Isolated olecranon fractures in children affected by osteogenesis imperfecta type I treated with single screw or tension band wiring system: outcomes and pitfalls in relation to bone mineral density

The purpose of this study is to compare the results of 2 techniques, tension band wiring (TBW) and fixation with screws, in olecranon fractures in children affected with osteogenesis imperfecta (OI) type I. Between 2010 and 2014, 21 olecranon fractures in 18 children with OI (average age: 12 years old) were treated surgically. Ten patients were treated with the screw fixation and 11 with TBW. A total of 65% of olecranon fractures occurred as a result of a spontaneous avulsion of the olecranon during the contraction of the triceps muscle. The average follow-up was 36 months. Among the children treated with 1 screw, 5 patients needed a surgical revision with TBW due to a mobilization of the screw. In this group, the satisfactory results were 50%. In patients treated with TBW, the satisfactory results were 100% of the cases. The average Z-score, the last one recorded in the patients before the trauma, was -2.53 in patients treated with screw fixation and -2.04 in those treated with TBW. TBW represents the safest surgical treatment for patients suffering from OI type I, as it helps to prevent the rigidity of the elbow through an earlier recovery of the range of motion, and there was no loosening of the implant. In analyzing the average Z-score before any fracture, the fixation with screws has an increased risk of failure in combination with low bone mineral density

Hall-effect in the MnBi_2Te_4 crystal using silicon nitride nanomembrane via contacts

Utilizing an interplay between band topology and intrinsic magnetism, the two-dimensional van der Waals (vdW) system MnBi_2Te_4 provides an ideal platform for realizing exotic quantum phenomena and offers great opportunities in the emerging field of antiferromagnetic spintronic technology. Yet, the fabrication of MnBi_2Te_4-based nanodevices is hindered by the high sensitivity of this material, which quickly degrades when exposed to air or to elevated temperatures. Here, we demonstrate an alternative route of fabricating vdW-MnBi_2Te_4-based electronic devices using the cryogenic dry transfer of a printable circuit embedded in an inorganic silicon nitride membrane. The electrical connections between the thin crystal and the top surface of the membrane are established through via contacts. Our magnetotransport study reveals that this innovative via contact approach enables exploring the MnBi_2Te_4-like sensitive 2D materials and engineering synthetic heterostructures as well as complex circuits based on the two-dimensional vdW systems

Enhancement of the Biological and Mechanical Performances of Sintered Hydroxyapatite by Multiple Ions Doping

In the present work, hydroxyapatite (HA) nanoparticles doped with Mg2+, Sr2+, and Zn2+ ions are developed by wet neutralization method and then sintered at 1,250°C to obtain bulk consolidated materials. Physicochemical and microstructural analyses show that the presence of doping ions in the HA structure induced the formation of βTCP as secondary phase, during the sintering process, and we found that this effect is depending on the stability of the various doping ions in the hydroxyapatite lattice itself. We also found that the formation of βTCP as secondary phase, in turn, confines the grain growth of HA induced by the high-temperature sintering process, thus leading to a strong increase of the flexural strength of the bulk materials, according to Hall-Petch-like law. Furthermore, we found that the doping ions enter also in the structure of the βTCP phase; besides the grain growth confinement, also the solubility and ion release ability of the final materials were enhanced. In addition to ameliorate the mechanical performance, the described phenomena also activate multiple biofunctionalities: (i) ability to upregulate various genes involved in the osteogenesis, as obtained by human adipose stem cells culture and evaluated by array technology; (ii) enhanced resistance to the adhesion and proliferation of Gram+ and Gram– bacterial strains. Hence, our results open a perspective for the use of sintered multiple ion-doped HA to develop ceramic biodevices, such as plates, screws, or other osteosynthesis media, with enhanced strength, osteointegrability, and the ability to prevent post-surgical infections

Early Circulating Tumor DNA Dynamics and Efficacy of Lorlatinib in Patients With Treatment-Naive, Advanced, ALK-Positive NSCLC

Introduction: Circulating tumor DNA (ctDNA) has been used as a biomarker for prognostication and response to treatment. Here, we evaluate ctDNA as a potential biomarker for response to lorlatinib, a third-generation ALK tyrosine kinase inhibitor in patients with treatment-naive, advanced, ALK-positive NSCLC in the ongoing phase 3 CROWN study (NCT03052608). Methods: Molecular responses were calculated using mean variant allele frequency (VAF), longitudinal mean change in VAF (dVAF), and ratio to baseline. Efficacy assessments (progression-free survival [PFS] and objective response rate) were paired with individual patient ctDNA and analyzed for association. Results: Compared with baseline, mean VAF at week 4 was decreased in both treatment arms. Considering all detected somatic variants, a reduction in dVAF (≤0) was associated with a longer PFS in the lorlatinib arm. The hazard ratio (HR) for a dVAF less than or equal to 0 versus more than 0 was 0.50 (95% confidence interval [CI]: 0.23–1.12) in the lorlatinib arm. A similar association was not observed for crizotinib (HR = 1.00, 95% CI: 0.49–2.03). Comparing molecular responders with nonresponders, patients treated with lorlatinib who had a molecular response had longer PFS (HR = 0.37, 95% CI: 0.16–0.85); patients treated with crizotinib who had a molecular response had similar PFS as those without a molecular response (HR = 1.48, 95% CI: 0.67–3.30). Conclusions: In patients with treatment-naive, advanced, ALK-positive NSCLC, early ctDNA dynamics predicted better outcome with lorlatinib but not with crizotinib. These results suggest that ctDNA may be used to monitor and potentially predict efficacy of lorlatinib treatment.</p

Early Circulating Tumor DNA Dynamics and Efficacy of Lorlatinib in Patients With Treatment-Naive, Advanced, ALK-Positive NSCLC

Introduction: Circulating tumor DNA (ctDNA) has been used as a biomarker for prognostication and response to treatment. Here, we evaluate ctDNA as a potential biomarker for response to lorlatinib, a third-generation ALK tyrosine kinase inhibitor in patients with treatment-naive, advanced, ALK-positive NSCLC in the ongoing phase 3 CROWN study (NCT03052608). Methods: Molecular responses were calculated using mean variant allele frequency (VAF), longitudinal mean change in VAF (dVAF), and ratio to baseline. Efficacy assessments (progression-free survival [PFS] and objective response rate) were paired with individual patient ctDNA and analyzed for association. Results: Compared with baseline, mean VAF at week 4 was decreased in both treatment arms. Considering all detected somatic variants, a reduction in dVAF (≤0) was associated with a longer PFS in the lorlatinib arm. The hazard ratio (HR) for a dVAF less than or equal to 0 versus more than 0 was 0.50 (95% confidence interval [CI]: 0.23–1.12) in the lorlatinib arm. A similar association was not observed for crizotinib (HR = 1.00, 95% CI: 0.49–2.03). Comparing molecular responders with nonresponders, patients treated with lorlatinib who had a molecular response had longer PFS (HR = 0.37, 95% CI: 0.16–0.85); patients treated with crizotinib who had a molecular response had similar PFS as those without a molecular response (HR = 1.48, 95% CI: 0.67–3.30). Conclusions: In patients with treatment-naive, advanced, ALK-positive NSCLC, early ctDNA dynamics predicted better outcome with lorlatinib but not with crizotinib. These results suggest that ctDNA may be used to monitor and potentially predict efficacy of lorlatinib treatment.</p

Selective distortion of body image by asynchronous visuotactile stimulation

In the rubber hand illusion (RHI), a rubber hand is felt as being part of one’s body. This illusion is evoked by providing synchronous visuotactile stimulation to the fake and real hands. Asynchronous visuotactile stimulation is known not to produce such an illusion of ownership, being commonly used as the control condition. Here we explored the impact of synchronous and asynchronous visuotactile stimulation on the body image. We combined the induction of the RHI with a quantitative test for the internal representation of body metrics (i.e., the positions of key fiducial points on the body relative to each other). We found a significant recalibration of the upper/lower arm lengths following asynchronous visuotactile stimulation. In particular, we observed a selective elongation of the lower arm, a distortion typical of deafferentation. Conversely, synchronous visuotactile stimulation did not alter the estimation of the arm segments' length. Our findings are consistent with a dynamic internal representation of body image that is continuously updated based on incoming multisensory information. Furthermore, the use of asynchronous multisensory stimulation as a neutral condition should be reconsidered since it introduces changes in the body image

Fulminant hepatitis: a clinical review of 11 years

24 cases of fulminant hepatitis (FH) hospitalized in the Clínica de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo during the period from January 1976 to December 1986 were reviewed from their clinical, epidemiological and laboratorial aspects. 88% of the patients died; 20 patients (83%) presented hemorrhages and, of these, 19 died. Bacterial infections occurred in 14 patients (58%) all of whom died. Ascitis was noted in 3 cases; cerebral edema was present in 16 cases. Maximal ALT levels for each patient during hospitalization ranged widely from 81 to 4,460 UI/l. Thirteen patients presented high creatinine levels (54%). Prothrombin time activity ranged from 2.1% to 67%. Fever was present in 20 cases (83%). Encephalopathy occurred within the first 2 weeks of illness in 72% of the cases. In 7 cases other illnesses were present. The etiology could not be determined in 13 cases. In 3 cases it was due to yellow fever and 6 cases were caused by viruses other than yellow fever. In one case the cause was drug usage and in another case, possibly alcohol. The authors believe that the clinical definition of FH requires further discussion before it is established. In this study FH is a young person's disease. The mortality found was similar to that by other authors. Factors that contributed to death were: hemorrhages and bacterial infection. Factors that worsened the prognosis of hepatitis were: associated illnesses and surgical procedure. The levels of ALT during hospitalization did not correlate well with the severity of the hepatitis. The authors believe that yellow fever should be considered a cause of FH where the clinical picture meets the criteria for such, although its mechanisms of encephalopathy remain obscure. The clinical details of the 3 cases of yellow fever are presented

Mug20, a novel protein associated with linear elements in fission yeast meiosis

In the fission yeast, Schizosaccharomyces pombe, homologous chromosomes efficiently pair and recombine during meiotic prophase without forming a canonical synaptonemal complex (SC). Instead, it features simpler filamentous structures, the so-called linear elements (LinEs), which bear some resemblance to the axial/lateral element subunits of the SC. LinEs are required for wild-type recombination frequency. Here, we recognized Mug20, the product of a meiotically upregulated gene, as a LinE-associated protein. GFP-tagged Mug20 and anti-Mug20 antibody co-localized completely with Rec10, one of the major constituents of LinEs. In the absence of Mug20, LinEs failed to elongate beyond their initial state of nuclear dots. Foci of recombination protein Rad51 and genetic recombination were reduced. Since meiotic DNA double-strand breaks (DSBs), which initiate recombination, are induced at sites of preformed LinEs, we suggest that reduced recombination is a consequence of incomplete LinE extension. Therefore, we propose that Mug20 is required to extend LinEs from their sites of origin and thereby to increase DSB proficient regions on chromosomes