suggesting that an alternate pathway may provide for the functions of this reductase in S. cerevisiae.