Despite severe lymphopenia, no patient treated for URTID progress

Despite severe lymphopenia, no patient treated for URTID progressed to LRTID. Neutrophil recovery was delayed in 3 patients.

Conclusions. We show that IV and oral RBV were efficacious in preventing progression and reducing mortality of RSV infection in this small series of allogeneic HSCT recipients. Randomized studies are not to be expected for this condition and therefore reporting case series could help in determining optimal RSV treatment.”
“BACKGROUND: Protein stability this website of therapeutic monoclonal antibodies during processing and final storage is imperative for the commercial

success of the product. Amino acid addition is one of the options for stabilization of proteins that can be employed during the manufacturing process and storage.

RESULTS: Use of arginine in the elution buffer during Protein

A purification and subsequent neutralization doubled the yield of antibody compared with the original glycine-based elution buffer. The role of amino acids in stabilizing monoclonal antibody liquid formulations was then studied using differential scanning calorimetry. Increase in the unfolding transition temperatures (T(m)) of immunoglobulin G(IgG) was measured after supplementing a glycine buffer with a range of amino acids. The basic amino acids histidine, lysine, and arginine stabilized all three domains of IgG. The neutral amino acids serine and alanine provided less stabilization; glutamine, proline, and the acidic amino acids provided 3-MA cost negligible stabilization.

CONCLUSION: The positive charge on the side-chain of histidine, lysine, and arginine appears to be the most important factor affecting the IgG stabilization. It is probable that the mechanism for IgG stabilisation is the same for all of the basic amino acids and that it binds

transiently to IgG side chains, altering water populations in the solvation shell, making unfolding and aggregation less energetically favourable. (C) 2011 Society of Chemical Industry”
“Background: IGF-1R inhibitor Patellofemoral pain syndrome is one of the most common knee problems and may be related to abnormal patellar tracking. Our purpose was to compare, in vivo and noninvasively, the patellar tracking patterns in symptomatic patients with patellofemoral pain and those in healthy subjects during squatting. We tested the hypothesis that patients with patellofemoral pain exhibit characteristic patterns of patellar tracking that are different from those of healthy subjects.

Methods: Three-dimensional patellar kinematics were recorded in vivo with use of a custom-molded patellar clamp and an optoelectronic motion capture system in ten healthy subjects and nine subjects with patellofemoral pain. The position of osseous knee landmarks was digitized while subjects stood upright, and then patellofemoral kinematics were recorded during squatting. The tracking technique was validated with use of both in vitro and in vivo methodologies, and the average absolute error was <1.2 degrees and <1.1 mm.

alpha-Man and beta-Hex RNAi fruits were approximately two times f

alpha-Man and beta-Hex RNAi fruits were approximately two times firmer compared with the control and fruit deterioration was delayed by approximately 7 d. It is shown that silencing of Selleckchem BLZ945 alpha-Man

and beta-Hex enhances fruit shelf life due to the reduced degradation of N-glycoproteins which resulted in delayed softening. Altogether, the results provide evidence for the involvement of N-glycan processing in non-climacteric fruit softening. In conclusion, genetic engineering of N-glycan processing can be a common strategy in both climacteric and non-climacteric species to reduce the post-harvest crop losses.”
“The goal of this study was to observe the therapeutic efficacy of cyclophosphamide, vincristine and prednisone combined chemotherapy mTOR inhibitor (COP) in treating adult haemophagocytic lymphohistiocytosis (HLH). Fifteen cases diagnosed with HLH were enrolled in our study. Each of them was treated with the COP regimen. Two of the fifteen patients had autoimmune disease-associated HLH (13.3%), 2/15 had lymphoma-associated HLH

(13.3%), 7/15 had infection-associated HLH (IAHLH) (46.7%), and the remaining 4/15 developed the disease in the absence of apparent underlying disease (26.7%). A complete response (CR) was achieved in 7/15 patients (46.7%), while a partial response (PR) was achieved in 5/15 patients (33.3%). With a mean follow-up of 72.5 weeks, the one-year overall survival was 66.7%. HLH of varying aetiology exhibited differing sensitivity and response to the COP regimen. In combination with aetiological and supportive treatment, the COP regimen as a mild and cost-effective chemotherapy is especially favourable for check details IAHLH, autoimmune disease-associated HLH, and disease severity precluding intensive treatment.”
“The optical second harmonic (SH) response from gold metallic nanocylinders with diameters of 80 and 120 nm arranged in hexagonal arrays has been determined as a function of the input fundamental polarization angle for the on- and off-axis transmission geometries and crossed

output polarization configurations. For the on-axis transmission geometry, the nonlinear response of the nanocylinders is shown to be mainly incoherent, of pure electric dipole nature and arising from the breaking of the centrosymmetric shape of the body of the cylinders in a plane parallel to the substrate surface. Small angle off-axis experiments however show that the coherent contribution to the nonlinear response is size dependent suggesting that, besides the out-of-plane nonlinearity, retardation effects may also play a nonnegligible role. (C) 2011 American Institute of Physics. [doi:10.1063/1.3603007]“
“In Arabidopsisfloral meristems are specified on the periphery of the inflorescence meristem by the combined activities of the FLOWERING LOCUS T (FT)-FD complex and the flower meristem identity gene LEAFY.

The need for a certain self-determination and personal


The need for a certain self-determination and personal

responsibility of the athletes should be respected. Therefore, the screening should not be mandatory. However, adequate information about the issue is crucial for an informed decision.”
“Mitochondrial alterations are believed to play a critical role in the pathophysiology of neurodegenerative diseases and in some well-described myopathies. In the present study, we evaluated muscle changes in vivo after blocking selleck chemicals llc the mitochondrial complex II of the respiratory chain by using 3-nitropropionic acid (3-NP). This neurotoxin has been used as a pharmacological tool in animal models to address some of the metabolic modifications that might underlie central neurodegeneration; however, changes in peripheral musculature have not been documented. We believe that skeletal muscles must be affected because their integrity highly depends on oxidative metabolism. Therefore, histochemical, ultrastructural, and biochemical changes were studied in the muscles of mice treated with low doses of 3-NP (15 mg/kg,

i.p., for 5 days). 3-NP-treated mice displayed changes in alkaline phosphatase (APase), succinic dehydrogenase (SDH), and cytochrome c oxidase (COX) levels in the gracilis and gastrocnemius muscles. These changes were statistically significant for APase and SDH in both muscles and for COX only in the gastrocnemius. No significant alterations in acetylcholinesterase (AChE) expression AR-13324 solubility dmso check details were observed in either muscle. Analysis of the muscle ultrastructure revealed mitochondrial atrophy as well as sarcomere and nuclei disorganization. At the biochemical level, nitric oxide (NO) and lipid peroxidation (LPO) changed in the muscles of 3-NP-treated mice, suggesting metabolic alterations due to oxidative stress. Early damage in the striatal tissue and behavioral modifications are also documented.”
“Bisphosphonate-related osteonecrosis of the jaw (BRONJ) adversely affects the quality of life, producing significant morbidity in afflicted patients. Strategies for the treatment of patients with, or at risk of, BRONJ were set forth in the American

Association of Oral and Maxillofacial Surgeons (AAOMS) Position Paper on Bisphsphonate-Related Osteonecrosis of the jaws (Position Paper) and approved by the Board of Trustees in September 2006.(1) The Position Paper was developed by a Task Force appointed by the Board and composed of clinicians with extensive experience in caring for these patients and basic science researchers. The knowledge base and experience in addressing BRONJ has expanded, necessitating modifications and refinements to the original Position Paper. The Task Force was reconvened in August 2008 to review the 2006 recommendations, appraise the current published data, and revise the Position Paper and recommendations, where indicated. This update contains revisions to the diagnosis and staging and management strategies and highlights the status of basic science research.

Among all the varieties, Bigarade presents the highest capacity t

Among all the varieties, Bigarade presents the highest capacity to slow the rate of oxidation of linoleic acid and beta carotene (77%) followed by Portugaise (71%). On the other hand, the results show that the antiradical activity varies from 58.48 to 92.55% for leaves and 55.46 to 88% for peels. We also note that Bigarade presents the highest antiradical activity. (C) 2013 Elsevier B.V. All rights reserved.”
“The association between osteoporosis and jawbones remains an argument of debate. Both osteoporosis and periodontal diseases are bone resorptive diseases; it has been hypothesized that osteoporosis could be a risk factor for the progression of periodontal disease and vice versa.

Hypothetical models linking

the two conditions exist: in particular, it is

supposed that the osteoporosis-related bone mass density reduction may accelerate GSK2399872A manufacturer alveolar bone resorption caused by periodontitis, resulting in a facilitated periodontal bacteria invasion. Invading bacteria, in turn, may alter the normal homeostasis of bone tissue, increasing osteoclastic activity and reducing local and systemic bone density by both direct effects (release of toxins) and/or indirect mechanisms (release of inflammatory mediators). Current evidence provides conflicting results due to potential biases related to study design, samples size and endpoints. The aim of this article is to review and summarize the published literature on the associations between osteoporosis and different oral conditions

such as bone loss in the jaws, periodontal diseases, and tooth loss.

Further well-controlled studies are needed to better elucidate the inter-relationship between systemic and oral bone loss and to clarify whether dentists could usefully provide early warning for osteoporosis risk.”
“The individualization of radiotherapy treatment would be beneficial for cancer patients; however, there are no predictive biomarkers of radiotherapy resistance in routine clinical use. This article describes the body of work in this field where comparative proteomics methods have been used for the discovery of Pexidartinib chemical structure putative biomarkers associated with radiotherapy resistance. A large number of differentially expressed proteins have been reported, mostly from the study of novel radiotherapy-resistant cell lines. Here, we have assessed these putative biomarkers through the discovery, confirmation and validation phases of the biomarker pipeline, and inform the reader on the current status of proteomics-based findings. Suggested avenues for future work are discussed.”
“Stevia rebaudiana (Bertoni) Bertoni is well known because of its accumulation of the sweet-tasting ent-kaurene diterpeneoid glycoside, which tastes about 300 times as sweet as sucrose. Although stevioside is one of the most abundant and best analyzed, more than 30 additional steviol glycosides so far have been identified and described.

“Chloroplasts from plants of transgenic lines expressing p

“Chloroplasts from plants of transgenic lines expressing prokaryotic choline oxidase gene (the codA(ps) gene; GenBank accession number-AY589052) and wild-type of chickpea and Indian mustard were evaluated for their efficacy to withstand photoinhibitory damage, by exposing them to high light intensity (similar to 1200 mu mol m(-2) s(-1) photon flux density) at 10 and 25 degrees C. Western

analysis confirmed presence of choline oxidase in chloroplasts of only transgenic lines. The loss in PS II activity in chloroplasts of wild-type exposed to high light intensity was significantly higher than that in chloroplasts of transgenic chickpea as well as Indian mustard. Although, chloroplasts of both wild-type and transgenic chickpea as well as Indian mustard find more were more sensitive to photoinhibitory damage at 10 than at 25 degrees C, the damage recorded in chloroplasts harboring choline oxidase was significantly lower than those of wild-type. High light promotes H(2)O(2) production in chloroplasts more significantly at low temperature

(10 degrees C) than at 25 degrees C. We Compared low temperature accelerated photoinhibition of chloroplasts with that caused due to exogenously applied H(2)O(2). Although exogenous H(2)O(2) accelerated high light intensity induced loss in PS II activity of chloroplasts of wild-type, it caused only a little alteration in PS II activity of chloroplasts from transgenic lines of both chickpea and Indian mustard, demonstrating that the chloroplasts harboring choline oxidase are better equipped to resist photoinhibition. We hypothesize that H(2)O(2) produced by choline oxidase selleck compound Alvespimycin manufacturer as a byproduct during synthesis of glycinebetaine is responsible for building stronger antioxidant system in chloroplasts of transgenic lines compared to that of wild-type. (C) 2009 Elsevier Masson SAS. All rights reserved.”
“Background: Site preparation is a pre-requesite in conducting

malaria vaccines trials. This study was conducted in 12 villages to determine malariometric indices and associated risk factors, during long and short rainy seasons, in an area with varying malaria transmission intensities in Korogwe district, Tanzania. Four villages had passive case detection (PCD) of fever system using village health workers.

Methods: Four malariometric cross-sectional surveys were conducted between November 2005 and May 2007 among individuals aged 0-19 years, living in lowland urban, lowland rural and highland strata. A total of 10,766 blood samples were collected for malaria parasite diagnosis and anaemia estimation. Blood smears were stained with Giemsa while haemoglobin level was measured by HaemoCue. Socio-economic data were collected between Jan-Apr 2006.

Results: Adjusting for the effect of age, the risk of Plasmodium falciparum parasitaemia was significantly lower in both lowland urban, (OR = 0.26; 95%CI: 0.23-0.29, p < 0.001) and highlands, (OR = 0.21; 95%CI: 0.17-0.25, p < 0.

“Goal: The desire for shared decision making arises especi

“Goal: The desire for shared decision making arises especially for frequently occurring cases of solid cancer. For hematological

cancer conditions, there are no analogous results. This study compares the participation patients’ desires concerning medical decisions dealing with their solid and hematological tumors.

Patients and Methods: The 533 inpatients with solid cancer (age < 65: 61.0%; female: 39.6 %) and 177 patients with hematological cancer (inpatient: 62.1%, outpatient: 37.9%; age < 65: 63.3%; female: 42.4%) were given a questionnaire after admission to a hospital or medical practice. The dependent variable was patient preference for control in decision making for eight different medical areas of decision.

Results: Descriptive results showed that patients with solid cancer had a stronger desire to participate in the decisions in six of a total of eight survey Z-DEVD-FMK fields (p < 0.01). When considering medical and socio-demographic control variables, the multivariate regression shows that the differences between the patient groups remain in all areas (p < 0.01). Further predictor variables are educational background and age (p < 0.05). No influence resulted from the factors of gender, medical or treatment characteristics.

Conclusion: The results show differences between

patients with hematological cancer and patients with solid tumors, and these differences concern the preference to participate in medical decisions. Hemato-oncological patients desire less active participation and prefer a more dominant role of the physician in the various Emricasan areas requiring decisions. Physicians should respect this in the course of the treatment. Copyright (C) 2010 John Wiley & Sons, Ltd.”
“Unfractionated heparin, low-molecular-weight heparins, and sulodexide belong to the family of glycosaminoglycans. Recent studies report on properties other than anticoagulant activities of these medications. They include modulation

of cell growth and proliferation via actions on numerous growth factors affecting the immune system and matrix molecules production and degradation. Long-term peritoneal dialysis remarkable influences peritoneal cavity homeostasis by mechanisms mediated by growth factors. They initiate progression of pathological processes and further account selleck kinase inhibitor for morphological and functional alterations of the peritoneal membrane. The best-recognized pathologies in peritoneal cavity under these conditions encompass inflammation, fibrosis, and vasculopathy, often leading to fatal encapsulating peritoneal sclerosis. Intraperitoneal heparin and its derivatives, by their pleiotropic actions, may influence these crucial processes and improve the peritoneal dialysis technique survival in a complex and so far understudied way. These issues, novel medical approaches, and their likely mechanisms have been reviewed.

Methods: Using an enzyme-linked immunosorbent assay, we assessed

Methods: Using an enzyme-linked immunosorbent assay, we assessed pericardial and serum VEGF levels in patients with malignant pericardial effusion (n = 19), in patients with nonmalignant pericardial effusion (n = 30), and for control, in patients without pericardial disease (n = 26). Results: Vascular endothelial growth factor pericardial levels in malignant pericardial effusion (13 593.8 +/- 22 410.24 pg/mL) were significantly higher compared with VEGF in nonmalignant effusion (610.63 +/- 1289.08 pg/mL; P = 0.001) and pericardial fluid (5.5 +/- 15.97 pg/mL; P < 0.001).

In serum, VEGF was significantly higher in patients with nonmalignant pericardial effusion GSK2126458 (188.3 +/- 240.35 pg/mL) compared with patients with malignant pericardial effusion (67.52 +/- 125.77 pg/mL; P = 0.024) and coronary artery disease patients (29.13 +/- 76.26 pg/mL; P < 0.001). Pericardial VEGF levels were significantly higher than matched serum levels only in patients with malignant pericardial effusion (P = 0.023). Pericardial VEGF levels

=2385 pg/mL had 75% sensitivity and 90% specificity for the recognition of malignant pericardial effusion in patients Go 6983 molecular weight with breast or lung cancer. Conclusions: Vascular endothelial growth factor levels in pericardial effusion are markedly elevated in patients with malignant pericardial effusion, indicating abundant local release within the pericardial cavity. It is thus possible that VEGF participates in the pathogenesis of malignant pericardial

effusion. Measurement of VEGF in pericardial effusion offers potential as a diagnostic tool to discriminate malignant from benign effusions in patients with breast or lung cancer. The authors have no funding, financial relationships, or conflicts of interest to disclose.”
“The total synthesis of epothilone D with six-fold application in the intermediate stages of successive cyclopropanation – opening or cleavage of the three-membered ring was performed. These transformations underlie the new stereoselective method developed for coupling fragments C-7-C-12 and C-13-C-21 in the target molecule.”
“Methods. aEuro integral Twenty patients received metronidazole (Flagyl (R) A (R), Pfizer, 235 East 42nd Street, NY, NY 10017) oral dose 500 mg twice a day for 3 consecutive days. Pharmacokinetic analyses of metronidazole were performed after a single oral dose on the morning of day 4.


“Powassan virus is a rarely diagnosed cause of encephaliti

“Powassan virus is a rarely diagnosed cause of encephalitis, and is associated

with significant neurologic sequelae. Although symptomatic infections with Powassan virus occur primarily in adults, we report a case of confirmed Powassan neuroinvasive disease in a child presenting to a Tennessee hospital, with symptoms and imaging studies suggestive of acute disseminated encephalomyelitis.”
“In recent years polarization fatigue in ferroelectric polymers has attracted much attention due to their potential use in nonvolatile memories, though the mechanism is still an open question. Here we mainly focus on the experimental observations on two physical phenomena occurring during fatigue process: The frequency dependence of the fatigue rate Nepicastat and the change in the coercive field with increased fatigue cycles. The frequency dependence of fatigue rate shows that at lower fatigue frequencies the rate obeys a universal scaling behavior with respect to N/f, where N is the fatigue cycles and f is the fatigue frequency, while at much higher frequencies this scaling behavior is broken and the fatigue rate is N/f dependent. In addition, both the increase and the decrease of the coercive field are observed, which ACY-241 indicates that the change in the coercive field should be dominated

by different mechanisms. Based on the understanding of the crucial influence of space charges on electrical fatigue, we give a detailed discussion on both phenomena. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3607316]“
“The PDGFR inhibitor protective role of exogenously supplied selenium (Se) and polyamines (PAs) such as putrescine (Put) and spermine (Spm) in detoxifying the cadmium (Cd) induced toxicity was studied in the marine red alga Gracilaria dura in laboratory conditions. The Cd exposure

(0.4 mM) impede the growth of alga while triggering the reactive oxygen species (ROS viz. O-2(center dot-) and H2O2) generation, inhibition of antioxidant system, and enhancing the lipoxygenase (LOX) activity, malondialdehyde (MDA) level and demethylation of DNA. Additions of Se (50 mu M) and/or Spm (1 mM) to the culture medium in contrast to Put, efficiently ameliorated the Cd toxicity by decreasing the accumulation of ROS and MDA contents, while restoring or enhancing the level of enzymatic and nonenzymatic antioxidants and their redox ratio, phycobiliproteins and phytochelatins, over the controls. The isoforms of antioxidant enzymes namely superoxide dismutase (Mn-SOD, similar to 150 kDa; Fe-SOD similar to 120 kDa), glutathione peroxidase (GSH-Px, similar to 120 and 140 kDa), glutathione reductase (GR, similar to 110 kDa) regulated differentially to Se and/or Spm supplementation. Furthermore, it has also resulted in enhanced levels of endogenous PAs (specially free and bound insoluble Put and Spm) and n-6 PUFAs (C20-3, n-6 and C20-4, n-6).

The influence of both geometry and material on the resonance prop

The influence of both geometry and material on the resonance properties is evaluated. Such field enhancement will aid in terahertz spectroscopy, and allow realization of terahertz resonant-gap chain and other waveguides that have been studied using metals at optical frequencies.”
“Background: Sipuleucel-T is an autologous cellular immunotherapy approved by the US Food and Drug Administration for the treatment of asymptomatic or minimally

symptomatic metastatic castration-resistant prostate cancer. Its mechanism of action is based on stimulation of the patient’s own immune system to target prostate cancer. Peripheral blood mononuclear cells, including antigen-presenting cells and T cells, are obtained from patients via leukapheresis and treated ex vivo with PA2024, a fusion protein consisting of prostatic acid phosphatase/granulocyte-macrophage DNA Synthesis inhibitor colony-stimulating factor antigen.

Methods: Data relating to the potential

pharmacodynamic.biomarkers associated with sipuleucel-T activity are reviewed, as well as considerations for patient selection and for sequencing sipuleucel-T with other prostate cancer treatments. Possible directions for future development are also discussed, including treatment of less advanced prostate cancer LB-100 supplier populations, combination treatment, and immune modulation.

Results: Data from three

randomized, double-blind, placebo-controlled phase III clinical trials of sipuleucel-T in patients with metastatic castration-rresistant prostate cancer have shown improvement in overall survival vs control. Here, we review its developing role in prostate cancer therapy and future directions for development.

Conclusions: There is potential to build on sipuleucel-T to further advance immunotherapy of prostate cancer.”
“To analyze the influence of the percentage of glycidyl methacrylate (GMA) coupled with polymeric chains to determine their effect on molecular weight (M(w)) and refractive index (n(D)), a Mixture Tozasertib cost Design of Experiments (MDOE) has been used. A “”d”" optimal mixture design for four components was used for planning the runs and analyzing the information using statistical tools. The prototypes generated were synthesized using styrene (St) 73-89.98%, methylmethacrylate (MMA) 8-22%, and glydicyl methacrylate (GMA) 2-10%, at different ratios according to the experiment design. In this sense, the prototypes are terpolymers (St-MMA-GMA). According to the desired properties of the prototypes reviewed in literature and market studies, this is expressed in materials with a preferred n(D) (ca. 1.5750-1.5894) and molecular weight (ca. 300,000 g/mol) the ratios were established.

F(CF2)(n)CO2-; n = 6-11,13) and perfluoroalkane sulfonic acids (P

F(CF2)(n)CO2-; n = 6-11,13) and perfluoroalkane sulfonic acids (PFSAs, F(CF2)(n)SO3-; n = 6,8,10). Survey results of surface sediment and water indicated that shorter chained PFASs were predominant in and near urban/industrial area watersheds, SU5402 cost while longer chained PFASs were predominant in fine-grained sediment from major depositional basins. Niagara River suspended solids (1981-2006) demonstrated temporal trends that may have been influenced by recent changes in North American production and use of PFASs. Perfluorooctane sulfonate (PFOS) reached a peak concentration in 2001 of 1.1 ng/g, followed by a decrease from 2001 to 2006 (half-life

= 9 years). Perfluorooctanoic acid (PFOA) increased from 2001 to 2006

4SC-202 chemical structure (doubling time = 2 years) reaching a peak concentration of 0.80 ng/g. In contrast, three sediment cores from western, central, and eastern lake Ontario showed increasing temporal trends to surface sediment for all PFASs. PFOA and PFOS concentrations increased from 1988 to 2004 (doubling time = -4 years) in the western Lake Ontario core. The observed variations in temporal trends from different environmental compartments may be a result of the physicochemical properties of PFASs, ongoing emissions, and the environmental transformation and degradation of PFAS precursor compounds. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.”
“P>Psoriatic arthritis (PsA) is an immunologically triggered, chronic inflammatory arthropathy, which can have a lasting influence on the quality of life of affected individuals. An early diagnosis is essential in order to institute adequate therapy. Both dermatologists and rheumatologists should be involved in the diagnosis and management of the disorder.

Mild forms can be managed with NSAID and systemic corticosteroids. In acute forms with a confirmed diagnosis VX-689 and oligo- to polyarticular involvement,

disease-modifying therapy with DMARD (Disease-Modifying Antirheumatic Drugs) is indicated. New studies of PsA show that tumor necrosis factor (TNF) plays a central role in mediating inflammation. For this reason, TNF-alpha antagonists have become more and more important as a second-line therapy for PsA.”
“A statistical model was developed using satellite remote sensing data and meteorological parameters to evaluate the effectiveness of air pollution control measures during the 2008 Beijing Olympic Games. Custom satellite retrievals under hazy conditions were included in the modeling dataset to represent the air pollution levels more accurately. This model explained 70% of the PM2.5 variability during the modeling period from June to October 2008. Using this tool, we estimate that the aggressive emission reduction measures alone effectively lowered PM2.