Association between genetic variants in key vitamin-D-pathway genes and external apical root resorption linked to orthodontic treatment.

This study evaluated the association between single-nucleotide polymorphisms (SNPs) in vitamin-D-related genes and the amount of external apical root resorption linked to orthodontic treatment. One hundred and forty-three individuals were assessed. The amount of external apical root resorption of upper central incisors (EARRinc ) and lower first molars (EARRmol ) were evaluated in radiographs. Seven SNPs were genotyped across four genes including the vitamin D receptor [VDR], group-specific component [GC], cytochrome P450 family 27 subfamily B member 1 [CYP27B1], and cytochrome P450 family 24 subfamily A member 1 [CYP24A1]. Linear regressions were implemented to determine allele-effects on external apical root resorption. Individuals carrying the AA genotype in VDR rs2228570 had a 21% higher EARRmol than those having AG and GG genotypes (95% CI: 1.03,1.40). EARRmol in heterozygous rs2228570, was 12% lower than for homozygotes (95%CI: 0.78,0.99). Participants with the CCG haplotype (rs1544410-rs7975232-rs731236) in VDR had an EARRmol 16% lower than those who did not carry this haplotype. Regarding CYP27B1 rs4646536, EARRinc in participants who had at least one G allele was 42% lower than for homozygotes AA (95%CI: 0.37,0.93). Although these results did not remain significant after multiple testing adjustment, potential associations may still be suggested. Further replication studies are needed to confirm or refute these findings.

Association Between Demodex Infestation and Severe Acne Vulgaris: A Cross-Sectional Study of 168 Patients. / Asociación entre la infestación por el Demodex sp. y el acné vulgar grave. Estudio transversal de 168 pacientes.

BACKGROUND AND OBJECTIVES: Infestation with Demodex mites has been associated with acne vulgaris. The aim of this study was to explore the association between Demodex infestation and severe acne vulgaris in outpatients seen at Hospital Regional Lambayeque in Chiclayo, Peru. MATERIAL AND METHODS: We conducted a cross-sectional study of 46 patients with severe acne and 92 patients with nonsevere acne. Severe acne vulgaris was diagnosed if the score was 3 or more on the Spanish Acne Severity Scale (EGAE, in its Spanish acronym). Demodex infestation was diagnosed when a skin surface biopsy showed more than 5 mites/cm2. RESULTS: The patients had a median age of 18 years (interquartile range, 15-20 years), 60.9% were male, 81.9% lived in an urban area, and 29.7% were infested with Demodex mites. In the bivariate analysis, severe acne vulgaris was significantly associated with Demodex infestation (P=.001), sex (P=.003), residence (P=.015), a paternal history of acne (P=.045), a maternal history of acne (P=.045), and type of skin (P<.001). In the multivariate analysis, after adjustment for male sex, urban residence, previous treatment, maternal and paternal history of acne vulgaris, and an oily skin type, patients with Demodex infestation were 4.2 times more likely to have severe acne vulgaris (95% CI: 1.6-10.9, P=.003). CONCLUSION: Demodex infestation was associated with severe acne vulgaris in outpatients at our hospital.

Atypical phenotype and response of B cells in patients with seropositive rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) may be classified as seropositive or seronegative according to the presence of autoantibodies. An abnormal B cell phenotype and function could be one of the main components of the immunopathology of seropositive patients; however, there is little information regarding B cell defects in these patients. This study shows a broad characterization of the B cell phenotype and function in patients with seropositive RA. We focused mainly on the evaluation of subsets, the expression of modulatory molecules of cell activation (CD22, FcÉ£RIIb and FcµR), calcium mobilization, global tyrosine phosphorylation, expression of activation markers, cytokine and immunoglobulin (Ig) production, proliferation and the in-vitro generation of plasma cells. Increased frequency of CD27- IgM- IgD- and CD21- B cells was observed in patients with seropositive RA compared with healthy donors (HD). Decreased expression of CD22 was primarily found in memory B cells of patients with RA regardless of seropositivity. B cells from seropositive patients exhibited normal proliferation, calcium mobilization kinetics and global tyrosine phosphorylation, but showed an increased frequency of CD86+ B cells compared with HD. B cells of seropositive patients secrete less interleukin-10 after in-vitro activation and showed a decreased frequency of plasma cell differentiation and IgM production compared with HD. Our data indicate that patients with seropositive RA have an increased frequency of atypical B cell populations previously associated with chronic activation and antigen exposure. This may result in the observed low responsiveness of these cells in vitro.

Strain Modulation of Si Vacancy Emission from SiC Micro- and Nanoparticles.

Single-photon emitting point defects in semiconductors have emerged as strong candidates for future quantum technology devices. In the present work, we exploit crystalline particles to investigate relevant defect localizations, emission shifting, and waveguiding. Specifically, emission from 6H-SiC micro- and nanoparticles ranging from 100 nm to 5 µm in size is collected using cathodoluminescence (CL), and we monitor signals attributed to the Si vacancy (VSi) as a function of its location. Clear shifts in the emission wavelength are found for emitters localized in the particle center and at the edges. By comparing spatial CL maps with strain analysis carried out in transmission electron microscopy, we attribute the emission shifts to compressive strain of 2-3% along the particle a-direction. Thus, embedding VSi qubit defects within SiC nanoparticles offers an interesting and versatile opportunity to tune single-photon emission energies while simultaneously ensuring ease of addressability via a self-assembled SiC nanoparticle matrix.

Tuberculous sacroiliitis in a patient with systemic lupus erythematosus: a case report and literature review.

Systemic lupus erythematosus (SLE) patients are at higher risk of developing opportunistic infections such as tuberculosis (TB), especially extrapulmonary forms like osteoarticular TB, compared to the general population. However, tuberculous sacroiliitis has been scarcely reported in these patients. We present a 34-year-old woman with SLE who developed articular tuberculosis simultaneously affecting the right sacroiliac joint and the left knee. The patient was successfully treated with antituberculosis therapy for nine months. In this case, in addition to the immunological abnormalities of lupus, the long-term glucocorticoid therapy at high dosages was the main risk factor for the development of osteoarticular tuberculosis.

Urinary neutrophil gelatinase-associated lipocalin and monocyte chemoattractant protein 1 as biomarkers for lupus nephritis in Colombian SLE patients.

Background Information regarding urinary biomarkers in Mestizo and Afro-Latin-American patients is very limited. We investigated whether levels of urinary neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemoattractant protein 1 (MCP-1) are good biomarkers to differentiate patients with lupus nephritis among Latin-American systemic lupus erythematosus (SLE) patients. Methods SLE patients meeting the revised American College of Rheumatology classification criteria for SLE were recruited. Urinary levels of NGAL and MCP-1 were measured using a commercial ELISA kit. Serum anti-C1q antibodies were measured by ELISA. SLE activity was measured with the systemic lupus erythematosus disease activity index (SLEDAI). Mann-Whitney tests were used to compare data and Spearman's rank correlations were used to examine associations between continuous variables. In addition, receiver operating characteristic curves were performed. Results One hundred and twenty SLE patients were recruited (87% women) with a median age of 32.8 ± 12.1 years and median disease duration of 7.3 ± 6.9 years. Afro-Latin-Americans had a significantly higher prevalence of lupus nephritis and higher SLEDAI scores than Mestizos. The three biomarkers were significantly higher in patients with lupus nephritis than in patients without lupus nephritis. In addition, urinary NGAL and MCP-1 were significantly higher in patients with active lupus nephritis than in inactive lupus nephritis. Urinary NGAL levels were significantly higher in Afro-Latin-American patients. A receiver operating characteristic curve for urinary biomarkers for lupus nephritis in all SLE patients showed a good level of sensitivity and specificity. Conclusion In our cohort of SLE patients, we found that urinary NGAL and MCP-1 in addition to anti-C1q antibodies were useful biomarkers for the identification of renal involvement and discrimination of active lupus nephritis among patients with renal disease.

Silicon surface passivation by PEDOT: PSS functionalized by SnO2 and TiO2 nanoparticles.

In this paper, we present a study of silicon surface passivation based on the use of spin-coated hybrid composite layers. We investigate both undoped poly(3,4-ethylenedioxythiophene)/poly-(styrenesulfonate) (PEDOT:PSS), as well as PEDOT:PSS functionalized with semiconducting oxide nanomaterials (TiO2 and SnO2). The hybrid compound was deposited at room temperature by spin coating-a potentially lower cost, lower processing time and higher throughput alternative compared with the commonly used vacuum-based techniques. Photoluminescence imaging was used to characterize the electronic properties of the Si/PEDOT:PSS interface. Good surface passivation was achieved by PEDOT:PSS functionalized by semiconducting oxides. We show that control of the concentration of semiconducting oxide nanoparticles in the polymer is crucial in determining the passivation performance. A charge carrier lifetime of about 275 µs has been achieved when using SnO2 nanoparticles at a concentration of 0.5 wt.% as a filler in the composite film. X-ray diffraction (XRD), scanning electron microscopy, high resolution transmission electron microscopy (HRTEM), energy dispersive x-ray in an SEM, and µ-Raman spectroscopy have been used for the morphological, chemical and structural characterization. Finally, a simple model of a photovoltaic device based on PEDOT:PSS functionalized with semiconducting oxide nanoparticles has been fabricated and electrically characterized.

Major and trace elements in Boletus aereus and Clitopilus prunulus growing on volcanic and sedimentary soils of Sicily (Italy).

The aim of this study was to determine and compare the content of 28 elements (Ag, Al, As, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Mo, Na, Ni, Pb, Rb, Sb, Se, Sr, Tl, U, V and Zn) in fruiting bodies of Boletus aereus Bull. and Clitopilus prunulus P. Kumm collected from eleven unpolluted sites of Sicily (Italy) and, also to relate the abundance of chemical elements in soil with their concentration in mushrooms. Median concentrations of the most abundant elements in Boletus aereus ranged from 31,290 µg/g (K) to 107 µg/g (Zn) in caps and from 24,009 µg/g (K) to 57 µg/g (Zn) in stalks with the following abundance order: K > Na > Ca > Mg > Fe > Al > Rb > Zn. The same elements, in the whole fruiting body of Clitopilus prunulus samples, varied in the range 54,073-92 µg/g following the abundance order: K > Na > Mg > Ca > Fe > Al > Rb > Zn. Metal contents in Boletus aereus and in the whole fruiting body of Clitopilus prunulus, collected from the same sampling sites, showed statistically significant differences for most elements. In particular, Clitopilus prunulus contained around two to four times more Co, Cr, Fe, Mg, Mo, Pb, U and V than caps and stalks of Boletus aereus species which, in turn, was from two to four times more enriched in Cu, Se and Tl. Thus, the elemental content of Boletus aereus and Clitopilus prunulus appeared to be species-dependent. The distribution of chemical elements in Boletus aereus was not uniform throughout the whole fruiting body as most elements were significantly bioconcentrated in caps. Furthermore, the fruit bodies of Boletus aereus from the volcanic soil differed both in major and minor elements concentrations from those collected from sedimentary soils. Cadmium and lead concentrations were below the threshold limits for wild mushrooms proposed by EU Directives (2008 and 2015). The elemental content was not significantly influenced by soil pH.

The Lymphocytes Stimulation Induced DNA Release, a Phenomenon Similar to NETosis.

The release of DNA into the extracellular milieu by neutrophil during a process called NETosis has been postulated as an additional source of autoantigens; a process believed to be important in the pathogenesis of some autoimmune disease, such as systemic lupus erythematosus (SLE). However, it is not established if the B and T cells undergo the release of DNA to the extracellular milleu, in response to different stimuli. In this study, it was observed that the treatment of B and T cells with PMA, ionomycin and the serum from patients with SLE induced the extracellular DNA presence in B and T cells. These findings suggest that the phenomenon were similar to those observed in neutrophil's Etosis; B and T cells also released their DNA into the extracellular milieu. The findings express that serum from patients with SLE and SLEDAI ≤ 8 triggers the release of extracellular DNA in neutrophils, B and T cells, that suggested the presence of soluble factors in the serum that favoured this phenomenon.

Pleuropulmonary involvement in patients with systemic lupus erythematosus from a Latin American inception cohort (GLADEL).

Objectives The objectives of this study were to examine the demographic and clinical features associated with the occurrence of pleuropulmonary manifestations, the predictive factors of their occurrence and their impact on mortality in systemic lupus erythematosus (SLE) patients. Materials and methods The association of pleuropulmonary manifestations with demographic and clinical features, the predictive factors of their occurrence and their impact on mortality were examined in GLADEL patients by appropriate univariable and multivariable analyses. Results At least one pleuropulmonary manifestation occurred in 421 of the 1480 SLE patients (28.4%), pleurisy being the most frequent (24.0%). Age at SLE onset ≥30 years (OR 1.42; 95% CI 1.10-1.83), the presence of lower respiratory tract infection (OR 3.19; 95% CI 2.05-4.96), non-ischemic heart disease (OR 3.17; 95% CI 2.41-4.18), ischemic heart disease (OR 3.39; 95% CI 2.08-5.54), systemic (OR 2.00; 95% CI 1.37-2.91), ocular (OR 1.58; 95% CI 1.16-2.14) and renal manifestations (OR 1.44; 95% CI 1.09-1.83) were associated with pleuropulmonary manifestations, whereas cutaneous manifestations were negatively associated (OR 0.47; 95% CI 0.29-0.76). Non-ischemic heart disease (HR 2.24; 95% CI 1.63-3.09), SDI scores ≥1 (OR 1.54; 95% CI 1.10-2.17) and anti-La antibody positivity (OR 2.51; 95% CI 1.39-4.57) independently predicted their subsequent occurrence. Cutaneous manifestations were protective of the subsequent occurrence of pleuropulmonary manifestations (HR 0.62; 95% CI 0.43-0.90). Pleuropulmonary manifestations independently contributed a decreased survival (HR: 2.79 95% CI 1.80-4.31). Conclusion Pleuropulmonary manifestations are frequent in SLE, particularly pleuritis. Older age, respiratory tract infection, cardiac, systemic and renal involvement were associated with them, whereas cutaneous manifestations were negatively associated. Cardiac compromise, SDI scores ≥1 and anti-La positivity at disease onset were predictive of their subsequent occurrence, whereas cutaneous manifestations were protective. They independently contributed to a decreased survival in these patients.

Capsule impairs efficient adherence of Streptococcus agalactiae to intestinal epithelium in tilapias Oreochromis sp.

Streptococcosis caused by Streptococcus agalactiae is one of the most important diseases in the tilapia aquaculture industry. The role of the capsule of Streptococcus agalactiae in adherence to fish surfaces has not been evaluated and the mechanism of capsular regulation during adhesion has not been described. The aim of this study was to evaluate the role of the capsule of S. agalactiae during adhesion to intestinal epithelium of tilapia (Oreochromis sp.) in an ex vivo infection model. We show that the capsule impairs the adhesion of bacteria to host intestinal epithelium. Wild type (WT) strain SaTiBe08-18 (S. agalactiae recovered from tilapia) had reduced adhesion (P < 0.0001) in comparison with its unencapsulated mutant of SaTiBe08-18 (Δcps). When WT was treated with sterile saline solution (pH 5) before infection of intestine explants, the adhesion was reached. The results suggest that the capsule impairs the adhesion of S. agalactiae to tilapia intestine and that the acidic milieu could regulate adherence of encapsulated strains. We found GlcNAc on the surface of adherent Δcps but not over the capsule in WT. This difference could be explained by the GlcNAc composition of Lancefield group B antigen and the peptidoglycan in GBS (Group B Streptococcus) and also may be related with better exposure of glycosylated adhesins in unencapsulated fish GBS. Understanding capsular regulation during adhesion of S. agalactiae may provide new leads to find a successful anti-adherence therapy to prevent streptococcosis in tilapia.

Experimental early pathogenesis of Streptococcus agalactiae infection in red tilapia Oreochromis spp.

Streptococcus agalactiae causes a severe systemic disease in fish, and the routes of entry are still ill-defined. To address this issue, two groups of 33 red tilapia Oreochromis spp. each of 10 g were orally infected with S. agalactiae (n = 30), and by immersion (n = 30), six individuals were control-uninfected fish. Three tilapias were killed at each time point from 30 min to 96 h post-inoculation (pi); controls were killed at 96 h. Samples from most tissues were examined by haematoxylin-eosin (H&E), indirect immunoperoxidase (IPI) and periodic acid-Schiff; only intestine from fish infected by gavage was evaluated by transmission electron microscopy. The results of both experiments suggest that the main entry site of S. agalactiae in tilapia is the gastrointestinal epithelium; mucus seems to play an important defensive role, and environmental conditions may be an important predisposing factor for the infection.

Acute necrotizing pancreatitis: can tigecycline be included in a therapeutic strategy?

INTRODUCTION: Acute necrotizing pancreatitis is a severe and life-threatening disease. Infection, which occurs in about 30% of cases, is the most feared complication. Antibiotic therapy is still discussed and there are no clear recommendation in literature. These clinical series underline the importance of having a clear antibiotic protocol, including tigecycline, in the management of acute necrotizing pancreatitis. Clinical series. Six patients with clinical and radiological diagnosis of necrotizing acute pancreatitis are treated in Emergency Surgery Department, following a conservative management, which includes fluid resuscitation, intensive care unit and radiological monitoring, ultrasound-guided percutaneous drainage and an antibiotic treatment protocol, that includes tigecycline. No one of the six patient undergo surgery (mean hospital stay: 44 days). In a six months follow-up all patients are alive and in good clinical conditions. DISCUSSION: Infection is the most important factor which determinate prognosis and outcome of acute necrotizing pancreatitis. Antibiotic prophylaxis is still discussed and there are no clear antibiotic treatment guidelines in literature. Despite its side effects on pancreatic gland, tigecycline is successful in resolution of sepsis, caused by infected pancreatic necrosis. CONCLUSIONS: Collaboration with infectivologist and a clear antibiotic protocol is fundamental to solve infected necrosis. Antibiotic treatment, set up as soon as possible, is successful in our six patients, as they recover without undergoing surgical procedures. Tigecycline offers broad coverage and efficacy against resistant pathogens for the treatment of documented pancreatic necrosis infection. However, further studies are necessary to fully understand the safety profile and efficacy of tigecycline.

Colonic stent placement as a bridge to surgery in patients with left-sided malignant large bowel obstruction. An observational study.

BACKGROUND: Acute left-sided malignant colonic obstruction is common in elderly patients, in which emergency surgery is related with high morbidity and mortality rates, and often necessitates a two-step resection. Although the use of self-expanding metallic stents (SEMS) in elderly patients has not been adequately described yet, there are almost two international important trials which are still in progress, the stenting technique is established to be, by the international literature, an useful treatment with low morbidity and mortality. It's also a bridge to surgery, since the insertion of a SEMS can decompress the obstruction, making bowel and patient preparation possible and facilitating singlestage surgical resection. Palliative stenting can improve quality of life when compared to surgery in patients with metastasis or high co-morbidity. The aim of this study is to analyze mortality, avoidance of stoma, short- and long-term survival in patient with malignant left-sided large bowel obstruction who underwent to stent placement in our Emergency Surgery Unit, which is operative since November 2010 in our city Hospital in Ferrara. PATIENTS AND METHODS: Between November 2010 and December 2012 a total of 15 patients with acute left-sided malignant large bowel obstruction suitable for colonic stent application were admitted to Emergency Surgery Unit. Among these patients, 9 underwent to self-expanding metallic stent placement (group A), the other (group B) 6 patient underwent to emergency surgery. In this observational not-randomized study we analyzed the efficacy and safety of SEMS placement for patients either as a bridge to surgery or as a palliation, beside the short term and long term outcomes, versus those patients operated straight. RESULTS: Self-expanding metallic stents were successfully implanted in 9 of the 15 patients with acute left-sided malignant large bowel obstruction. No acute procedure-related complication was observed. All the patients in group A kept the stent in place for an average of 7,7 days, then everyone underwent to surgery. A large bowel resection with one-time recanalization was performed in 8 of the 9 patients. None Hartmann resection was necessary. Only one underwent again to surgery because of a dehiscence, a stoma was necessary. Between the other 6 patients in group B who underwent directly to surgery, In one case was necessary an Hartmann resection, another one incurred in dehiscence of the anastomosis that required reoperation with stoma creation. CONCLUSIONS: Placement of SEMS seems to be an useful alternative to emergent surgery in the management of acute left-sided bowel obstruction, both as a bridge to surgery and as a palliative procedure. SEMS can provide an effective and safe therapeutic option compared to emergency surgery, most of all in elderly patients, with a lower mortality rate, a significantly higher rate of primary anastomosis and the avoidance of stoma. However, to fully determine their role for these indications, more data and more high level evidence is required.

Mestizos with systemic lupus erythematosus develop renal disease early while antimalarials retard its appearance: data from a Latin American cohort.

OBJECTIVES: The objective of this paper is to assess the predictors of time-to-lupus renal disease in Latin American patients. METHODS: Systemic lupus erythematosus (SLE) patients (n = 1480) from Grupo Latino Americano De Estudio de Lupus (GLADEL's) longitudinal inception cohort were studied. Endpoint was ACR renal criterion development after SLE diagnosis (prevalent cases excluded). Renal disease predictors were examined by univariable and multivariable Cox proportional hazards regression analyses. Antimalarials were considered time dependent in alternative analyses. RESULTS: Of the entire cohort, 265 patients (17.9%) developed renal disease after entering the cohort. Of them, 88 (33.2%) developed persistent proteinuria, 44 (16.6%) cellular casts and 133 (50.2%) both; 233 patients (87.9%) were women; mean (± SD) age at diagnosis was 28.0 (11.9) years; 12.2% were African-Latin Americans, 42.5% Mestizos, and 45.3% Caucasians (p = 0.0016). Mestizo ethnicity (HR 1.61, 95% CI 1.19-2.17), hypertension (HR 3.99, 95% CI 3.02-5.26) and SLEDAI at diagnosis (HR 1.04, 95% CI 1.01-1.06) were associated with a shorter time-to-renal disease occurrence; antimalarial use (HR 0.57, 95% CI 0.43-0.77), older age at onset (HR 0.90, 95% CI 0.85-0.95, for every five years) and photosensitivity (HR 0.74, 95% CI 0.56-0.98) were associated with a longer time. Alternative model results were consistent with the antimalarial protective effect (HR 0.70, 95% CI 0.50-0.99). CONCLUSIONS: Our data strongly support the fact that Mestizo patients are at increased risk of developing renal disease early while antimalarials seem to delay the appearance of this SLE manifestation. These data have important implications for the treatment of these patients regardless of their geographic location.

Spontaneous rupture of a hepatic epithelioid angiomyolipoma: damage control surgery. A case report.

BACKGROUND: Angiomyolipoma (AML) is a rare mesenchymal tumor composed by blood vessels, adipose tissue and smooth muscle cells in variable proportions. Although it is most often diagnosed in the kidney, this tumor may originate from any part of the liver. It is often misdiagnosed as hepatocellular carcinoma (HCC) or other benign liver tumor. We describe a case of spontaneous rupture of hepatic angiomyolipoma in a young woman, with evidence of internal hemorrhage and hemoperitoneum. CASE REPORT: Liver tumor rupture is a rare but real surgical emergency. In our case it has been managed according to the trauma principles of the damage control surgery. At the time of the observation, the patient presented an instable condition, so the decision-making was oriented toward a less invasive first step of liver packing instead of a more aggressive intervention such as one shot hepatic resection. CONCLUSION: Damage control surgery with deep parenchymal sutures of the liver and pro-coagulant tissue adhesives packing abbreviates surgical time before the development of critical and irreversible physiological endpoints and permits a more confident second time surgery. This surgical management concept helps to reduce the mortality rate and the incidence of complications not only in traumatic liver damages, it works very well in spontaneous liver ruptures as well.

CLASP2 facilitates dynamic actin filament organization along the microtubule lattice.

Coordination between the microtubule and actin networks is essential for cell motility, neuronal growth cone guidance, and wound healing. Members of the CLASP (cytoplasmic linker-associated protein) family of proteins have been implicated in the cytoskeletal cross-talk between microtubules and actin networks; however, the molecular mechanisms underlying the role of CLASP in cytoskeletal coordination are unclear. Here, we investigate CLASP2α's cross-linking function with microtubules and F-actin. Our results demonstrate that CLASP2α cross-links F-actin to the microtubule lattice in vitro. We find that the cross-linking ability is retained by L-TOG2-S, a minimal construct containing the TOG2 domain and serine-arginine-rich region of CLASP2α. Furthermore, CLASP2α promotes the accumulation of multiple actin filaments along the microtubule, supporting up to 11 F-actin landing events on a single microtubule lattice region. CLASP2α also facilitates the dynamic organization of polymerizing actin filaments templated by the microtubule network, with F-actin forming bridges between individual microtubules. Finally, we find that depletion of CLASPs in vascular smooth muscle cells results in disorganized actin fibers and reduced coalignment of actin fibers with microtubules, suggesting that CLASP and microtubules contribute to higher-order actin structures. Taken together, our results indicate that CLASP2α can directly cross-link F-actin to microtubules and that this microtubule-CLASP-actin interaction may influence overall cytoskeletal organization in cells.

Mitochondria as a key player in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a heterogeneous, multisystemic autoimmune disease with a broad clinical spectrum. Loss of self-tolerance and chronic inflammation are critical markers of SLE pathogenesis. Although alterations in adaptive immunity are widely recognized, increasing reports indicate the role of mitochondrial dysfunction in activating pathogenic pathways involving the innate immune system. Among these, disarrangements in mitochondrial DNA copy number and heteroplasmy percentage are related to SLE activity. Furthermore, increased oxidative stress contributes to post-translational changes in different molecules (proteins, nucleic acids, and lipids), release of oxidized mitochondrial DNA through a pore of voltage-dependent anion channel oligomers, and spontaneous mitochondrial antiviral signaling protein oligomerization. Finally, a reduction in mitophagy, apoptosis induction, and NETosis has been reported in SLE. Most of these pathways lead to persistent and inappropriate exposure to oxidized mitochondrial DNA, which can stimulate plasmacytoid dendritic cells, enhance autoreactive lymphocyte activation, and release increased amounts of interferons through stimulation of toll-like receptors and cytosolic DNA sensors. Likewise, abnormal T-cell receptor activation, decreased regulatory T cells, enhanced Th17 phenotypes, and increased monocyte maturation to dendritic cells have also been observed in SLE. Targeting the players involved in mitochondrial damage can ultimately help.

Worldwide trends on molar incisor and deciduous molar hypomineralisation research: a bibliometric analysis over a 19-year period.

AIM: To identify the worldwide trends in scientific evidence and gaps in knowledge regarding molar incisor hypomineralisation (MIH) and deciduous molar hypomineralisation/hypomineralised second primary molars (DMH/HSPM), exploring the contribution of authors and countries, possible etiological factors and proposed treatments, in order to guide future research in the area. METHODS: Searches were conducted in MEDLINE, Scopus, Web of Science, Cochrane Library, Lilacs/BBO, Embase and Google Scholar. Studies employing the terms MIH, DMH/HSPM and their linguistic variations were included. The following data were extracted: title, authors, year and journal of publication and first author's affiliation country. Studies were categorized according to topic, dentition, study design, etiological factors and types of treatments. Categories were analysed in relation to their distribution, co-occurrence, cross-correlation and/or autocorrelation. RESULTS: Five hundred and three studies were included. The most published authors were Manton D (n = 47), de Souza JF (n = 22) and Ghanim A (n = 22) and four main collaboration clusters have been identified. Most of the studies were conducted on permanent dentition (MIH) (87.4%); with observational design (57.2%). The "European Archives of Paediatric Dentistry" was the most published journal (13.3%) and a significant increase in the number of publications was observed in the last decade. MIH was most studied in relation to prevalence/incidence, systemic factors involved in its aetiology and treatment with composite restorations, while a gap in knowledge was observed for extraction and sealants. Less studies were published on DMH/HSPM and most of them evaluated risk factors or prevalence/incidence. The gap of knowledge was observed in relation to treatments and patient's quality of life. CONCLUSIONS: This bibliometric review provided a comprehensive overview of research in MIH and DMH/HSPM over the past 19 years. Within the limitations of the present study, the following conclusions can be drawn: global trends point to an increasing peak of scientific publication, especially in the last decade, while there is a shortage of clinical studies on treatments, mainly evaluating tooth extractions. Finally the multifactorial nature should be further explored, considering environmental and systemic factors together.