Is the ‘rejection reaction’ inducing ability in sporophytic self-incompatible systems restricted only to pollen and tapetum?

Summary The present investigation describes the stigmatic rejection response, induced by anther or pollen at developmental stages ranging from anther primordia to mature pollen, as well as in other floral and vegetative tissues. This has been studied in a sporophytic self-incompatible system, Brassica campestris (Brassicaceae). The implications of these observations have been discussed.     

An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution

Cancer cells’ ability to inhibit apoptosis is key to malignant transformation and limits response to therapy. Here, we performed multiplexed immunofluorescence analysis on tissue microarrays with 373 cores from 168 patients, segmentation of 2.4 million individual cells, and quantification of 18 cell lineage and apoptosis proteins. We identified an enrichment for BCL2 in immune, and BAK, SMAC, and XIAP in cancer cells. Ordinary differential equation-based modeling of apoptosis sensitivity at single-cell resolution was conducted and an atlas of inter- and intra-tumor heterogeneity in apoptosis susceptibility generated. Systems modeling at single-cell resolution identified an enhanced sensitivity of cancer cells to mitochondrial permeabilization and executioner caspase activation compared to immune and stromal cells, but showed significant inter- and intra-tumor heterogeneity.Subject terms: Cancer microenvironment, Tumour heterogeneity     

DNA biosensor for detection of Neisseria gonorrhoeae causing sexually transmitted disease

A sequence-specific electrochemical sexually transmitted disease (STD) sensor based on self-assembled monolayer of thiolated DNA probe specific to target opa gene for detection of Gonorrhoea, a sexually transmitted disease has been fabricated. 6-Mercapto-1-hexanol (MCH) has been used as a blocking agent to facilitate oligos "stand" up at the surface, a configuration favoring subsequent DNA hybridization and to repel non-specific adsorption of undesired DNA. The results of differential pulse voltammetric studies of this STD sensor reveal low detection limit (1.0 × 10(-18)M) and a wide dynamic range (from 1.0 × 10(-6)M to 0.5 × 10(-18)M) arising due to the stable hybridization using methylene blue as an electro-active DNA hybridization indicator. The experimental results with genomic DNA, clinical patient sample of Neisseria gonorrhoeae, culture of non-N. gonorrhoeae Neisseria species (NgNS) and gram negative bacteria indicate that the fabricated sensor is specific to this STD.     

Patient–physician language concordance and quality and safety outcomes among frail home care recipients admitted to hospital in Ontario,Canada

Background:When patients and physicians speak the same language, it may improve the quality and safety of care delivered. We sought to determine whether patient–physician language concordance is associated with in-hospital and postdischarge outcomes among home care recipients who were admitted to hospital.Methods:We conducted a population-based study of a retrospective cohort of 189 690 home care recipients who were admitted to hospital in Ontario, Canada, between 2010 and 2018. We defined patient language (obtained from home care assessments) as English (Anglophone), French (Francophone) or other (allophone). We obtained physician language from the College of Physicians and Surgeons of Ontario. We defined hospital admissions as language concordant when patients received more than 50% of their care from physicians who spoke the patients’ primary language. We identified in-hospital (adverse events, length of stay, death) and post-discharge outcomes (emergency department visits, readmissions, death within 30 days of discharge). We used regression analyses to estimate the adjusted rate of mean and the adjusted odds ratio (OR) of each outcome, stratified by patient language, to assess the impact of language-concordant care within each linguistic group.Results:Allophone patients who received language-concordant care had lower risk of adverse events (adjusted OR 0.25, 95% confidence interval [CI] 0.15–0.43) and in-hospital death (adjusted OR 0.44, 95% CI 0.29–0.66), as well as shorter stays in hospital (adjusted rate of mean 0.74, 95% CI 0.66–0.83) than allophone patients who received language-discordant care. Results were similar for Francophone patients, although the magnitude of the effect was smaller than for allophone patients. Language concordance or discordance of the hospital admission was not associated with significant differences in postdischarge outcomes.Interpretation:Patients who received most of their care from physicians who spoke the patients’ primary language had better in-hospital outcomes, suggesting that disparities across linguistic groups could be mitigated by providing patients with language-concordant care.

A growing number of people in Canada (more than 6.1 million in 2016) are faced with the challenge of living in a situation in which their primary language is not spoken by most of the population and is not recognized as an official provincial or territorial language. ^1,2 We refer to this as a minority language situation, and such people include Francophones living outside of Quebec, Anglophones living in Quebec, and all residents of Canada whose primary language is a language other than English or French (allophones). Numerous studies have shown that people in North America with limited English proficiency generally have poorer access to health care and receive health care services of lower quality and safety, resulting in higher risk of adverse events and increased health resource use.^3–8 Despite these findings, few authors have considered the impact of patient–provider language concordance, whereby patients and providers have proficiency in a shared language.⁹ Studies in the United States have shown that patients with asthma who receive language-concordant primary care are less likely to omit medications, miss appointments or visit the emergency department.¹⁰ Patients with diabetes who receive language-concordant care have improved glycemic and low-density-lipoprotein control,^11,12 as well as increased participation in diabetic foot care programs.¹³ Although patient language is generally considered to be a nonmodifiable risk factor, language discordance represents a potentially modifiable variable, which could be the target of interventions (e.g., by referring patients to providers who have proficiency in their primary language).Frail patients are more likely to have communication problems and poor health outcomes than the general population; thus, language concordance may be particularly important in this patient population.^14,15 The risk of harm for frail, older patients has been attributed to medical complexity and multi-morbidity; ^16–18 however, since communication barriers also increase with age, older patients may also be more likely to experience harm because of poor patient–provider communication. ¹⁹ Most studies of language concordance have been limited to the primary care setting. We are aware of 2 studies conducted in the acute care setting, with 1 showing that Francophones residing in Ontario were less likely to experience harm when they were treated in hospitals that were required by law to provide services French. ^20,21We sought to compare the risk of adverse, hospital-related outcomes among frail patients living in Ontario, Canada, after stratifying by patient language and patient–physician language concordance or discordance. We hypothesized that patients receiving language-concordant care would have better outcomes than those receiving language-discordant care.     

Karyotypic analysis of adult pluripotent stem cells

Three categories of precursor cells have been identified in postnatal mammals: tissue-committed progenitor cells, germ layer lineage-committed stem cells and lineage-uncommitted pluripotent stem cells. Progenitor cells are the immediate precursors of differentiated tissues. Germ layer lineage stem cells can be induced to form multiple cell types belonging to their respective ectodermal, mesodermal, and endodermal embryological lineages. Pluripotent stem cells will form somatic cell types from all three primary germ layer lineages. Progenitor cells demonstrate a finite life span before replicative senescence and cell death occur. Both germ layer lineage stem cells and pluripotent stem cells are telomerase positive and display extensive capabilities for self-renewal. Stem cells which undergo such extensive replication have the potential for undergoing mutations that may subsequently alter cellular functions. Gross mutations in the genome may be visualized as chromosomal aneuploidy and/or chromosomes that appear aberrant. This study was designed to determine whether any gross genomic mutations occurred within the adult pluripotent stem cells. Karyotypic analysis was performed using pluripotent stem cells purified from adult male rats using established procedures. Giemsa Banding was used in conjunction with light microscopy to visualize metaphase chromosome spreads. To date over 800 metaphase spreads have been analyzed. We found that the metaphase spreads averaged 42 chromosomes and concluded that these pluripotent stem cells isolated from adult rats have a normal karyotype.     

Cytologic diagnosis of pulmonary nocardiosis: a report of 3 cases

BACKGROUND: Nocardiosis is an uncommon infection and presents as an opportunistic infection in an immunocompromised host. Pulmonary infection by Nocardia may be difficult to diagnose based on clinical and radiologic features, as these are not specific. Sputum examination, bronchoalveolar lavage and transthoracic ultrasound/computed tomography-guided fine needle aspiration cytology offer a simple means of procuring material for diagnostic evaluation. Very few articles have described the morphologic appearance of this uncommon pathogen in cytologic material. CASES: Three cases occurred in patients with an underlying immunocompromised state. Patient 1 was on steroid therapy for nephrotic syndrome, patient 2 was on immunosuppressant therapy after renal transplantation, and patient 3 was HIV positive. A diagnosis of pulmonary nocardiosis was suspected on Papanicolaou stain. Modified Ziehl-Neelsen stain and silver methanamine stains were useful in confirming the diagnosis. CONCLUSION: A high index of suspicion for nocardiosis must be maintained while assessing cytologic material in immunosuppressed individuals as it may be masked by the intense inflammatory exudate associated with this infection. A meticulous search may reveal the presence of delicate, thin, faintly stained, branching filaments of Nocardia on routine Papanicolaou stain. Special stains and culture studies are useful in confirming the diagnosis.     

Cytotoxic T-lymphocyte elicited therapeutic vaccine candidate targeting cancer against MAGE-A11 carcinogenic protein

Immunotherapy is a breakthrough approach for cancer treatment and prevention. By exploiting the fact that cancer cells have overexpression of tumor antigens responsible for its growth and progression, which can be identified and removed by boosting the immune system. In silico techniques have provided efficient ways for developing preventive measures to ward off cancer. Herein, we have designed a potent cytotoxic T-lymphocyte epitope to elicit a desirable immune response against carcinogenic melanoma-associated antigen-A11. Potent epitope was predicted using reliable algorithms and characterized by advanced computational avenue CABS molecular dynamics simulation, for full flexible binding with HLA-A*0201 and androgen receptor to large-scale rearrangements of the complex system. Results showed the potent immunogenic construct (KIIDLVHLL), from top epitopes using five algorithms. Molecular docking analyses showed the strong binding of epitope with HLA-A*0201 and androgen receptor with docking score of −780.6 and −641.06 kcal/mol, respectively. Molecular dynamics simulation analysis revealed strong binding of lead epitope with androgen receptor by involvement of 127 elements through atomic-model study. Full flexibility study showed stable binding of epitope with an average root mean square deviation (RMSD) 2.21 Å and maximum RMSD value of 6.48 Å in optimal cluster density area. The epitope also showed remarkable results with radius of gyration 23.0777 Å, world population coverage of 39.08% by immune epitope database, and transporter associated with antigen processing (TAP) affinity IC₅₀ value of 2039.65 nm. Moreover, in silico cloning approach confirmed the expression and translation capacity of the construct within a suitable expression vector. The present study paves way for a potential immunogenic construct for prevention of cancer.