The breakdown of the cytokine network subsequent to human immunodeficiency virus infection

The acquired immunodeflciency syndrome (AIDS) is a clinically multifaceted disease induced by infection with the human immunodeficiency virus (HIV). HIV infection results in a complex pattern of immunologic alterations that leads to the development of AIDS in the majority of HIV seropositive (HIV+) individuals. The reduction in CD4 T lymphocyte counts is the hallmark of HIV infection; nevertheless, long before the reduction in CD4 counts reaches critical levels, a series of profound and complex defects that impair the function of CD4 T lymphocytes can be detected. Thus, HIV infection is characterized by quantitative and qualitative defects affecting CD4 T lymphocytes. It was suggested recently that programmed cell death (PCD) is an important mechanism leading to CD4 depletion in HIV infection, and that susceptibility of peripheral lymphocytes to PCD is differentially regulated by diverse cytokines. Thus, type 1 cytokines would protect CD4 lymphocytes against PCD, whereas type 2 cytokines would not protect against, and could augment, PCD. We suggest that the qualitative alterations of the immune response provoke the CD4 depletion characteristic of HIV disease via type 2 cytokinemediated augmentation of PCD, and are therefore ultimately responsible for the progression of HIV infection. Finally, we summarize recent data showing that three correlates of disease progression: emergence of HIV strains with syncitium-inducing ability (SI), type 1-to-type 2 cytokine shift, and CD4 depletion, are significantly associated, suggesting a complex interconnected virologic-immunologic pathogenesis of HIV infection

Reply to Comment on: Hawking radiation from ultrashort laser pulse filaments

A comment by R. Schutzhold et al. raises possible concerns and questions regarding recent measurements of analogue Hawking radiation. We briefly reply to the opinions expressed in the comment and sustain that the origin of the radiation may be understood in terms of Hawking emission

Synthesis, Conformation and Antiproliferative Activity of Isothiazoloisoxazole 1,1-dioxides

Sixteen new isothiazoloisoxazole 1,1-dioxides, one new isothiazolotriazole and one new isothiazolopyrazole have been synthesised by using 1,3-dipolar cycloadditions to isothiazole 1,1-dioxides. One sub-set of these isothiazoloisoxazoles showed low μM activity against a human breast carcinoma cell line, whilst a second sub-set plus the isothiazolotriazole demonstrated an interesting restricted rotation of sterically hindered bridgehead substituents. A thiazete 1,1-dioxide produced from one of the isothiazole 1,1-dioxides underwent conversion into an unknown 1,2,3-oxathiazolin-2-oxide upon treatment with Lewis acids, but was inert towards 1,3-dipoles and cyclopropenones. Six supporting crystal structures are included

Predictive Values of Transcutaneous Oxygen Tension for Above-the-ankle Amputation in Diabetic Patients with Critical Limb Ischemia

ObjectiveTo assess the values of transcutaneous oxygen tension (TcPO2) capable of predicting above-the-ankle amputation in diabetic patients diagnosed for critical limb ischemia (CLI) according to the criteria of the TransAtlantic Inter-Society Consensus.DesignRetrospective study.MethodsFrom January 1999 to December 2003, 564 diabetic patients were consecutively hospitalized for CLI in one limb. Revascularization with angioplasty or bypass graft was performed when possible and, if not possible, prostanoid therapy was used. In patients in whom therapies did not relieve the rest pain or the gangrene was extended above the Chopart joint, an above-the-ankle-amputation was performed. After treatment TcPO2 values were evaluated in all patients at the dorsum of the foot.ResultsFifty-five (9.8%) patients underwent an above-the-ankle amputation: 22 of 420 patients who underwent angioplasty, 17 of 117 patients who underwent bypass (14.5%) and 16 of 27 patients in whom revascularization was not possible. Post-treatment TcPO2, measured by a receiver operating characteristic (ROC) curve, showed a value 34mmHg as the best threshold for determining the need for revascularization, with an area under the curve of 0.89 (95%CI 0.85–0.94).Using logistic regression analysis the probability of above-the-ankle amputation for this threshold is 9.7% and reduces to 3% for TcPO2>40mmHg.ConclusionTcPO2 levels<34mmHg indicate the need for revascularization, while for values ≥ 34<40mmHg this need appears less pressing, although there remains a considerable probability of amputation. TcPO2 levels greater than 40mmHg suggest that revascularization is dependent on the severity of tissue loss and possible morbidity caused by the procedure

Wideband THz time domain spectroscopy based on optical rectification and electro-optic sampling

We present an analytical model describing the full electromagnetic propagation in a THz time-domain spectroscopy (THz-TDS) system, from the THz pulses via Optical Rectification to the detection via Electro Optic-Sampling. While several investigations deal singularly with the many elements that constitute a THz-TDS, in our work we pay particular attention to the modelling of the time-frequency behaviour of all the stages which compose the experimental set-up. Therefore, our model considers the following main aspects: (i) pump beam focusing into the generation crystal; (ii) phase-matching inside both the generation and detection crystals; (iii) chromatic dispersion and absorption inside the crystals; (iv) Fabry-Perot effect; (v) diffraction outside, i.e. along the propagation, (vi) focalization and overlapping between THz and probe beams, (vii) electro-optic sampling. In order to validate our model, we report on the comparison between the simulations and the experimental data obtained from the same set-up, showing their good agreement

The geometrical nature of optical resonances : from a sphere to fused dimer nanoparticles

We study the electromagnetic response of smooth gold nanoparticles with shapes varying from a single sphere to two ellipsoids joined smoothly at their vertices. We show that the plasmonic resonance visible in the extinction and absorption cross sections shifts to longer wavelengths and eventually disappears as the mid-plane waist of the composite particle becomes narrower. This process corresponds to an increase of the numbers of internal and scattering modes that are mainly confined to the surface and coupled to the incident field. These modes strongly affect the near field, and therefore are of great importance in surface spectroscopy, but are almost undetectable in the far field

Screening for carriage of carbapenem-resistant Enterobacteriaceae in settings of high endemicity: A position paper from an Italian working group on CRE infections

A variety of national and international guidelines exist around the management of carbapenem resistant Enterobacteriaceae (CREs), but some of these are several years old and do not reflect current epidemiology and they also do not necessarily give pragmatic advice around active surveillance of CREs in countries with a high burden of cases and limited resources. This paper aims to provide a best practice position paper to guide active surveillance in a variety of scenarios in these settings, and discusses which patients should be screened, what methods could be used for screening, and how results might influence infection prevention interventions

Cerebral blood flow and cerebrovascular reactivity correlate with severity of motor symptoms in Parkinson&#8217;s disease

Background: Parkinson\u2019s disease (PD) is a progressive neurodegenerative disorder that is mainly characterized by movement dysfunction. Neurovascular unit (NVU) disruption has been proposed to be involved in the disease, but its role in PD neurodegenerative mechanisms is still unclear. The aim of this study was to investigate cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) within the regions belonging to the motor network, in patients with mild to moderate stages of PD. Methods: Twenty-eight PD patients (66.6 \ub1 8.6 years, 22 males, median [interquartile range, IQR] Hoehn &amp; Yahr = 1.5 [1\u20131.9]) and 32 age- and sex-matched healthy controls (HCs) were scanned with arterial spin labeling (ASL) magnetic resonance imaging (MRI) for CBF assessment. ASL MRI was also acquired in hypercapnic conditions to induce vasodilation and subsequently allow for CVR measurement in a subgroup of 13 PD patients and 13 HCs. Median CBF and CVR were extracted from cortical and subcortical regions belonging to the motor network and compared between PD patients and HCs. In addition, the correlation between these parameters and the severity of PD motor symptoms [quantified with Unified Parkinson\u2019s Disease Rating Scale part III (UPDRS III)] was assessed. The false discovery rate (FDR) method was used to correct for multiple comparisons. Results: No significant differences in terms of CBF and CVR were found between PD patients and HCs. Positive significant correlations were observed between CBF and UPDRS III within the precentral gyrus, postcentral gyrus, supplementary motor area, striatum, pallidum, thalamus, red nucleus, and substantia nigra (pFDR &lt; 0.05). Conversely, significant negative correlation between CVR and UPDRS III was found in the corpus striatum (pFDR &lt; 0.05). Conclusion: CBF and CVR assessment provides information about NVU integrity in an indirect and noninvasive way. Our findings support the hypothesis of NVU involvement at the mild to moderate stages of PD, suggesting that CBF and CVR within the motor network might be used as either diagnostic or prognostic markers for PD