Hand hygiene behaviours monitored by an electronic system in the intensive care unit - a prospective observational study.

BACKGROUND: It is difficult to improve compliance with hand hygiene (HH), and underlying behaviours are not clearly understood among healthcare workers. AIM: To study HH behaviours among healthcare workers. METHODS: This was a prospective observational study. A Sanibit electronic HH system was installed in a 10-bed surgical intensive care unit (ICU) that detected HH opportunities automatically when healthcare workers entered or exited a patient room, and tracked the HH compliance of healthcare workers. The HH compliance rate and patient contact time were calculated and analysed at both ICU level and individual level over time. FINDINGS: In total, 27,692 HH opportunities were recorded over this 6-month trial period. The HH compliance rate was significantly higher when healthcare workers exited patient rooms than when they entered patient rooms (37.3% vs 26.1%; P<0.001). Full, partial and total HH compliance rates of 'quick in and quick out' (in room for <3 s) events were significantly lower than those of 'long in and long out' (in room for >30 s) events (23.45% vs 32.77%, 21.44% vs 35.03% and 44.88% vs 67.81%, respectively; P<0.001). There were also significant differences in HH compliance between individual healthcare workers (P<0.001). No significant differences in overall HH compliance rate and patient contact time were found between hours of the day or days of the week, except partial HH compliance rates. CONCLUSION: Patterns of HH behaviours among healthcare workers are complex and variable, which could facilitate targeted and personalized interventions to improve HH compliance. CLINICAL TRIAL REGISTRATION: NCT03948672.

Combining 3D human in vitro methods for a 3Rs evaluation of novel titanium surfaces in orthopaedic applications.

In this study, we report on a group of complementary human osteoblast in vitro test methods for the preclinical evaluation of 3D porous titanium surfaces. The surfaces were prepared by additive manufacturing (electron beam melting [EBM]) and plasma spraying, allowing the creation of complex lattice surface geometries. Physical properties of the surfaces were characterized by SEM and profilometry and 3D in vitro cell culture using human osteoblasts. Primary human osteoblast cells were found to elicit greater differences between titanium sample surfaces than an MG63 osteoblast-like cell line, particularly in terms of cell survival. Surface morphology was associated with higher osteoblast metabolic activity and mineralization on rougher titanium plasma spray coated surfaces than smoother surfaces. Differences in osteoblast survival and metabolic activity on titanium lattice structures were also found, despite analogous surface morphology at the cellular level. 3D confocal microscopy identified osteoblast organization within complex titanium surface geometries, adhesion, spreading, and alignment to the biomaterial strut geometries. Mineralized nodule formation throughout the lattice structures was also observed, and indicative of early markers of bone in-growth on such materials. Testing methods such as those presented are not traditionally considered by medical device manufacturers, but we suggest have value as an increasingly vital tool in efficiently translating pre-clinical studies, especially in balance with current regulatory practice, commercial demands, the 3Rs, and the relative merits of in vitro and in vivo studies. Biotechnol. Bioeng. 2016;113: 1586-1599. © 2015 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.

Characterization of Porcine Epidemic Diarrhea Virus Isolate US/Iowa/18984/2013 Infection in 1-Day-Old Cesarean-Derived Colostrum-Deprived Piglets.

Porcine epidemic diarrhea virus (PEDV) was first recognized in North America in April 2013 and has since caused devastating disease. The objective of this study was to characterize disease and viral detection associated with an original North American PEDV isolate inoculated in neonatal piglets. Thirty-six 1-day-old cesarean-derived and colostrum-deprived piglets were randomly assigned to the control (n = 16) or challenged group (n = 20); the latter were orogastrically inoculated with 1 ml of US/Iowa/18984/2013 PEDV isolate titered at 1 × 10(3) plaque-forming units per milliliter. Rectal swabs were collected from all piglets prior to inoculation and every 12 hours postinoculation (hpi) thereafter, with 4 control and 5 challenged piglets euthanized at 12, 24, 48, and 72 hpi. One piglet had a positive real-time quantitative polymerase chain reaction test on rectal swab at 12 hpi, and all remaining piglets were positive thereafter, with highest viral quantities detected at 24 and 36 hpi. Diarrhea was evident in 30% and 100% of challenged piglets at 18 and 24 hpi, respectively. Viral antigen was detected in enterocytes by immunohistochemistry in the duodenum and ileum of piglets euthanized at 12 hpi and was apparent throughout the small intestine of all piglets thereafter, with villus height:crypt depth ratios consistently below 4:1. Viremia was confirmed in 18 of 20 pigs at euthanasia. Clinical disease was severe and developed rapidly following infection with an original North American PEDV isolate, with lesions, viremia, and antigen detection possible by 12 hpi.

Polychlorinated biphenyl (PCB) and dioxin concentrations in residential dust of pregnant women.

Polychlorinated biphenyls (PCBs) and dioxins are well known for their persistence in the environment. PCBs can be found in the residential environment long after the use of these chemicals in domestic products and industrial processes has ceased. Dioxins have been assessed in Australia as being of very low concentrations. Despite concerns about residential dust as a source of human exposure to persistent chemicals, there has been limited testing of PCBs and dioxins in dust in Australia. As part of an assessment of maternal exposure to a variety of persistent toxic substances, we analysed 30 residential dust samples from a variety of geographical settings for their dioxin and PCB concentrations. PCBs were found in most samples, the median and range concentrations (pg g(-1)) of dominant congeners of PCB were as follows: PCB118 (315; <35.0-29 000), PCB105 (130; 14.0-16 000) and PCB156 (440; <5.00-2800). Dioxin concentrations were generally low with median concentrations for the total sum of dioxin-like polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) of 3.75 pg g(-1) each. There was a very high percentage of non-detects. Concentrations of both PCBs and dioxins were low compared with most studies reporting residential dust concentrations internationally. Age of dwelling was the only factor observed to influence both PCB congener concentrations and dioxin isomers in multivariate regression analyses. No other housing or sociodemographic variables, including proximity to industry, were important predictors in multivariate linear regression models.

Pathogenesis of porcine epidemic diarrhea virus isolate (US/Iowa/18984/2013) in 3-week-old weaned pigs.

Porcine epidemic diarrhea virus (PEDV) is associated with clinical diarrhea in naïve swine of all ages. This report describes timing of antibody generation and disease progression following infection with a US PEDV isolate by assessing fecal viral shedding, morphometric analysis of intestinal lesions, and magnitude of immunohistochemical staining. Sixty-three, 3-week-old pigs were randomly allocated into control (n=27) and challenged (n=36) groups. Challenged pigs were administered 1 mL of 1 × 10(3) PFU/mL of US/Iowa/18984/2013 PEDV isolate by oro-gastric gavage. Three control and four challenged pigs were necropsied on days post-inoculation (dpi) 1, 2, 3, 4, 7, and weekly thereafter, until study termination on dpi 35. Clinical disease, fecal shedding, body weight, and temperature were monitored during the study period. Diarrhea was observed in challenged pigs beginning for some on dpi 2, affecting a majority of pigs by dpi 6 and subsiding by dpi 10. Average daily gain was significantly lower (P<0.001) for one week post-infection in challenged pigs. PEDV was detected in feces by PCR on dpi 1 and continued in a subset of pigs until dpi 24. PEDV-specific antigen was detected in villous enterocytes of challenged pigs by immunohistochemistry (IHC) on dpi 1, 2, 3, 4, 7, and 14. Microscopic lesions included severe diffuse atrophic enteritis with significantly reduced (P<0.001) villous length observed on dpi 3, 4, and 7. Under the conditions of this study, fecal shedding of PEDV and IHC staining can precede and continue beyond the observation of clinical signs, thus increasing the risk of viral transmission.

Elsevier Trophoblast Research Award Lecture: Searching for an early pregnancy 3-D morphometric ultrasound marker to predict fetal growth restriction.

Fetal growth restriction (FGR) is a major cause of perinatal morbidity and mortality, even in term babies. An effective screening test to identify pregnancies at risk of FGR, leading to increased antenatal surveillance with timely delivery, could decrease perinatal mortality and morbidity. Placental volume, measured with commercially available packages and a novel, semi-automated technique, has been shown to predict small for gestational age babies. Placental morphology measured in 2-D in the second trimester and ex-vivo post delivery, correlates with FGR. This has also been investigated using 2-D estimates of diameter and site of cord insertion obtained using the Virtual Organ Computer-aided AnaLysis (VOCAL) software. Data is presented describing a pilot study of a novel 3-D method for defining compactness of placental shape. We prospectively recruited women with a singleton pregnancy and BMI of <35. A 3-D ultrasound scan was performed between 11 and 13 + 6 weeks' gestation. The placental volume, total placental surface area and the area of the utero-placental interface were calculated using our validated technique. From these we generated dimensionless indices including sphericity (ψ), standardised placental volume (sPlaV) and standardised functional area (sFA) using Buckingham π theorem. The marker for FGR used was small for gestational age, defined as <10th customised birth weight centile (cSGA). Regression analysis examined which of the morphometric indices were independent predictors of cSGA. Data were collected for 143 women, 20 had cSGA babies. Only sPlaV and sFA were significantly correlated to birth weight (p < 0.001). Regression demonstrated all dimensionless indices were inter-dependent co-factors. ROC curves showed no advantage for using sFA over the simpler sPlaV. The generated placental indices are not independent of placental volume this early in gestation. It is hoped that another placental ultrasound marker based on vascularity can improve the prediction of FGR offered by a model based on placental volume.

Developmental changes in spiral artery blood flow in the human placenta observed with colour Doppler ultrasonography.

OBJECTIVES: Our current knowledge of the physiological dilatation of spiral arteries in pregnancy, is based on histology. Real-time ultrasound visualisation of these changes may aid understanding of abnormal placentation. This study aimed to investigate if changes in the spiral artery blood flow can be followed 'in vivo' and explore the novel phenomenon of the larger 'mega-jets'. METHODS: Colour Doppler ultrasonography was used to identify the most prominent jets at blood from the spiral artery into the intervillous space. Their velocity, width and length were recorded seven set time points during pregnancy. RESULTS: Fifty two uncomplicated, term normotensive pregnancies were studied. Width and length of the jets' Doppler signals increased with gestation, the velocity decreased. The length of the jets shows a bi-modal frequency distribution. The width of the signals of longer ('mega') jets was significantly greater (p = 0.001) than that of the jets (mean 4.3 mm (3.1-5.9) versus 3.8 mm (1.8-5.8) respectively) at 34 weeks. However, there was no significant difference in the peak systolic velocity (p = 0.2). CONCLUSION: This study confirms that ultrasound can be used to study the gestation dependent changes in the haemodynamics of the placental basal plate predicted, but not proven, by histologic data. The bi-modal distribution of jet lengths suggests that mega-jets are a separate entity to 'normal' jets. That they are significantly wider than 'normal' jets and yet maintain the same velocity of blood flow suggests that they have a greater volume of blood flow. The mechanism for this is hypothesised and their apparent relationship with simple placental lakes discussed.

Inapplicability of fractional moving blood volume technique to standardize Virtual Organ Computer-aided AnaLysis indices for quantified three-dimensional power Doppler.

OBJECTIVE: To determine whether the technique of fractional moving blood volume (FMBV) is applicable to Virtual Organ Computer-aided AnaLysis II (VOCAL II™)-based indices to quantify three-dimensional power Doppler ultrasound (3D-PDU) by investigating the effect of gain level on the indices measured at a possible reference point for standardization. METHODS: Ten women with singleton pregnancy between 33+3 and 37+5 weeks' gestation were recruited. The optimal position for 3D acquisition of cord insertion into the placenta was identified and static 3D-PDU volumes were acquired using consistent machine configurations. Without moving the probe or the participant changing position, successive 3D volumes were stored at -3, -5, -7 and -9 dB and at the individualized sub-noise gain (SNG) level. Volumes were excluded if flash artifact was present, in which case all five volumes were reacquired. Using 4D View software, the cord insertion was magnified and the smallest sphere possible was used to measure vascularization index (VI), flow index (FI) and vascularization flow index (VFI). The associations between VOCAL indices and gain level were assessed using Pearson's correlation coefficient. RESULTS: VOCAL indices for cord insertion correlated poorly with gain level, whether fundamental or relative to SNG level (R(2) = 0.07 and 0.04, respectively). VI was consistently 100% and mean FI and VFI were 99.5 (SD, 0.57), with all values > 97 irrespective of gain level. CONCLUSIONS: Whilst previous work has shown that gain correlates well with placental tissue VOCAL indices, the correlation between gain level and VOCAL indices in an area of 100% vascularity at the cord insertion is poor. Regions of 100% vascularity appear to be artificially assigned a value approaching 100% for all VOCAL indices irrespective of gain level. This precludes using the technique of VOCAL indices from large vessels to standardize power Doppler measurements and the FMBV index is therefore not applicable to image analysis using VOCAL.

Influence of power Doppler gain setting on Virtual Organ Computer-aided AnaLysis indices in vivo: can use of the individual sub-noise gain level optimize information?

OBJECTIVES: To demonstrate the influence of gain setting on the calculated Virtual Organ Computer-aided AnaLysis (VOCAL(™)) three-dimensional (3D) indices and define a point, the sub-noise gain (SNG), at which maximum information is available without noise artifact. METHODS: Pregnant women were recruited at the time of their pregnancy-dating scan. Five identical static 3D power Doppler volumes of the placenta were acquired using identical machine settings apart from altering the power Doppler gain setting. The gain settings included the individualized SNG setting (determined by increasing gain until noise artifact was visible, then reducing it until the artifact just disappeared). The data were analyzed using VOCAL II. Vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were calculated for the same sample at five different power Doppler gain levels. The relationship between the values calculated for the VOCAL indices and the gain value was explored using linear regression analysis. RESULTS: Results from 50 women were analyzed. The percentage difference in VI and VFI from that observed at the SNG level in each woman was significantly linearly related to the gain setting relative to that at the SNG point (VI: r(2) = 0.68, P < 0.0001; VFI: r(2) = 0.72, P < 0.0001), with the values produced for VI and VFI decreasing as the gain was turned down. There was a distinct 'turning point' at the SNG level with linear relationships above and below, but with significantly different gradients (P ≤ 0.001). This relationship was not demonstrated for FI. CONCLUSION: The SNG setting appears to represent each individual's optimum gain level. Using this may improve meaningful comparisons of VI and VFI between patients.

Cursor on target: research for a sensor network.

Terrorism, epidemics, natural, and man-made disasters have increased over the last decade, prompting ongoing evaluation and incremental rebuilding of the American public health system (Chan, Killeen, Griswold, & Lenert, 2004a; Yu, Brock, Mecozzi, Tran, & Kost, 2010). In February 2002, the Center for Disease Control (CDC) identified six focus areas to generate response capacities to bioterrorism and public emergencies. According to one focus area, information sharing and alert notifications between systems and public health agencies must be continuous and automatic (Popovich, Henderson, & Stinn, 2002) Advancements in technology set the stage for this uninterrupted data-sharing requirement to be met; for example, "smart devices" can digitally record and transmit information and text messages from remote disaster sites using wireless ad hoc networks. In this context, medical systems and personnel can provide enhanced patient support from the extraction point to the hospital, even when normal landline infrastructure has been damaged. However, care may be restricted due to the limited recognition of proprietary information and the distance between the transmitter and collector system. This article suggests that overcoming these limitations necessitates the adoption of interoperability by basic operations and illustrates how an Internet Protocol called Cursor-on-Target can facilitate communication between open source and propriety systems.

Measurement of spiral artery jets: general principles and differences observed in small-for-gestational-age pregnancies.

OBJECTIVE: To investigate whether the jets of blood from the mouths of the spiral arteries could be measured reliably, as well as their relationship with the uterine artery (UtA) and any differences in small-for-gestational-age (SGA) pregnancies. METHODS: Participants underwent serial ultrasound scans, from 11 weeks' gestation. Pulsatility index (PI) and resistance index (RI) of jets into the intervillous space (IVS) and UtA were recorded at every visit. Intra- and interobserver variability studies were performed. Customized birth weight centiles were calculated and SGA was defined as < 10(th) centile. Linear mixed model analysis was used to allow for the longitudinal nature of the data. RESULTS: Sixty-six women were recruited; 58 remained normotensive and delivered at term. Of these, six women delivered SGA newborns and 52 delivered appropriate-for-gestational-age newborns. All had pulsatile jets until 20 weeks' gestation. The PI and RI of the jets decreased with advancing gestation, following a trend similar to that of the UtAs. There was no correlation between the jets and UtA waveforms when gestational age was controlled for. For intraobserver variability the intraclass correlation coefficient was 0.9. The interobserver study showed no significant difference between the observers. Mixed model analysis demonstrated that PI and RI of jets were different in SGA pregnancies (P < 0.06). This difference was not seen for the UtAs (P = 0.8). CONCLUSION: This technique enables examination of characteristics of the jets of blood flowing from spiral arteries into the IVS. It is both precise and reproducible, with biologically plausible results. Further work is required to assess differences in pregnancies with adverse outcomes.

Vascular lesions in pigs experimentally infected with porcine circovirus type 2 serogroup B.

Vasculitis is a hallmark lesion of the severe form of systemic porcine circovirus-associated disease (PCVAD). In 2 experimental studies with porcine circovirus type 2 serogroup b (PCV2b), 2 pigs developed fatal PCVAD with acute vasculitis, and 5 related pigs developed chronic lymphohistiocytic and plasmacytic peri- and endarteritis. Five of these pigs (1 with acute vasculitis and 4 with chronic vasculitis) had also been inoculated with bovine viral diarrhea virus type 1 (BVDV1) or BVDV1-like virus. Vascular lesions were similar, independent of whether pigs had been inoculated singly with PCV2b or dually with PCV2b and BVDV1 or BVDV1-like virus. The acute vasculitis was accompanied by marked pulmonary and mesenteric edema and pleural effusion. In situ hybridization demonstrated abundant intracytoplasmic porcine circovirus type 2 (PCV2) nucleic acid in endothelial, smooth muscle-like, and inflammatory cells within and around affected arteries. The pigs with lymphohistiocytic and plasmacytic vasculitis had lesions of systemic PCVAD, including multisystemic lymphoplasmacytic and histiocytic or granulomatous inflammation. PCV2 nucleic acid was detected in renal tubule epithelial cells, mononuclear inflammatory cells, and rare endothelial cells in noninflamed vessels in multiple tissues of these animals. The 2 pigs with acute vasculitis had no PCV2-specific antibodies (or a low titer of), whereas the pigs with lymphohistiocytic and plasmacytic vasculitis developed high antibody titers against this virus. These observations suggest that (1) acute vasculitis observed in the current studies is directly caused by PCV2b, (2) chronic vasculitis may in part be mediated by the subsequent immune response, and (3) host factors and viral strain may both contribute to vasculitis in animals infected with PCV2b.

A mental health assessment and support team for community elders in Fife (EAST).

BACKGROUND: The aging population combined with the increased recognition of the need to assess elderly patients with mental health difficulties in their own environment encouraged service redesign in Fife with the focus on community assessment of older people with mental health needs. AIMS: To establish and assess the functioning of a joint Health and Social Services enhanced assessment and support team (EAST) for community-dwelling elders with significant mental health needs living in a Scottish health region, and to determine the impact of this team on the requirement for acute psychogeriatric hospital services. METHODS: Prospective three-year data collection of service activity involving EAST and the local psychogeriatric acute inpatient and day hospital facilities. RESULTS: EAST assessed 111 patients during the study, 83% with a diagnosis of dementia. The mean duration of assessment was six weeks with 9% of patients receiving an overnight home assessment and 6% requiring hospital admission. Overall there was a substantial reduction in utilization of both acute psychogeriatric admission beds and day hospital placements. CONCLUSIONS: Multi-agency community assessment of elders with mental health problems can be addressed effectively without recourse to hospital admission, which may allow resource release for further service developments.

Cutaneous and systemic poxviral disease in red (Tamiasciurus hudsonicus) and gray (Sciurus carolinensis) squirrels.

From September 2005 through October 2006, fibromatosis was diagnosed in 2 red squirrels (Tamiasciurus hudsonicus) and 1 gray squirrel (Sciurus carolinensis). All 3 squirrels had multifocal to coalescing, tan, firm alopecic cutaneous nodules. Two squirrels also had pulmonary nodules. Histologically, the cutaneous nodules had marked epidermal hyperplasia, with ballooning degeneration of keratinocytes, spongiosis, and eosinophilic cytoplasmic inclusions. The dermis was expanded by proliferation of atypical mesenchymal cells with cytoplasmic inclusions. Additional findings included pulmonary adenomatous hyperplasia with cytoplasmic inclusions, renal tubular epithelial hyperplasia with cytoplasmic inclusions, atypical mesenchymal proliferation in the liver, and atypical mesenchymal proliferation with cytoplasmic inclusions in the seminal vesicles. Ultrastructurally, poxviral particles were observed in skin scrapings and sections of cutaneous and pulmonary nodules. Polymerase chain reaction targeting the highly conserved Leporipoxvirus DNA polymerase gene was positive using DNA extracted from the cutaneous lesions of all 3 squirrels. Nucleotide sequence of the 390 base PCR amplicons was closely related to that of other members of the genus Leporipoxvirus. To the authors' knowledge, this is the first report of cutaneous and systemic poxviral disease in American red squirrels with molecular characterization of the squirrel fibroma virus.

Vascular lesions in nine Göttingen minipigs with thrombocytopenic purpura syndrome.

Tissues from 9 Göttingen minipigs, aged 7 weeks to 1 year, with clinically diagnosed thrombocytopenic purpura syndrome were examined microscopically. All pigs had a history of spontaneous cutaneous purpura that was generally accompanied by disseminated visceral hemorrhages. Hematologic abnormalities included anemia (8 out of 9 pigs) and thrombocytopenia (7 out of 9 pigs), with platelet counts consistently below 20,000/microl. Microscopically, degenerative vascular lesions with morphologic features of arteriosclerosis were present in all 9 pigs. Vascular lesions affected small- to medium-sized muscular arteries and arterioles in various organs and extraparenchymal tissues; vessels of the renal pelvis and coronary arteries were consistently involved. Microscopic lesions in small- to medium-sized muscular arteries consisted of neointimal proliferation, medial thickening, luminal stenosis, thrombosis, disruption and fragmentation of the internal elastic lamina, necrosis of the tunica media, and medial deposits of myxoid matrix material. Microscopic lesions in arterioles included concentric laminar thickening of vessel walls (onion-skin pattern), endothelial cell hypertrophy, smooth muscle cell vacuolation, necrosis of the tunica media, thrombosis, and partial to complete luminal stenosis. Arteritis and/or periarteritis were also noted in 4 out of 9 pigs. Additional microscopic lesions included membranoproliferative glomerulonephritis (3 out of 9), myocardial microinfarcts (4 out of 7), renal interstitial fibrosis (2 out of 9), extramedullary hematopoiesis (6 out of 9), and intracapillary hyaline thrombi (2 out of 9). Degenerative vascular lesions have not been previously described in Göttingen minipigs with thrombocytopenic purpura syndrome. The etiopathogenesis of both the vascular lesions and thrombocytopenic purpura syndrome is currently unknown.

Mask fear in children presenting for anesthesia: aversion, phobia, or both?

BACKGROUND: Anesthesia induction in children is commonly accomplished by introducing volatile agents by mask. Occasionally a child describes an excessive fear of the anesthesia facemask. Little is known of the cause of the fear or of the quality or magnitude of the feelings the child is experiencing. The purpose of this study was to allow children who have established mask fear as demonstrated by volunteering the presence of fear and requesting no mask be placed on the face during the induction of anesthesia and their parents to describe and compare the distress from the mask to the alternative intravenous anesthesia induction. METHODS: Eight children describing mask fear on the preanesthetic examination were studied. An Anesthesia Mask Fear questionnaire developed by the investigators was answered by the children and their parents. RESULTS: Six children and their parents completed the study. The age at presentation of mask fear ranged from 1.4 to 14 years. There were one to 16 anesthetic exposures prior to reporting mask fear. One child described an aversion to the odor of the mask. Another boy developed mask fear after a single anesthetic exposure. He was subsequently diagnosed with a generalized anxiety disorder. Four female children developed mask fear after repeated anesthetic exposures. These children rated mask fear with the greatest discomfort possible while venous cannulation was scored at half or less that of the mask discomfort. CONCLUSIONS: Care must be taken when developing a plan for anesthesia induction in children requiring multiple procedures. Children may develop an aversion to the odor or feel of the mask, or have a true phobia (irrational fear) of the mask. Those children with a phobia might also have other underlying anxieties.

Extensive lesions of monkeypox in a prairie dog (Cynomys sp).

Monkeypox with extensive lesions was diagnosed in a prairie dog that was involved in a recent human outbreak of monkeypox in the Midwestern United States. Gross lesions included oral ulcers, pulmonary consolidation, enlarged cervical and thoracic lymph nodes, and multifocal, small, white umbilicated plaques in the gastrointestinal wall. Microscopic lesions were extensive in the lungs and consisted of fibrinonecrotic bronchopneumonia with vasculitis and poorly defined eosinophilic intracytoplasmic inclusion bodies in cells thought to be alveolar epithelial cells, histiocytes, and fibroblasts. Multifocal necrotizing lesions, often accompanied by myxedema, were also present in most of the other examined organs. Aggregates of pox viral particles were observed within lesions by transmission electron microscopy. Monkeypox virus infection was confirmed by real-time polymerase chain reaction and virus culture at the Centers for Disease Control and Prevention. This report highlights the difficulties of rapid diagnosis of exotic or emerging diseases and further substantiates the prairie dog as an animal model of monkeypox.

Engineered antibody for treating lymphoma.

One approach to improving the results of antibody treatment of posttransplant and other lymphomas is to alter the geometry of the antibody molecule so as to enhance its cytotoxicity. When antibody alights on a cell, cytotoxicity can be exerted by initiation of apoptotic signals at the cell surface, and by recruitment of effectors to specific sites on the antibody Fc region. Other routes to cytotoxicity have been described but their generality is debatable. The effectors consist of complement, and a series of potentially cytotoxic cells (macrophages, NK cells, neutrophils and others) bearing Fc-receptors (FcR). Recent evidence suggests that the FcR-bearing cells are the more important in dealing with antibody-coated autologous cells, including tumor cells. If the antibody happens to be of the host IgG class then its Fc region (Fcgamma) will contain a site for attachment of a non-cytotoxic FcR known as FcRB (the Brambell receptor): it is this receptor, present on endothelial cells, which recycles the molecule intact if it happens to be endocytosed and thus prolongs its metabolic life. Replacement of the mouse Fcgamma by human Fcgamma is expected to have three beneficial effects: better recruitment of human effector cells, better persistence of the antibody in extracellular fluid, and removal of a major source of immunogenic epitopes. Chemical manipulations of Fab'gamma and Fcgamma modules, linking them in different geometries via their hinge regions, offers constructs with further enhancements of cytotoxicity. These include Fab2Fc2, in which the presence of dual Fc regions enhances recruitment of both complement and cellular effectors; and bispecific antibody of the same modular formula in which one of the Fab arms is specific for tumor while the other is specific for, and recruits powerfully, a cellular effector.