Anosognosia Is Associated With Greater Caregiver Burden and Poorer Executive Function in Huntington Disease.

BACKGROUND: Anosognosia, or unawareness of one's deficits, is estimated to occur in 25% to 50% of Huntington disease (HD). The relationship between anosognosia and increased caregiver burden found in other dementias has not been determined in HD. METHODS: Patient-caregiver dyads presenting to a statewide HD clinic were assessed using the Anosognosia Scale and grouped into "anosognosia" and "no anosognosia." Caregiver burden, measured by Zarit Burden Interview (ZBI) and Caregiver Burden Inventory (CBI), demographic data, and Unified Huntington's Disease Rating Scale, including Mini-Mental State Examination, Stroop, Trail Making, Verbal Fluency, and Symbol Digit Modalities Tests, were compared between groups. RESULTS: Of the 38 patients recruited, 10 (26.3%) met criteria for anosognosia. Patients with anosognosia elicited higher caregiver burden ratings on both the ZBI (mean difference 16.4 [12.1], P < .001) and CBI (16.7 [15.0], P < .005) while also demonstrating poorer executive function. Except for CAG burden score, between-group characteristics did not differ significantly. Stroop Interference predicted both anosognosia and caregiver burden. CONCLUSIONS: In HD, anosognosia is associated with greater caregiver burden and executive deficits. Its occurrence should prompt further patient assessment and increased caregiver support.

Risk factors for and management of anterior chamber intravitreal dexamethasone implant migration.

BACKGROUND: This study aimed to investigate the incidence of and risk factors for the anterior chamber migration of an intravitreal dexamethasone implant (Ozurdex®). METHODS: A retrospective review of 640 consecutive intravitreal dexamethasone implant injections was conducted from February 2011 through February 2018 at the University Eye Hospital in Tübingen, Germany. Those patients who experienced anterior chamber dexamethasone implant migrations were identified, as well as the reasons for the anterior chamber migration. The surgical histories were obtained and comprehensive ophthalmic examinations were conducted for all of the eyes. Cross-tabulations, chi-squared tests, and Fisher's exact tests were used to assess the influences of different factors on the anterior chamber implant migrations. RESULTS: Overall, 4 eyes of four patients (0.63%) showed anterior chamber implant migrations. All four of the eyes were pseudophakic, and they had undergone prior vitrectomies. Three eyes had sclerally-fixated intraocular lenses, and one eye had a posterior chamber intraocular lens in the capsular bag, with a capsular tension ring due to partial zonular dehiscence. When comparing the vitrectomized eyes with reduced zonular/capsular bag complex integrity to the vitrectomized pseudophakic eyes with intact zonular/capsular bags, the former were significantly associated with an increased risk of anterior chamber implant migration (P = 0.008). The vitrectomized pseudophakic eyes, in contrast to the nonvitrectomized pseudophakic eyes, were significantly associated with an increased risk of anterior chamber implant migration (P = 0.009). CONCLUSIONS: The anterior chamber migration of an intravitreal dexamethasone implant is a serious complication. To minimize the risk of permanent corneal edema, immediate removal of the implant with a 20-gauge alligator forceps over a 2.75-mm long clear corneal tunnel is important. Those patients with insufficient zonular support, defects, or missing posterior capsular membranes and vitrectomy histories present a high risk of anterior chamber dexamethasone implant migration.

African swine fever virus serotype-specific proteins are significant protective antigens for African swine fever.

African swine fever (ASF) is an emerging disease threat for the swine industry worldwide. No ASF vaccine is available and progress is hindered by lack of knowledge concerning the extent of ASFV strain diversity and the viral antigens conferring type-specific protective immunity in pigs. Available data from vaccination/challenge experiments in pigs indicate that ASF protective immunity may be haemadsorption inhibition (HAI) serotype-specific. Recently, we have shown that two ASFV proteins, CD2v (EP402R) and C-type lectin (EP153R), are necessary and sufficient for mediating HAI serological specificity (Malogolovkin et al., 2015).. Here, using ASFV inter-serotypic chimeric viruses and vaccination/challenge experiments in pigs, we demonstrate that serotype-specific CD2v and/or C-type lectin proteins are important for protection against homologous ASFV infection. Thus, these viral proteins represent significant protective antigens for ASFV that should be targeted in future vaccine design and development. Additionally, these data support the concept of HAI serotype-specific protective immunity.

Factors that influence the suitability of human organ-cultured corneas.

PURPOSE: The purpose was to assess the influence of donor and storage factors on the suitability of organ-cultured corneas for transplantation. METHODS: Data from 1340 donor corneas stored between 2009 and 2015 were analyzed retrospectively. Logistic regression analysis was used to assess the influence of different factors on the suitability of grafts for transplantation. RESULTS: Forty-one percent (553/1340) of corneas were discarded. The leading causes were medical contraindication (20.2 %) and poor endothelial quality (19.3 %). Donor age influenced suitability for transplantation significantly. Corneas from donors aged 80 years and older were more likely to be discarded because of endothelial insufficiency (P < 0.0001). The cause of donor death including infection and multiple organ dsyfunction syndrom (MODS) increased the risk of bacterial or fungal contamination during organ culture (P = 0.007 and P = 0.014, respectively). Prolonged time between death and enucleation was associated with an increased risk of unsuitability for transplantation (P < 0.0001). The amount of time between death and corneoscleral disc excision and duration of storage influenced the suitability for transplantation (P = 0.0007 and P < 0.0001, respectively). CONCLUSION: Donor age, cause of death, storage time, death to enucleation and death to disc excision times influenced transplantation suitability. The percentage of discarded corneas may be reduced by shortening storage time, death to enucleation, and death to corneoscleral disc excision times. Setting a maximum donor age could reduce the percentage of discarded corneas. However, as long as there is a lack of donor corneas, we do not recommend any donor age limit.

African swine fever virus CD2v and C-type lectin gene loci mediate serological specificity.

African swine fever (ASF) is an emerging disease threat for the swine industry worldwide. No ASF vaccine is available and progress is hindered by lack of knowledge concerning the extent of ASF virus (ASFV) strain diversity and the viral antigens responsible for protection in the pig. Available data from vaccination/challenge experiments in pigs indicate ASF protective immunity is haemadsorption inhibition (HAI) serotype-specific. A better understanding of ASFV HAI serological groups and their diversity in nature, as well as improved methods to serotype ASFV isolates, is needed. Here, we demonstrated that the genetic locus encoding ASFV CD2v and C-type lectin proteins mediates HAI serological specificity and that CD2v/C-type lectin genotyping provides a simple method to group ASFVs by serotype, thus facilitating study of ASFV strain diversity in nature, and providing information necessary for eventual vaccine design, development and efficacious use.

Disrupted seasonal biology impacts health, food security and ecosystems.

The rhythm of life on earth is shaped by seasonal changes in the environment. Plants and animals show profound annual cycles in physiology, health, morphology, behaviour and demography in response to environmental cues. Seasonal biology impacts ecosystems and agriculture, with consequences for humans and biodiversity. Human populations show robust annual rhythms in health and well-being, and the birth month can have lasting effects that persist throughout life. This review emphasizes the need for a better understanding of seasonal biology against the backdrop of its rapidly progressing disruption through climate change, human lifestyles and other anthropogenic impact. Climate change is modifying annual rhythms to which numerous organisms have adapted, with potential consequences for industries relating to health, ecosystems and food security. Disconcertingly, human lifestyles under artificial conditions of eternal summer provide the most extreme example for disconnect from natural seasons, making humans vulnerable to increased morbidity and mortality. In this review, we introduce scenarios of seasonal disruption, highlight key aspects of seasonal biology and summarize from biomedical, anthropological, veterinary, agricultural and environmental perspectives the recent evidence for seasonal desynchronization between environmental factors and internal rhythms. Because annual rhythms are pervasive across biological systems, they provide a common framework for trans-disciplinary research.

Causes that influence the detachment rate after Descemet membrane endothelial keratoplasty.

PURPOSE: To investigate Descemet graft (DG) detachment rate after Descemet membrane endothelial keratoplasty (DMEK) in relation to DG position. METHODS: A total of 175 consecutive pseudophakic eyes that underwent DMEK (175 eyes for Fuchs endothelial dystrophy) from September 2009 through February 2014 at the Tübingen Eye Hospital DG position were studied retrospectively by surgical video at the end of an operation. A group of 45 eyes showed a decentration of the DG with a stromal gap of ≥1.5 mm over at least 3 clock hours between the descematorhexis edge and the DG. DG detachment was documented at a mean follow-up of 13.9 ± 3.7 months after surgery. DG detachment was defined as a detachment of 20 % or more of the DG surface area. Various donor characteristics and patient characteristics were analyzed. RESULTS: The best spectacle-corrected visual acuity (BCVA) in the group of eyes with central well-positioned DG differed significantly from those of eyes with decentered DG. The preoperative BCVA in the central well-positioned DG group was 0.63 ± 0.40 logMAR, and in the decentered DG group 0.91 ± 0.51 logMAR (P < 0.001). The postoperative BCVA in the group of eyes with central well-positioned DG was 0.12 ± 0.11 logMAR, and in the group with decentered DG 0.23 ± 0.29 logMAR (P < 0.001). Endothelial cell density and patient characteristics such as age, gender, and intraocular pressure did not differ significantly between the two groups. The group of eyes with central well-positioned DG showed DG detachment in 12 %; the group with decentered DG findings had DG detachment in 87 % (P < 0.001) at the 12 month follow up. CONCLUSION: The present findings demonstrate the importance of central well-positioned DG and the relation of disease severity. Central well-positioned DG may reduce the incidence of DG detachment. Overlapping of the donor DG and the host Descemet membrane seems to be responsible for DG detachment. One possible way to enhance graft adhesion could be a larger descematorhexis, which avoids an overlapping. The second possible way could be not waiting too long for surgery to reduce disease severity.

Novel gammaherpesvirus functions encoded by bovine herpesvirus 6 (bovine lymphotropic virus).

The genus Macavirus of the subfamily Gammaherpesvirinae includes viruses that infect lymphoid cells of domestic and wild ruminants and swine, causing asymptomatic latent infections in reservoir hosts. Here, we describe the genome of bovine herpesvirus 6 (BoHV-6), a macavirus ubiquitous in healthy cattle populations. The BoHV-6 genome exhibited architecture conserved in macaviruses, including a repetitive H-DNA region and unique 141 kbp L-DNA region predicted to encode 77 genes. BoHV-6 encoded, in variable genomic regions, a novel complement of genes relative to other characterized macaviruses, probably contributing to distinctive aspects of BoHV-6 infection biology and host range. Most notably, BoHV-6 encoded the first herpesviral protein (Bov2.b2) similar to cellular ornithine decarboxylase, an enzyme that catalyses the first and rate-limiting step in the biosynthesis of polyamines. Bov2.b2 conceivably mediates a novel mechanism by which BoHV-6 promotes cell-cycle-dependent viral replication.

The influence of axial length on confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography size measurements: a pilot study.

PURPOSE: To investigate the influence of axial length on SD-OCT and cSLO size measurements from the Heidelberg Spectralis. METHODS: In this pilot study, eight emmetropic pseudophakic eyes with subretinal visual implant were selected. The axial length was measured in three short (<22.5 mm), three medium (22.51-25.50 mm) and two long (>25.52 mm) eyes. The known size of subretinal implant sensor field (2800 × 2800 µm) was measured on 15 images per eye with cSLO and SD-OCT. RESULTS: The mean axial length was 20.8 ± 0.8 mm in short eyes, 23.3 ± 0.4 mm in medium eyes, and 26.3 ± 0.5 mm in long eyes respectively. We found in short eyes, in medium eyes and in long eyes a mean value of sensor field size measurements from cSLO of 3327 ± 9 µm, 2800 ± 9 µm and 2589 ± 12 µm and from SD-OCT of 3328 ± 9 µm, 2800 ± 12 µm and 2585 ± 19 µm respectively. The size measurements decreased in SD-OCT and cSLO measurements with longer axial lengths significantly (p < 0.0001). CONCLUSION: The present findings demonstrate accuracy of the scaling in cSLO and SD-OCT measurements of the Heidelberg Spectralis for emmetropic medium eyes. The size measurements from SD-OCT to those from cSLO were approximately equal. Caution is recommended when comparing the measured values of short and long eyes with the normative database of the instrument. Further studies with larger sample sizes are needed to confirm findings.

[Using intracameral cefuroxime reduces postoperative endophthalmitis rate: 5 years experience at the University Eye Hospital Tübingen]. / Reduktion der postoperativen Endophthalmitisrate durch intrakamerale Cerfuroximgabe: Ergebnisse aus 5 Jahren Erfahrungen an der Universitäts-Augenklinik Tübingen.

BACKGROUND: Cataract surgery is the most commonly performed surgical procedure in developed countries. The annual number of cataract surgeries in Germany is about 600,000. Acute postoperative endophthalmitis is a very severe and the most dreaded complication of cataract surgery. Various operative and non-operative measures have been suggested to prevent this serious complication. The European Society of Cataract & Refractive Surgeons (ESCRS) study of intracameral cefuroxime was the first prospective, randomised and partially placebo-controlled clinical trial showing the efficacy of antibiotic prophylaxis to prevent endophthalmitis in 2007. The aim of this retrospective study is to investigate a possible reduction of intracameral cefuroxime to prevent postoperative endophthalmitis at the University Eye Hospital Tübingen. PATIENTS AND METHODS: During the period from January 2002 to August 2013, 2 time periods were determined based on the adoption of intracameral cefuroxime injections after cataract surgery. From January 2002 to May 2009 patients received at the end of cataract surgery a subconjunctival administration of 50 mg of mezlocillin and postoperative antibiotic eye drops (gentamicin) without intracameral injection. From June 2009 to August 2013, patients received an intracameral injection of cefuroxime while antibiotic drops (moxifloxacin) were used too. The rates of postoperative infectious endophthalmitis during these 2 periods were calculated. RESULTS: 31 cases of endophthalmitis occurred in 31,386 cataract surgeries. The overall cumulative incidence was 0.99 per 1000 patients. The incidence in the first period without intracameral cefuroxime injection was 1.38 (95 % confidence interval [CI]: 1.03-1.72) per 1000 patients and in the second period 0.44 (95 % CI: 0.34-0.54) per 1000 patients (p < 0.001). CONCLUSION: Intracameral injection of cefuroxime reduces the rate of postoperative infectious endophthalmitis in cataract surgery significantly.

Orf virus ORFV121 encodes a novel inhibitor of NF-kappaB that contributes to virus virulence.

Orf virus (ORFV), the type member of the genus Parapoxvirus of the Poxviridae, has evolved novel strategies (proteins and/or mechanisms of action) to modulate host cell responses regulated by the nuclear factor-κB (NF-κB) signaling pathway. Here, we present data indicating that ORFV ORFV121, a gene unique to parapoxviruses, encodes a novel viral NF-κB inhibitor that binds to and inhibits the phosphorylation and nuclear translocation of NF-κB-p65. The infection of cells with an ORFV121 deletion mutant virus (OV-IA82Δ121) resulted in increased NF-κB-mediated gene transcription, and the expression of ORFV121 in cell cultures significantly suppressed NF-κB-regulated reporter gene expression. ORFV ORFV121 physically interacts with NF-κB-p65 in the cell cytoplasm, thus providing a mechanism for the inhibition of NF-κB-p65 phosphorylation and nuclear translocation. Notably, the deletion of ORFV121 from the viral genome markedly decreased ORFV virulence and disease pathogenesis in sheep, indicating that ORFV121 is a virulence determinant for ORFV in the natural host.

A nuclear inhibitor of NF-kappaB encoded by a poxvirus.

Poxviruses have evolved various strategies to inhibit cytoplasmic events leading to activation of the nuclear factor κB (NF-κB) signaling pathway, with individual viruses often encoding multiple NF-κB inhibitors. Here, the novel orf virus (ORFV)-encoded protein ORFV002 was shown to inhibit nuclear events regulating NF-κB transcriptional activity. ORFV002 expression in cell cultures significantly decreased wild-type-virus-, tumor necrosis factor alpha (TNF-α)-, and lipopolysaccharide (LPS)-induced NF-κB-mediated gene expression. Expression of ORFV002 in cells, while not affecting phosphorylation or nuclear translocation of NF-κB-p65, markedly decreased TNF-α- and wild-type-virus-induced acetylation of NF-κB-p65, a p300-mediated nuclear modification of NF-κB-p65 that regulates its transactivating activity. ORFV002 was shown to colocalize and interact with NF-κB-p65, and expression of ORFV002 in cell cultures resulted in a reduced interaction of NF-κB-p65 with p300, suggesting that ORFV002 interferes with NF-κB-p65/p300 association. Deletion of ORFV002 from the OV-IA82 genome had no significant effect on ORFV pathogenesis in sheep, indicating that ORFV002 is nonessential for virus virulence in the natural host. This represents the first description of a nuclear inhibitor of NF-κB encoded by a poxvirus.

Comparative full genome analysis of four infectious laryngotracheitis virus (Gallid herpesvirus-1) virulent isolates from the United States.

Gallid herpesvirus-1 (GaHV-1), commonly named infectious laryngotracheitis (ILT) virus, causes the respiratory disease in chickens known as ILT. The molecular determinants associated with differences in pathogenicity of GaHV-1 strains are not completely understood, and a comparison of genomic sequences of isolates that belong to different genotypes could help identify genes involved in virulence. Dideoxy sequencing, 454 pyrosequencing and Illumina sequencing-by-synthesis were used to determine the nucleotide sequences of four genotypes of virulent strains from GaHV-1 groups I-VI. Three hundred and twenty-five open reading frames (ORFs) were compared with those of the recently sequenced genome of the Serva vaccine strain. Only four ORFs, ORF C, U(L)37, ICP4 and U(S)2 differed in amino acid (aa) lengths among the newly sequenced genomes. Genome sequence alignments were used to identify two regions (5' terminus and the unique short/repeat short junction) that contained deletions. Seventy-eight synonymous and 118 non-synonymous amino acid substitutions were identified with the examined ORFs. Exclusive to the genome of the Serva vaccine strain, seven non-synonymous mutations were identified in the predicted translation products of the genes encoding glycoproteins gB, gE, gL and gM and three non-structural proteins U(L)28 (DNA packaging protein), U(L)5 (helicase-primase) and the immediate early protein ICP4. Furthermore, our comparative sequence analysis of published and newly sequenced GaHV-1 isolates has provided evidence placing the cleavage/packaging site (a-like sequence) within the inverted repeats instead of its placement at the 3' end of the U(L) region as annotated in the GenBank's entries NC006623 and HQ630064.

[Clinical results after Descemet membrane endothelial keratoplasty]. / Klinische Ergebnisse nach Descemet-Membran-Endothelzelltransplantation.

BACKGROUND: Diseases of the endothelial cell layer represent a common indication for perforating keratoplasty. In recent years posterior lamellar keratoplasty techniques have undergone a revival. The latest and most promising advancement is the isolated transplantation of Descemet's membrane (DM) with the endothelial layer - also known as Descemet's membrane endothelial keratoplasty (DMEK). This study was conducted to evaluate the clinical results of our DMEK patients and to assess the perioperative management. PATIENTS AND METHODS: 70 patients (75 eyes) with endothelial cell decompensation (50 eyes with Fuchs endothelial dystrophy and 25 eyes with bullous keratopathy) had undergone DMEK surgery at the Tübingen Eye Clinic. Visual acuity, refractive error, intraocular pressure, slit lamp examination, pachymetry and endothelial cell density were considered and re-examined at intervals of 1, 2 and 4 weeks postoperatively with further 3 monthly follow-ups. RESULTS: The mean age of the 45 female and 25 male patients at time of surgery was 73 years (36 to 91 years). The mean follow-up period was 12.1 months. One patient received an autologous and 4 patients a triple procedure. The mean preoperative LogMAR visual acuity was 0.87 ± 0.41. After 1 week a LogMAR visual acuity of 0.82 ± 0.4 was observed (p = 0.544). At the final examination the LogMAR visual acuity was 0.32 ± 0.35 (p < 0.001, a highly significant result as compared to the preoperative value). The most common and important complication was the dislocation of the transplant which was seen in 23 eyes (31 %). The use of intracameral air pressurisation re-appositioned most transplants. Complications such as highly elevated intraocular pressure, epithelial inclusions or endophthalmitis were not noted in any patient. CONCLUSIONS: DMEK surgery lead to a significant visual rehabilitation in a majority of patients in a relatively short postoperative period. It may be considered as a gold standard to treat isolated endothelial diseases as has been implicated by other studies. Thus, the safety and efficiency of this new type of posterior lamellar keratoplasty technique has been confirmed.

[Precut technique for Descemet's membrane endothelial keratoplasty, preparation and storage in organ culture]. / Precut Verfahren für Descemet-Membran-Endothelzelltransplantation, Präparation und Aufbewahrung in Kultur.

BACKGROUND: The preparation of the Descemet's membrane (DM) with the endothelial cell layer may be performed directly prior to surgery or as a precut tissue procedure. The purpose of the current study was the evaluation of the preparation technique and the tissue culture of 10 days regarding potential endothelial cell loss. MATERIALS AND METHODS: Ten corneoscleral rims with an average age of 64.3 years were dissected to obtain 8.5 mm in diameter endothelial-DM complexes, which subsequently were organ cultured for 10 days. The endothelial cell density (ECD) was assessed during the cell culture period at days 1., 4., 7. and 10. In addition, time of preparation and transplant morphology were evaluated. RESULTS: The DM with the endothelial cell layer could successfully be dissected from all corneoscleral rims. The average preparation time was 8.3 min. The average ECD count was 2183 ± 77 cells/mm2 prior to, 2094 ± 110 cells/ mm2 at day 1, 2078 ± 134 cells/mm2 at day 4, 1977 ± 107 cells/mm2 at day 7 and 1898 ± 170 cells/mm2 at day 10 after preparation, respectively. Endothelial cell loss was 4.1 %, 4.8 %, 9.4 % and 13.1 % after preparation, respectively. None of the transplants exhibited large, centrally-located cell deficits. CONCLUSION: The isolated storage of DM with the endothelial layer, without any stromal remnants, showed gratifying results under storage conditions in organ culture with a moderate ECD decrease. Hence, the implementation of a precut DMEK is conceivable.

[Histological and ultrastructural analysis of the Descemet's membrane after descemetorhexis in DMEK surgery]. / Histologische und ultrastrukturelle Untersuchung der Descemet-Membran nach Descemetorhexis bei der DMEK- Operation.

BACKGROUND: In order to obtain an optimal visual outcome in the isolated transplantation of Descemet's membrane (DM) with the endothelial cell layer, a regular interface between the receiver cornea and the graft is important for the prognosis. The purpose of this histological and ultrastructural study was to investigate how precise the descemetorhexis works using the Sinskey hook and whether the precision of DM removal depends on the clinical and pathological diagnosis of the underlying corneal endothelial disease. PATIENTS AND METHODS: 22 DM specimens of 22 patients obtained after descemetorhexis in DMEK using a Sinskey hook were examined using histological analyses and transmission electron microscopy for the presence of residual stroma, thickness of the DM, endothelial cell count, and presence of guttae. 17 patients had a Fuchs corneal dystrophy, 5 pseudophakic bullous keratopathy. RESULTS: Light and electron microscopy showed no evidence of adherent stroma in all 22 specimes after descemetorhexis independent of the different underlying endothelial pathological abnormalities. The mean total thickness of the DM was 20.58 ± 4.23 µm in patients with Fuchs endothelial dystrophy and 21.31 ± 5.41 µm in patients with bullous keratopathy. There was no significant difference between both pathological abnormalities. The anterior banded layer measured a mean of 3.04 ± 0.40 µm and 3.25 ± 0.22 µm thick; the posterior non-banded layer 17. 63 ± 4.07 µm and 17.60 ± 5.0 µm thick in each case of Fuchs corneal dystrophy and pseudophakic bullous keratopathy. There was no significant difference between the two diseases. CONCLUSIONS: Descemetorhexis allows a selective removal of the DM without adherent stroma in different underlying endothelial pathological abnormalities and in different variability of disease expression.

A novel inhibitor of the NF-{kappa}B signaling pathway encoded by the parapoxvirus orf virus.

The parapoxvirus orf virus (ORFV) is a pathogen of sheep and goats that has been used as a preventive and therapeutic immunomodulatory agent in several animal species. However, the functions (genes, proteins, and mechanisms of action) evolved by ORFV to modulate and manipulate immune responses are poorly understood. Here, the novel ORFV protein ORFV024 was shown to inhibit activation of the NF-kappaB signaling pathway, an important modulator of early immune responses against viral infections. Infection of primary ovine cells with an ORFV024 deletion mutant virus resulted in a marked increase in expression of NF-kappaB-regulated chemokines and other proinflammatory host genes. Expression of ORFV024 in cell cultures significantly decreased lipopolysaccharide (LPS)- and tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB-responsive reporter gene expression. Further, ORFV024 expression decreased TNF-alpha-induced phosphorylation and nuclear translocation of NF-kappaB-p65, phosphorylation, and degradation of IkappaBalpha, and phosphorylation of IkappaB kinase (IKK) subunits IKKalpha and IKKbeta, indicating that ORFV024 functions by inhibiting activation of IKKs, the bottleneck for most NF-kappaB activating stimuli. Although ORFV024 interferes with activation of the NF-kappaB signaling pathway, its deletion from the OV-IA82 genome had no significant effect on disease severity, progression, and time to resolution in sheep, indicating that ORFV024 is not essential for virus virulence in the natural host. This represents the first description of a NF-kappaB inhibitor encoded by a parapoxvirus.

Virological and clinico-pathological features of orf virus infection in experimentally infected rabbits and mice.

Many aspects of the biology of orf virus (ORFV) infection remain poorly understood and attempts to establish animal models have yielded conflicting and non-reproducible results. We herein describe the characterization of ORFV infection and disease in rabbits and mice. A protocol of intradermal inoculation was employed to inoculate 10(8.5)TCID50/mL of ORFV strain IA-82 in the skin of ears, of the back and labial commissures. All inoculated rabbits presented a clinical course characterized by erythema, macules, papules/vesicles or pustules that eventually dried originating scabs. Local signs started around days 3 and 4 post-inoculation (pi) and lasted 3-10 days. Virus was recovered from lesions between days 2 and 14pi. Histological examination of lesions revealed focal proliferative dermatitis with ballooning degeneration and eosinophilic intracytoplasmic inclusion bodies in keratinocytes, histological hallmarks of contagious ecthyma in sheep. A similar, albeit milder clinical course occurred in 5/10 inoculated mice; virus was recovered from lesions from three animals. Inoculated lambs - used as controls - developed severe lesions of contagious ecthyma. VN tests performed at day 28pi failed to detect neutralizing antibodies in all inoculated animals. In contrast, convalescent rabbit sera were positive by ELISA at dilutions from 100 to 400. These results show that rabbits are susceptible to ORFV infection and thus may be used to study selected aspects of ORFV biology.

'Social dysmetria' in first-episode psychosis patients.

OBJECTIVE: The 'embodied cognition' hypothesis suggests a close relationship between internal self-representations and the outward expression of social behaviours and emotions. Given self-awareness disturbances in patients with first-rank symptoms (FRS), we hypothesized that these patients would show abnormal social behaviours. In this study, we examined the social interactive skills of patients with first-episode psychosis during an interview, together with changes in performance over time. METHOD: We analysed previously unreported data from 227 patients with first-episode psychosis (90 with, and 137 without, FRS) who took part in the WHO multicentre study on the Determinants of Outcome of Severe Mental Disorders. They were assessed on the Psychological Impairment Rating Schedule (PIRS) and examined again after 2 years. RESULTS: A principal component analysis on the Psychosocial Impairment Rating Schedule produced two factors (interactive skills; withdrawal from interactions). Patients with FRS showed greater impairments in the domain linked to 'interactive skills', which remained 2 years after the first experience of a psychotic illness. These findings were not explained by clinical characteristics, or presence of non-FRS delusions. CONCLUSION: Self-awareness deficits, as indexed by the FRS symptom cluster, are linked to deficits in social interactive behaviours. These abnormalities are indicative of 'social dysmetria' in this group, which involves difficulties conveying motor aspects of behaviours, volition and affect to facilitate mutual communication. These findings point to the utility of behavioural assessment scales in clinical and research settings.

African swine fever virus.

African swine fever virus (ASFV) is a large, intracytoplasmically-replicating DNA arbovirus and the sole member of the family Asfarviridae. It is the etiologic agent of a highly lethal hemorrhagic disease of domestic swine and therefore extensively studied to elucidate the structures, genes, and mechanisms affecting viral replication in the host, virus-host interactions, and viral virulence. Increasingly apparent is the complexity with which ASFV replicates and interacts with the host cell during infection. ASFV encodes novel genes involved in host immune response modulation, viral virulence for domestic swine, and in the ability of ASFV to replicate and spread in its tick vector. The unique nature of ASFV has contributed to a broader understanding of DNA virus/host interactions.