DNA mismatch repair system expression in salivary gland tumors: A Systematic Review.

BACKGROUND: The DNA mismatch repair (MMR) system serves as a sophisticated guardian of the precise functioning of the human genome. Dysregulation within this system is linked to the oncogenesis process. Reduced expression of MMR system proteins identified in salivary gland tumors (SGTs) suggests an increased risk of tumoral occurrence. This study aims to analyze the expression of MMR proteins in SGTs and discuss the relevance of this association to the development of these neoplasms. MATERIAL AND METHODS: This review was conducted following the PRISMA guidelines and was registered in PROSPERO (CRD42023465590). A comprehensive search of the PubMed/MEDLINE, Web of Science, Scopus, Embase, and ProQuest (non-peer reviewed platform) was performed to answer the question "Do DNA MMR system proteins exhibit expression in SGTs?". The methodological quality of the selected studies was assessed using the JBI's Critical Appraisal Tool. RESULTS: A total of 142 patients with benign SGTs and 84 with malignant SGTs were included in this review. The literature analysis showed a notable reduction in the expression of DNA MMR system proteins (hHMS2, hMLH1, hMSH3 and hMSH6) in the percentage of marked cells. CONCLUSIONS: The reduction in the expression of the DNA MMR system proteins suggests an interesting correlation with the development of malignant and benign SGTs. Nevertheless, further investigations are warranted to better clarify the precision of measuring biomarker protein expression.

Frequency of BRAF V600E immunoexpression in ameloblastomas: a multi-institutional analysis of 86 cases in Latin America and comprehensive review of the literature.

BACKGROUND: Paracoccidioidomycosis (PCM) is the leading cause of death among systemic mycoses in Brazil. On the other hand, oral squamous cell carcinoma (OSCC) is the most prevalent malignant neoplasm of the mouth. Both lesions rarely affect the tongue dorsum and may share similar clinical characteristics. This study aimed to retrieve cases of single oral ulcers diagnosed as PCM or OSCC. MATERIAL AND METHODS: A cross-sectional retrospective study was conducted. All patients who had a single ulcer on dorsum of the tongue and confirmed diagnosis of PCM or OSCC were evaluated. RESULTS: A total of 9 patients (5 women and 4 men) were evaluated, 5 patients had OSCCs (mean age = 69,8 years old), and 4 patients PCM (mean age = 51 years old). Most of the lesions were infiltrated and indurated in the palpation exam. Duration ranged from 1 to 12 months (mean time of 5.2 months and 4.7 months for OSCC and PCM, respectively). OSCC was the main clinical diagnosis hypothesis. CONCLUSIONS: Although uncommon, PCM and OSCC should be considered as a differential diagnosis hypothesis in infiltrated ulcers on the tongue dorsum. Incisional biopsy is mandatory to confirm the diagnosis and indicate the appropriate treatment.

Synchronous cemento-ossifying fibromas: a systematic review.

BACKGROUND: This systematic review aimed to incorporate published data regarding synchronous cemento-ossifying fibromas (COF), with an analysis of their demographic and clinicopathological characteristics. MATERIAL AND METHODS: Case reports and case series of synchronous COF were searched in PubMed, Web of Science, Scopus, EMBASE, and LILACS according to the PRISMA (2020) statement. Also, a manual search was carried out and the grey literature was assessed. A descriptive statistical analysis was performed. RESULTS: Nineteen studies comprising 20 cases of synchronous COF were included. The mean age at diagnosis was 35 years (±13.8), with a predominance of female patients (n=12/60%). In 13 cases (65%) the mandible and the maxilla were affected simultaneously. In two cases (10%) first-degree relatives (parents or siblings) had been previously diagnosed with COF. The diagnostic hypotheses were reported in 8 cases (40%), with florid cemento-osseous dysplasia, ameloblastic fibroodontoma, calcifying cystic odontogenic tumor, osteoma and cementoblastoma being cited in the differential diagnosis. Among the cases with details about management (n=17), eleven were treated by surgical enucleation and/or excision (64.7%). Follow-up was provided for 10 cases (50%), with a mean period of 44.7±62.19 months. Recurrence occurred in three of informed cases. CONCLUSIONS: Synchronous manifestation of COF is rare. Female patients around the 3rd decade of life are more commonly affected. Bilateral involvement of the mandible and maxilla is the most common clinical presentation.

Stafne's bone defect: a systematic review.

BACKGROUND: This systematic review integrated the available data published in the literature on Stafne's bone defect (SBD), considering the clinical, imaging and histopathological results. MATERIAL AND METHODS: An electronic search was undertaken in six databases. Eligibility criteria were: articles in English, Spanish, and Portuguese describing case reports or case series of SBD, reported up to September/2021. Risk of bias was assessed using the Joanna Briggs Institute tool. RESULTS: A total of 98 articles were retrieved, involving 465 individuals with SBD and were included for quantitative analysis. Mean age was 52.78 years (range: 11-89 years), with male predilection (n=374/80.85%). Radiographs were the most frequent imagiological exams (n=298/64.09%), followed by computed tomography (n=98/21.08%). SBD was more prevalent in the posterior mandible (n=361/93.77%) as a hypodense radiolucent lesion (n=250/77.40%). Mean size was 1.58 cm (range: 0.3-.8.0 cm). Two-hundred-and-two lesions (97.37%) were unilocular and 126 (91.97%) were classified as well-defined. Clinical symptoms were reported in 73 cases, while 68 cases (93.15%) were asymptomatic. Only 34 cases (12.32%) were submitted to histopathological examination. Mean follow-up time was 26.42 ±25.39 months. CONCLUSIONS: SBD is more frequent in male patients in the fifth and sixth decade of life. Classic SBD is radiographically characterized as a single, unilocular and well-defined lesion in the posterior region of the jaw with a radiolucent/hypodense appearance.

Awareness on oral cancer among patients attending dental school clinics in Brazil.

BACKGROUND: Oral cancer is considered a public health problem worldwide. Dental schools may play an important role in educating patients about oral cancer. This study aimed at evaluating the knowledge of patients attending clinics at two dental schools in Brazil. MATERIAL AND METHODS: From March 2017 to April 2017, 251 patients who were attending clinics at two dental schools in Recife, Brazil, were included in the study. Patients were contacted in the waiting rooms of the clinic. Each participant completed a self-administered questionnaire, which consists of 21 questions, including socio-demographic and specific information on the disease. Data were analyzed using descriptive statistics, and a chi-square test (with a 5% significance level) was used to assess the correlation between the variables, education and family income and other variables. RESULTS: Most participants were women (64.9%) with a mean age of 42.72 years. Most participants were knowledgeable about oral cancer and identified tobacco use (48.6%), alcohol consumption (25.1%), and solar radiation (12%) as the primary risk factors for the disease. Only 36.7% of the participants reported having received counselling on oral cancer, of which 18.3% received the information from a dentist. All patients with an income higher than six minimum wages were aware about oral cancer (p = 0.001). CONCLUSIONS: These findings emphasize the importance of educational programs in dental schools as well providing integrated services for patients seeking care at school clinics, including population's awareness on oral cancer.

Voriconazole and squamous cell carcinoma after lung transplantation: A multicenter study.

This study evaluated the independent contribution of voriconazole to the development of squamous cell carcinoma (SCC) in lung transplant recipients, by attempting to account for important confounding factors, particularly immunosuppression. This international, multicenter, retrospective, cohort study included adult patients who underwent lung transplantation during 2005-2008. Cox regression analysis was used to assess the effects of voriconazole and other azoles, analyzed as time-dependent variables, on the risk of developing biopsy-confirmed SCC. Nine hundred lung transplant recipients were included. Median follow-up time from transplantation to end of follow-up was 3.51 years. In a Cox regression model, exposure to voriconazole alone (adjusted hazard ratio 2.39, 95% confidence interval 1.31-4.37) and exposure to voriconazole and other azole(s) (adjusted hazard ratio 3.45, 95% confidence interval 1.07-11.06) were associated with SCC compared with those unexposed after controlling for important confounders including immunosuppressants. Exposure to voriconazole was associated with increased risk of SCC of the skin in lung transplant recipients. Residual confounding could not be ruled out because of the use of proxy variables to control for some confounders. Benefits of voriconazole use when prescribed to lung transplant recipients should be carefully weighed versus the potential risk of SCC. EU PAS registration number: EUPAS5269.

Significant bone loss after stopping long-term denosumab treatment: a post FREEDOM study.

We evaluate 38 elderly women who had received long-term denosumab treatment after stopping the drug. Taking into account the gain during treatment and the loss after stopping treatment, they lost 35.5% of the total gain in the spine, 44.6% of the total gain in the femoral neck, and 103.3% in the total hip. INTRODUCTION: Denosumab (DMAb) is a soluble inhibitor of the receptor activator of nuclear factor-kappaB ligand (RANKL) and, therefore, does not incorporate into the bone matrix. Consistently, DMAb discontinuation is associated with reversal of the effects attained with treatment. PURPOSE: The aim of this study is to assess changes in BMD after a year of discontinuation of DMAb in a group of postmenopausal women treated with DMAb for 7 or 10 years. Secondly, is to evaluate the occurrence of fragility fractures. METHODS: Women who had participated in the FREEDOM study and its extension were invited to participate in this follow-up study. BMD at LS and hip and spine X-rays were obtained. Results were compared to the last value obtained while in treatment to assess changes after discontinuation. RESULTS: Thirty-eight women, mean age: 81 ± 3.4 years completed study procedures; none had received bisphosphonates after stopping DMAb. Mean gap time between DMAb last dose and the follow-up visit was 17 months (range 16-20 months). Bone mineral density (BMD) decreased significantly in all regions: - 8.1% in LS, - 6% in FN, and - 8.4% in TH. Five (5/38, 13.15%) patients had a fragility fracture, one suffered a wrist fracture, and four experienced vertebral fractures. Three patients suffered one vertebral fracture and one of them had two vertebral fractures. Laboratory results showed the following mean values: CTX = 996 ± 307 pg/ml (normal values 550 ± 226 pg/ml); osteocalcin = 55.2 ± 18.6 ng/ml (normal value 42 ng/ml); and 25 OH vitamin D = 23.7 ± 6.9 ng/ml. CONCLUSION: Our results describe the rapid bone loss occurring after cessation of denosumab treatment. Further studies are needed to assess if patients have a higher risk of fracture after stopping DMAb and if so, which patients have the highest risk, and assess the role of transitioning to bisphosphonates in the long term.

Epidemiology and outcomes of Clostridium difficile infection in allogeneic hematopoietic cell and lung transplant recipients.

BACKGROUND: Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described. METHODS: We performed a prospective, multicenter study of CDI within 365 days post-allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post-transplant and while hospitalized and contacted monthly up to 18 months post-transplantation. RESULTS: Six sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post-index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post-index date (HR = 4.7, P = .09). CONCLUSIONS: The epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post-transplant period.

Mycobacterium bovis hip bursitis in a lung transplant recipient.

We present a report of extrapulmonary Mycobacterium bovis infection in a lung transplant recipient. M. bovis is acquired predominantly by zoonotic transmission, particularly from consumption of unpasteurized foods. We discuss epidemiologic exposure, especially as relates to the Mexico-US border, clinical characteristics, resistance profile, and treatment.

Differential Recruitment of Dendritic Cells Subsets to Lymph Nodes Correlates with a Protective or Permissive T-Cell Response during Leishmania (Viannia) Braziliensis or Leishmania (Leishmania) Amazonensis Infection.

Leishmania (L.) amazonensis (La) and L. (V.) braziliensis (Lb) are responsible for a large clinical and immunopathological spectrum in human disease; while La may be responsible for anergic disease, Lb infection leads to cellular hypersensitivity. To better understand the dichotomy in the immune response caused by these Leishmania species, we evaluated subsets of dendritic cells (DCs) and T lymphocyte in draining lymph nodes during the course of La and Lb infection in BALB/c mice. Our results demonstrated a high involvement of DCs in La infection, which was characterized by the greater accumulation of Langerhans cells (LCs); conversely, Lb infection led to an increase in dermal DCs (dDCs) throughout the infection. Considering the T lymphocyte response, an increase of effector, activated, and memory CD4(+) T-cells was observed in Lb infection. Interleukin- (IL-) 4- and IL-10-producing CD4(+)and CD8(+) T-cells were present in both La and Lb infection; however, interferon- (IFN-) γ-producing CD4(+)and CD8(+) T-cells were detected only in Lb infection. The results suggest that during Lb infection, the dDCs were the predominant subset of DCs that in turn was associated with the development of Th1 immune response; in contrast La infection was associated with a preferential accumulation of LCs and total blockage of the development of Th1 immune response.

Population structure of Annona crassiflora: an endemic plant species of the Brazilian Cerrado.

Habitat fragmentation has numerous consequences, particularly to endemic species, and has a negative impact on the genetic diversity of neglected species, leading to genetic drift. Annona crassiflora Mart. is a species that is endemic to Brazil, and its incidence in the Cerrado biome has decreased. The identification and characterization of its remaining diversity is necessary for its conservation. Our aim was to study the population structure of A. crassiflora populations from different Cerrado regions in Minas Gerais State, Brazil (Corinto, Curvelo, Carmo da Mata, Boa Esperança, and Paraguaçu) using inter-simple sequence repeat (ISSR) markers and DNA content. Nuclear DNA content was estimated by flow cytometry using 10 individuals from each population. ISSR markers were used for genotyping accessions in order to study their genetic diversity and population structures. We found considerable genetic variation among populations, with the highest variability observed in the Curvelo population. There was a significant positive correlation between DNA content and latitude (r = 0.46, P = 0. 0003). A Bayesian-based cluster analysis grouped the populations into three clusters, which followed their geographical origins. There was some level of genetic diversity and differentiation among the populations, suggesting the need for a conservation plan for this species. The ISSR markers and DNA content analysis were effective in studying the genetic diversity and population structure of A. crassiflora.

Targeted versus universal antifungal prophylaxis among liver transplant recipients.

Guidelines recommend targeted antifungal prophylaxis for liver transplant (LT) recipients based on tiers of risk, rather than universal prophylaxis. The feasibility and efficacy of tiered, targeted prophylaxis is not well established. We performed a retrospective study of LT recipients who received targeted prophylaxis (n = 145; voriconazole [VORI; 54%], fluconazole [8%], no antifungal [38%]) versus universal VORI prophylaxis (n = 237). Median durations of targeted and universal prophylaxis were 11 and 6 days, respectively (p < 0.0001). The incidence of invasive fungal infections (IFIs) in targeted and universal groups was 6.9% and 4.2% (p = 0.34). Overall, intra-abdominal candidiasis (73%) was the most common IFI. Posttransplant bile leaks (p = 0.001) and living donor transplants (p = 0.04) were independent risk factors for IFI. IFIs occurred in 6% of high-risk transplants who received prophylaxis and 4% of low-risk transplants who did not receive prophylaxis (p = 1.0). Mortality rates (100 days) were 10% (targeted) and 7% (universal) (p = 0.26); attributable mortality due to IFI was 10%. Compliance with prophylaxis recommendations was 97%. Prophylaxis was discontinued for toxicity in 2% of patients. Targeted antifungal prophylaxis in LT recipients was feasible and safe, effectively prevented IFIs and reduced the number of patients exposed to antifungals. Bile leaks and living donor transplants should be considered high-risk indications for prophylaxis.

The association of HPV genotype with the regression, persistence or progression of low-grade squamous intraepithelial lesions.

BACKGROUND: Human papillomavirus (HPV) is a highly prevalent sexually transmitted virus causing cytological alterations that precede cervical cancer. Approximately 130 genotypes have been sequenced. Low-grade squamous intraepithelial lesions (LSIL) are the most frequent cytological alteration and have an uncertain behavior. OBJECTIVES: To analyze the frequency of HPV types in LSIL and their association with the regression, persistence or progression of these lesions. METHODS: A cohort study of forty patients with LSIL cytology was conducted from December 2007 to March 2011. The follow-up lasted two years and included cytology and colposcopy. HPV detection was performed using PCR, and genotyping was performed using PCR-specific and RFLP techniques. RESULTS: DNA-HPV was detected in 87% (35/40) of the cases, with oncogenic HPV accounting for 76%; type 16 in 32% (11/35) and type 18 in 20%. LSIL regression, persistence and progression rates at the end of the study were 60%, 23% and 17%, respectively. There was 50% regression in lesions in the high oncogenic risk group (types 16 and 18). CONCLUSION: HPV 16 was the most frequent genotype found in LSIL. The persistence and progression of the LSIL were related to the persistence of oncogenic HPV. The longer the follow-up time, the lower the LSIL persistence rate and the higher its regression rate; the progression rate remained stable. In addition to the presence of oncogenic HPV, other factors are necessary for the progression of LSIL.

Safety and tolerability of clofazimine as salvage therapy for atypical mycobacterial infection in solid organ transplant recipients.

BACKGROUND: The treatment of Mycobacterium avium complex (MAC) requires prolonged, multidrug therapy, which is often not well tolerated. In solid organ transplant (SOT) recipients, drug-drug interactions complicate treatment further. Failure or intolerance requires the use of salvage regimens, and clofazimine is one of the drugs that can be used. No data are available on the safety and tolerability of clofazimine for the treatment of MAC in SOT recipients. METHODS: Retrospective review of all SOT recipients treated for MAC infection with clofazimine at a large transplant center between 2006 and 2013. RESULTS: Five SOT recipients received clofazimine as salvage therapy. Transplanted organs were lungs in 3 patients, and kidney and liver in 1 patient each. Infection was diagnosed at a median of 22 months (range 4-57) post transplant. Sites of infection were the lungs in 2 patients, and septic arthritis, mesenteric, and disseminated disease in 1 patient each. All patients received standard anti-MAC therapy for a median of 26 weeks (range 18-45) before starting clofazimine. Indications for use of clofazimine included a lack of response to previous therapy (3 patients), and poor tolerance of other regimens (3 patients). All patients received at least 2 additional drugs besides clofazimine. Median duration of clofazimine-containing regimen was 8 months (range 2-18). Clofazimine was discontinued because of gastrointestinal intolerance in 1 of the 5 patients. The most common adverse event from clofazimine was skin discoloration, in 60% of patients. No hepatotoxicity or hematologic toxicity occurred. Microbiological clearance and resolution of clinical disease was documented in 2 of 5 patients; and 2 of the 5 patients died of other causes while on therapy. CONCLUSIONS: Clofazimine appears safe and may be considered as a salvage therapeutic option in SOT recipients with MAC infection who are intolerant or unresponsive to standard therapy. The small sample size does not allow conclusions regarding efficacy.

Compression-induced crossovers for the ground state of classical dipole lattices on a Möbius strip.

We explore the ground-state properties of a lattice of classical dipoles spanned on the surface of a Möbius strip. The dipole equilibrium configurations depend significantly on the geometrical parameters of the Möbius strip, as well as on the lattice dimensions. As a result of the variable dipole spacing on the curved surface of the Möbius strip, the ground state can consist of multiple domains with different dipole orientations which are separated by domain-wall-like boundaries. We analyze in particular the dependence of the ground-state dipole configuration on the width of the Möbius strip and highlight two crossovers in the ground state that can be correspondingly tuned. A first crossover changes the dipole lattice from a phase which resists compression to a phase that favors it. The second crossover leads to an exchange of the topological properties of the two involved domains. We conclude with a brief summary and an outlook on more complex topologically intricate surfaces.

Donor-derived Trypanosoma cruzi infection in solid organ recipients in the United States, 2001-2011.

Although Trypanosoma cruzi, the parasite that causes Chagas disease, can be transmitted via organ transplantation, liver and kidney transplantation from infected donors may be feasible. We describe the outcomes of 32 transplant recipients who received organs from 14 T. cruzi seropositive donors in the United States from 2001 to 2011. Transmission was confirmed in 9 recipients from 6 donors, including 3 of 4 (75%) heart transplant recipients, 2 of 10 (20%) liver recipients and 2 of 15 (13%) kidney recipients. Recommended monitoring posttransplant consisted of regular testing by PCR, hemoculture, and serology. Thirteen recipients had no or incomplete monitoring; transmission was confirmed in five of these recipients. Four of the five recipients had symptomatic disease and all four died although death was directly related to Chagas disease in only one. Nineteen recipients had partial or complete monitoring for T. cruzi infection with weekly testing by PCR, hemoculture and serology; transmission was confirmed in 4 of 19 recipients with no cases of symptomatic disease. Our results suggest that liver and kidney transplantation from T. cruzi seropositive donors may be feasible when the recommended monitoring schedule for T. cruzi infection is followed and prompt therapy with benznidazole can be administered.

Epidemiology and outcomes of deep surgical site infections following lung transplantation.

We conducted a retrospective study of deep surgical site infections (SSIs) among consecutive patients who underwent lung transplantation (LTx) at a single center from 2006 through 2010. Thirty-one patients (5%) developed SSIs at median 25 days after LTx. Empyema was most common (42%), followed by surgical wound infections (29%), mediastinitis (16%), sternal osteomyelitis (6%), and pericarditis (6%). Pathogens included Gram-positive bacteria (41%), Gram-negative bacteria (41%), fungi (10%) and Mycobacterium abscessus, Mycoplasma hominis and Lactobacillus sp. (one each). Twenty-three percent of SSIs were due to pathogens colonizing recipients' native lungs at time of LTx, suggesting surgical seeding as a source. Patient-related independent risk factors for SSIs were diabetes and prior cardiothoracic surgery; procedure-related independent risk factors were LTx from a female donor, prolonged ischemic time and number of perioperative red blood cell transfusions. Mediastinitis and sternal infections were not observed among patients undergoing minimally invasive LTx. SSIs were associated with 35% mortality at 1 year post-LTx. Lengths of stay and mortality in-hospital and at 6 months and 1 year were significantly greater for patients with SSIs other than empyema. In conclusion, deep SSIs were uncommon, but important complications in LTx recipients because of their diverse microbiology and association with increased mortality.

Epidemiology and molecular characterization of bacteremia due to carbapenem-resistant Klebsiella pneumoniae in transplant recipients.

We conducted a retrospective study of 17 transplant recipients with carbapenem-resistant Klebsiella pneumoniae bacteremia, and described epidemiology, clinical characteristics and strain genotypes. Eighty-eight percent (15/17) of patients were liver or intestinal transplant recipients. Outcomes were death due to septic shock (18%), cure (24%) and persistent (>7 days) or recurrent bacteremia (29% each). Thirty- and 90-day mortality was 18% and 47%, respectively. Patients who were cured received at least one active antimicrobial agent and underwent source control interventions. Forty-one percent (7/17) of patients had intra-abdominal infections; all except one developed persistent/recurrent bacteremia despite drainage. Two patients tolerated persistent bacteremia for >300 days. All patients except one were infected with sequence type 258 (ST258), K. pneumoniae carbapenemase (KPC)-2-producing strains harboring a mutant ompK35 porin gene; the exception was infected with an ST37, KPC-3-producing strain. Seventy-one percent (12/17) of patients were infected with ST258 ompK36 mutant strains. In two patients, persistent bacteremia was caused by two strains with different ompK36 genotypes. Three ompK36 mutations were associated with significantly higher carbapenem minimum inhibitory concentrations than wild-type ompK36. Pulse-field gel electrophoresis identified a single ST258 lineage; serial strains from individual patients were indistinguishable. In conclusion, KPC-K. pneumoniae bacteremia exhibited highly diverse clinical courses following transplantation, and was caused by clonal ST258 strains with different ompK36 genotypes.

Fundamental solution of diffusion equation for Kappa gas: Diffusion length for suprathermal electrons in solar wind.

A recent numerical treatment of data obtained by the Parker Solar Probe spacecraft describes the electron concentration in solar wind as a function of the heliocentric distance based on a Kappa distribution with spectral index κ=5. In this work, we derive and, subsequently, solve an entirely different class of nonlinear partial differential equations describing the one-dimensional diffusion of a suprathermal gas. The theory is applied to describe the aforementioned data and we find a spectral index κ≳1.5 providing the widely acknowledged identification of Kappa electrons in solar wind. We also find that suprathermal effects increase the length scale of classical diffusion by one order of magnitude. Such a result does not depend on the microscopic details of the diffusion coefficient since our theory is based on a macroscopic formulation. Forthcoming extensions of our theory by including magnetic fields and relating our formulation to nonextensive statistics are briefly addressed.

ATPergic signaling disruption in human sepsis as a potential source of biomarkers for clinical use.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated inflammatory response to infection. To date, there is no specific treatment established for sepsis. In the extracellular compartment, purines such as adenosine triphosphate (ATP) and adenosine play essential roles in the immune/inflammatory responses during sepsis and septic shock. The balance of extracellular levels among ATP and adenosine is intimately involved in the signals related to immune stimulation/immunosuppression balance. Specialized enzymes, including CD39, CD73, and adenosine deaminase (ADA), are responsible to metabolize ATP to adenosine which will further sensitize the P2 and P1 purinoceptors, respectively. Disruption of the purinergic pathway had been described in the sepsis pathophysiology. Although purinergic signaling has been suggested as a potential target for sepsis treatment, the majority of data available were obtained using pre-clinical approaches. We hypothesized that, as a reflection of deregulation on purinergic signaling, septic patients exhibit differential measurements of serum, neutrophils and monocytes purinergic pathway markers when compared to two types of controls (healthy and ward). It was observed that ATP and ADP serum levels were increased in septic patients, as well as the A2a mRNA expression in neutrophils and monocytes. Both ATPase/ADPase activities were increased during sepsis. Serum ATP and ADP levels, and both ATPase and ADPase activities were associated with the diagnosis of sepsis, representing potential biomarkers candidates. In conclusion, our results advance the translation of purinergic signaling from pre-clinical models into the clinical setting opening opportunities for so much needed new strategies for sepsis and septic shock diagnostics and treatment.