Invasive lobular carcinoma of the breast; clinicopathologic profile and response to neoadjuvant chemotherapy over a 15-year period.

INTRODUCTION: Invasive lobular carcinoma (ILC) accounts for 5-15% of invasive breast cancers. Typical ILC is oestrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative. Atypical biomarker profiles (ER- and HER2+, ER+ and HER2+ or triple negative) appear to differ from typical ILCs. This study compared subtypes of ILC in terms of clinical and pathological parameters, and response to neoadjuvant chemotherapy (NACT) according to biomarker profile. METHODS: All patients with ILC treated in a single centre from January 2005 to December 2020 were identified from a prospectively maintained database. Clinicopathologic and outcome data was collected and analysed according to tumour biomarker profile. RESULTS: A total of 582 patients with ILC were treated. Typical ILC was observed in 89.2% (n = 519) and atypical in 10.8% (n = 63). Atypical ILCs were of a higher grade (35% grade 3 vs 9.6% grade 3, p < 0.001). A larger proportion of atypical ILC received NACT (31.7% vs 6.9% p < 0.001). Atypical ILCs showed a greater response to NACT (mean RCB (Residual Cancer Burden Score) 2.46 vs mean RCB 3.41, p = 0.0365), and higher pathological complete response rates (15% vs 0% p = 0.017). Despite this, overall 5-year disease-free survival (DFS) was higher in patients with typical ILC (91% vs 83%, p = 0.001). CONCLUSIONS: Atypical ILCs have distinct characteristics. They are more frequently of a higher grade and demonstrate a superior response to NACT. Despite the latter, atypical ILCs have a worse 5-year DFS which should be taken into consideration in terms of prognostication and may assist patient selection for NACT.

Factors associated with the reporting of Down syndrome as the underlying cause of death on US death certificates.

BACKGROUND: Efforts aimed at preventing premature mortality for people with Down syndrome are hindered by the practice of reporting disability as the underlying cause of death. Prior research suggests this form of diagnostic overshadowing may be the result of increased uncertainty surrounding the death. METHODS: This study uses bivariable analysis and multivariable logistic regression models to investigate associations between sociodemographic characteristics, comorbidities, and death context and processing characteristics with the reporting of Down syndrome as the underlying cause of death in 2005-2017 US Multiple Cause of Death data files. RESULTS: The reporting of Down syndrome as the underlying cause of death was associated with characteristics indicative of an increased amount of uncertainty surrounding the death. Results also suggest other mechanisms may inform inaccurate reporting, such as racial bias, and the continued conflation of disability and health. CONCLUSIONS: Medical personnel certifying death certificates should strive for accuracy when reporting the causes of death. To ensure this outcome, even in the midst of increased uncertainty, Down syndrome should not be reported as the underlying cause of death unless the decedent was diagnosed with Alzheimer's disease or unspecified dementia. Future research should further explore the possibility that increased death certification errors for adults with Down syndrome, or other developmental disabilities, are associated with racial bias.

Centennial Review: History and husbandry recommendations for raising Pekin ducks in research or commercial production.

By some accounts, ducks were domesticated between 400 and 10,000 yr ago and have been a growing portion of the poultry industry for decades. Ducks specifically, and waterfowl in general, have unique health, housing, nutrition and welfare concerns compared to their galliform counterparts. Although there have been many research publications in regards to health, nutrition, behavior, and welfare of ducks there have been very few reviews to provide an overview of these numerous studies, and only one text has attempted to review all aspects of the duck industry, from breeders to meat ducks. This review covers incubation, hatching, housing, welfare, nutrition, and euthanasia and highlights the needs for additional research at all levels of duck production. The purpose of this review is to provide guidelines to raise and house ducks for research as specifically related to industry practices.

Cause of death in adults with intellectual disability in the United States.

BACKGROUND: Prior studies report that adults with intellectual disability (ID) have cause of death patterns distinct from adults in the general population but do not provide comparative analysis by specific causes of death. METHODS: Data are from the National Vital Statistics System 2005-2017 US Multiple Cause-of-Death Mortality files. We utilised adjusted odds ratios to identify causes of death that were more common for adults whose death certificate indicated ID (N = 22 512) than for adults whose death certificate did not indicate ID (N = 32 738 229), controlling for severity level of ID. We then examine the associations between biological sex and race-ethnicity and causes of death solely among adults with ID. RESULTS: The leading cause of death for adults with and without ID indicated on their death certificate was heart disease. Adults with ID, regardless of the severity of the disability, had substantially higher risk of death from pneumonitis, influenza/pneumonia and choking. Adults with mild/moderate ID also had higher risk of death from diabetes mellitus. Differences in cause of death trends were associated with biological sex and race-ethnicity. CONCLUSIONS: Efforts to reduce premature mortality for adults with ID should attend to risk factors for causes of death typical in the general population such as heart disease and cancer, but also should be cognisant of increased risk of death from choking among all adults with ID, and diabetes among adults with mild/moderate ID. Further research is needed to better understand the factors determining comparatively lower rates of death from neoplasms and demographic differences in causes of death among adults with ID.

Twenty-Four-Hour Ex Vivo Perfusion with Acellular Solution Enables Successful Replantation of Porcine Forelimbs.

BACKGROUND: A critical barrier to successful limb replantation and allotransplantation is the maximum allowable limb ischemia time of 4 to 6 hours. The current gold standard is to preserve amputated limbs on an ice slurry. Experimental machine perfusion has yielded promising results as an alternative. In particular, hypothermic acellular perfusion has enabled preservation of amputated limbs for up to 12 hours thus far. METHODS: Amputated forelimbs of Yorkshire pigs were preserved on static cold storage at 4°C for 4 hours (static cold storage group) or perfused at 8°C for 24 hours (perfusion group) with oxygenated modified STEEN Solution perfusate before replantation. Animals were followed up for 7 days after replantation. RESULTS: Eight animals underwent replantation (cold storage group, n = 4; perfusion group, n = 4). Seventy-five and 100 percent of animals in the static cold storage and perfusion groups survived for 7 days, respectively. Glycogen and adenosine triphosphate remained stable throughout perfusion. Heart and respiratory rate after replantation were increased in the static cold storage group. There was increased damage in muscle biopsy specimens obtained from animals in the static cold storage group after 7 days when compared with those from animals in the perfusion group. CONCLUSIONS: Hypothermic acellular ex vivo perfusion of limbs for up to 24 hours enables tissue preservation comparable to that obtained with conventional static cold storage for 4 hours and may reduce muscle damage and systemic reactions on limb replantation. Translation to human limbs may help improve limb replantation and allotransplantation outcomes.

Heterogeneity in age at death for adults with developmental disability.

BACKGROUND: Although increased attention has been devoted to mortality trends for adults with developmental disability, research has not accounted for possible differences in age at death between disability types. We examine whether heterogeneity is present in age at death between adults with different types of developmental disability. METHODS: Data were from the 2012-2016 U.S. Multiple Cause-of-Death Mortality files. Mean age at death and age at death distributions were analysed for adults, aged 18-126, with and without developmental disability collectively and then stratified by biological sex. RESULTS: There were 33 154 decedents with and 13 026 759 without developmental disability. Compared with adults without developmental disability, age at death was lower for all decedents with developmental disability but varied markedly by disability type and biological sex. Among adults with developmental disability, those with intellectual disability had the highest age at death, and those with cerebral palsy or other rare developmental disabilities, especially if co-morbid for a second developmental disability, had the lowest age at death. CONCLUSION: Research on age at death for adults with developmental disability must account for heterogeneity among disability types in order to ensure reliable estimates. Failure to do so conceals important differences between disability types, which can misguide public health and preventive care efforts to reduce premature mortality and/or provide aging-related supports.

Imbalances in protein homeostasis caused by mutant desmin.

AIMS: We investigated newly generated immortalized heterozygous and homozygous R349P desmin knock-in myoblasts in conjunction with the corresponding desminopathy mice as models for desminopathies to analyse major protein quality control processes in response to the presence of R349P mutant desmin. METHODS: We used hetero- and homozygous R349P desmin knock-in mice for analyses and for crossbreeding with p53 knock-out mice to generate immortalized R349P desmin knock-in skeletal muscle myoblasts and myotubes. Skeletal muscle sections and cultured muscle cells were investigated by indirect immunofluorescence microscopy, proteasomal activity measurements and immunoblotting addressing autophagy rate, chaperone-assisted selective autophagy and heat shock protein levels. Muscle sections were further analysed by transmission and immunogold electron microscopy. RESULTS: We demonstrate that mutant desmin (i) increases proteasomal activity, (ii) stimulates macroautophagy, (iii) dysregulates the chaperone assisted selective autophagy and (iv) elevates the protein levels of αB-crystallin and Hsp27. Both αB-crystallin and Hsp27 as well as Hsp90 displayed translocation patterns from Z-discs as well as Z-I junctions, respectively, to the level of sarcomeric I-bands in dominant and recessive desminopathies. CONCLUSIONS: Our findings demonstrate that the presence of R349P mutant desmin causes a general imbalance in skeletal muscle protein homeostasis via aberrant activity of all major protein quality control systems. The augmented activity of these systems and the subcellular shift of essential heat shock proteins may deleteriously contribute to the previously observed increased turnover of desmin itself and desmin-binding partners, which triggers progressive dysfunction of the extrasarcomeric cytoskeleton and the myofibrillar apparatus in the course of the development of desminopathies.

Comparison of the mechanical properties of platelet-rich fibrin and ankaferd blood stopper-loaded platelet-rich fibrin.

BACKGROUND AND AIM: Platelet-rich fibrin (PRF) can be named as a natural fibrin-based biomaterial favorable to increasing vascularization and able to guide epithelial cell migration to its surface. The membrane has a significant positive effect on protecting open wounds and accelerating healing. Similar to PRF Ankaferd Blood Stopper (ABS) also has positive effects on wound healing. The aim of this study was to detect if we can improve known physical properties of PRF combining with ABS. This idea was based on the known mechanism of ABS in forming protein network without damaging any blood cells. Materials and Methods: A total of 25 adult rabbits used for collecting 5-7 ml of blood passively with the help of winged blood collection needle to the test tube. Collected samples were centrifuged at 3000 rpm for 10 min. Two similar samples obtained from each animal and one of the samples was placed in 20% ABS 80% saline solution for 5 min. Mechanical properties of the membrane samples were measured using Universal Testing Machine. Results: There is the statistically significant difference between PRF and ABS added PRF in elongation/mm (dL) and elongation/% at break values. Maximum force (fMax) and modulus values did not show any statistically significant differences. CONCLUSION: ABS loaded PRF causes better physical properties. This combination seems to exhibit superior performance when used as a membrane barrier solely. Advanced studies can be done on biological properties of ABS loaded PRF, especially on tissue healing.

Histo-cytochemistry and scanning electron microscopy for studying spatial and temporal extraction of metabolites induced by ultrasound. Towards chain detexturation mechanism.

There are more than 1300 articles in scientific literature dealing with positive impacts of Ultrasound-Assisted Extraction (UAE) such as reduction of extraction time, diminution of solvent and energy used, enhancement in yield and even selectivity, intensification of diffusion, and eliminating wastes. This present study aims to understand what are the mechanism(s) behind these positive impacts which will help to design a decision tool for UAE of natural products. Different microscopic observations (Scanning Electron Microscopy (SEM), Environmental Scanning Electron Microscopy (e-SEM), Cyto-histochemistry) have been used for spacial and temporal localization of metabolites in rosemary leaves, which is one of the most studied and most important plant for its antioxidant metabolites used in food industry, during conventional and ultrasound extraction. The study permits to highlight that ultrasound impacted rosemary leaves not by a single or different mechanisms in function of ultrasound power, as described by previous studies, but by a chain detexturation mechanism in a special order: local erosion, shear forces, sonoporation, fragmentation, capillary effect, and detexturation. These detexturation impacts followed a special order during ultrasound treatment leading at the end to the total detexturation of rosemary leaves. These mechanisms and detexturation impacts were identified in glandular trichomes, non-glandular-trichomes and the layer adaxial and abaxial cuticle. Modelling metabolites diffusion phenomenon during conventional and ultrasound extraction with the second Fick's law allowed the estimation of diffusivities and solvent penetration into the inner tissues and in meantime to accelerate the release of valuable metabolites.

Successful rapid subcutaneous desensitization to anakinra in a case with a severe immediate-type hypersensitivity reaction.

Summary: Anakinra, one of the novel biological agents, is a recombinant human IL-1 receptor antagonist. It is preferred as an alternative drug for familial Mediterranean fever cases where colchicine is not sufficient or cannot be used due to its side effects. Like all other biologics, hypersensitivity reactions to anakinra are quite rare. This is the first case which was successfully desensitized with anakinra after a severe immediate-type hypersensitivity reaction.

Ecological quality status of the Adriatic coastal waters evaluated by the organotin pollution biomonitoring.

The aim of this study was to evaluate the post-legislation change in tributyltin (TBT) pollution at Croatian Adriatic coast. Gastropod Hexaplex trunculus and sediments were collected, nearly 10years after TBT based antifouling paints were banned, at 12 locations along the coast where a previous study was conducted in 2005. The study showed a decline of TBT levels over the investigated period, although all gastropods populations were highly affected by imposex meaning that prohibition did not result in the recovery of populations. The further aim was to propose the Ecological Quality Ratio (EQR) boundaries for potential use of H. trunculus as a principal bioindicator in the assessment of the ecological status of the Mediterranean regarding TBT pollution, under the Water Framework Directive (WFD). According to the proposed EQR classes, the WFD target for achieving the Good ecological status of the marine environment by 2015 was not reached.

Lactococcus lactis carrying a DNA vaccine coding for the ESAT-6 antigen increases IL-17 cytokine secretion and boosts the BCG vaccine immune response.

AIMS: A regimen utilizing Bacille Calmette-Guerin (BCG) and another vaccine system as a booster may represent a promising strategy for the development of an efficient tuberculosis vaccine for adults. In a previous work, we confirmed the ability of Lactococcus lactis fibronectin-binding protein A (FnBPA+) (pValac:ESAT-6), a live mucosal DNA vaccine, to produce a specific immune response in mice after oral immunization. In this study, we examined the immunogenicity of this strain as a booster for the BCG vaccine in mice. METHODS AND RESULTS: After immunization, cytokine and immunoglobulin profiles were measured. The BCG prime L. lactis FnBPA+ (pValac:ESAT-6) boost group was the most responsive group, with a significant increase in splenic pro-inflammatory cytokines IL-17, IFN-γ, IL-6 and TNF-α compared with the negative control. CONCLUSIONS: Based on the results obtained here, we demonstrated that L. lactis FnBPA+ (pValac:ESAT-6) was able to increase the BCG vaccine general immune response. SIGNIFICANCE AND IMPACT OF THE STUDY: This work is of great scientific and social importance because it represents the first step towards the development of a booster to the BCG vaccine using L. lactis as a DNA delivery system.

Transformation of Face Transplants: Volumetric and Morphologic Graft Changes Resemble Aging After Facial Allotransplantation.

Facial allotransplantation restores normal anatomy to severely disfigured faces. Although >30 such operations performed worldwide have yielded promising short-term results, data on long-term outcomes remain scarce. Three full-face transplant recipients were followed for 40 months. Severe changes in volume and composition of the facial allografts were noted. Data from computed tomography performed 6, 18 and 36 months after transplantation were processed to separate allograft from recipient tissues and further into bone, fat and nonfat soft tissues. Skin and muscle biopsies underwent diagnostic evaluation. All three facial allografts sustained significant volume loss (mean 19.55%) between 6 and 36 months after transplant. Bone and nonfat soft tissue volumes decreased significantly over time (17.22% between months 6 and 18 and 25.56% between months 6 and 36, respectively), whereas fat did not. Histological evaluations showed atrophy of muscle fibers. Volumetric and morphometric changes in facial allografts have not been reported previously. The transformation of facial allografts in this study resembled aging through volume loss but differed substantially from regular aging. These findings have implications for risk-benefit assessment, donor selection and measures counteracting muscle and bone atrophy. Superior long-term outcomes of facial allotransplantation will be crucial to advance toward future clinical routine.

Synthesis and characterization of poly(glycerol-co-sebacate-co-ε-caprolactone) elastomers.

In this study, poly(glycerol-co-sebacate-co-ε-caprolactone) (PGSCL) elastomers were synthesized for the first time from the respective monomers. The structural analysis of PGSCL elastomers by nuclear magnetic resonance ((1)H-NMR) and Fourier transform infrared spectroscopy (FTIR) revealed that the elastomers have a high number of hydrogen bonds and crosslinks. X-ray diffraction (XRD) and thermal analysis indicated an amorphous state. Differential scanning calorimetry (DSC) analysis showed that the elastomers has a glass transition temperature (T(g)) of -36.96°C. The Young's modulus and compression strength values were calculated as 46.08 MPa and 3.192 MPa, respectively. Calculations based on acid number and end groups analysis revealed a number average molecular weight of 148.15 kDa. Even though the foaming studies conducted by using supercritical CO2 resulted in a porous structure; the obtained morphology tended to disappear after 48 h, leaving small cracks on the surface. This phenomenon was interpreted as an indication of self-healing due to the high number of hydrogen bonds. The PGSCL elastomers synthesized in this study are flexible, robust to compression forces and have self-healing capacity. Thanks to good biocompatibility and poor cell-adhesion properties, the elastomers may find diverse applications where a postoperative adhesion barrier is required.

PANNOTATOR: an automated tool for annotation of pan-genomes.

Due to next-generation sequence technologies, sequencing of bacterial genomes is no longer one of the main bottlenecks in bacterial research and the number of new genomes deposited in public databases continues to increase at an accelerating rate. Among these new genomes, several belong to the same species and were generated for pan-genomic studies. A pan-genomic study allows investigation of strain phenotypic differences based on genotypic differences. Along with a need for good assembly quality, it is also fundamental to guarantee good functional genome annotation of the different strains. In order to ensure quality and standards for functional genome annotation among different strains, we developed and made available PANNOTATOR (http://bnet.egr.vcu.edu/iioab/agenote.php), a web-based automated pipeline for the annotation of closely related and well-suited genomes for pan-genome studies, aiming at reducing the manual work to generate reports and corrections of various genome strains. PANNOTATOR achieved 98 and 76% of correctness for gene name and function, respectively, as result of an annotation transfer, with a similarity cut-off of 70%, compared with a gold standard annotation for the same species. These results surpassed the RAST and BASys softwares by 41 and 21% and 66 and 17% for gene name and function annotation, respectively, when there were reliable genome annotations of closely related species. PANNOTATOR provides fast and reliable pan-genome annotation; thereby allowing us to maintain the research focus on the main genotype differences between strains.

A New Biased Discriminant Analysis Using Composite Vectors for Eye Detection.

We propose a new biased discriminant analysis (BDA) using composite vectors for eye detection. A composite vector consists of several pixels inside a window on an image. The covariance of composite vectors is obtained from their inner product and can be considered as a generalization of the covariance of pixels. The proposed composite BDA (C-BDA) method is a BDA using the covariance of composite vectors. We construct a hybrid cascade detector for eye detection, using Haar-like features in the earlier stages and composite features obtained from C-BDA in the later stages. The proposed detector runs in real time; its execution time is 5.5 ms on a typical PC. The experimental results for the CMU PIE database and our own real-world data set show that the proposed detector provides robust performance to several kinds of variations such as facial pose, illumination, eyeglasses, and partial occlusion. On the whole, the detection rate per pair of eyes is 98.0% for the 3604 face images of the CMU PIE database and 95.1% for the 2331 face images of the real-world data set. In particular, it provides a 99.7% detection rate for the 2120 CMU PIE images without glasses. Face recognition performance is also investigated using the eye coordinates from the proposed detector. The recognition results for the real-world data set show that the proposed detector gives similar performance to the method using manually located eye coordinates, showing that the accuracy of the proposed eye detector is comparable with that of the ground-truth data.

Optimization of gene delivery to HEK293T cells by microporation using a central composite design methodology.

Microporation is an efficient method for delivering plasmid DNA molecules into cultured cells. Herein, we present the optimization of gene delivery by microporation using a Central Composite Design methodology. It was given relevance not only to the transfection efficiency but also to the cell recovery. Different amounts of DNA (1 and 3 µg) mainly affected cell viabilities and cell recoveries, which decrease from 93 to 76% and from 47 to 25% respectively, when higher DNA quantity is used. With this work we suggest an easy methodology to improve transfection of mammalian cells underlining the feasibility to achieve 60% of gene delivery efficiencies whilst recovering 50% of cells, with 90% of viability.

A persistent virus vector confers superior anti-tumor immunity, compared with a non-persistent vector.

Active vaccination strategies using viral vectors often give disappointing protection from tumor development, and usually require multiple immunizations. These approaches normally use viruses that cause acute infections, as they provoke potent CD8 T cell responses. Persistent virus vectors have not been used in this setting due to the perception that exhaustion of the T cell response occurs and would lead to poor anti-tumor protection. However, such exhaustion generally only occurs in high-load virus infections, whereas T cell function is intact in lower-load persistent infections. In fact, CD8 T cell responses in these infections, which are adapted for long-term immune surveillance, have properties that may make them more desirable for long-term anti-tumor immunity. In this report, we show that a persistent gammaherpesvirus vector provides superior protection against melanoma, relative to a non-persistent mutant of the same virus. These data suggest that vaccine vectors derived from persistent viruses may perform better than those from acute viruses at mediating anti-tumor protection.

Functional impairment severity is associated with health status among older persons with intellectual disability and cerebral palsy.

BACKGROUND: Studies have noted high rates of specific health disorders in adults with cerebral palsy (CP). However, it remains unclear how growing older with a lifelong neuromotor physical disability confers risk for health outcomes in adults who have both intellectual disability (ID) and CP. AIM: To assess the relationship between health status in older adults with ID either with or without coincident diagnoses of CP. METHOD: Health status data were drawn from 1373 adults aged 33 to 79 years with ID living in small group homes in New York State. Their health status was defined by the presence of common health disorders. Of these, 177 subjects had coincident CP. Prevalence data for nine diseases representing different organ systems were obtained and compared in individuals with and without CP. A Severity of Functional Impairment Index (SFII) was developed based on subjects' capabilities in activities of daily living (ADLs) and mobility. Two logistic regression analyses were conducted to determine if CP diagnosis was an independent predictor of health disorder prevalence, or rather exerted effects similar to those without CP via severity of functional impairment as determined by SFII scores. In addition, older age, gender, and severity of intellectual disability were examined as predictors of health disorder prevalence in all study subjects. RESULTS: Individuals with CP had higher frequencies in four out of the nine health disorders (overweight/obesity, gastroesophageal reflux, urinary tract infections and dysphagia). Analysis revealed a statistically significant association between SFII score and CP diagnosis. CP diagnosis alone was a statistically significant predictor for all of the above four common disorders; however, after adjustment for SFII score was included in health disorder models, only dysphagia showed an independent correlation with a CP diagnosis. CONCLUSION: With the exception of dysphagia, impairment in ADLs and walking capabilities, and not CP diagnosis alone, accounted for disparities in specific diseases. Although the diagnosis of CP may be correlated with functional impairment, it alone may play a minor role in determining health trajectories in older persons with conjoint ID and CP.