An earlier study identified quantitative trait loci (QTLs) lb4, lb5b, and lb11b for quantitative resistance to Phytophthora infestans (late blight) in a backcross population derived from crossing ...susceptible cultivated tomato ( Lycopersicon esculentum) with resistant L. hirsutum. The QTLs were located in intervals spanning 28-47 cM. Subsequently, near-isogenic lines (NILs) were developed for lb4, lb5b, and lb11b by marker-assisted backcrossing to L. esculentum. Sub-NILs containing overlapping L. hirsutum segments across each QTL region were selected and used to validate the QTL effects, fine-map QTLs, and evaluate potential linkage drag between resistance QTLs and QTLs for horticultural traits. The NILs and sub-NILs were evaluated for disease resistance and eight horticultural traits at three field locations. Resistance QTLs were detected in all three sets of NIL lines, confirming the BC(1) mapping results. Lb4 mapped near TG609, and between TG182 and CT194, on chromosome 4, a 6.9-cM interval; lb5b mapped to an 8.8-cM interval between TG69a and TG413 on chromosome 5, with the most likely position near TG23; and lb11b mapped to a 15.1-cM interval on chromosome 11 between TG194 and TG400, with the peak centered between CT182 and TG147. Most QTLs for horticultural traits were identified in intervals adjacent to those containing the late blight resistance QTLs. Fine mapping of these QTLs permits the use of marker-assisted selection for the precise introgression of L. hirsutum segments containing late blight resistance alleles separately from those containing deleterious alleles at horticulturally important QTLs.
Reconstructive surgery with endoprostheses is the chosen method for treating bone malignancies. Postoperative infections are frequent complications, and their treatment involves prolonged hospital ...stays and antibiotic therapy. Among the advancements aimed at reducing the rate of postoperative infection, the use of incisional negative pressure therapy (iNPT) has shown promising results, with no reports in the literature regarding its use in patients with such conditions.
To evaluate the effectiveness of iNPT in reducing postoperative complications in surgeries for resection of bone tumors associated with modular endoprosthesis reconstruction.
Retrospective case series of 16 patients diagnosed with osteosarcoma, who underwent resection and reconstruction with endoprosthesis associated with iNPT during the postoperative period. Follow-up was performed for a period of six months, and the evaluated outcomes were the incidence of postoperative infection and complications of the surgical wound.
The use of iNPT for a postoperative period of seven days resulted in only three (18.7%) cases of postoperative infection. No cases of wound dehiscence, seroma formation, or hematoma at the surgical site were observed.
The rate of surgical wound complications in our case series is lower than that reported in most of the literature, and iNPT appears to be an efficient way to reduce the rate of local complications in reconstructive surgeries with endoprosthesis after resection of bone malignancies.
Clinical simulation in undergraduate nursing programs is prevalent. It is unclear if skills taught by simulation are effectively transferred into clinical practice. This study evaluated the ...effectiveness of clinical simulation compared with classroom teaching in teaching the assessment of the deteriorating patient.
This study used a phase II, single, randomized, controlled trial with single-blinded assessments. Students were randomly assigned to either a control or an experimental group. Participants underwent pre and post intervention Objective Structured Clinical Examination (OSCE) with objective performance criteria. Participants completed self-reported competence and self-efficacy questionnaires both pre- and post-test OSCE and a student satisfaction form.
The experimental group displayed a significantly better performance on post intervention OSCE. There was no correlation between self-reported confidence and self-efficacy and OSCE performance. Participants who received clinical simulation teaching were significantly more satisfied with their teaching experience.
The study suggests that clinical simulation is a more effective teaching strategy than classroom teaching for the development of the assessment skills of the deteriorating patient.
Gluten consumption has previously been implicated in the development of schizophrenia while an immunological link between gluten and schizophrenia was established by the detection of circulating ...antibodies against gliadin, a major component of wheat gluten. Several studies have reported an increase in circulating antibodies against native gliadin molecules that are unlikely to survive degradation in the digestive system. In this study, therefore, we measured plasma immunoglobulin G (IgG) and IgA antibodies against indigestible gliadin-derived peptide antigens using an in-house enzyme-linked immunosorbent assay (ELISA) among 169 patients with schizophrenia and 236 control subjects. We also examined the plasma levels of IgG and IgA antibodies against the mixture of native gliadins using commercially available ELISA kits. The results showed that patients with schizophrenia had the increased levels of plasma IgG against the γ-gliadin-derived fragment, namely AAQ6C, but decreased levels of plasma IgG against the α- and γ3-gliadin-derived antigens, as compared with control subjects. This study also demonstrated a uniform decrease in plasma IgA antibodies against gliadin-derived antigens. There was no significant difference in the levels of plasma antibodies against native gliadins between the patient group and the control group. Of eight gliadin-derived antigens tested, four showed a sensitivity of >20% against the specificity of ⩾95% for detection of their corresponding antibodies in plasma. These four tests may thus have a potential to serve as biomarkers for the identification of schizophrenia subgroups that may need an alternative therapy or precision treatment. Further investigation with clinical trials should be carried out to explore this possibility.
Background
Airway hyperresponsiveness (AHR) is a key pathophysiological feature of asthma and causes exercise-induced bronchoconstriction (EIB). Indirect bronchial provocation tests (BPTs) (e.g., ...exercise, mannitol) aid to diagnose asthma and identify EIB. Daily inhaled corticosteroids (ICS) can abolish AHR caused by indirect stimuli. Where strenuous physical exertion is integral to an occupation, identification of those at risk of EIB is important and documentation of inhibition of AHR with ICS is required before recruitment.
Methods/Objectives
A retrospective analysis was performed on 155 potential recruits with AHR to mannitol who underwent follow-up assessment after daily ICS treatment to determine the proportion that can abolish AHR using ICS and to determine any predictors of the persistence of AHR.
Results
Airway hyperresponsiveness was abolished in the majority (84%,
n
= 130) over the treatment period (mean ± SD 143 ± 72days), and it was defined as the provoking dose of mannitol to cause a 15% fall in FEV1 (cumulative inhaled dose of mannitol to cause 15% fall in FEV
1
, PD
15
) improved from (GeoMean) 183 to 521 mg. Compared with recruits in whom AHR was abolished with daily ICS (i.e., no 15% fall in FEV
1
to the maximum cumulative dose of mannitol of 635 mg), in those where AHR remained (16%,
n
= 25), baseline AHR was more severe (PD15: 85 mg vs. 213 mg,
P
< 0.001), baseline FEV
1
% was lower (89 vs. 96%; 95%CI:2–12,
P
=0.004), and they had a longer follow-up duration (180 vs. 136 days; 13–74,
P
= 0.006). Baseline FEV
1
% (adjusted odds ratio 0.85; 95%CI:0.77–0.93), FEV
1
/FVC (0.78; 0.67–0.90), FEF
25−75%
(1.15; 1.06–1.25), and airway reactivity to mannitol (%Fall/cumulative dose of mannitol multiplied by 100) (1.07; 1.03–1.11) predicted AHR remaining after daily ICS.
Conclusion
Airway hyperresponsiveness to mannitol can be abolished after 20 weeks of daily treatment with ICS. Inhibition of AHR is likely due to attenuation of airway inflammation in response to ICS treatment. Increased airway reactivity and lower spirometry variables predicted the persistence of AHR. Thus, those with a slower response to daily ICS on AHR can potentially be identified at the commencement of monitoring ICS using inhaled mannitol.
Comparison of spirometry parameters between Indigenous and non-Indigenous patients with underlying chronic obstructive pulmonary disease (COPD) has been sparsely reported in the past. In this study, ...differences in the lung function parameters (LFPs), in particular spirometry values for forced vital capacity (FVC), forced expiratory volume in one second (FEV
) and FEV
/FVC ratio between Indigenous and non-Indigenous patients with COPD were assessed.
In this retrospective study, Indigenous and non-Indigenous patients with a diagnosis of COPD between 2012-2020 according to spirometry criteria (ie; post-bronchodilator (BD) FEV
/FVC < 0.7) were included. A further analysis was undertaken to compare the differences in the spirometry parameters, including lower limit of normal (LLN) values matching for age, sex, height and smoking status between these two diverse ethnic populations.
A total of 240/742 (32%) Indigenous and 873/4579 (19%) non-Indigenous patients were identified to fit the criteria for COPD. Indigenous patients were significantly younger (mean difference 9.9 years), with a greater proportion of females (50% vs 33%), underweight (20% vs 8%) and current smokers (47% vs 32%). Prior to matching, Indigenous patients' post-BD percent predicted values for FVC, FEV
, and FEV
/FVC ratio were 17, 17%, and -2 points lower (Hedges G measure of effect size large (0.91), large (0.87), and small (0.25), respectively). Among the matched cohort (111 Indigenous and non-Indigenous), Indigenous patients LFPs remained significantly lower, with a mean difference of 16%, 16%, and -4, respectively (Hedges G large (0.94), large (0.92) and small (0.41), respectively). The differences persisted despite no significant differences in LLN values for these parameters.
Indigenous Australian patients with COPD display a significantly different demographic and clinical profile than non-Indigenous patients. LFPs were significantly lower, which may or may not equate to greater severity of disease in the absence of normative predictive lung function reference values specific to this population.
NK Cell Responses Redefine Immunological Memory Adams, Nicholas M; O'Sullivan, Timothy E; Geary, Clair D ...
The Journal of immunology (1950),
10/2016, Letnik:
197, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Immunological memory has traditionally been regarded as a unique trait of the adaptive immune system. Nevertheless, there is evidence of immunological memory in lower organisms and invertebrates, ...which lack an adaptive immune system. Despite their innate ability to rapidly produce effector cytokines and kill virally infected or transformed cells, NK cells also exhibit adaptive characteristics such as clonal expansion, longevity, self-renewal, and robust recall responses to antigenic or nonantigenic stimuli. In this review, we highlight the intracellular and extracellular requirements for memory NK cell generation and describe the emerging evidence for memory precursor NK cells and their derivation.
Left-right asymmetrical brain function underlies much of human cognition, behavior and emotion. Abnormalities of cerebral asymmetry are associated with schizophrenia and other neuropsychiatric ...disorders. The molecular, developmental and evolutionary origins of human brain asymmetry are unknown. We found significant association of a haplotype upstream of the gene LRRTM1 (Leucine-rich repeat transmembrane neuronal 1) with a quantitative measure of human handedness in a set of dyslexic siblings, when the haplotype was inherited paternally (P=0.00002). While we were unable to find this effect in an epidemiological set of twin-based sibships, we did find that the same haplotype is overtransmitted paternally to individuals with schizophrenia/schizoaffective disorder in a study of 1002 affected families (P=0.0014). We then found direct confirmatory evidence that LRRTM1 is an imprinted gene in humans that shows a variable pattern of maternal downregulation. We also showed that LRRTM1 is expressed during the development of specific forebrain structures, and thus could influence neuronal differentiation and connectivity. This is the first potential genetic influence on human handedness to be identified, and the first putative genetic effect on variability in human brain asymmetry. LRRTM1 is a candidate gene for involvement in several common neurodevelopmental disorders, and may have played a role in human cognitive and behavioral evolution.
Antagonists of the N-methyl-D-aspartate (NMDA)-type glutamate receptor induce psychosis in healthy individuals and exacerbate schizophrenia symptoms in patients. In this study we have produced an ...animal model of NMDA receptor hypofunction by chronically treating rats with low doses of the NMDA receptor antagonist MK-801. Subsequently, we performed an expression study and identified 20 genes showing altered expression in the brain of these rats compared with untreated animals. We then explored whether the human orthologs of these genes are associated with schizophrenia in the largest schizophrenia genome-wide association study published to date, and found evidence for association for 4 out of the 20 genes: SF3B1, FOXP1, DLG2 and VGLL4. Interestingly, three of these genes, FOXP1, SF3B1 and DLG2, have previously been implicated in neurodevelopmental disorders.
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