Prevalence of antibodies against orthopoxviruses among residents of Likouala region, Republic of Congo: evidence for monkeypox virus exposure

Monkeypox virus is a zoonotic orthopoxvirus (OPX) of west and central sub-Saharan Africa. We conducted a cross-sectional serosurvey in Likouala region, Republic of Congo to assess exposure to OPX. Whole blood was collected using Nobuto blood filter strips (NBFS). Titers of IgM and IgG to OPX were assessed using an enzyme-linked immunosorbent assay. Demographic and clinical characteristics were compared with serostatus using the chi-square test or Fisher's exact test. Multivariate logistic regression was performed to evaluate factors for independent association with serostatus. A total of 994 specimens were analyzed; the overall seroprevalence for OPX IgM was 1.7%. Age < 25 years reduced the likelihood of OPX exposure, and persons living in Ngangania village had independently higher odds (odds ratio = 33.5, 95% confidence interval = 7.2-166). Blood collection for serosurveys using NBFS is feasible and practical. Adult activities such as hunting and carcass preparation may play an important role in exposure to Monkeypox virus.     

Impact of female sex on death and bleeding after fibrinolytic treatment of myocardial infarction in GUSTO V

BACKGROUND: Women with acute myocardial infarction are more likely than men to experience reinfarction, bleeding, or death. This difference has been hypothesized to be due to older age, treatment delay, and comorbidities in women. Use of diagnostic and therapeutic modalities may also differ. There is controversy regarding whether female sex is an independent risk factor for death and/or bleeding. METHODS: The GUSTO (Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes) V Investigators studied standard-dose reteplase vs standard-dose abciximab plus half-dose reteplase in patients with myocardial infarction. RESULTS: Women were older and more often had diabetes mellitus and hypertension. Angiography and percutaneous coronary intervention were less frequent in women. Death (9.8% vs 4.4% at 30 days; odds ratio [OR], 2.00; 95% confidence interval, 1.59-2.53; P < .001) and bleeding (6.4% vs 2.5%; OR, 1.31; 95% confidence interval, 1.18-1.45; P < .01) were more common in women. There was no association between treatment assignment and death in either sex; bleeding was more common in both sexes receiving combination therapy. Female sex was independently associated with mortality. After Killip class greater than 1 (OR, 4.7), female sex (OR, 2.0) was the strongest correlate of death. Female sex was independently associated with bleeding for both treatments. CONCLUSIONS: Female sex is independently associated with death and bleeding complications among fibrinolytic-treated patients with myocardial infarction. There remains a sex differential in the use of angiography and, therefore, percutaneous coronary intervention after fibrinolysis. Further research will determine what mediates excess risk in women.     

Vascular endothelial growth factor promoter-based conditionally replicative adenoviruses for pan-carcinoma application

Treatment of advanced lung cancer is one of the major challenges in current medicine because of the high morbidity and mortality of the disease. Advanced stage lung cancer is refractory to conventional therapies and has an extremely poor prognosis. Thus, new therapeutic approaches are needed. Lung tumor formation depends on angiogenesis in which the vascular endothelial growth factor (VEGF) produced by cancer cells plays a pivotal role. Neutralizing VEGF with a soluble VEGF receptor suppresses tumor growth; however, the anticancer effect with this therapy is weakened after the intratumoral vascular network is completed. In this study, we turned the expression of VEGF by tumors to therapeutic advantage using a conditionally replication-competent adenovirus (CRAd) in which the expression of E1 is controlled by the human VEGF promoter. This virus achieved good levels of viral replication in lung cancer cells and induced a substantial anticancer effect in vitro and in vivo. As a further enhancement, the cancer cell killing effect was improved with tropism modification of the virus to express the knob domain of Ad3, which improved infectivity for cancer cells. These VEGF promoter-based CRAds also showed a significant cell killing effect for various types of cancer lines other than lung cancer. Conversely, the VEGF promoter has low activity in normal tissues, and the CRAd caused no damage to normal bronchial epithelial cells. Since tumor-associated angiogenesis via VEGF signalling is common in many types of cancers, these CRAds may be applicable to a wide range of tumors. We concluded that VEGF promoter-based CRAds have the potential to be an effective strategy for cancer treatment.     

Disparate host response and donor survival after the transplantation of mesenchymal or neuroectodermal cells to the intact rodent brain

BACKGROUND: To circumvent ethical and legal complications associated with embryonic cell sources, investigators have proposed the use of nonneural donor sources for use in neural transplantation strategies. Leading candidate sources include autologous marrow stromal cells (MSCs) and fibroblasts, which are mesodermal derivatives. However, we recently reported that MSCs transplanted to the adult brain are rapidly rejected by an inflammatory response. Whether extrinsic variables or intrinsic mesenchymal traits stimulated inflammation and rejection is unknown. To determine the future utility of these cells in neural transplantation, we have now performed a systematic analysis of MSC transplantation to the brain. METHODS: To examine the effects of extrinsic variables on transplantation, green fluorescent protein (GFP)-expressing rat MSCs, cultured under distinct conditions, were transplanted stereotactically to the normal adult rat striatum, and donor survival and the host response was compared. To examine whether intrinsic donor traits promoted rejection, 50,000 GFP-expressing rat MSCs, fibroblasts, or astrocytes were transplanted stereotactically to the adult rat striatum and graft survival and the host response was compared. RESULTS: Irrespective of preoperative culture conditions, MSCs elicited an inflammatory response and were rejected by 14 days, indicating acute rejection was not mediated by culture conditions. Comparison of MSC, fibroblast, or astrocyte grafts revealed that mesenchymal derivatives, MSCs and fibroblasts, elicited an inflammatory response and were rapidly rejected, whereas neuroectodermal astrocytes demonstrated robust survival in the absence of inflammation. CONCLUSIONS: Our findings suggest that intrinsic characteristics of mesenchymal cells may stimulate host inflammation, and thus may not represent an ideal donor source for transplantation to the adult brain.     

Alpha-glucosidase inhibitor proteins from Sesbania grandiflora flowers

Two alpha-glucosidase inhibitors were isolated from the flowers of Sesbania grandiflora and named SGF60 and SGF90. The procedure involved extraction with phosphate buffer, precipitation with ammonium sulfate, ion-exchange chromatography on DEAE-cellulose and gel filtration on Superdex-200. These proteins were identified by using tandem mass spectrometry. The results show partial amino acid sequences of SGF60 similar to p27SJ, a protein from Hypericum perforatum found to suppress HIV-1 gene expression. SGF90 matched a beta-glucosidase from Arabidopsis thaliana.     

A review of heat shock protein induction following cerebellar injury

Exposure of cells to stressful environments such as heat shock, ischemia, trauma and disease, induces the cellular expression of heat shock proteins (Hsps). Since the discovery of heat shock proteins in the early 1960s, efforts to understand their function in both stressed and non-stressed cells have remained the focus of a vast collection of researchers. Post-injury heat shock protein induction is believed to identify regions of reversible cell injury as well as contribute to repair and protective mechanisms following stress. With the role of cerebellum expanding to include a number of cognitive processes in addition to contributing to motor coordination, research contributions that further our understanding of cerebellar repair strategies following injury are significant. Following cellular stress, heat shock protein expression was observed in both neuronal and glial cell populations in the injured cerebellum. Specifically, Hsp27 expression was localized primarily in Purkinje cells and glial cells within the injured cerebellum, whereas Hsp72 induction was more prominent in the granule cell layer of the cerebellum. Thus, there appears to be a preferential expression of different families of heat shock proteins in different cell populations in the injured cerebellum. There are also distinct post-injury time frames of induction for each family of heat shock protein, emphasizing differences in cellular functional requirements for each family of heat shock protein. Hsp27 was expressed immediately following injury and continued up to 20 days post-injury whereas Hsp72 was expressed immediately following injury and disappeared by 4 days post-injury, suggesting the latter contributes to processes involved in the initial repair of injured cells. This review discusses heat shock protein induction patterns in both in vivo and in vitro cerebellar injury models and provides suggestions as to the functional role of heat shock proteins in the injured cerebellum.     

Todd, Faraday, and the electrical basis of brain activity

Robert Bentley Todd (1809-60) was the UK's first eminent neurologist and neuroscientist. An anatomist, physiologist, and clinical scientist with an interest in the nervous system, he was the first to confirm the electrical basis of brain activity in the 1840s. He was influenced by his contemporary, Michael Faraday at the Royal Institution, and by two colleagues at King's College, John Daniell and Charles Wheatstone, who were also working at the cutting edge of electrical science. Todd conceived of nervous polarity (force) generated in nervous centres and compared this with the polar force of voltaic electricity developed in the galvanic battery. He brilliantly foresaw each nerve vesicle (cell) and its related fibres (ie, neuron) as a distinct apparatus for the development and transmission of nervous polarity. Epilepsy was the result of periodic unnatural development of nervous force leading to the "disruptive discharge" described by Faraday. Faraday, who studied animal electricity in the Gymnotus (electric eel), and Todd saw nervous polarity as a higher form of interchangeable energy.     

Women's experiences of increasing subjective well-being in CFS/ME through leisure-based arts and crafts activities: a qualitative study

PURPOSE: To understand the meanings of art-making among a group of women living with the occupational constraints and stigma of CFS/ME. The study explored their initial motives for art-making, and then examined how art-making had subsequently influenced their subjective well-being. METHOD: Ten women with CFS/ME were interviewed; three provided lengthy written accounts to the interview questions. FINDINGS: Illness had resulted in devastating occupational and role loss. Participants took many years to make positive lifestyle changes. Art-making was typically discovered once participants had accepted the long-term nature of CFS/ME, accommodated to illness, and reprioritized occupations. Several factors then attracted participants specifically to art-making. It was perceived as manageable within the constraints of ill-health. Participants also tended to be familiar with craft skills; had family members interested in arts and crafts, and some desired a means to express grief and loss. Once established as a leisure activity, art-making increased subjective well-being mainly through providing increased satisfaction in daily life, positive self-image, hope, and contact with the outside world. Participants recommended provision of occupational/recreational counselling earlier in the illness trajectory. CONCLUSIONS: Creative art-making occurred as part of a broader acceptance and adjustment process to CFS/ME, and allowed some psychological escape from a circumscribed lifeworld.     

Lactate profiles as a resuscitation assessment tool in a rat model of battlefield hemorrhage resuscitation

Time profiles of arterial lactate concentrations have been proposed as markers for both the degree of physiological derangement during shock and effectiveness of clinical resuscitation, but have not been evaluated for use in short-term experimental protocols. We developed two quantitative mixed models of sequential arterial lactate concentrations to evaluate competing low-volume (<4 mL/kg) battlefield resuscitation therapies in a rat model of acute severe hemorrhagic shock: a simple linear additive model and a nonlinear mechanistic model that described lactate profiles in a continuous trajectory with a defined turning point. Data were obtained during a study evaluating a novel hemoglobin polymer (OxyVita) in a cocktail of hypertonic saline and Hextend as an alternative to standard Hextend. Fluids were either infused by titration to a mean systolic pressure of 60 mmHg or as a single bolus. Parameter estimates derived from both models were assessed for evidence of treatment efficacy and as indicators of short-term survival. A cocktail of hypertonic saline and Hextend was superior to standard Hextend in enhancing survival; however, lactate profiles did not differ between treatments. Regardless of resuscitation regimen, animals surviving to at least 60 min posthemorrhage can be discriminated from nonsurvivors by significantly lower peak lactates (a difference of at least 3 mM; P < 0.001), and all survivors exhibited a decline in lactate with resuscitation. Sequential measurements of lactate over relatively short time frames during resuscitation are of value in assessing both response to resuscitation and short-term mortality.     

Automated versus manual blood pressure measurement: a randomized crossover trial

This study evaluated the accuracy and reliability of the Dinamap 8100 automated blood pressure machine against three internationally recognized criteria. Systolic and diastolic blood pressures were taken concurrently by two nurses using the automated machine and a manual sphygmomanometer. Results demonstrated agreement between automated and manual readings on one set of criteria for both systolic and diastolic pressures, and support for systolic readings only on one other criterion. Comparison of mean differences between automated and manual measures showed the automated machine consistently under-read both systolic and diastolic blood pressures. The conclusion from this study was that the Dinamap 8100 machine can be used with some degree of confidence to assess systolic blood pressures in a general population of adult hospital inpatients, but with caution when taking diastolic readings.