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Content analysis of 463 student surveys was used to uncover the nature and prevalence of bullying behaviors within volunteer middle schools across the Southern United States. After completing a training to understand and distinguish between bullying and cyberbullying, students in grades six through eight from three southern states completed surveys and were given the opportunity to participate in face-to-face interviews. Of those surveyed, over 37% reported being bullied either face-to-face or online, with under 31% reporting bullying incidents to adults. Additional findings addressing the nature of bullying, as well as factors related to student reporting, are discussed.

Cytomegalovirus(CMV) persistently infects more than 60% of the worldwide population. In immunocompetent hosts, it has been implicated in several diseases, including cardiovascular disease, possibly through the induction of inflammatory pathways. Cardiovascular risk factors promote an inflammatory phenotype in the microvasculature long before clinical disease is evident. This study determined whether CMV also impairs microvascular homeostasis and synergizes with hypercholesterolemia to exaggerate these responses. Intravital microscopy was used to assess endothelium-dependent and -independent arteriolar vasodilation and venular leukocyte and platelet adhesion in mice after injection with either mock inoculum or murine CMV (mCMV). Mice were fed a normal (ND) or high-cholesterol (HC) diet beginning at 5 weeks postinfection (p.i.), or a HC diet for the final 4 weeks of infection. mCMV-ND mice exhibited impaired endothelium-dependent vasodilation versus mock-ND at 9 and 12 weeks and endothelium-independent arteriolar dysfunction by 24 weeks. Transient mild leukocyte adhesion occurred in mCMV-ND venules at 7 and 21 weeks p.i. HC alone caused temporary arteriolar dysfunction and venular leukocyte and platelet recruitment, which were exaggerated and prolonged by mCMV infection. The time of introduction of HC after mCMV infection determined whether mCMV+HC led to worse venular inflammation than either factor alone. These findings reveal a proinflammatory influence of persistent mCMV on the microvasculature, and suggest that mCMV infection enhances microvasculature susceptibility to both inflammatory and thrombogenic responses caused by hypercholesterolemia.

Human T cell leukemia virus type 1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) is characterized by the generation of an intense CTL cell response directed against the viral transactivator protein Tax. In addition, patients diagnosed with HAM/TSP exhibit rapid activation and maturation of dendritic cells (DC), likely contributing to the robust, Tax‐specific CTL response. In this study, extracellular Tax has been shown to induce maturation and functional alterations in human monocyte‐derived DC, critical observations being confirmed in freshly isolated myeloid DC. Tax was shown to promote the production of proinflammatory cytokines and chemokines involved in the DC activation process in a dose‐ and time‐dependent manner. Furthermore, Tax induced the expression of DC activation (CD40, CD80, and CD86) and maturation (CD83) markers and enhanced the T cell proliferation capability of DC. Heat inactivation of Tax resulted in abrogation of these effects, indicating a requirement for the native structure of Tax, which was found to bind efficiently to the DC membrane and was internalized within a few hours, suggesting that extracellular Tax may possess an intracellular mechanism of action subsequent to entry. Finally, inhibitors of cellular signaling pathways, NF‐κB, protein kinase, tyrosine kinase, and phospholipase C, were shown to inhibit Tax‐mediated DC activation. This is the first study reporting the immunomodulatory effects of extracellular Tax in the DC compartment. These results suggest that DC, once exposed to Tax by uptake from the extracellular environment, can undergo activation, providing constant antigen presentation and costimulation to T cells, leading to the intense T cell proliferation and inflammatory responses underlying HAM/TSP.

Equine herpesvirus 1 (EHV-1)-specific antibody-secreting cells (ASC) isolated from the lung and spleen of mice at 12 months after immunization with attenuated EHV-1 KyA, heat-killed KyA, or recombinant viral glycoprotein D (rgD) assessed by ELISPOT showed a three- to fivefold increase in three immunoglobulin isotypes at 3 days post-challenge with pathogenic EHV-1 RacL11 as compared to control mice. ELISPOT assays demonstrated a high frequency of cells secreting proinflammatory tumor necrosis factor-alpha (TNF-α), interferon gamma (IFN-γ), and interleukin 4 (IL-4) in the lungs in response to infection with KyA or RacL11 or immunization with rgD. Cytokine production elicited by EHV-1 KyA or RacL11 infection revealed similar frequencies of EHV-1-specific IFN-γ and IL-4 spot forming cells in the mediastinal lymph nodes and spleen. However, KyA induced significantly greater amounts of IFN-γ producing cells in the lungs than did RacL11. Intranasal immunization with KyA or rgD induced long-term immunity that provided protection against pathogenic EHV-1 challenge infection at 12 months post-immunization. Overall, the data indicate that immunization with infectious KyA or rgD induces significant levels of cytokines, virus-specific ASC in the lungs and spleen, and long-term virus specific B-cell responses.

Inflammatory bowel disease (IBD) is associated with Th1/Th2 cytokine dysregulation, leukocyte extravasation, and tissue edema, but the mechanisms for cytokine-mediated vascular dysfunction are not understood. To investigate how cytokines might control edema in IBD, we determined vascular permeability and IFN-γ expression in two models of murine colitis: SCID mice reconstituted with CD45RBhighT-lymphocytes (CD45RBhigh/SCID mice), and interleukin-10 gene deficient (IL-10−/−) mice. We also investigated the in vitroeffects of IFN-γ and IL-10 on human endothelial solute barrier and junction protein expression. Vascular permeability in CD45RBhigh/SCID and IL-10−/−mice was quantified using tissue 131I-IgG accumulation. The IFN-γ message was quantified using the ribonuclease protection assay. Endothelial barrier integrity in vitrowas measured by transmonolayer electrical resistance, and junctional proteins were examined by immunoblotting and fluorescence microscopy. Both CD45RBhigh/SCID and IL-10−/−mice exhibit enhanced colonic microvascular leakage and IFN-γ message levels compared to their respective controls. In vitro,IFN-γ also reduced endothelial barrier (monolayer electrical resistance, increased albumin permeability) and reduced tight junction (occludin) expression and staining. These effects were reversed by pretreatment of monolayers with IL-10. Therefore, in vivoIFN-γ and IL-10 may modulate microvascular leakage in IBD partly by controlling the expression of intestinal endothelial tight junctional proteins.

ABSTRACTThe CBA mouse model was used to investigate the immunopathology induced in the lung by the pathogenic equine herpesvirus 1 (EHV-1) strain RacL11 in comparison to infection with the attenuated vaccine candidate strain KyA. Intranasal infection with KyA resulted in almost no inflammatory infiltration in the lung. In contrast, infection with the pathogenic RacL11 strain induced a severe alveolar and interstitial inflammation, consisting primarily of lymphocytes, macrophages, and neutrophils. Infection with either EHV-1 strain resulted in the accumulation of similar numbers and ratios of CD4 and CD8 T lymphocytes in the lung and bronchoalveolar lavage (BAL) fluid. Further analysis of these T-cell populations revealed identical EHV-1-specific cytotoxic T-lymphocyte responses. RNase protection analysis of RNA isolated from the BAL fluid of RacL11-infected mice on day 3 postinfection revealed much higher levels of RNA specific for macrophage inflammatory protein 1a (MIP-1a), MIP-1ß, and MIP-2 than were observed for KyA-infected mice. Furthermore, significantly higher levels of transcripts specific for tumor necrosis factor alpha were induced on day 3 postinfection with RacL11 compared with KyA. These findings suggest that the early production of proinflammatory beta chemokines plays a major role in the severe, most often lethal, respiratory inflammatory response induced by the pathogenic EHV-1 strain RacL11.

The antibody responses of CBA/J mice infected intranasally (i.n.) with either the attenuated KyA strain or the pathogenic RacL11 strain of equine herpesvirus 1 (EHV-1) or immunized with recombinant glycoprotein D (rgD) were investigated using the ELISPOT assay to measure EHV-1-specific antibody-secreting cells (ASC) in the regional lymphoid tissue of the respiratory tract. IgG, IgA, and IgM ASC specific for EHV-1 were detected in the mediastinal lymph nodes (MLN) and lungs 2 weeks after i.n. infection with EHV-1 strain KyA or RacL11, or immunization with heat-killed KyA or rgD. EHV-1-specific ASC were present in the MLN and lungs at 4 and 8 weeks, but declined in frequency by fivefold in the lung at 8 weeks. However, i.n. immunized (2 × 106pfu KyA or 50 μg rgD/mouse) mice infected at 8 weeks with pathogenic EHV-1 RacL11 resisted challenge and showed eight- and tenfold increases in MLN ASC and lung ASC, respectively, by 3 days after challenge. In contrast to the intranasal route of immunization, intraperitoneal immunization yielded ASC frequencies in the MLN and lungs that were only slightly above those of nonimmunized control mice. These data indicate that immunization with infectious or heat-killed EHV-1 KyA, or rgD, induces significant levels of virus-specific ASC both in the MLN and lungs, a specific memory B-cell response, and long-term protective immunity. The finding that the numbers of ASC induced by the pathogenic strain versus the attenuated strain of EHV-1, which were virtually identical, indicated that the ability to generate a B-cell response is independent of and does not contribute to EHV-1 virulence.

The aims of this review are to: (a) describe and interpret structures in valley glaciers in relation to strain history; and (b) to explore how these structures inform our understanding of the kinematics of large ice masses, and a wide range of other aspects of glaciology. Structures in glaciers give insight as to how ice deforms at the macroscopic and larger scale. Structures also provide information concerning the deformation history of ice masses over centuries and millennia. From a geological perspective, glaciers can be considered to be models of rock deformation, but with rates of change that are measurable on a human time‐scale. However, structural assemblages in glaciers are commonly complex, and unraveling them to determine the deformation history is challenging; it thus requires the approach of the structural geologist. A wide range of structures are present in valley glaciers: (a) primary structures include sedimentary stratification and various veins; (b) secondary structures that are the result of brittle and ductile deformation include crevasses, faults, crevasse traces, foliation, folds, and boudinage structures. Some of these structures, notably crevasses, relate well to measured strain‐rates, but to explain ductile structures analysis of cumulative strain is required. Some structures occur in all glaciers irrespective of size, and they are therefore recognizable in ice streams and ice shelves. Structural approaches have wide (but as yet under‐developed potential) application to other sub‐disciplines of glaciology, notably glacier hydrology, debris entrainment and transfer, landform development, microbiological investigations, and in the interpretation of glacier‐like features on Mars. Glacier ice covers about 10% of Earth's land surface and has a profound influence on human activity. As ice continues to melt around the world in response to anthropogenic and natural global heating, the dynamics of glaciers and ice sheets are changing. As this review emphasizes, understanding glacier dynamics is achieved by investigating the brittle and ductile structures that characterize glaciers. The importance of this aspect of glaciology is increasingly being recognized, and draws on its close affinity with structural geology, although interaction between the disciplines to date has been limited. Brittle structures include crevasses, crevasse traces, and a wide variety of faults. Ductile structures include foliation (a layered structure that results from deformation), folds on many scales, and less universally known structures such as ogives and boudins. This review describes, illustrates, and explains the origin of these structures in terms of stress and strain. It also considers areas of controversy, unresolved issues, and offers pointers to future research. A more comprehensive understanding of glacier and ice sheet dynamics is needed to better predict their response to climate change, and ultimately their contribution to sea‐level rise. Structural glaciology can play a large part in this process. Glaciers and ice sheets display a wide range of structures that inform us about past and present ice dynamicsGlaciers reveal structures that are analogous to those in rocks that have deformed close to their melting point in the Earth's crustGlacier structures influence hydrology, glacial sedimentology and geomorphology, ice microbiology, and help the interpretation of landforms Glaciers and ice sheets display a wide range of structures that inform us about past and present ice dynamics Glaciers reveal structures that are analogous to those in rocks that have deformed close to their melting point in the Earth's crust Glacier structures influence hydrology, glacial sedimentology and geomorphology, ice microbiology, and help the interpretation of landforms

Class I MHC-restricted, HSV-1-specific CD8+cytolytic T lymphocyte (CTL) function is rarely detected in lymphocytes isolated directly from the lymph node draining the site of infection. However, culture in vitrofor 24 to 72 h in the absence of exogenous antigen results in the development of easily detectable levels of HSV-1-specific CTL effectors. The inability to detect virus-specific CTL in HSV-1-infected mice is not well understood. However, since the in vitroculture of HSV-1-immune lymphocytes results in the transition to CTL function, studies of the changes occurring to the CD8+T cell subpopulation may provide important insights into the development of virus-specific CTL. Therefore, the phenotypic changes taking place in the CD8+population of T cells from draining popliteal lymph nodes of HSV-1-infected C57BL/6 (B6) mice were investigated, focusing on changes in the expression of cell surface markers associated with T lymphocyte activation. The results demonstrate an increase in the percentage of CD8+T cells expressing the activation markers CD44 and CD25 in parallel with the acquisition of HSV-specific CTL effector function. Cytolytic function was found exclusively within the CD8+CD44hiCD25hifraction of cells in culture, but, surprisingly, was not detectable in CD8+CD44hiCD25loT cells. This suggested that the acquisition of high levels of the high-affinity IL-2 receptor was closely linked to cytolytic function and may define an important developmental stage in the transition from noncytolytic to cytolytic effector cell. In support of this, CD8+CD25hiT cells isolated from the regional lymph node exhibited direct ex vivocytolytic function, indicating that cytolytic effector cells were present in the lymph node, but must emigrate rapidly after attaining this level of differentiation.

The immune response to HSV infection in C57BL/6 mice includes a CTL population that recognizes the virion envelope glycoprotein gB. However, previous studies showed that CTL specific for other vital determinants were also responding to HSV infection. These studies demonstrate that an additional determinant is the HSV immediate-early protein ICP27. During the primary response, both gB- and ICP27-specific CTL were detected in the draining lymph node. In response to reinfection, ICP27-specific CTL were present early in the lymph node, while the appearance of gB-specific CTL activity was delayed. Analysis of the primary amino acid sequence of ICP27 predicted two potential K^b-binding epitopes, one of which sensitized uninfected cells for lysis by HSV-specific CTL. In addition, ICP27 epitope-specific CTL activity was detected in the splenic memory CTL pool. These results show that CTL which recognize different antigens may also exhibit differences in how they respond to HSV reinfection in vivo. Copyright 1995, 1999 Academic Press

Previous studies (C. C. Flowers and D. J. O'Callaghan, 1992, Virology190, 307-315) employed peptide-specific antibodies to identify the product of the glycoprotein D (gD) gene of equine herpesvirus 1 strain Kentucky A (KyA), gD polypeptides of 55 and 58 kDa were detected in EHV-1-infected L-M cells, and the 58-kDa protein was observed in the membrane fraction of EHV-1 virions. In this report, the kinetics of synthesis and processing of gD polypeptides are described. One-hour pulse-labeling of EHV-1-infected L-M cells revealed that gD proteins are first detected at 6 hr after infection and that maximal synthesis of gD occurs between 5 and 8 hr postinfection. gD polypeptides accumulate progressively with time of infection as shown by immunoprecipitation analysis of gD proteins. Pulse-chase analysis of gD revealed that the 55-kDa protein is a precursor to the 58-kDa species and that processing of all pulse-labeled precursor protein requires approximately 2.5 hr. Analysis of the carbohydrate content of gD proteins, as judged by their sensitivity to digestion with endoglycosidases, revealed that the 55-kDa 9D precursor contains high-mannose N-linked oligosaccharides, while the 58-kDa gD mature polypeptide possesses complex type oligosaccharides. Expression of the mature form of gD on the cell surface, as determined by fluorescent flow cytometric analysis, is delayed compared to the accumulation of the mature form of gD within the cell. The gD ORF encodes a potential protein of 442 amino acids but analysis of the translated sequence of gD indicated that the gD polypeptide is 392 amino acids, a size predicted by previous mapping of the transcription start site of the gD mRNA. Coupled in vitrotranscription/translation of a pGEM-3Z construct containing the 392-amino-acid gD ORF, in the absence or presence of canine pancreatic microsomes, demonstrated that the 43-kDa gD polypeptide undergoes processing in vitro. These studies demonstrate that the EHV-1 strain KyA gD is processed in a fashion similar to that of the gD proteins of other alphaherpesviruses.

It is well established that T lymphocytes play a critical role in the control and clearance of herpes simplex virus (HSV) infections. However, the role of the CD4⁺ and CD8⁺ T cell subsets in the recovery process has not been clearly elucidated. Cutaneous HSV infection of the footpad tissue of C57BL/6 (B6) mice provides a model to determine the relative contribution of each T cell subset during the important early phase of the response to infection. In this study, we observed that the elimination of mature peripheral T lymphocytes by depletion in vivo with a combination of CD4- and CD8-specific monoclonal antibodies prevented recovery from acute infection in this model. However, mice depleted of either the CD4⁺ or CD8⁺ subpopulation alone recovered completely, with only a slight delay in the total clearance of infectious virus, Adoptive transfer studies revealed that lymph node cells from donor mice selectively depleted of either CD4⁺ or CD8⁺ T cell subset in vivo, or from normal donors selectively depleted in vitro, were able to mediate recovery. As CD4-depleted mice fail to generate a CD8⁺ T cell-mediated cytolytic T lymphocyte (CTL) response, this suggested that the control of cutaneous HSV infections may be mediated by a cytokine-dependent mechanism common to both the CD4⁺ and CD8⁺ T cell subpopulations. It was subsequently found that the neutralization of IFN-γ in vivo diminished the ability of mice to clear infectious HSV from the skin, and treatment with anti-IFN-γ in vivo ablated the ability of transferred T cells to mediate recovery. These studies suggested that IFN-γ-mediated mechanisms play a critical role in the control of and recovery from acute cutaneous HSV infection. Copyright 1994, 1999 Academic Press

The aim of regional planning is to better manage, or at least influence, the development of a region in the interests of society. Unfortunately much regional planning activity often fails to clear the ‘plan formulation-implementation gap’. Much of the regional planning in Western Australia, with a few notable exceptions, is illustrative of this problem. But recent activity and initiatives in regional planning and development in and for the State suggest that there are some reasons to be hopeful. This paper provides an update on Federal initiatives (partly disturbed by the advent of the Coalition Government), and especially on State initiatives. The latter include, inter alia, the new Regional Development Commissions, Regional Planning activity for country regions, the State Planning Strategy and aspirations for regional empowerment, whole of government and whole of environment approaches. However the paper also identifies several unresolved problems which may limit the regional revival. A number of suggestions for possible ways forward conclude the paper.

ABSTRACTThe cytolytic T-lymphocyte (CTL) response to respiratory infection with equine herpesvirus 1 (EHV-1) in CBA (H-2k) mice was investigated. Intranasal (i.n.) inoculation of mice with the attenuated EHV-1 strain KyA resulted in the generation of a primary virus-specific CTL response in the draining mediastinal lymph nodes 5 days following infection. EHV-1-specific CTL could be restimulated from the spleen up to 26 weeks after the resolution of infection, indicating that a long-lived memory CTL population was generated. Depletion of CD8+T cells by treatment with antibody and complement prior to assay eliminated CTL activity from both primary and memory populations, indicating that cytolytic activity in this model was mediated by class I major histocompatibility complex-restricted, CD8+T cells. A single i.n. inoculation with KyA induced protective immunity against infection with the pathogenic EHV-1 strain, RacL11. The adoptive transfer of splenocytes from KyA-immune donors into sublethally irradiated recipients resulted in a greater than 250-fold reduction in RacL11 in the lung. The elimination of both CD4+and CD8+T cells from the transferred cells abrogated clearance of RacL11, while the selective depletion of either subpopulation alone had little effect. These results suggested that both lymphocyte subpopulations contribute to viral clearance, with either subpopulation alone being sufficient.

ABSTRACTA low-molecular-weight recombinant Brucella abortusprotein reactive with antibodies from a variety of naturally and experimentally infected hosts and T lymphocytes from experimentally infected mice was identified and given the designation BA14K. The gene encoding BA14K was cloned and characterized, and the predicted amino acid sequence of this immunoreactive protein showed no significant homology with previously described proteins. Sequences homologous to the cloned fragment encoding BA14K were identified by Southern blot analysis of genomic DNAs from representatives of all of the currently recognized Brucellaspecies. Studies employing BA14K should contribute to our efforts to better understand the antigenic specificity of protective immunity to brucellosis.

Exercise is critical for health maintenance in late life. The COVID-19 shelter in place and social distancing orders resulted in wide-scale interruptions of exercise therapies, placing older adults at risk for the consequences of decreased mobilization. The purpose of this paper is to describe rapid transition of the Gerofit facility-based group exercise program to telehealth delivery. This Gerofit-to-Home (GTH) program continued with group-based synchronous exercise classes that ranged from 1 to 24 Veterans per class and 1 to 9 classes offered per week in the different locations. Three hundred and eight of 1149 (27%) Veterans active in the Gerofit facility-based programs made the transition to the telehealth delivered classes. Participants’ physical performance testing continued remotely as scheduled with comparisons between most recent facility-based and remote testing suggesting that participants retained physical function. Detailed protocols for remote physical performance testing and sample exercise routines are described. Translation to remote delivery of exercise programs for older adults could mitigate negative health effects.

Objectives:A case is described in which squamous cell carcinoma was found during surgery for a recurrent pharyngeal pouch previously treated by endoscopic stapling. A search of the English language literature suggests this is the first reported case of a carcinoma developing in a pharyngeal pouch previously treated by endoscopic stapling.

A 20-year-old woman underwent cholecystectomy and common bile duct exploration. Seven days later, T-tube cholangiography showed two stones retained in a developmentally anomalous cystic duct stump. She was treated with thrice-daily flushings of large amounts of saline through the T tube, and after 7 days of treatment the biliary system was free of stones. The conditions necessary for successful non-operative management of retained cystic duct stones are discussed.

The author discusses the decision of the Iowa Supreme Court on the financial records of film companies receiving tax incentives which should be released to the public.

The resistance of cytotoxic T cells (Tc) to CSA may be related to the way they handle purines such as Ado. Ado has previously been shown to be toxic to Tc. We tested the effect of CSA, Ado, and the ADA inhibitor EHNA on the cytotoxicity of IL-2 dependent cloned Tc cells derived from C57/BL6 mice directed against syngeneic targets bearing SV40 antigen. No effect was seen if Tc were treated only with Ado 10-3M, EHNA 10-3M or CSA 10 ug/ml or 25 ug/ml.Significant inhibition of cytotoxicity occurred when Ado, EHNA, and CSA (25 ug/ml) were combined. Mild inhibition of cytotoxicity occurred when Ado was combined with EHNA. Marked inhibition occurred if Ado was added. These data suggest that if ADA is inhibited, CSA can potentiate the toxicity of Ado to cytototoxic T cell function. This may have relevance to antirejection therapy in organ transplantation.