Self-reported health and comfort in 'modern' office buildings: first results from the European OFFICAIR study.

In the European research project OFFICAIR, a procedure was developed to determine associations between characteristics of European offices and health and comfort of office workers, through a checklist and a self-administered questionnaire including environmental, physiological, psychological, and social aspects. This procedure was applied in 167 office buildings in eight European countries (Portugal, Spain, Italy, Greece, France, Hungary, the Netherlands, and Finland) during the winter of 2011-2012. About 26 735 survey invitation e-mails were sent, and 7441 office workers were included in the survey. Among respondents who rated an overall comfort less than 4 (23%), 'noise (other than from building systems)', air 'too dry', and temperature 'too variable' were the main complaints selected. An increase of perceived control over indoor climate was positively associated with the perceived indoor environment quality. Almost one-third of office workers suffered from dry eyes and headache in the last 4 weeks. Physical building characteristics were associated with occupants' overall satisfaction (acoustical solutions, mold growth, complaints procedure, cleaning activities) and health (number of occupants, lack of operable windows, presence of carpet and cleaning activities). OFFICAIR project provides a useful database to identify stressors related to indoor environmental quality and office worker's health.

Differential activation of mitochondrial apoptotic pathways by vasculotropic amyloid-beta variants in cells composing the cerebral vessel walls.

Cerebral amyloid angiopathy (CAA) is an age-associated condition and a common finding in Alzheimer's disease in which amyloid-beta (Abeta) vascular deposits are featured in >80% of the cases. Familial Abeta variants bearing substitutions at positions 21-23 are primarily associated with CAA, although they manifest with strikingly different clinical phenotypes: cerebral hemorrhage or dementia. The recently reported Piedmont L34V Abeta mutant, located outside the hot spot 21-23, shows a similar hemorrhagic phenotype, albeit less aggressive than the widely studied Dutch E22Q variant. We monitored the apoptotic events occurring after stimulation of human brain microvascular endothelial and smooth muscle cells with nonfibrillar structures of both variants and wild-type Abeta40. Induction of analogous caspase-mediated mitochondrial pathways was elicited by all peptides, although within different time frames and intensity. Activated pathways were susceptible to pharmacological modulation either through direct inhibition of mitochondrial cytochrome c release or by the action of pan- and pathway-specific caspase inhibitors, giving a clear indication of the independent or synergistic engagement of both extrinsic and intrinsic mechanisms. Structural analyses of the Abeta peptides showed that apoptosis preceded fibril formation, correlating with the presence of oligomers and/or protofibrils. The data support the notion that rare genetic mutations constitute unique paradigms to understand the molecular pathogenesis of CAA.

[Assessment of comfort and health status of Call Center's workers]. / La valutazione del comfort e dello stato di salute in lavoratori di un Call Center.

BACKGROUND: Call Centers are workplaces in which there are a lot of occupational health hazards. METHODS: The aim of the study was to investigate Call Center operators' health status, using: "Ambiente/Salute" questionnaire, VHI questionnaire, health surveillance data analysis. RESULTS: "Negative" Microclimate rating: 68%; "negative" noise rating: 51%. "Negative" eye symptoms rating: 30%; "negative" postural disorders rating: 21%. "Negative" VHI value (over the limit of 30): 6%. CONCLUSIONS: It's necessary to develop and validate an appropriate health surveillance protocol

Tauroursodeoxycholic acid prevents E22Q Alzheimer's Abeta toxicity in human cerebral endothelial cells.

The vasculotropic E22Q mutant of the amyloid-beta (Abeta) peptide is associated with hereditary cerebral hemorrhage with amyloidosis Dutch type. The cellular mechanism(s) of toxicity and nature of the AbetaE22Q toxic assemblies are not completely understood. Comparative assessment of structural parameters and cell death mechanisms elicited in primary human cerebral endothelial cells by AbetaE22Q and wild-type Abeta revealed that only AbetaE22Q triggered the Bax mitochondrial pathway of apoptosis. AbetaE22Q neither matched the fast oligomerization kinetics of Abeta42 nor reached its predominant beta-sheet structure, achieving a modest degree of oligomerization with a secondary structure that remained a mixture of beta and random conformations. The endogenous molecule tauroursodeoxycholic acid (TUDCA) was a strong modulator of AbetaE22Q-triggered apoptosis but did not significantly change the secondary structures and fibrillogenic propensities of Abeta peptides. These data dissociate the pro-apoptotic properties of Abeta peptides from their distinct mechanisms of aggregation/fibrillization in vitro, providing new perspectives for modulation of amyloid toxicity.

Single-cell analysis of cytokine production shows different immune profiles in multiple sclerosis patients with active or quiescent disease.

Peripheral blood mononuclear cells of multiple sclerosis (MS) patients were stimulated with myelin basic protein (MBP) together with anti-CD28 monoclonal antibody and staphylococcal enterotoxin B to optimize cytokine production by antigen-specific cells. Type 1 (IL-2, IL-12, IFNgamma) and pro-inflammatory (TNFalpha, IL-1beta, IL-6) cytokines were augmented in CD4+, CD8+, and CD14+ cells of acute MS patients and of patients undergoing disease reactivation. These cytokines were reduced in IFNbeta-treated and in stable MS patients; type 2 cytokines (IL-4, IL-10) were increased in these patients. Similar immune profiles are seen in MS patients in whom remission is naturally or pharmacologically (IFNbeta) achieved. Cytokine alterations are particularly evident in CD14+ cells, underlying their critical role in the modulation of the immune response.

Functional analysis of HIV-specific cytotoxic T lymphocytes in antiviral-treated- and-naive patients: a preliminary report.

HIV-specific CTL functions were analyzed in HIV-infected individuals who did or did not receive antiretroviral therapy (ART). Results showed that gp 160 (env)-stimulated perforin- and granzyme-expressing CTL, as well as perforin and granzyme-specific mRNA, were reduced in treated patients whereas TNFalpha was increased in ART-treated compared to naive individuals. Reduction of perforin and granzyme-expressing cells was not secondary to impaired IFNgamma production. A defect of CTL is observed in ART-treated individuals; this defect is not dependent on impaired Th cell function. These results reinforce the need for immunomodulants to successfully approach therapy of HIV infection.

Photopheresis in cutaneous T-cell lymphoma: five-year experience.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) includes several lymphoproliferative disorders involving mature T-lymphocyte proliferation initially confined to the cutis. These affections, after variable periods, may progress to the blood, limph nodes and visceral organs. Mycosis fungoides (MF) is the most frequent form of CTCL and has an indolent clinical course. The therapy of CTCL depends on the stage of the disease and the patient's general conditions. For advanced cases it includes chemotherapy, retinoids, and interferon-alpha. Since 1987 extracorporeal photochemotherapy (ECP), a novel immunomodulatory approach based on apheresis and photoirradiation of leukocytes, has been successfully introduced for the treatment of advanced CTCL. It can prolong survival of patients with erythrodermic CTCL without significant side effects. OBJECTIVE: To review our five-year experience with ECP in CTCL. METHODS: Since June 1994, 33 CTCL patients have been recruited for ECP, using two different regimens: two procedures on two consecutive days at four-week intervals for six months, or at two-week intervals for three months with progressive tapering in the second three-month period for the more severe forms. Six patients received ECP with IFN-alpha. ECP was done using the photopheresis UVAR system and UVAR XTS (Therakos, West Chester, Pa) and always with 8-MOP liquid formulation injected directly into the buffy coat bag. Lymphocytes in peripheral blood were immunophenotypically characterized for each patient and every ECP session. RESULTS: All patients tolerated ECP well, without significant side effects. Thirty patients are clinically evaluable (at least three ECP cycles). A favourable clinical response was obtained in 80.9% (16/21) of MF patients (complete response 33%, partial response 47.6%) and in 66% (6/9) of patients in the Sézary's syndrome phase (complete response 33.3%, partial response 33.3%). Five of the six patients given IFN-alpha as adjunctive therapy had a PR and one a CR. Four patients are in CR without therapy at follow-ups of 46, 20, 10 and 8 months. There have been no changes in the peripheral lymphocyte immunophenotype during the follow-up. In 19/30 patients the CD95 antigen, correlated with cellular apoptosis, was expressed and was frequently associated with a good clinical response. CONCLUSIONS: In our experience ECP achieved favourable clinical responses in 73% of patients, in monotherapy or in combination with IFN-alpha, without significant side effects.

[Discipline or liberalization of abortion? Proposal for the Fortuna law: its function and applicability in Italy]. / Disciplina o liberalizzazione dell'aborto? La proposta di legge Fortuna: sua funzione e applicabilità in Italia.

PIP: It is impossible to eliminate abortion, and therefore it must be evaluated in all its medical, moral, religious, as well as, unfortunately, convenience aspects. From a religious viewpoint, abortion is inadmissible; there are, however, social, emotional and psychological problems. Many countries have solved the problem of abortion more or less satisfactorily. Conditions in Italy, however, are rather special, as a resllt of a range of factors, not least of which is a powerful religious pressure which conditions many expressions of private and social life. The physician involved in this problem is confronted with very difficult decisions from the viewpoint of conscienc e, morality, and professional ethics. Abortion requests cannot be granted unconditionally and abortions of convenience must be drastically rejected. On the other hand, in many cases humane considerations demand a solution, and in very exceptional cases abortion is appropriate. But it is impossible to draw up a document to codify rigidly invidual cases, and the physician must rely on his own scientific knowledge, perhaps supported by that of a competent colleague, and on his professional cons cience. A thorough program of prevention of damaging or dangerous pregnancies is recommended, by means of health and sex education. Knowledge of both pharmaceutical and mechanical contraceptives must be popularized at all levels.^ieng

TRAIL death receptors DR4 and DR5 mediate cerebral microvascular endothelial cell apoptosis induced by oligomeric Alzheimer's Aß.

Vascular deposition of amyloid-ß (Aß) in sporadic and familial Alzheimer's disease, through poorly understood molecular mechanisms, leads to focal ischemia, alterations in cerebral blood flow, and cerebral micro-/macro-hemorrhages, significantly contributing to cognitive impairment. Here, we show that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptors DR4 and DR5 specifically mediate oligomeric Aß induction of extrinsic apoptotic pathways in human microvascular cerebral endothelial cells with activation of both caspase-8 and caspase-9. The caspase-8 inhibitor cellular FLICE-like inhibitory protein (cFLIP) is downregulated, and mitochondrial paths are engaged through BH3-interacting domain death agonist (Bid) cleavage. Upregulation of DR4 and DR5 and colocalization with Aß at the cell membrane suggests their involvement as initiators of the apoptotic machinery. Direct binding assays using receptor chimeras confirm the specific interaction of oligomeric Aß with DR4 and DR5 whereas apoptosis protection achieved through RNA silencing of both receptors highlights their active role in downstream apoptotic pathways unveiling new targets for therapeutic intervention.

Pertussis epidemiology in Argentina: trends over 2004-2007.

OBJECTIVES: Pertussis continues causing significant morbidity and mortality worldwide. Although its epidemiology has been studied in many developed countries, the current pertussis situation in South America is scarcely known. This review summarizes the most important recent data concerning pertussis in a country of South America, Argentina. METHODS: CDC criteria were used for pertussis diagnosis. Proportion of pertussis cases by age, immunization status, and immunization coverage rate evaluated at the Argentinean National Pertussis Reference Centers was reported. Bordetella pertussis isolates were characterized and compared with vaccine strains. RESULTS: From 2002 to nowadays, a steady increase of pertussis cases was observed. Most of these cases correspond to patients younger than six months old that received less than three doses of vaccine. However, cases in adolescent and adults have also been detected. For this situation, which is not peculiar to Argentina, several explanations have been proposed. Among them, the inability of current vaccines to induce long-lasting immunity is the most widely accepted as a cause of pertussis resurgence. Furthermore, antigenic divergence between local clinical isolates and vaccine strains may have aggravated the effect of waning immunity. CONCLUSIONS: Pertussis is an important problem for public health in Argentina. Divergence between vaccine strains and local isolates could contribute to the described pertussis epidemiology.

High mobility group box 1 protein is released by neural cells upon different stresses and worsens ischemic neurodegeneration in vitro and in vivo.

High mobility group proteins are chromatin binding factors with key roles in maintenance of nuclear homeostasis. The evidence indicates that extracellularly released high mobility group box 1 (HMGB1) protein behaves as a cytokine, promoting inflammation and participating to the pathogenesis of several disorders in peripheral organs. In this study, we have investigated the expression levels and relocation dynamics of HMGB1 in neural cells, as well as its neuropathological potential. We report that HMGB1 is released in the culture media of neurons and astrocytes challenged with necrotic but not apoptotic stimuli. Recombinant HMGB1 prompts induction of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-1beta, and tumor necrosis factor alpha, and increases excitotoxic as well as ischemic neuronal death in vitro. Dexamethasone reduces HMGB1 dependent immune glia activation, having no effect on the protein's neurotoxic effects. HMGB1 is expressed in the nucleus of neurons and astrocytes of the mouse brain, and promptly (1 h) translocates into the cytoplasm of neurons within the ischemic brain. Brain microinjection of HMGB1 increases the transcript levels of pro-inflammatory mediators and sensitizes the tissue to the ischemic injury. Together, data underscore the neuropathological role of nuclear HMGB1, and point to the protein as a mediator of post-ischemic brain damage.