Impact of community-based technology training with low-income older adults.

OBJECTIVES: Compared with younger and middle-aged adults, older adults are less likely to adopt new computer technology, potentially limiting access to healthcare and many other important resources available online. This limitation could impact cognitive abilities, well-being, and mental health outcomes of older adults. The aims of the present study were to increase access to online county and healthcare resources, while also assessing the impact of technology access on cognitive functioning and multiple well-being domains. METHODS: A pilot community collaboration provided a two-month tablet training intervention, focused on increasing digital independence via tablet navigation, resources access, and fraud and scam prevention, to 20 low-income older adult participants (75% female, Mage = 70.85). Pre- and post-test phone interviews were conducted to measure any changes in digital independence, cognitive abilities, well-being, mental health, and mindset. RESULTS: Linear mixed effects models revealed no significant changes in outcome measures from pre- to post-test. However, we found effects of digital independence on several well-being measures, providing important information for the impact of technology access and training for low-income older adults. CONCLUSION: This pilot intervention offers limited but promising results, inspiring further investigations that may inform public health and policy services to address barriers to access and potentially improve psychological health.

Expression and degranulation of mast cells in laser photobiomodulated mucositis chemo-induced: pilot study in hamsters.

This study aimed to evaluate the influence of laser photobiomodulation on the expression and degranulation of mast cells in chemo-induced oral mucositis (OM) lesions in hamsters. Twelve adult male Syrian hamsters (Mesocricetus auratus), golden lineage, were submitted to OM induction. They were divided into three groups: control-OM without treatment (C), OM treated with red laser (RL), OM treated with infrared laser (IL) and analyzed in the experimental time of 7 days. Three and 4 days after the intraperitoneal injection of the chemotherapy drug fluorouracil, the OM lesions were induced by making grooves in the right cheek pouch. Immediately after chemoinduction, the hamsters were submitted to photobiomodulation every 48 h for 7 days. The specimens were processed and stained using the hematoxylin-eosin and toluidine blue techniques. There was a predominance of mild chronic inflammation in the experimental groups and a greater persistence of neutrophils in the control group (C), although not statistically significant. The group irradiated with red laser (RL) had the highest mean mast cell expression (38.28 ± 19.05) (p < 0.001). As for the degranulation activity in mast cells, the control group (C) showed a greater number of fields with more than 50% of degranulated cells, presenting statistical significance when comparing it with the RL (p < 0.009) and IL (p = 0.036) group. It can be concluded that photobiomodulation, at both wavelengths, decreased mast cell degranulation, accelerating the inflammatory process. The use of infrared laser provided, in addition to less degranulation, the quantitative reduction of mast cells.

Cognitive and Functional Improvement via Novel Skill Learning for Low-Income Minoritized Middle-Aged and Older Adults.

Prior research has demonstrated beneficial outcomes for learning new skills in older adulthood, including increased cognitive and functional abilities, which help prevent age-related declines and foster healthy aging. However, these studies largely have included participants not typically considered at risk for cognitive and functional decline (i.e., White, highly educated, higher income). Cognitive and functional disparities exist among minoritized racial and ethnic individuals, particularly Black and Latinx populations, because of a lifetime of inequalities associated with low socioeconomic status, low education, and discrimination. This theoretical paper proposes a potential pathway in which such disparities could be mitigated by increasing cognitive and functional abilities via novel skill learning in these at-risk populations in middle and later life to prevent decline. We also discuss indirect barriers (e.g., financial and health issues), direct barriers (e.g., limited learning opportunities), and motivational barriers (e.g., self-beliefs, values) that these adults may encounter. We further highlight that addressing these barriers to novel skill learning by providing appropriate resources is necessary to maximize the feasibility and potential effectiveness of this pathway. Lastly, we encourage future research to test this pathway and help inform policymakers and existing learning programs to implement better ways of promoting lifelong learning in an inclusive and equitable manner to prevent decline.

Climate-driven mosquito-borne viral suitability index: measuring risk transmission of dengue, chikungunya and Zika in Mexico.

BACKGROUND: Climate variability influences the population dynamics of the Aedes aegypti mosquito that transmits the viruses that cause dengue, chikungunya and Zika. In recent years these diseases have grown considerably. Dengue is now the fastest-growing mosquito-transmitted disease worldwide, putting 40 per cent of the global population at risk. With no effective antiviral treatments or vaccines widely available, controlling mosquito population remains one of the most effective ways to prevent epidemics. This paper analyses the temporal and spatial dynamics of dengue in Mexico during 2000-2020 and that of chikungunya and Zika since they first appeared in the country in 2014 and 2015, respectively. This study aims to evaluate how seasonal climatological variability affects the potential risk of transmission of these mosquito-borne diseases. Mexico is among the world's most endemic countries in terms of dengue. Given its high incidence of other mosquito-borne diseases and its size and wide range of climates, it is a good case study. METHODS: We estimate the recently proposed mosquito-borne viral suitability index P, which measures the transmission potential of mosquito-borne pathogens. This index mathematically models how humidity, temperature and precipitation affect the number of new infections generated by a single infected adult female mosquito in a host population. We estimate this suitability index across all Mexico, at small-area level, on a daily basis during 2000-2020. RESULTS: We find that the index P predicted risk transmission is strongly correlated with the areas and seasons with a high incidence of dengue within the country. This correlation is also high enough for chikungunya and Zika in Mexico. We also show the index P is sensitive to seasonal climatological variability, including extreme weather shocks. CONCLUSIONS: The paper shows the dynamics of dengue, chikungunya and Zika in Mexico are strongly associated with seasonal climatological variability and the index P. This potential risk of transmission index, therefore, is a valuable tool for surveillance for mosquito-borne diseases, particularly in settings with varied climates and limited entomological capacity.

VPS32, a member of the ESCRT complex, modulates adherence to host cells in the parasite Trichomonas vaginalis by affecting biogenesis and cargo sorting of released extracellular vesicles.

Trichomonas vaginalis is a common sexually transmitted extracellular parasite that adheres to epithelial cells in the human urogenital tract. Extracellular vesicles (EVs) have been described as important players in the pathogenesis of this parasite as they deliver proteins and RNA into host cells and modulate parasite adherence. EVs are heterogeneous membrane vesicles released from virtually all cell types that collectively represent a new dimension of intercellular communication. The Endosomal Sorting Complex Required for Transport (ESCRT) machinery contributes to several key mechanisms in which it reshapes membranes. Based on this, some components of the ESCRT have been implicated in EVs biogenesis in other cells. Here, we demonstrated that VPS32, a member of ESCRTIII complex, contribute to the biogenesis and cargo sorting of extracellular vesicles in the parasite T. vaginalis. Moreover, we observe that parasites overexpressing VPS32 have a striking increase in adherence to host cells compared to control parasites; demonstrating a key role for this protein in mediating host: parasite interactions. These results provide valuable information on the molecular mechanisms involved in extracellular vesicles biogenesis, cargo-sorting, and parasite pathogenesis.

Impact of photobiomodulation therapy on the morphological aspects of submandibular gland submitted to excretory duct ligation and hypothyroidism: an animal study.

The aim of this study was to evaluate the impact of photobiomodulation therapy (PBMT) on histomorphological aspects of submandibular gland (SMG) submitted to salivary gland duct obstruction in hypothyroid rats. Fifty-six male Wistar rats (250 to 300 g) were divided into 4 groups (n = 14): euthyroid (EU), EU + PBMT, hypothyroid (HYPO), and HYPO + PBMT. Duct obstruction of the left submandibular gland (LSMG) was performed in all animals by a ligature procedure. For the induction of hypothyroidism, total thyroidectomy was performed. PBMT groups received irradiation with AlGaInP diode laser (808 nm, 0.04 W, 0.04cm2 spot size, 60 s, 2.4 J per point, 60 J/cm2, 1 W/cm2). Irradiation was performed immediately, 24 h, and 48 h after the obstruction of the salivary gland duct, in one point, extra oral and perpendicular to the gland. Animals were sacrificed after 24 h and 72 h after duct ligature. Our results indicated that salivary duct obstruction and hypothyroidism caused negative modifications on the salivary glands' histomorphology, especially acinar atrophy, after 24 h and 72 h. HYPO + PBMT showed a significant reduction of the inflammatory infiltrate, congested blood vessels, and acinar atrophy in the SMG submandibular salivary gland in 72 h compared to 24 h (p < 0.05). In conclusion, obstruction of the salivary gland excretory duct and hypothyroidism causes severe sialoadenitis with expressive atrophy of the glandular parenchyma. However, PBMT was able to modulate the inflammatory process and delaying acinar atrophy. This study provided insights to better understand the role of the PBMT on the altered salivary gland by duct ligation and associate hypothyroidism.

FUSARIUM-ID v.3.0: An Updated, Downloadable Resource for Fusarium Species Identification.

Species within Fusarium are of global agricultural, medical, and food/feed safety concern and have been extensively characterized. However, accurate identification of species is challenging and usually requires DNA sequence data. FUSARIUM-ID (http://isolate.fusariumdb.org/blast.php) is a publicly available database designed to support the identification of Fusarium species using sequences of multiple phylogenetically informative loci, especially the highly informative ∼680-bp 5' portion of the translation elongation factor 1-alpha (TEF1) gene that has been adopted as the primary barcoding locus in the genus. However, FUSARIUM-ID v.1.0 and 2.0 had several limitations, including inconsistent metadata annotation for the archived sequences and poor representation of some species complexes and marker loci. Here, we present FUSARIUM-ID v.3.0, which provides the following improvements: (i) additional and updated annotation of metadata for isolates associated with each sequence, (ii) expanded taxon representation in the TEF1 sequence database, (iii) availability of the sequence database as a downloadable file to enable local BLAST queries, and (iv) a tutorial file for users to perform local BLAST searches using either freely available software, such as SequenceServer, BLAST+ executable in the command line, and Galaxy, or the proprietary Geneious software. FUSARIUM-ID will be updated on a regular basis by archiving sequences of TEF1 and other loci from newly identified species and greater in-depth sampling of currently recognized species.

Pressure injuries during the SARS-CoV-2 pandemic: A retrospective, case-control study.

AIM OF STUDY: The main objective of this study was to ascertain whether severe alterations in hypoxemic, inflammatory, and nutritional parameters in patients diagnosed with SARS-CoV-2 infection were associated with the occurrence and severity of developed dependency-related injuries. The secondary objective was to determine whether there were prognostic factors associated with the occurrence and severity of developed dependency-related injuries during the SARS-CoV-2 pandemic. MATERIAL AND METHODS: A retrospective, single-centre, case-control study was conducted to compare SARS-CoV-2 patients who developed dependency-related injuries after the first 48 h after admission with a control group made up of SARS-CoV-2 patients without dependency-related injuries. The cases of the 1987 patients diagnosed with SARS-CoV-2 infection during the study period were reviewed. Data from 94 patients who developed dependency-related injuries and from 190 patients who did not develop them during hospital admission were analysed. RESULTS: High baseline dependency levels, prolonged hospital stays, and low oxygen saturation levels on arrival in emergency department triage were associated with the occurrence of dependency-related injuries among patients diagnosed with SARS-CoV-2 infection. CONCLUSIONS: SARS-CoV-2 infection can lead to complications such as dependency-related injuries. Although there are several non-modifiable variables associated with the occurrence of dependency-related injuries in these patients, it is essential to conduct further research and introduce consensus guidelines to reduce their incidence and prevalence.

TCR-based therapy for multiple myeloma and other B-cell malignancies targeting intracellular transcription factor BOB1.

Immunotherapy for hematological malignancies or solid tumors by administration of monoclonal antibodies or T cells engineered to express chimeric antigen receptors or T-cell receptors (TCRs) has demonstrated clinical efficacy. However, antigen-loss tumor escape variants and the absence of currently targeted antigens on several malignancies hamper the widespread application of immunotherapy. We have isolated a TCR targeting a peptide of the intracellular B cell-specific transcription factor BOB1 presented in the context of HLA-B*07:02. TCR gene transfer installed BOB1 specificity and reactivity onto recipient T cells. TCR-transduced T cells efficiently lysed primary B-cell leukemia, mantle cell lymphoma, and multiple myeloma in vitro. We also observed recognition and lysis of healthy BOB1-expressing B cells. In addition, strong BOB1-specific proliferation could be demonstrated for TCR-modified T cells upon antigen encounter. Furthermore, clear in vivo antitumor reactivity was observed of BOB1-specific TCR-engineered T cells in a xenograft mouse model of established multiple myeloma. Absence of reactivity toward a broad panel of BOB1- but HLA-B*07:02+ nonhematopoietic and hematopoietic cells indicated no off-target toxicity. Therefore, administration of BOB1-specific TCR-engineered T cells may provide novel cellular treatment options to patients with B-cell malignancies, including multiple myeloma.

Regulated Expansion and Survival of Chimeric Antigen Receptor-Modified T Cells Using Small Molecule-Dependent Inducible MyD88/CD40.

Anti-tumor efficacy of T cells engineered to express chimeric antigen receptors (CARs) is dependent on their specificity, survival, and in vivo expansion following adoptive transfer. Toll-like receptor (TLR) and CD40 signaling in T cells can improve persistence and drive proliferation of antigen-specific CD4+ and CD8+ T cells following pathogen challenge or in graft-versus-host disease (GvHD) settings, suggesting that these costimulatory pathways may be co-opted to improve CAR-T cell persistence and function. Here, we present a novel strategy to activate TLR and CD40 signaling in human T cells using inducible MyD88/CD40 (iMC), which can be triggered in vivo via the synthetic dimerizing ligand, rimiducid, to provide potent costimulation to CAR-modified T cells. Importantly, the concurrent activation of iMC (with rimiducid) and CAR (by antigen recognition) is required for interleukin (IL)-2 production and robust CAR-T cell expansion and may provide a user-controlled mechanism to amplify CAR-T cell levels in vivo and augment anti-tumor efficacy.

Effect of low-level laser therapy (λ780 nm) on the mechanically damaged dentin-pulp complex in a model of extrusive luxation in rat incisors.

In order to regenerate the dental pulp, many strategies have been developed as phototherapy. In the pulp repair, we do not know if gallium-aluminum-arsenide (GaAlAs) laser preserves the primary odontoblasts or stimulates the formation of more dentin matrix when dental pulp is damaged. The aim of the present study was to examine the effect of laser phototherapy (λ780 nm) on vascularization, inflammation, density of the primary odontoblast layer, and formation of reactionary and reparative dentin in the dental pulp by provoking extrusion of the rat incisor. The upper incisors were extruded 3 mm and then repositioned into their original sockets followed by a laser irradiation of the palatal mucosa (λ = 780 nm; p = 70 mW; CW; 4.2 J/cm2; 60 s) every 48 h. Non-traumatized and/or non-irradiated incisors were used as the controls. At 8 and 30 days after surgery, incisors were processed for histological and histomorphometric analysis. Morphological analysis revealed no differences in vascularization between groups, but showed discrete inflammation in some non-irradiated and injured specimens, which correlated with a more irregular reparative dentin. The density of primary odontoblasts in the groups treated with lasers was higher when compared to non-irradiated groups, but no statistically significant difference between groups (p > 0.05). The thickness of the tertiary dentin was increased in both traumatized groups with no statistically significant difference between non-irradiated and irradiated groups (p > 0.05).The present findings revealed that the GaAlAs laser induced small changes on dentin-pulp complex, with more regular dentin matrix in the irradiated dental pulps.

Laser phototherapy improves early stage of cutaneous wound healing of rats under hyperlipidic diet.

The aim of this study was to evaluate the influence of laser photobiomodulation in cutaneous healing of rats under a hyperlipidic diet. Forty-eight Wistar Albinus rats, weaned, received standard diet (SD) or hyperlipidic diet (HD) for 20 weeks. The groups were divided into SD rats and HD rats, SD-irradiated rats (LSD), and HD-irradiated rats (LHD). Standard cutaneous wound (1 cm(2)) was created on the dorsum of each rat. The irradiation started immediately after surgery and every 48 h for 7 or 14 days (λ660 nm, 40 mW, 6 J/cm(2), ϕ 0,04 cm(2), CW), when they were killed under deep anesthesia. The specimens were removed, routinely processed, stained with hematoxylin/eosin (H/E), and evaluated by light microscopy. Rats fed with hyperlipidic diet had greater intensity in the inflammatory process and prolonged hyperemia. At day 7, the intensity of inflammation was reduced in LSD and LHD groups when compared to their control groups, SD (p = 0.002) and HD (p = 0.02). There was an increase in fibroblast proliferation and collagen deposition, especially in the LHD group. At day 14, the HD group presented more intensive hyperemia than the SD group. It can be concluded that the hyperlipidic diet modified the inflammation pattern in wound healing and that laser light has a positive biomodulative effect on the healing process only in early stages.

Influence of laser photobiomodulation (GaAlAs) on salivary flow rate and histomorphometry of the submandibular glands of hypothyroid rats.

The aim of this study was to analyze the influence of laser photobiomodulation in salivary flow, weight, and histomorphometry of the submandibular glands of hypothyroid rats. Fifty-six male Wistar albino rats were divided in euthyroid group and hypothyroid group, treated with propylthiouracil (PTU) to induce hypothyroidism. Each group was divided into control (without laser) and laser groups (GaAlAs): λ660 nm (40 mW), λ780 nm (40 mW), and λ780 nm (70 mW). The laser application on the submandibular gland occurred after 2 weeks of PTU treatment and repeatedly during 2 weeks every 48 h. The rats were anesthetized, tracheostomized, and the evaluation of the salivary flow rate (µL/min/100 g body weight) was made by the weight of the saliva collected for 15 min from the first drop. After the animals' death, the glands were dissected and processed for histological analysis. There was an evident reduction of the salivary flow of hypothyroid rats in all groups in comparison to euthyroid group (Mann-Whitney test, p < 0.05). No significant difference was found in the salivary flow of rats that received laser photobiomodulation compared with their control groups. Histological analysis revealed a decrease in the parenchyma of the salivary glands of hypothyroid rats, but the laser was not able to reverse this process. Hypothyroid rats irradiated or not with laser showed acini and acinar cells with significantly smaller areas than euthyroid groups. The laser photobiomodulation protocol used was not able to change salivary flow or reverse the acinar atrophy process in the submandibular glands of hypothyroid rats.

SIGLEC-G deficiency increases susceptibility to develop B-cell lymphoproliferative disorders.

The sialic-acid-binding immunoglobulin-like lectin SIGLEC-G is a negative regulator of B-cell receptor-mediated calcium signaling. Its deficiency leads to reduced turnover and increased proliferation and survival of murine B-1a cells. Siglecg(-/-) mice show a premature expansion of polyclonal CD5(+) B cells in the spleen and the peritoneal cavity. Here we studied the fate of B lymphocytes in Siglecg(-/-) mice over time. We demonstrate that in aging animals SIGLEC-G deficiency promotes progressive accumulation of monoclonal B lymphocytes and increases the susceptibility to develop B-cell lymphoproliferative disorders. Lymphoid tumors arising in aged Siglecg(-/-) mice are monoclonal and histologically heterogeneous as they include diffuse large B-cell lymphoma, follicular lymphoma, and medium-to-large B-cell monomorphic lymphoma but surprisingly not chronic lymphocytic leukemia. The tumors express high levels of BCL-2 and are transplantable. In keeping with these findings we have also observed a remarkable down-regulation of the human ortholog SIGLEC10 in human B-cell lymphoma and leukemia cell lines. Taken together, these observations indicate that the down-regulation of negative B-cell receptor regulators such as SIGLEC-G/SIGLEC10 may represent another mechanism relevant to the pathogenesis of B-cell lymphomas.

Effects of LED phototherapy on relative wound contraction and reepithelialization during tissue repair in hypothyroid rats: morphometric and histological study.

The aim of this study was to assess morphometrically and histologically, the effects of light-emitting diode (LED) (λ630 ± 20 nm) phototherapy on reepithelialization and wound contraction during tissue repair in hypothyroid rats. Thyroid hormone deficiency has been associated with disorders of tissue repair. LED phototherapy has been studied using several healing models, but their usefulness in the improvement of hypothyroidism wound healing remains unknown. Under general anesthesia, a standard surgical wound (1 cm(2)) was produced on the dorsum of 48 male Wistar rats divided into four groups of 12 animals each: EC-control euthyroid, ED-euthyroid + LED, HC-control hypothyroid, and HD-Hypothyroid + LED. The irradiation started immediately after surgery and was repeated every other day for 7 and 14 days. Photographs of the wound were taken at the day of the surgical procedure and on days 8 and 15 after surgery, when animals' deaths occurred. The specimens were removed, routinely processed, and stained with hematoxylin/eosin. Seven days after the surgery, it was possible to observe statistically significant reductions in the wound area of the irradiated euthyroid group, in comparison to hypothyroid group, irradiated and non-irradiated (ANOVA, p < 0.05). The reepithelialization was significantly higher in the euthyroid and hypothyroid groups irradiated with LED than in the non-irradiated groups (Fisher's test, p < 0.05). No significant difference was found in the experimental period of 14 days among the groups. The hypothyroidism delayed wound healing and the LED phototherapy, at these specific parameters, improved the process of reepithelialization in the presence of hypothyroidism.

Chimeric TßRII-SE/Fc overexpression by a lentiviral vector exerts strong antitumoral activity on colorectal cancer-derived cell lines in vitro and on xenografts.

The TGF signaling pathway is a key regulator of cancer progression. In this work, we report for the first time the antitumor activity of TßRII-SE/Fc, a novel peptibody whose targeting domain is comprised of the soluble endogenous isoform of the human TGF-ß type II receptor (TßRII-SE). Overexpression of TßRIISE/Fc reduces in vitro cell proliferation and migration while inducing cell cycle arrest and apoptosis in human colorectal cancer-derived cell lines. Moreover, TßRII-SE/Fc overexpression reduces tumorigenicity in BALB/c nude athymic mice. Our results revealed that TRII-SE/Fc-expressing tumors were significantly reduced in size or were even incapable of developing. We also demonstrated that the novel peptibody has the ability to inhibit the canonical TGF-ß and BMP signaling pathways while identifying SMAD-dependent and independent proteins involved in tumor progression that are modulated by TßRII-SE/Fc. These findings provide insights into the underlying mechanism responsible for the antitumor activity of TßRII-SE/Fc. Although more studies are required to demonstrate the effectiveness and safety of the novel peptibody as a new therapeutic for the treatment of cancer, our initial in vitro and in vivo results in human colorectal tumor-derived cell lines are highly encouraging. Our results may serve as the foundation for further research and development of a novel biopharmaceutical for oncology.

Genetic Evidence of Endocannabinoid System on Perceived Stress and Restricted Food Intake: The Role of Variants rs324420 in FAAH Gene and rs1049353 in CNR1 Gene.

Background: The endocannabinoid system (ECS) is active in brain regions involved in stress, food intake, and emotional regulation. The CB1 receptor and the fatty acid amide hydrolase (FAAH) enzyme regulate the ECS. Genetic variants in the FAAH gene (rs324420) and in the CNR1 gene (rs1049353) have been involved in both chronic stress and obesity. As a maladaptive strategy to evade the stress, three dysfunctional eating patterns may appear: cognitive restriction, disinhibition, and emotional eating. Aim: To evaluate the association of variants rs324420 in the FAAH gene and rs1049353 in the CNR1 gene with perceived stress, dysfunctional eating patterns, and anthropometric and body composition variables. Methods: This cross-sectional study included 189 participants from western Mexico. The Spanish version of the Three-Factor Eating Questionnaire and the Perceived Stress Scale were applied. Genotyping was performed with TaqMan® probes. Results: It was found that subjects with CA/AA genotypes in FAAH had a higher risk of presenting high scores in stress perception than CC genotype carriers (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.007-3.339; p = 0.048); in addition, the CC genotype of this genetic variant was related to higher body weight and body fat, but no association was found with dysfunctional eating patterns. As for the CNR1 single-nucleotide polymorphism, this variant showed no significant association with stress perception scores, but subjects with GA/AA genotypes in CNR1 had a lower risk of presenting high scores of restriction in food intake compared with GG genotype carriers (OR 0.11, 95% CI 0.046-0.322; p < 0.001). Therefore, this study suggests a differential role of the ECS genes FAAH and CNR1 in perceived stress and dysfunctional eating patterns, respectively. Further studies in other populations are required.

Lack of TIR8/SIGIRR triggers progression of chronic lymphocytic leukemia in mouse models.

Inflammation is involved in the initiation and progression of several chronic lymphoid malignancies of B-cell type. Toll-like receptors (TLR) are transmembrane inflammatory receptors that on recognition of pathogen-associated molecular patterns trigger an innate immune response and bridge the innate and adaptive immune response by acting as costimulatory signals for B cells. Fine tuning of TLR and IL-1R-like (ILR) activity is regulated by TIR8 (SIGIRR), a transmembrane receptor of the TLR/ILR family which inhibits other family members. To test the hypothesis that TLR and/or ILR may play a role in the natural history of chronic B-cell tumors, we crossed Eµ-TCL1 transgenic mice, a well established model of chronic lymphocytic leukemia (CLL), with mice lacking the inhibitory receptor TIR8 that allow an unabated TLR-mediated stimulation. We here report that in the absence of TIR8 the appearance of monoclonal B-cell expansions is accelerated and mouse life span is shortened. The morphology and phenotype of the mouse leukemic expansions reproduce the progression of human CLL into an aggressive and frequently terminal phase characterized by the appearance of prolymphocytes. This study reveals an important pathogenetic implication of TLR in CLL development and progression.

The therapeutic potential of the humoral pattern recognition molecule PTX3 in chronic lung infection caused by Pseudomonas aeruginosa.

Chronic lung infections by Pseudomonas aeruginosa strains are a major cause of morbidity and mortality in cystic fibrosis (CF) patients. Although there is no clear evidence for a primary defect in the immune system of CF patients, the host is generally unable to clear P. aeruginosa from the airways. PTX3 is a soluble pattern recognition receptor that plays nonredundant roles in the innate immune response to fungi, bacteria, and viruses. In particular, PTX3 deficiency is associated with increased susceptibility to P. aeruginosa lung infection. To address the potential therapeutic effect of PTX3 in P. aeruginosa lung infection, we established persistent and progressive infections in mice with the RP73 clinical strain RP73 isolated from a CF patient and treated them with recombinant human PTX3. The results indicated that PTX3 has a potential therapeutic effect in P. aeruginosa chronic lung infection by reducing lung colonization, proinflammatory cytokine levels (CXCL1, CXCL2, CCL2, and IL-1ß), and leukocyte recruitment in the airways. In models of acute infections and in in vitro assays, the prophagocytic effect of PTX3 was maintained in C1q-deficient mice and was lost in C3- and Fc common γ-chain-deficient mice, suggesting that facilitated recognition and phagocytosis of pathogens through the interplay between complement and FcγRs are involved in the therapeutic effect mediated by PTX3. These data suggested that PTX3 is a potential therapeutic tool in chronic P. aeruginosa lung infections, such as those seen in CF patients.