Outcome of revision total knee arthroplasty with bone allograft in 30 cases

Revision Total Knee Arthroplasty is often complicated by large bone defects in the distal femur and proximal tibia. These defects can be managed in a variety of ways including the use of allograft bone. The purpose of this study was to retrospectively evaluate the clinical outcome of revision total knee arthroplasty cases where allograft bone was used. Thirty revision TKA's (27 patients) performed between 1994 and 2009 were followed for a mean of 5 years (1- 14 years). Preoperative bone defects were classified using the Anderson Orthopaedic Research Institute classification system. Patient follow-up entailed calculation of the Knee Society Score and radiological assessment of the revision joint replacement in addition to review of complications. Kaplan Meier analysis predicted survivorship at 5 years as 93%, with further revision surgery as end point. The average Knee Society Score was 76.4, with 19 (63%) of knees scoring "excellent" results, 4 (14%) "good", 1 (3%) "fair" and 6 (20%) were "poor". The overall complication rate was 23.3%. Radiological lucency was demonstrated on recent radiographs for one patient. Three knees were re-revised at 1 year, 6 years and 8 years respectively. Our study demonstrates promising short to medium term results with the use of allograft bone in revision total knee replacement presenting with significant bone loss

Microglia promote anti-tumor immunity and suppress breast cancer brain metastasis

Breast cancer brain metastasis (BCBM) is a lethal disease with no effective treatments. Prior work has shown that brain cancers and metastases are densely infiltrated with anti-inflammatory, protumorigenic tumor associated macrophages (TAMs), but the role of brain resident microglia remains controversial because they are challenging to discriminate from other TAMs. Using single-cell RNA-sequencing (scRNA-seq), genetic, and humanized mouse models, we specifically identify microglia and find that they play a distinct pro-inflammatory and tumor suppressive role in BCBM. Animals lacking microglia show increased metastasis, decreased survival, and reduced NK and T cell responses, showing that microglia are critical to promote antitumor immunity to suppress BCBM. We find that the pro-inflammatory response is conserved in human microglia, and markers of their response are associated with better prognosis in BCBM patients. These findings establish an important role for microglia in anti-tumor immunity and highlight them as a potential immunotherapy target for brain metastasis

Observation of Complete Photonic Bandgap in Low Refractive Index Contrast Inverse Rod-Connected Diamond Structured Chalcogenides

Three-dimensional complete photonic bandgap materials or photonic crystals block light propagation in all directions. The rod-connected diamond structure exhibits the largest photonic bandgap known to date and supports a complete bandgap for the lowest refractive index contrast ratio down to nhigh/nlow ∼ 1.9. We confirm this threshold by measuring a complete photonic bandgap in the infrared region in Sn–S–O (n ∼ 1.9) and Ge–Sb–S–O (n ∼ 2) inverse rod-connected diamond structures. The structures were fabricated using a low-temperature chemical vapor deposition process via a single-inversion technique. This provides a reliable fabrication technique of complete photonic bandgap materials and expands the library of backfilling materials, leading to a wide range of future photonic applications

The epidemiology of atopic dermatitis in older adults: A population-based study in the United Kingdom

Background Atopic dermatitis is known to be common among children, but there are few studies examining the epidemiology across the life course. In particular, there is a paucity of data on atopic dermatitis among older adults. Objective To evaluate participant characteristics, patterns of disease activity and severity, and calendar trends in older adult atopic dermatitis in comparison to other age groups in a large population-based cohort. Methods This was a cohort study of 9,154,936 individuals aged 0-99 years registered in The Health Improvement Network, a database comprised of electronic health records from general practices in the United Kingdom between 1994 and 2013. Atopic dermatitis was defined by a previously validated algorithm using a combination of at least one recorded atopic dermatitis diagnostic code in primary care and two atopic dermatitis therapies recorded on separate days. Cross-sectional analyses of disease prevalence were conducted at each age. Logistic mixed effect regression models were used to identify predictors of prevalent disease over time among children (0-17 years), adults (18-74 years), and older adults (75-99 years). Results Physician-diagnosed atopic dermatitis was identified in 894,454 individuals with the following proportions in each age group: 18.3% of children, 7.7% of adults, and 11.6% of older adults. Additionally, atopic dermatitis prevalence increased across the 2-decade period (beta from linear regression test for trend in the change in proportion per year = 0.005, p = 0.044). In older adults, atopic dermatitis was 27% less common among females (adjusted OR 0.73, 95% CI 0.70-0.76) and was more likely to be active (59.7%, 95% CI 59.5-59.9%) and of higher severity (mean annual percentage with moderate and severe disease: 31.8% and 3.0%, respectively) than in other age groups. Conclusion In a large population-based cohort, the prevalence of physician-diagnosed atopic dermatitis has increased throughout adulthood and was most common among males age 75 years and above. Compared to children ages 0-17 and adults ages 18-74, older adult atopic dermatitis was more active and severe. Because the prevalence of atopic dermatitis among older adults has increased over time, additional characterization of disease triggers and mechanisms and targeted treatment recommendations are needed for this population

Phenotypic screening identifies a trisubstituted imidazo[1,2-a]pyridine series that induces differentiation in multiple AML cell lines

Acute myeloid leukaemia (AML) is an aggressive type of leukaemia with low rates of long-term survival. While the current standard of care is based on cytotoxic chemotherapy, a promising emerging approach is differentiation therapy. However, most current differentiating agents target specific mutations and are effective only in certain patient subtypes. To identify agents which may be effective in wider population cohorts, we performed a phenotypic screen with the myeloid marker CD11b and identified a compound series that was able to differentiate AML cell lines in vitro regardless of their mutation status. Structure-activity relationship studies revealed that replacing the formamide and catechol methyl ether groups with sulfonamide and indazole respectively improved the in vitro metabolic profile of the series while maintaining the differentiation profile in multiple cell lines. This optimisation exercise enabled progression of a lead compound to in vivo efficacy testing. Our work supports the promise of phenotypic screening to identify novel small molecules that induce differentiation in a wide range of AML subtypes

Forming-free resistive switching of tunable ZnO films grown by atomic layer deposition

Undoped ZnO thin films with tunable electrical properties have been achieved by adjusting the O2 plasma time in the plasma enhanced atomic layer deposition process. The structural, compositional and electrical properties of the deposited ZnO films were investigated by various characterization techniques. By tuning the plasma exposure from 2 to 8 s, both resistivities and carrier concentrations of the resultant ZnO films can be modulated by up to 3 orders of magnitude. Forming-free TiN/ZnO/TiN resistive memory devices have been achieved by choosing the ZnO film with the plasma exposure time of 6 s. This deposition method offers a great potential for producing other un-doped metal oxides with tunable properties as well as complex multilayer structures in a single deposition

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected nearly 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease-2019 (COVID-19) including two novel mRNA-based vaccines. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S), receptor binding domain (RBD) binding titers. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes epitopes in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy