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Youth with severe emotional and behavioral problems receiving services in public behavioral health systems have strengths that are understudied in research and underutilized in practice. This study explores four alternative strategies (individual item scores, the number of "actionable" strengths, subscales, and a total composite) for summarizing the strengths of youth assessed with the Child and Adolescent Needs and Strengths (CANS) in a large, urban, public behavioral health system. The paper examines whether these summarization strategies produce divergent understandings of the prevalence of strengths across gender, age, and racial groups. Analyses suggest that youth enter this system with high levels of strengths. There are few group differences in strengths across the diverse summarization strategies. Though the practice-preferred method of using individual strengths items provides the most interpretable information about strengths, the aggregation strategies may be useful for programs and systems. Implications for policy and practice are discussed.

Bortezomib-based induction followed by autologous stem cell transplantation is a common treatment for multiple myeloma (MM). Stem cell (SC) mobilization with granulocyte-colony stimulating factor (G-CSF) alone has become an alternative to G-CSF combined with chemotherapeutic agents. This study aimed to compare the efficacy of the two mobilization modalities following induction with a uniform regimen containing bortezomib, cyclophosphamide and dexamethasone (VCD). We retrospectively evaluated results of SC mobilization using either G-CSF alone or combined with high-dose cyclophosphamide (HD-CY) in MM patients after VCD induction. The primary endpoints of the study were engraftment and mobilization-associated toxicity. Parameters of stem cell collection, transplantation and engraftment were assessed. Data of 92 patients were analyzed [56 (61%) mobilized with HD-CY + G-CSF and 36 (39%) with G-CSF only]. HD-CY + G-CSF provided a higher number of CD34 + cells (15.9 vs 8.1 × 10 6 /kg, p = 0.001) with fewer apheresis sessions. However, while no adverse events were observed in patients receiving G-CSF alone, nine patients (16%) receiving HD-CY + G-CSF developed neutropenic fever requiring hospitalization. Although a greater number of cells was transplanted following mobilization with HD-CY + G-CSF, neutrophil and platelet engraftment and duration of transplant-related hospitalization were similar in both cohorts. G-CSF alone provided a sufficient SC amount, without exposing patients to additional toxicity. While HD-CY + G-CSF resulted in a superior SC yield in MM patients induced with VCD, this advantage should be balanced against adverse effects of this mobilization regimen.

Arrival of encephalitogenic T cells at inflammatory foci represents a critical step in development of experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. EBI2 and its ligand, 7α,25-OHC, direct immune cell localization in secondary lymphoid organs. CH25H and CYP7B1 hydroxylate cholesterol to 7α,25-OHC. During EAE, we found increased expression of CH25H by microglia and CYP7B1 by CNS-infiltrating immune cells elevating the ligand concentration in the CNS. Two critical pro-inflammatory cytokines, interleukin-23 (IL-23) and interleukin-1 beta (IL-1β), maintained expression of EBI2 in differentiating Th17 cells. In line with this, EBI2 enhanced early migration of encephalitogenic T cells into the CNS in a transfer EAE model. Nonetheless, EBI2 was dispensable in active EAE. Human Th17 cells do also express EBI2, and EBI2 expressing cells are abundant within multiple sclerosis (MS) white matter lesions. These findings implicate EBI2 as a mediator of CNS autoimmunity and describe mechanistically its contribution to the migration of autoreactive T cells into inflamed organs., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Alzheimer's disease (AD) is associated with the accumulation of β-amyloid (Aβ) as senile plaques in the brain, thus leading to neurodegeneration and cognitive impairment. Plaque formation depends not merely on the amount of generated Aβ peptides, but more importantly on their effective removal. Chronic infections with neurotropic pathogens, most prominently the parasite Toxoplasma (T.) gondii, are frequent in the elderly, and it has been suggested that the resulting neuroinflammation may influence the course of AD. In the present study, we investigated how chronic T. gondii infection and resulting neuroinflammation affect plaque deposition and removal in a mouse model of AD., Results: Chronic infection with T. gondii was associated with reduced Aβ and plaque load in 5xFAD mice. Upon infection, myeloid-derived CCR2(hi) Ly6C(hi) monocytes, CCR2(+) Ly6C(int), and CCR2(+) Ly6C(low) mononuclear cells were recruited to the brain of mice. Compared to microglia, these recruited mononuclear cells showed highly increased phagocytic capacity of Aβ ex vivo. The F4/80(+) Ly6C(low) macrophages expressed high levels of Triggering Receptor Expressed on Myeloid cells 2 (TREM2), CD36, and Scavenger Receptor A1 (SCARA1), indicating phagocytic activity. Importantly, selective ablation of CCR2(+) Ly6C(hi) monocytes resulted in an increased amount of Aβ in infected mice. Elevated insulin-degrading enzyme (IDE), matrix metalloproteinase 9 (MMP9), as well as immunoproteasome subunits β1i/LMP2, β2i/MECL-1, and β5i/LMP7 mRNA levels in the infected brains indicated increased proteolytic Aβ degradation. Particularly, LMP7 was highly expressed by the recruited mononuclear cells in the brain, suggesting a novel mechanism of Aβ clearance., Conclusions: Our results indicate that chronic Toxoplasma infection ameliorates β-amyloidosis in a murine model of AD by activation of the immune system, specifically by recruitment of Ly6C(hi) monocytes and by enhancement of phagocytosis and degradation of soluble Aβ. Our findings provide evidence for a modulatory role of inflammation-induced Aβ phagocytosis and degradation by newly recruited peripheral immune cells in the pathophysiology of AD.

Course-based undergraduate research is known to improve science, technology, engineering, and mathematics student achievement. We tested "The Small World Initiative, a Citizen-Science Project to Crowdsource Novel Antibiotic Discovery" to see if it also improved student performance and the critical thinking of non-science majors in Introductory Biology at Florida Atlantic University (a large, public, minority-dominant institution) in academic year 2014-15. California Critical Thinking Skills Test pre- and posttests were offered to both Small World Initiative (SWI) and control lab students for formative amounts of extra credit. SWI lab students earned significantly higher lecture grades than control lab students, had significantly fewer lecture grades of D+ or lower, and had significantly higher critical thinking posttest total scores than control students. Lastly, more SWI students were engaged while taking critical thinking tests. These results support the hypothesis that utilizing independent course-based undergraduate science research improves student achievement even in nonscience students.

Abstarct: Semaphorin 3A (sema3A) plays a regulatory role in immune responses, mainly affecting the activation of regulatory T cells. It has been found to correlate with disease activity in rheumatoid arthritis and systemic lupus erythematosus (SLE). To investigate the expression of sema3A in patients with systemic sclerosis (SSc) compared to healthy controls and SLE disease controls and to correlate it with clinical characteristics, 27 SSc patients, 42 SLE patients and 28 healthy controls were enrolled. Serum level of sema3A was measured by ELISA, and expression of sema3A on regulatory T cells was evaluated by FACS analysis. SSc patients were evaluated for demographics, clinical manifestations, routine laboratory results, nailfold videocapillaroscopy, pulmonary function tests, echocardiograms, modified Rodnan skin score, and disease activity and severity scores. Serum levels of semaphorin 3A were lower in SSc compared to healthy controls 14.38 ± 5.7 versus 27.14 ± 8.4 ng/ml, p < 0.0001 and similar to SLE 15.7 ± 4.3 ng/ml. The expression of semaphorin 3A on regulatory T cells was also lower in SSc compared to healthy controls 61.7 ± 15.7 versus 88.7 ± 3. 7 % (p < 0.0001). Semaphorin 3A serum level inversely correlated with the duration of disease: r = -0.4, p = 0.036 and with low C4 level r = 0.66, p = 0.026. SCL-70 antibody positivity was associated with a lower semaphorin 3A level (difference in mean of 3.44, p = 0.06). Sema3A expression is low in SSc serum and more specifically on regulatory T cells. This may help explain the reduced activation of regulatory T cells in SSc.

The aim of the present study was to develop and validate an objective index for nociception level (NoL) of patients under general anesthesia, based on a combination of multiple physiological parameters. Twenty-five patients scheduled for elective surgery were enrolled. For clinical reference of NoL, the combined index of stimulus and analgesia was defined as a composite of the surgical stimulus level and a scaled effect-site concentration of opioid. The physiological parameters heart rate, heart rate variability (0.15-0.4 Hz band power), plethysmograph wave amplitude, skin conductance level, number of skin conductance fluctuations, and their time derivatives, were extracted. Two techniques to incorporate these parameters into a single index representing the NoL have been proposed: NoLlinear, based on an ordinary linear regression, and NoLnon-linear, based on a non-linear Random Forest regression. NoLlinear and NoLnon-linear significantly increased after moderate to severe noxious stimuli (Wilcoxon rank test, p < 0.01), while the individual parameters only partially responded. Receiver operating curve analysis showed that NoL index based on both techniques better discriminated noxious and non-noxious surgical events [area under curve (AUC) = 0.97] compared with individual parameters (AUC = 0.56-0.74). NoLnon-linear better ranked the level of nociception compared with NoLlinear (R = 0.88 vs. 0.77, p < 0.01). These results demonstrate the superiority of multi-parametric approach over any individual parameter in the evaluation of nociceptive response. In addition, advanced non-linear technique may have an advantage over ordinary linear regression for computing NoL index. Further research will define the usability of the NoL index as a clinical tool to assess the level of nociception during general anesthesia.

Introduction: Human parechoviruses (HPeV) have been recognized as the causative agents of central nervous system (CNS) infection of infants and young children in different parts of the world. The role of HPeV in CNS infection of Israeli infants and children is unknown., Objectives: To assess the detection rate of HPeV in enterovirus RT-PCR-negative cerebrospinal fluid (CSF) samples obtained during the years 2007-2009 from children 0-5 years old with suspected CNS infection or from very young infants with unexplained fever in four medical centers in Israel., Study Design: A total of 367 CSF samples were retrospectively tested for the presence of HPeV RNA using nested RT-PCR assay. Positive samples were further typed on the basis of molecular sequencing. Retrospective analysis of the medical charts was performed., Results: HPeV3 RNA was detected in CSF obtained between May and September 2008 in 13 patients, all of whom were <3 months old (3.5% of all CSFs; 11.3% of all infants<3 months in 2008). The HPeV-positive CSF samples were without pleocytosis. All HPeV3-positive patients recovered without obvious short term sequelae., Conclusion: HPeV infection could play an important role in summertime febrile/CNS illness in young infants during specific years with high HPeV activity. PCR detection of parechoviral RNA in CSF should be included in the diagnostic evaluation of fever or CNS infection of neonates and very young infants. The rapid identification of HPeV in CSF could curtail unnecessary empirical antibiotic treatment and shorten hospital stay in selected patients., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Study Objective: To develop a whole-night snore sounds analysis algorithm enabling estimation of obstructive apnea hypopnea index (AHI(EST)) among adult subjects., Design: Snore sounds were recorded using a directional condenser microphone placed 1 m above the bed. Acoustic features exploring intra-(mel- cepstability, pitch density) and inter-(running variance, apnea phase ratio, inter-event silence) snore properties were extracted and integrated to assess AHI(EST)., Setting: University-affiliated sleep-wake disorder center and biomedical signal processing laboratory., Patients: Ninety subjects (age 53 ± 13 years, BMI 31 ± 5 kg/m(2)) referred for polysomnography (PSG) diagnosis of OSA were prospectively and consecutively recruited. The system was trained and tested on 60 subjects. Validation was blindly performed on the additional 30 consecutive subjects., Measurements and Results: AHI(EST) correlated with AHI (AHI(PSG); r(2) = 0.81, P < 0.001). Area under the receiver operating characteristic curve of 85% and 92% for thresholds of 10 and 20 events/h, respectively, were obtained for OSA detection. Both Altman-Bland analysis and diagnostic agreement criteria revealed 80% and 83% agreements of AHI(EST) with AHI(PSG), respectively., Conclusions: Acoustic analysis based on intra- and inter-snore properties can differentiate subjects according to AHI. An acoustic-based screening system may address the growing needs for reliable OSA screening tool. Further studies are needed to support these findings.

Communities that undertake systems change in accordance with the system of care philosophy commit to creating new systems entities for children and adolescents with serious emotional disturbance. These new entities are values-based, voluntary, and cross-agency alliances that include formal child-serving entities, youth, and families. Describing the scope and intent of one such implementation of systems of care, a mental health administrator commented, "If we're going to change things, it has to be systemic" (B. Baxter, personal communication, December 2, 2005). This paper explores the concept of "systemic" in the context of systems of care. Systems theory is used to understand strategies of purposeful systems change undertaken by stakeholders in established system of care communities. The paper presents a conceptual model of systems change for systems of care that is grounded in data from a national study of system of care implementation (Research and Training Center for Children's Mental Health in Case Studies of system implementation: Holistic approaches to studying community-based systems of care: Study 2, University of South Florida, Louis de la Parte Florida Mental Health Institute, Research and Training Center for Children's Mental Health, Tampa, FL, 2004). The model is based on Soft Systems Methodology, an application of systems theory developed to facilitate practical action around systems change in human systems (Checkland in Systems thinking, systems practice, Wiley, Chichester, 1999). The implications of these findings to real world actions associated with systems change in systems of care are discussed.

Background: Antibiotic overuse is of great public health concern. This study assessed whether intervention among physicians and their treated population could achieve a sustained reduction in antibiotic use, specifically in classes known to promote antibiotic resistance among children in a community setting., Methods: We performed a cluster randomized controlled multifaceted trial among 52 primary care pediatricians and the 88,000 children registered in their practices. The intervention was led by local leaders and engaged the participating physicians. It included physician focus group meetings, workshops, seminars, and practice campaigns. These activities focused on self-developed guidelines, improving parent and physician knowledge, diagnostic skills, and parent-physician communication skills that promoted awareness of antibiotic resistance. The main outcome measure was the change in annual antibiotic prescription rates (APRs) of children treated by the intervention group physicians as compared with rates among those treated by control group physicians. The study comprised a 2-year pre-intervention period, a 3-year intervention period, and a 1-year follow-up period. Mixed-effect models were used to assess risk ratios to account for the clustered study design., Results: A decrease in the total APR among children treated by the intervention physicians compared with those treated by the control physicians was observed in the first intervention year (APR decrease among control physicians, 40%; APR decrease among intervention physicians, 22%; relative risk [RR], .76; 95% confidence interval [CI], .75-.78). This reduction crossed over all antibiotic classes but was most prominent for macrolides (macrolide prescription rate among control physicians, 58%; macrolide prescription rate among intervention physicians, 27%; RR, .58; 95% CI, .55-.62). The effect was sustained during the 4 following years. CONCLUSIONS. Multifaceted intervention that engages the physicians in an educational process is effective in reducing APRs and can be sustained., Clinical Trials Registration: NCT01187758., (© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.)

The aim of the present study was to estimate slow-wave activity (SWA), a marker of sleep homeostasis, in children with obstructive sleep apnoea (OSA) before and after adenotonsillectomy (AT) compared with untreated OSA children (comparison group). 14 children with OSA (mean ± sd age 6.4 ± 2.5 yrs; apnoea-hypopnoea index (AHI) 10.0 ± 10.3 events·h⁻¹) who underwent AT were consecutively recruited to the study. The comparison group comprised six retrospectively recruited children (age 5.4 ± 2.2 yrs; AHI 9.4 ± 7.6 events·h⁻¹) with OSA that did not undergo treatment. Electroencephalogram (derivation C3/A2) was analysed using spectral and waveform analysis to determine SWA energy and slow-wave slope. The same procedure was repeated 5.4 and 19 months later for the AT and comparison groups, respectively. AT improved respiration without a change in duration of sleep stages. Following AT, >50% elevation of SWA during the first two sleep cycles (p<0.01) and a more physiological decay of SWA across the night (p<0.0001) were noted. The slow-wave slope increased by >30% following AT (p<0.03). No significant changes were found in SWA in the comparison group. Sleep homeostasis is considerably impaired in pre-pubescent children with OSA. AT restores more physiological sleep homeostasis in children with OSA. SWA analysis may provide a useful addition to standard sleep-stage analyses in children with OSA.

Although uncommon, mycotic aneurysms in infants can be lethal because of the high risk of rapid expansion and rupture. Most catheter-associated mycotic aneurysms reported in the first year of life develop following umbilical artery catheterizations. We describe the sonographic detection of an early stage mycotic aneurysm in a 4-month-old following femoral artery catheterization complicated by methicillin-resistant Staphylococcus aureus (MRSA) septicemia. We also describe the sonographic and radiographic progression of this mycotic aneurysm before surgery.

This study examines changes in the characteristics of the homeless population before and after a period of extended economic expansion (1992-2002). Data from other sources suggest that, during this 10-year period, the size of the overall population of homeless persons may have declined slightly, though not significantly, both in the city studied and nationally. In-depth surveys of representative samples of homeless adults (N = 249 in 1992-94; N = 220 in 2000-2002) revealed significant differences in the composition of the homeless population across the time period, consistent with queuing theory. Persons experiencing homelessness after the expansion appeared to be a more "chronic," less readily employable population than those interviewed at the start of the expansion: Those interviewed after were older, spent more time living on the streets, had more health symptoms, were more likely to have a diagnosis of schizophrenia, and had more restricted social networks and social support. Policy, research, and service provision implications of the findings are discussed.

For more than 20 years, the system of care philosophy has comprised a central strategy of service reform in children's mental health at the federal, state, tribal, and local levels. System of care terminology has become widely used in many different service sectors but often without a shared understanding of what a system of care is. This manuscript, the feature article for this special issue of Evaluation and Program Planning, briefly traces the history of the system of care movement, discusses the more widely used definitions in the field of children's mental health, and offers an expanded version of the definition that takes into account the complex nature of systems of care. This manuscript was the product of a process used by the Case Studies of System Implementation research team to identify established system of care communities for inclusion in the research study. The purpose of this manuscript is to describe the process the research team engaged in while developing the revised definition and to open a public dialogue about how to characterize the essential properties of a system of care.

A novel method for screening obstructive sleep apnea syndrome (OSAs) based on nocturnal acoustic signal is proposed. Full-night audio signals from sixty subjects were segmented into snore, noise and silence events using semi-automatic algorithm based on Gaussian mixture models which achieves more than 90% (92%) sensitivity (specificity) and produces an average of 2,000 snores per subject. A classification into 3 groups is proposed for the diagnosis: comparison group - non-OSA subjects (apnea hypopnea index, AHI < 10), mild to moderate OSA (10 < AHI < 30) and severe OSA (AHI>30). A Bayes classifier was implemented, fed with five acoustic features, all correlated with the severity of the syndrome: (1) Inter Event Silence, which quantifies segments suspicious as apnea; (2) Mel Cepstability, measures the entire night stability of the spectrum, expressed using mel-frequency cepstrum; (3) Energy Running Variance, a criterion for the variation of the nocturnal acoustic pattern; (4) Apneic Phase Ratio, exploiting the finding that snores around apnea events expressing larger acoustic variation; and (5) Pitch Density. Correct classification of 92% for resubstitution method and 80% for 5-fold cross validation method was achieved. Moreover, in a case of two groups with a threshold of AHI=10, a sensitivity (specificity) of 96.5% (90.6%) and 87.5% (82.1%) for resubstitution and cross-validation respectively were obtained.

Busulphan (1, 4-bis [methanesulfonyl-y] butane) is a bi-functional alkylating agent that, in combination with cyclophosphamide, has been commonly used in conditioning regimens before hematological stem cell transplantation (HSCT) for nearly 20 years. Busulfan has a very narrow therapeutic index, and acute toxicity may be related to absorption and disposition of the drug and metabolites. Precise delivery of the oral formulation is compromised by erratic gastrointestinal absorption, particularly in infants and small children. An intravenous busulfan formula was approved nearly 40 years after the approval of the oral formulation. Busulfan levels expressed as the area under the concentration-time curve (AUC) higher than 1500 microM* minute were reported to increase the risk of developing veno-occlusive disease (VOD), while low levels may result in engraftment failure or disease relapse. VOD occurs in 11-40% of patients undergoing HSCT and is associated with death in 3.3% of patients. Measurement of individual plasma busulfan levels during oral or intravenous dosing to obtain an AUC is likely to provide the necessary elements to monitor the drug disposition, ensuring efficacy and preventing toxicity of patients undergoing HSCT. It is also important to consider the busulfan drug-drug interactions and adverse drug reactions that can develop during the therapeutic process. Busulfan therapeutic drug monitoring and dose-adjustment should be performed in specialized laboratories staffed by well-trained personnel.

Postnatal weight gain may predispose to the development of obesity during childhood. The aims of this study were to study the impact of weight gain during specific periods of the first year of life and of feeding patterns on the body mass index (BMI) of adolescents. Growth records during the first 24 months of life of 88 obese and 214 non-obese 12 year-old Arab children were evaluated. Birth weight and length were similar for obese and non-obese adolescents, while the rate of breastfeeding was significantly lower in the obese group (p < 0.01). Obese adolescents demonstrated a small yet significant accelerated weight gain at 4 (p = 0.002) and 12 (p = 0.01) months of age. Weight gain during the first 2 months of life and feeding pattern were independent predictors of BMI at the age of 12 years. Thus, early postnatal weight gain is associated with obesity in adolescence, while breastfeeding seems to have a protective effect.

The intestine is not considered to be a classic target tissue for insulin. Recent in vitro and in vivo experiments suggest that intestinal as well as systemic effects are observed following oral administration of insulin. Local effects include enhancement of intestinal growth, cell maturation, enzyme expression, gut adaptation after intestinal resection and reduction of intestinal permeability. Systemic effects, at least in animal models, include favorable effects on blood glucose and lipid profile and on the prevention of autoimmunity and attenuating the atherosclerotic process.

Host dependent idiosyncratic drug reactions, otherwise known as unpredictable type B reactions, are of a major concern in clinical practice and drug development. Hypersensitivity syndrome reactions are idiosyncratic in nature and may be induced by a variety of agents including antiepileptic drugs (AEDs). The AEDs hypersensitivity syndrome is a rare but potentially life-threatening syndrome that occurs after exposure to phenytoin, carbamazepine or phenobarbital. Phenobarbital, phenytoin and carbamazepine, have shown cross-reactivity; while, no evidence of cross reactivity between other antiepileptic drugs such as valproic acid, gabapentin or lamotrigine has been observed. True hypersensitivity reaction is a systemic disease defined by the triad of fever, skin eruption and multi-organ involvement that occurs 1-8 weeks after exposure to a drug. Because most reactions occur within two months of treatment initiation, it is likely that the true incidence of the syndrome is underestimated. It was hypothesized that reactive metabolite/s (RM) rather than the parent drug, is/are responsible for initiating the sequence of toxic and immunological events that culminate clinically in a drug hypersensitivity syndrome reaction. Cells that possess surface antigens for which T cells have specific receptors then present this antigen. Exanthemas are related to delayed T-cell hypersensitivity so it has been hypothesized that memory T cells might subsequently increase in number in the most severely affected cutaneous sites. To manage hypersensitivity syndrome successfully, the symptoms must recognized early, the use of the offending drug must be terminated immediately, and alternative antiepileptic medication should be prescribed. Currently, the diagnosis of AEDs-induced hypersensitivity syndromes is based on clinical grounds and on in vitro testing. In the field of pharmacogenetics, we bare witness to how effectively the combination of effective screening methods and understanding of the role of genetic polymorphisms play in the metabolic pathways of AEDs facilitating new therapies that allow scientists and physicians to better diagnose and treat patients.

Purpose: The aim of this survey was to characterize one urban Arab population who turns to complementary-alternative medicine (CAM)., Methods: Outpatient participants were selected randomly by their ethnical affiliation. The questionnaire was filled during patient visit to their assigned urban outpatient clinic. The answers to the first two questions determined whether the questionnaire was to be completed or not (if at least one answer was Yes, the questionnaire was completed)., Results: More males (19%) seek for CAM in the Arab group in comparison to more females in the Jewish population (27%). Fifteen per cent and 7% of the individuals in the Jewish and Arab groups who used CAM have academic education. Fifty-two per cent and 27% of the Jewish and Arab populations declared themselves seculars, 72% of the Arab individuals declared to be traditionalists-religious-orthodox in their believes in comparison to 47% in the Jewish population. Twenty-eight per cent and 0% in the Jewish and Arab populations, respectively, preferred a conventional doctor (MD) in CAM practice. More than 30% in both populations preferred CAM to be delivered in medical and nursing schools., Conclusions: Forty per cent and 31% in the Jewish and Arab groups experienced complementary medicine intervention at least once. When comparing people who used complementary medicine to those who did not, it is observed that the percentage of individuals holding academic degrees in the Jewish group is higher than in the Arab interviewed in the group utilizing complementary medicine. Traditionalist-religious-orthodox individuals seek more complementary medicine in the Arab population (72%) in comparison to 47% in the Jewish individuals. Only 17% of the Arab individuals and 19% in the Jewish group knew about the adverse reactions caused by CAM therapies. More than 30% in both ethnic groups were in favor of 'legalizing' complementary medicine.

Maternal milk feeding for more than 1 year is encouraged by many health care authorities. We demonstrate that human milk beyond 1 year of lactation had a small but significantly lower concentration of protein, calcium, and long-chain saturated fatty acids compared with human milk at 3 months after delivery.

Aims: To investigate the prevalence and clinical characteristics of heterozygotes of the glucokinase gene mutations G264S and IVS8+2 in the extended pedigree of two patients with permanent neonatal diabetes as a result of glucokinase deficiency (IVS8+2 homozygosity and IVS8+2/G264S compound heterozygosity)., Methods: Eighty-eight first, second and third degree family members of the two patients with permanent neonatal diabetes were genotyped. Clinical, laboratory and historical data were collected via chart reviews., Results: Thirty-one IVS8+2 and three G264S heterozygotes were identified. Of these, 18/34 (52.9%) had diabetes and 9/34 (26.5%) impaired fasting glucose (IFG), compared with 1/54 (1.9%) with diabetes and 2/54 (3.7%) with IFG in the non-carrier group. Odds ratio for heterozygotes was 70.4 (95% CI 16.9-293.5 and P < 0.001). Mean body mass index of heterozygotes (> 18 years of age) who had diabetes was 27.1 +/- 2.66, compared with 23.18 +/- 4.72 for heterozygotes with normal glucose levels (P < 0.05). While none of the non-carrier women had gestational diabetes, eight of the 10 heterozygotes developed gestational diabetes. Inheritance of a glucokinase mutation by the fetus from a carrier mother resulted in a significant reduction in birthweight (3600 +/- 570 vs. 2970 +/- 390 grams, P < 0.05)., Conclusions: These data support the association between carriage of GCK gene mutations, G264S and IVS8+2, and the development of diabetes, impaired fasting glucose and reduced birthweight. Moreover, in heterozygotes, a clear correlation between body mass index and the development of diabetes was observed. These findings underline the need for surveillance and prevention in individuals at risk.

Aortic valve disease is an increasingly common medical problem in the 20th century; however, its pathogenesis is poorly understood. The present paper reviews 247 cases of aortic valves surgically excised over a one-year period, with special attention to the morphological and histological changes observed in surgically excised aortic valves, and to how those changes relate to the mechanisms of valve failure. Patient age ranged from 17 to 86 years, with a mean of 64.1 +/-13.4 years, and there were 156 men (63.2%) and 91 women (36.8%). A total of 172 valves (69.6%) were tricuspid and 75 valves (30.4%) were congenitally abnormal, of which 67 valves (27.1%) were congenitally bicuspid, six valves (2.4%) were congenitally unicommissural and one valve (0.4%) was quadricuspid; the status of one valve could not be determined. Almost 70% of patients had features of aortic stenosis. Calcification was seen in the large majority of cases, with almost 70% of the valves showing either grade 3 or grade 4 calcification. Ulceration of calcific nodules was present in 42.0% of cases and in the majority of the valves with grade 4 calcification. A total of 15% of the valves showed evidence of postinflammatory changes consistent with rheumatic disease. Neovascularization was present in two-thirds of all valves, while one-half showed inflammatory cell infiltrates. Inflammatory cells were composed mainly of lymphocytes and macrophages, and were located primarily near areas of neovascularization. There was no significant difference in the pathological findings between men and women.

This article summarizes discussions that took place following Paul Toro's presidential address for the Society for Community Research and Action (SCRA). Toro argued that community psychology and SCRA are "big tents." He suggested growth through increasing the involvement of ethnic minorities, community practitioners, international colleagues, students and early career professionals and individuals from allied disciplines. Themes in the discussions included: the founding values of community psychology, diversity, and social action. Those present felt that the field was facing a 'mid-life crisis' and needed to re-establish its identity. Newer professionals looked to their seasoned colleagues to help define and establish that identity, and involve them in the process. Respondents were supportive of increased involvement of individuals from oppressed groups and practitioners in SCRA. Less attention was paid to increasing the role of international colleagues, professionals from allied disciplines, and members of the community.

A 50-year-old man who had chronic renal failure presented with neutropenic fever four days after ramipril was initiated. Agranulocytosis due to other causes was ruled out after a bone marrow aspiration and biopsy examination were performed. A relationship between the drug and the adverse effect was suggested. It was established by a novel lymphocyte cytotoxicity test.

Secondary prophylactic administration of recombinant human granulocyte colony stimulating factor (G-CSF) following an episode of febrile neutropenia is recommended if maintenance of dose-intensity is desired. This policy was adopted in our center in patients treated with an intent for cure or durable complete response. The purpose of this study was to evaluate the safety and feasibility of this policy. Patients in whom neutropenia was associated with a life-threatening infection and those who developed prolonged myelosuppression were excluded. Fifty-one patients who developed febrile neutropenia that required intravenous antibiotics following moderately myelotoxic chemotherapy were included. These patients received the next cycle of the same chemotherapy regime without dose modification but with the support of filgrastim (300 or 480 mg/d sc for at least 10 consecutive days). Diagnoses included lymphoma (n = 19), breast cancer (n = 15), germ cell tumor (n = 7), small-cell lung cancer (n = 5), and other solid tumors (n = 5). The incidence of febrile neutropenia during the first cycle given with filgrastim support (N1) was 8/51 (16%). Intravenous antibiotics were required for 3-7 d (median, 4.5 d). During the following cycle (N2), febrile neutropenia developed in 4/41 (10%) patients. Intravenous antibiotics were given for 2, 4, 5, and 7 d. Other dose-limiting toxicities developed in 1/51 patients who received N1 and in 1/41 patients who received N2. There was no drug-related death associated with either cycle. In conclusion, a policy of full-dose chemotherapy with secondary G-CSF support in patients who develop febrile neutropenia following moderately myelotoxic chemotherapy is relatively safe and feasible.

Background: The management of diabetes in preschool children poses unique difficulties for both the families and the medical team., Objective: To test the feasibility and safety of insulin pump therapy in the 1-6 year age group in order to improve quality of life and metabolic control., Methods: The study group comprised 15 type 1 diabetic children aged 1-6 years old (mean +/- SD, 3.8 +/- 1.2 years) from three diabetes centers. Insulin pump therapy was applied for 12 months. Data, including insulin dose, hemoglobin A1c, hypoglycemic events, as well as scores on the Diabetes Quality of Life Measure Questionnaire and the Diabetes Treatment Satisfaction Questionnaire, were collected and compared with the multiple daily injection treatment prior to entry into the study,, Results: HbA1c was measured at the beginning of the study and at 2, 4, 8 and 12 months later; the respective levels (mean +/- SD) were 8.82 +/- 0.98, 8.45 +/- 1.05, 8.37 +/- 0.85, 8.32 +/- 0.71, 8.18 +/- 0.90%. HbA1c measurements after 12 months were significantly lower than at the beginning of the study (P < 0.05). There were no significant differences in insulin dose and the total number of hypoglycemic events. In both the DQOL and DTSQ scales there were significant differences in scores in favor of the insulin pump period (43.7 +/- 8.0 versus 33.7 +/- 7.9, P < 0.001; and 10.9 +/- 2.3 versus 14.5 +/- 2.3, P < 0.001), respectively., Conclusions: For very young diabetic children, insulin pump therapy improves quality of life and is feasible and safe. It should be considered as an optional mode of therapy for this age group.

Background: Autoimmune diabetes can be prevented in animal models by hypoallergenic diets. Moreover, in animal models, oral administration of insulin can suppress the development of autoimmune diabetes and clinical trials on prevention of human Type 1 diabetes by oral administration of insulin are already taking place. However, it has been reported that autoimmune diabetes can be induced by oral administration of an auto-antigen (insulin), and great caution is therefore warranted when applying the oral tolerance approach to prevent Type 1 diabetes., Aim: To evaluate the effect of orally administered insulin on the development of autoimmune diabetes in non-obese diabetic mice fed a hypoallergenic diet., Methods: Four groups of mice were fed regular mouse chow (group 1, control mice), hypoallergenic diet, using the hydrolyzed infant formula Pregistimil (group 2), and Pregistimil with oral insulin (4 U/l of drinking water, group 3; and 8 U/l of drinking water, group 4)., Results: At 210 days of age, 11/20 (55%) mice in group 1 developed diabetes. In contrast, none of the mice from the Pregistimil-fed groups (0/16, 0/14, 0/17) developed the disease (p<0.001). The incidence of infiltrated islets and the severity of insulitis, at age 90 days, was significantly lower in mice fed with the hypoallegenic diet than in controls (p=0.028)., Conclusions: In NOD mice fed a diet that prevents the development of diabetes, oral insulin supplementation appears to be safe, since it does not promote the development of clinical diabetes.

We report that non-neurotropic rabies virus (RV) strains, currently used to immunize wildlife against rabies, induces not only a caspase-dependent apoptosis in the human lymphoblastoid Jurkat T cell line (Jurkat-vect), but also a caspase-independent pathway. Cell redistribution of the apoptosis-inducing factor (AIF) was observed in Jurkat-vect infected with RV vaccine strain. Bcl-2 overproduction in Jurkat T cells (Jurkat-Bcl-2) abolished both caspase activation and AIF distribution. In contrast, strain of neurotropic RV did not induce apoptosis. The inverse correlation of the induction of apoptosis and the capacity of a virus strain to invade the brain suggests that blockage of apoptosis could be a strategy selected by neurotropic virus to favor its progression through the nervous system.

This study explored risk factors for violence among a sample of adult women with physical disabilities. Fifty-six percent (100) of the 177 women participating in the study indicated a positive history of abuse. Of the women who reported abuse, most reported multiple abuse situations and abusers who were typically their male partners. In addition, only a small proportion of women sought and received adequate help. Women who indicated that they did not seek help were asked why this was the case. Their responses included: feeling that they could handle it themselves, having other sources of support available, being unaware of where to go, feeling embarrassed, feeling guilty about being a burden or that it was their fault, fear that abuser would come after them, fear of not being believed, and, to a lesser extent, concern that the shelter would lack appropriate accommodations. These findings highlight the importance of intervention strategies including advocacy activities for women with disabilities, activities with schools, activities to deter and prevent partner and caregiver violence, community awareness activities, and dissemination activities.

We report here that rabies virus strains, currently used to immunize wildlife against rabies, induce not only caspase-dependent apoptosis in the human lymphoblastoid Jurkat T cell line (Jurkat-vect), but also a caspase-independent pathway involving the apoptosis-inducing factor (AIF). In contrast, a strain of neurotropic RV that does not induce apoptosis did not activate caspases or induce AIF translocation. Bcl-2 overproduction in Jurkat T cells (Jurkat-Bcl-2) abolished both pathways. ERA infection and production were similar in Jurkat-vect and Jurkat-Bcl-2 cells, indicating Bcl-2 has no direct antiviral effects. Bcl-2 production is naturally upregulated by day 3 in ERA-infected Jurkat-vect cultures. The increase in Bcl-2 levels seems to be controlled by the virus infection itself and results in the establishment of long-term, persistently infected cultures that continue to produce virus. Thus, in infections with live RV vaccine strains, infected cells may be productive reservoirs of virus in the long term. This may account for the high efficacy of live rabies vaccines.

The placenta is a unique organ with dual blood circulation functioning throughout fetal development. The architecture and functions of the placenta, where maternal blood flows into the intervillous space, present haemostatic problems, mainly the risk of haemorrhage. Placental trophoblasts express and produce coagulation components, participating not only in haemostasis but also in placental vascular development and differentiation. The expression of tissue factor, membrane phosphatidylserine and fibrin render the trophoblasts pro-coagulant, thus compromising the risk of bleeding while exposing the placenta to pro-thrombotic risks. Local inhibitory mechanisms-TFPI-1 and TFPI-2, thrombomodulin, annexin V and the fibrinolytic system-limit coagulation activation and fibrin deposition. Pregnancy complications have been associated with abnormalities in the functions of these inhibitors. Haemostatic processes in placental cells change throughout gestation and are affected by the changing requirements of the organ.

Background and Objectives: The utility of on-line evidence-based summary databases for answering clinical questions at the point of care is not well understood. Our objectives were to determine if family physician faculty could answer their questions using on-line resources and the proportion of answers that influenced patient care., Methods: This was a prospective study in which clinical faculty in an urban residency training office recorded their clinical questions and their search results., Results: Faculty asked 92 questions. Therapy, prognosis, and epidemiology questions were the most common types of inquiries. Fifty-four percent of the questions were fully or partially answered by use of an on-line resource; obtaining an answer required 5-10 minutes of searching. Physicians reported that 62% of the obtained answers modified their opinion, influenced the care of the current patient 56% of the time, and would affect the care of future patients 70% of the time. Slow Internet connection and interruptions were the most frequent barriers reported., Discussion: Practicing physicians inexperienced in the use of on-line evidence-based resources answered a proportion of their clinical questions that was comparable to reports of more-experienced searchers; however, the time required to find answers limits the practical use of these databases during patient care time. On-line summary databases such as those used in this study show promise in providing answers that influence care during the patient's visit. With faster Internet connection (or handheld devices) and improved navigability, such resources have the potential to optimize health care in the primary care setting.

The placenta is a highly vascularized organ functioning as the interface between fetal blood, which is confined within the villous blood vessels, and maternal blood, which flows in decidual arteries and washes the intervillous spaces in contact with syncytiotrophoblast (STB) cells. The STB adopts vascular characteristics such as the presence of von Willebrand factor (vWF), CD31 markers, adhesion molecules, and coagulation components. The special structure of the placenta requires efficient mechanisms for fast activation and localized regulation of coagulation. The presence of procoagulant and anticoagulant components on placental vascular endothelial cells (EC) and STB is essential for hemostasis. Activation of coagulation may be a favored process, as suggested by elevated fibrin depositions documented in some pathologic states. Increased localized procoagulant components such as tissue factor (TF) and plasminogen activator inhibitors (PAI-1, PAI-2), are associated with some pregnancy complications. Several anticoagulants regulate placental coagulation: tissue factor pathway inhibitor (TFPI) is primarily produced in EC; TFPI-2, a variant of TFPI, has been purified from the placenta and was identified in the STB lining the villi; thrombomodulin, a membrane glycoprotein that activates protein C, is localized in EC and apical membranes of STB; annexin V, an anticoagulant that binds to negative membrane phospholipids, is abundant on normal placental STB, whereas reduced STB annexin V was associated with the presence of antiphospholipid antibodies. The placenta is a putative source of coagulation components. However, the interplay between local procoagulant and anticoagulant mechanisms and their association with pregnancy complications need to be assessed.

Background: [corrected] Insulin is substantially present in human milk. Suckling animal models have demonstrated local trophic effects of insulin on the gut mucosa, but the effects of oral insulin in the post-weaning period are controversial., Objective: To examine local and systemic effects of oral insulin supplementation in the post-weaning period., Materials and Methods: Balb/c mice received oral insulin supplementation in their drinking water (1 U/ml) from beyond weaning during 40 days (S group). Plasma glucose, lipid levels, amylase and insulin were measured. The liver and intestine were weighed and thiobarbituric acid-reactive substance (TBARS) levels were examined in liver tissue. These data were compared to a control group (C group)., Results: Fasting glucose levels (mean +/- SD) were lower in the S than in the C group (116. 5 +/- 10.7 vs 143.9 +/- 25.4 mg/dl; p < 0.001), as were prandial glucose levels (123.1 +/- 12.2 vs 145.1 +/- 18.0 mg/dl; p = 0.03). Plasma insulin levels were higher in the S than in the C group (1,110.28 +/- 721.59 vs 308.17 +/- 100.50 pmol/; p = 0.03). Total triglyceride levels (130.4 +/- 32.4 vs 193.6 +/- 48.4 mg/dl; p < 0.02) and total cholesterol levels (83.6 +/- 5.7 vs 93.3 +/- 7.9 mg/dl; p < 0.05) were lower in the S group compared with the C group. Liver weight was significantly higher in the S group compared with C (0.75 +/- 0.1 vs 0. 7 +/- 0.1 g, p = 0.05)., Conclusions: In the post-weaning period, oral insulin supplementation had a significant effect on plasma glucose levels and lipid profile, as well as on liver weight and protein content in Balb/c mice. The application of these findings in humans should be studied.

Objective: The present study was designed to analyze vancomycin disposition in adult patients undergoing coronary bypass grafting during and following cardiopulmonary bypass (CPB)., Methods: Coronary bypass surgery was performed on 11 adults with a mean age (SD) of 62.9 (9.0) years old, who received a mean (SD) vancomycin prophylactic dose of 12.7 (1.0) mg/kg in a mean period of 41 (0.7) min. Using a two-compartment open model for pharmacokinetic analysis, the following parameters were obtained: alpha half-life, minutes (t(1/2alpha)); beta half-life, hours (t(1/2beta)); apparent volume of distribution, (V(d) l/kg); volume of the central compartment, (V(c) l/kg), constant between the "central to the peripheral" compartment, (k(12)); constant between the "peripheral to the central" compartment, (k(21)); total area under the concentration-time curve, (AUC mg/lxh) and a vancomycin clearance, (Cl(van) ml/min), respectively., Results: The mean (SD) calculated pharmacokinetic parameters were: t(1/2alpha)17.6 (6) min, t(1/2beta) 8.4 (3.8) h, V(d) 0.803 (0.259) l/kg, V(c) 0.270 (0.162) l/kg, k(12) 0.03 (0.015), k(21) 0.012 (0.012), total AUC 10377.2 (3687.6) mg/lxh. The mean (SD) vancomycin clearance by the CPB machine was 9.51 (2.66) l/h, and the mean (SD) total vancomycin sequestrated by CPB was 331.7 (84) mg. A significant difference (6.3%; p = 0.001) was measured between the mean measured AUC during CPB (1088.1 +/- 253.9) and the same calculated parameter (1160.2 +/- 282). Five minutes after starting CPB, a decrease in vancomycin level was detected; this difference was found to be nearly 11% in absolute values., Conclusions: This confirmatory study demonstrated that the vancomycin blood concentrations obtained during the study allow recommending a safety prophylactic dose of 12mg/kg in adults who undergo open-heart surgery under CPB conditions. Sequestration of vancomycin by the oxygenator or/and tubing system of the CPB machine had occurred and had been measured in this study.

The aim of this study was to describe busulfan disposition in a pediatric population who underwent bone marrow transplantation (BMT). Busulfan administered dose was 1 mg/kg every 6 h for 4 days. Plasma determinations were performed after the first dosing at 0, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min. A noncompartment analysis model for extravascular absorption was used for the pharmacokinetic analysis. To obtain the area under the concentration-time curve (AUC) within the "therapeutic window" of 1,000-1,200 microM x minutes a busulfan dose adjustment Was performed at the fourth dose. Forty-five busulfan pharmacokinetic analyses were performed in 34 children. Eleven children had their dose adjusted [1.19 +/- 0.14) mg/kg] at the fourth dose and the AUC was monitored at the fifth one. The mean AUC +/- SD after the fifth dose (998.1 +/- 189.2 microM x min) was different (p = .006)from that after the first dose (1 mg/kg) (687.63 +/- 166.43 microM x min). Six children had their first AUC into the "therapeutic window," 17 children had their dose adjusted [1.2 (+/- 0.22) mg/kg], but the "adjusted" AUC was not available. These data suggest that it may be reasonable to recommend a busulfan dose of 1.2 mg/kg to achieve the accepted therapeutic target in children undergoing BMT.

Although controversial, exclusive breast milk feeding was shown to exert a protective effect in preventing type 1 diabetes. In contrast, an early introduction of cow's milk-based formula in young infants may enhance the risk of disease, especially in genetically susceptible children, presumably by an increase of intestinal permeability to macromolecules such as bovine serum albumin and beta-casein, which may arouse autoimmunity. We have shown that human milk contains insulin in substantial concentrations, while insulin is barely detectable (if at all) in infant formulas. Orally administered insulin was demonstrated to promote gut maturation and to reduce intestinal permeability to macromolecules. Furthermore, oral insulin may induce tolerance to insulin and protect against the development of type 1 diabetes. We herewith raise a hypothesis that human milk is protective against the development of type 1 diabetes by virtue of the effects of its substantial content of insulin.

The bark of Salix species contains several prodrugs of salicylate, mainly salicin. The aim of this study was to investigate if during pain treatment with Salicis cortex extract platelet aggregation was affected. A total of 51 patients were enrolled in the study. Thirty-five patients suffering from acute exacerbations of chronic low back pain received randomly and double-blind either Salicis cortex extract with 240 mg salicin/day (n = 19) or placebo (n = 16). Further sixteen patients with stable chronic ischemic heart disease were given 100 mg acetylsalicylate per day. Platelet aggregation was studied using an aggregometer. As aggregating agents, arachidonic acid (500 micrograms/ml), adenosine di-phosphate (2 x 10(-5) M) and collagen (0.18 microgram/ml) were used. The mean maximal arachidonic acid induced platelet aggregation was 61%, 78% and 13% in the Salicis cortex extract, placebo and acetylsalicylate groups. Acetylsalicylate had a significant inhibitory effect on platelet aggregation compared to Salicis cortex extract (p = 0.001) and placebo (p = 0.001). There was also a significant difference between the placebo and the willow bark-treated groups in the maximal platelet aggregation induced by arachidonic acid (p = 0.04) and ADP (p = 0.01). No statistical difference was found between the groups when collagen was applied to the human platelets. Daily consumption of Salicis cortex extract with 240 mg salicin per day affects platelet aggregation to a far lesser extent than acetylsalicylate. Further investigation needs to clarify if this finding is of clinical relevance in patients with impaired thrombocyte function.

Oral insulin promotes intestinal maturation and may prevent diabetes in animal models. The aim of this study was to evaluate the concentration of insulin in human milk and in different infant formulas. Our results show that the concentration of insulin in human milk is significantly higher (60.23 +/- 41.05 microU/ml mean +/- SD) compared with cow's milk (16.32 +/- 5.98 microU/ml mean +/- SD) and that insulin is hardly detectable in infant formulas. We propose the addition of human insulin to infant formula to match its composition more closely to human milk.

Background: The prevalence of Helicobacter pylori infection and its role in gastroduodenal disease in cystic fibrosis (CF) are controversial. Additionally, serologic determination of infection in this population may be inaccurate because of cross-reactivity with other bacterial species. The seroprevalence of H. pylori in a cohort of patients with CF and its cross-reactivity with Pseudomonas antibodies were investigated., Methods: A research enzyme-linked immunosorbent assay (ELISA), and three commercial serologic assays (PyloriStat; BioWhittaker, Walkersville, MD, U.S.A.; Flexsure; SmithKline Diagnostics, Inc., San Jose, CA, U.S.A.; and HM-CAP; EPI, Stony Brook, NY, U.S.A.) at three independent laboratories determined the seroprevalence of anti-H. pylori IgG antibodies in 70 patients with CF. Cross-reactivity between solid-phase H. pylori antigens and Pseudomonas antibodies was ascertained by a competitive inhibition assay, preadsorbing sera of patients with CF with whole cell proteins from different Pseudomonas species, and serum reanalysis by each assay. Western blot analysis before and after adsorption was performed to identify potential cross-reactive antigens., Results: The research ELISA, Flexsure, Pyloristat, and HM-CAP initially showed H. pylori seropositivity of 47%, 28%, 24%, and 37%, respectively. Postadsorption seropositivity declined to 8%, 0%, 0%, and 15%, respectively. All patients with research ELISA true-positive results were confirmed endoscopically to have H. pylori infection. Western blot analysis showed a 31-kDa H. pylori protein with antigenic epitopes common to both bacterial species., Conclusions: Cross-reactivity between solid-phase H. pylori antigens and anti-Pseudomonas antibodies occurs in patients with CF. A high index of suspicion should be assumed in evaluating results of serologic H. pylori tests in this population. Preadsorption of CF sera with Pseudomonas proteins should be used in serologic testing.

Israel is one of the Mediterranean countries in which Brucellosis is endemic. As recently there has been a Brucellosis outbreak in a kibbutz, the aim of this study is to identify asymptomatic infected Kibbutz members, and to delineate the manner of infection in this setting. Therefore, all the asymptomatic Kibbutz members were screened by the Rose Bengal test for Brucellosis, while both patients and healthy members were asked to fill in a questionnaire in order to pinpoint the manner of infection, and signs and symptoms of the disease. In addition to the 14 patients with Brucellosis, 2 other Kibbutz members were also found to be infected by the screening tests. Analysis of the data of the questionnaires from 142 healthy and 16 patients disclosed that almost all of the infected patients (15/16) worked in the cowshed, as opposed to only 24 out of 142 (16.9%) of the healthy members. The infected tended to participate more in calf deliveries, and had contact with cow's blood and placenta, compared with the healthy subjects (P<0.001), while there were no significant differences with respect to having cuts on hands, or working in the cowshed without gloves. In addition, 15 out of 16 (93.8%) infected persons also drank unpasteurized milk, as compared with only 17 of the 142 (12%) healthy members (P<0.001), and thus were exposed to 2 major risk factors (working in the cowshed and consumption of unpasteurized milk). As the cows of the Kibbutz's cowshed were affected by Brucella melitensis (which usually affects flocks of goats and sheep rather than cows), the microbe was probably transmitted to the cowshed from neighboring flocks by wandering dogs, and then to the infected humans.

Monocytes are precursors of tissue macrophages, which are major targets of human immunodeficiency virus type 1 (HIV-1) infection. Although few blood monocytes are infected, their resulting activation could play a key role in the pathogenesis of HIV disease by modulating their transendothelial migration and inducing the production of reactive oxygen species (ROS). ROS participate in chronic inflammation, HIV replication, and the apoptosis of immune system cells seen in HIV-infected subjects. Published data on monocyte activation are controversial, possibly because most studies have involved monocytes isolated from their blood environment by various procedures that may alter cell responses. We therefore used flow cytometry to study, in whole blood, the activation and redox status of monocytes from HIV-infected patients at different stages of the disease. We studied the expression of adhesion molecules, actin polymerization, and cellular levels of H2O2, Bcl-2, and thioredoxin. Basal H2O2 production correlated with viral load and was further enhanced by bacterial N-formyl peptides and endotoxin. The enhanced H2O2 production by monocytes from asymptomatic untreated patients with CD4(+) cell counts above 500/microliter was associated with a decrease in the levels of Bcl-2 and thioredoxin. In contrast, in patients with AIDS, Bcl-2 levels returned to normal and thioredoxin levels were higher than in healthy controls. Restoration of these antioxidant and antiapoptotic molecules might explain, at least in part, why monocyte numbers remain relatively stable throughout the disease. Alterations of adhesion molecule expression and increased actin polymerization could play a role in transendothelial migration of these activated monocytes.