Killer cell immunoglobulin-like receptors in Thai patients with leukemia and diffuse large B-cell lymphoma

Natural killer (NK) cells are key components of the innate immune system that have been implicated in the immune response against tumor cells. Killer cell immunoglobulin-like receptors (KIR) regulate NK cell activity by interaction with specific human leukocyte antigen (HLA) class I. In this study, KIR gene polymorphisms and their HLA ligands were investigated in Thai patients with chronic myelogenous leukemia (CML) (n = 60), acute myelogenous leukemia (AML) (n = 60), acute lymphoblastic leukemia (ALL) (n = 55), and diffuse large B-cell lymphoma (DLBCL) (n = 60) compared with 150 healthy controls. The frequency of KIR3DL1 with HLA-Bw4 was significantly lower in DLBCL patients than in controls (P = 0.0006, Pc = 0.02), whereas no significant differences were seen in KIR gene frequencies and their ligands between leukemia patients and controls. This study suggest a role of inhibitory KIR with its ligand in the protection against DLBCL.     

Validation of the Dutch functional,communicative and critical health literacy scales

Objective

While most existing health literacy (HL) measures focus primarily on reading comprehension, the functional, communicative and critical HL scales from Ishikawa et al. [19] aim to measure a broader HL spectrum. The objective of this study was to evaluate the validity of the Dutch translation of this instrument.

Methods

Two survey studies (n = 79 and n = 209) and one cognitive interview study (n = 18) were performed among samples of breast cancer patients and patients with rheumatic diseases.

Results

Analyses showed the scales measured three distinct factors and convergent validity was satisfactory for communicative and critical HL. Nevertheless, the comprehension of the items and the suitability of the response options raised some problems.

Conclusion

The HL scales seem promising to measure a broad definition of HL. By revising some of the items and response options as proposed in this article, the scale will become more understandable for people with low HL skills, which might increase the content validity and the distributional properties of the scale.

Practice implications

The scale should be revised and revalidated. An improved version should be used in practice to gain insight into HL levels of patients. This will help to develop suitable education programs for people with low HL skills.     

The association of health literacy with illness and medication beliefs among older adults with asthma

Objective

Suboptimal health literacy (HL) and asthma beliefs are associated with poor asthma self-management and outcomes. We tested the hypothesis that low HL is associated with inaccurate beliefs.

Methods

Asthmatics ≥60 were recruited from hospital and community practices in New York, NY and Chicago, IL (n = 420). HL was measured with the Short Test of Functional Health Literacy in Adults; validated instruments derived from the self regulation model were used to assess beliefs. The association of beliefs with HL was evaluated with multivariate models.

Results

Thirty-six percent of patients had low HL; 54% believed they only have asthma when symptoms are present, 29% believed they will not always have asthma and 20% believed that their doctor can cure asthma. HL was associated with beliefs of not having asthma all the time and that asthma can be cured (OR: 1.84, 95% CI: 1.2–2.82; OR: 2.22, 95% CI: 1.29–3.82, respectively). Patients with low HL were also more likely to be concerned about medication use (β = 0.92, p = .05), despite recognizing their necessity (β = −1.36, p = .01).

Conclusions

Older asthmatics with low HL endorse erroneous asthma beliefs.

Practice implications

Health communications for improving self-management behaviors in asthma should employ both health literacy-appropriate strategies and messages to counter illness-related misconceptions.     

Oral mucoceles: A clinical,histopathological and immunohistochemical study

The aim of study was to evaluate the clinicopathological features of oral mucoceles and the immunohistochemical expression of cellular and extracellular matrix components in these lesions. One hundred cases of oral mucoceles were examined for clinicopathological features. The expression of mast cell tryptase, CD68, MMP-1 (matrix metalloproteinase-1), MMP-9 (matrix metalloproteinase-9) and CD34 was investigated immunohistochemically in 32 cases. The lesions arose as nodules or blisters of variable color. The mean age was 23.2 years and a higher male frequency was observed. The most common locations were the lower lip (92%), followed by the floor of the mouth (7%), and palate (1%). The lesion size ranged from 0.4 to 3.0 cm. Unusual histopathological findings as superficial mucoceles (n = 16, 16%), pseudopapillary projections (n = 3, 3%), epithelioid histiocytes (n = 4, 4%), multinucleated giant cells (n = 1, 1%) and myxoglobulosis (n = 9, 9%) were also seen. Mast cells and CD68-positive macrophages, MMP-1, MMP-9 and CD34-positive blood vessels were seen in all cases. A significant association was seen between mast cells and MMP-1 (p = 0.03) and between macrophages and MMP-1 (p = 0.01). This study provided important insight into the demographic and histopathological occurrence of oral mucoceles. The tissue remodeling seen in these lesions mainly involved the migration and interaction of mast cells, macrophages and MMP-1.     

Urine formaldehyde level is inversely correlated to mini mental state examination scores in senile dementia

It is widely known that exogenous formaldehyde exposure induces human cognitive impairment and animal memory loss; and recent studies show that formaldehyde at pathological levels induces Aβ deposition and misfolding of tau protein to form globular amyloid-like aggregates. Endogenous formaldehyde may be a marker for progressive senile dementia.The aim of this study was to investigate the correlation of endogenous formaldehyde in urine of senile dementia and mini mental state examination (MMSE) scores.Formaldehyde level was analyzed by high-performance liquid chromatography (with fluorescence detection) in human urine from dementia patients (n = 141), patients with hypertension (n = 33) or diabetes (n = 16) and healthy individuals (n = 38), autopsy hippocampus samples from Alzheimer's disease (AD) patients and brains of three types of AD animal model: namely, senescence accelerated mice (SAMP8), APP-transgenic mice and APP/PS1-transgenic mice.In a double-blind study, there was marked elevation of urine formaldehyde levels in patients (n = 91) with dementia, and a slight increase in patients (n = 50) with mild cognitive impairment. Urine formaldehyde level was inversely correlated with mini mental state examination scores (Rs = −0.441, p < 0.0001). Furthermore, formaldehyde levels were significantly increased in the autopsy hippocampus from Alzheimer's patients (n = 4). In SAMP8 brains the formaldehyde level was significantly increased, suggesting that the endogenous formaldehyde is related to aging in mice. The brain formaldehyde level in APP/PS1-transgenic (n = 8) mice at age of 3 months and APP-transgenic (n = 8) mice at age of 6 months was increased (0.56 ± 0.02 mM), respectively, as compared with their respective age-matched controls, when these two types of AD-like animals, respectively, started to form Aβ deposits and memory loss obviously. According to the level of formaldehyde in the brain of the transgenic mice, we treated normal mice with formaldehyde (0.5 mM, intraperitoneal administration) and observed the memory loss of the animal in Morris water maze trial.Cognitive impairments for the senile dementia are probably related to endogenous formaldehyde levels; and the mini mental state examination scores referred to the evaluation of urine formaldehyde level in dementia patients may be used as a non-invasive method for the investigation and diagnosis of senile dementia.     

Genetic diversity of hepatitis C virus predicts recurrent disease after liver transplantation

Approximately 20% of patients receiving liver transplants for end-stage hepatitis C rapidly develop severe allograph fibrosis within the first 24 months after transplant. Hepatitis C virus (HCV) variants were studied in 56 genotype-1-infected subjects with end-stage hepatitis C disease at the time before and 12 months after liver transplant, and post-transplant outcome was followed with serial liver biopsies. In 15 cases, pre-transplant HCV genetic diversity was studied in detail in liver (n = 15), serum (n = 15), peripheral blood mononuclear cells (n = 13), and perihepatic lymph nodes (n = 10). Our results revealed that pre-transplant HCV genetic diversity predicted the histological outcome of recurrent hepatitis C disease after transplant. Mild disease recurrence after transplant was significantly associated with higher genetic diversity and greater diversity changes between the pre- and post-transplant time points (p = 0.004). Meanwhile, pre-transplant genetic differences between serum and liver were related to a higher likelihood of development of mild recurrent disease after transplant (p = 0.039).     

Combined T regulatory cell and Th2 expression profile identifies children with cow's milk allergy

The role of T regulatory cells in spontaneous recovery from cow's milk allergy (CMA) is unclear. We investigated the mRNA expression of 12 T-cell markers and the protein expression of CD4, CD25, CD127, FoxP3 after in vitro β-lactoglobulin stimulation of peripheral blood mononuclear cells from children with persisting CMA (n = 16), early recovery (n = 20) or no atopy (n = 21). Artificial neural networks with exhaustive search for all marker combinations revealed that markers FoxP3, Nfat-C2, IL-16 and GATA-3 distinguished patients with persisting CMA most accurately from other study groups. FoxP3 mRNA expression following β-lactoglobulin stimulation was highest in children with persisting CMA. Also the FoxP3 intensity in CD4⁺ CD25^highCD127^low cells was higher in children with CMA compared with non-atopic children. The expression profile of both Th2- and T regulatory cell-related genes thus reflects the clinical activity of CMA. Tolerance, in contrast, is not characterized by activation of circulating T regulatory cells.     

Educational group visits for the management of chronic health conditions: A systematic review

Objective

Review the effectiveness of group visits (appointments of multiple patients) on quality of life, function, self-efficacy, utilization, and biophysical outcomes in randomized controlled trials of patients with chronic conditions.

Methods

We searched MEDLINE^®, Cochrane, CINAHL, and PsycINFO to January 2013 for English-language trials of educational group visits led by non-prescribing facilitators (e.g., peer educators).

Results

We report on 80 arthritis/falls (n = 22), asthma/COPD (n = 10), CHF/hypertension (n = 12), diabetes (n = 29), multiple conditions (n = 4), and pain (n = 4) studies. We found moderate evidence of improved short-term self-efficacy in patients with arthritis (10 studies) and diabetes (10 studies). We found no consistent evidence of improved quality of life; however a moderately strong body of evidence suggests peer-led community-based programs might improve quality of life and utilization in patients with multiple chronic conditions. Meta-analyses found short- (14 studies; mean change HbA1c = −0.27, CI = −0.44, 0.11) and long-term (10 studies; mean change HbA1c = −0.23, CI = −0.44, −0.02) glycemic improvement.

Conclusions

Group visits may improve self-efficacy and glycemic control. There was little consistent evidence of improved quality of life, functional status, or utilization.

Practice implications

Group visits represent a reasonable alternative for educating patients with chronic illness, though varied participation/retention suggests they should not be the sole alternative.     

CXC chemokine expression profiles in aqueous humor of patients with different clinical entities of endogenous uveitis

Aqueous humor (AH) samples from patients with Behçet's disease (BD) (n = 29), Vogt-Koyanagi-Harada (VKH) disease (n = 21), and HLA-B27-associated uveitis (n = 8), and 42 control patients were assayed for the neutrophil chemoattractants CXCL1/GRO-α and CXCL8/IL-8 and the lymphocyte chemoattractants CXCL9/MIG, CXCL10/IP-10 and CXCL12/SDF-1 with the use of a multiplex chemokine assay. Chemokine levels except SDF-1 were significantly higher in the 3 disease groups than in normal controls. Considering all patients, mean GRO-α levels were 15-fold higher than IL-8 levels and mean IP-10 levels were 22-fold higher than MIG levels. In patients with the same disease activity, AH levels of GRO-α and IP-10 were significantly higher in patients with BD than in patients with VKH disease and HLA-B27-associated uveitis (p = 0.0474; p < 0.001, respectively). These data suggest that GRO-α and IP-10 are the predominant CXC chemokines involved in neutrophil and activated T lymphocyte chemoattraction in endogenous uveitis, particularly in BD.     

Diabetes self-management in patients with low health literacy: ordering findings from literature in a health literacy framework

Objective

To review studies on the association between health literacy (HL), diabetes self-management and possible mediating variables.

Methods

We systematically searched for empirical studies in PubMed. Findings were ordered by a HL framework that outlines routes between HL, sociocognitive determinants and health actions.

Results

Of the 11 relevant studies, three reported a significant positive association between HL and specific diabetes self-management domains. Ten studies investigated the association between HL and knowledge (n = 8), beliefs (n = 2), self-efficacy (n = 3) and/or social support (n = 1). Significant associations were found between HL and knowledge (n = 6), self-efficacy (n = 1) and social support (n = 1). Of the three studies evaluating the effect of these sociocognitive variables on diabetes self-management, only one found proof for a mediating variable (social support) in the pathway between HL and self-management.

Conclusion

There is only limited evidence for a significant association between HL and diabetes self-management, and for the mediating role of sociocognitive variables in this pathway.

Practice implications

Longitudinal studies, including HL, diabetes self-management and potential mediators, are needed to substantiate possible associations between these variables. Such research is essential to enable evidence-based development of interventions to increase adequate and sustainable self-management in diabetic patients with low HL.     

Toll like receptors in self-recovering hepatitis E patients with or without pregnancy

Hepatitis E virus (HEV) causes high mortality among pregnant women. Pathogenesis of HEV, especially during pregnancy, is poorly understood. Our aim was to assess the role of Toll-like-receptors (TLRs) in hepatitis E patients with pregnancy (Antenatal care, ANC) or without pregnancy (non-ANC). The patient categories included acute-phase, non-ANC (n = 46) and ANC patients (2nd/3rd trimesters, n = 13) and non-ANC patients (n = 31) during convalescence. Controls included apparently healthy non-ANC (n = 30) and ANC subjects in the first (n = 10) and later (2nd/3rd, n = 20) trimesters. TLR2/TLR3/TLR4/TLR7/TLR8 levels were determined by flow-cytometry. Cytokine responses induced by TLR-specific-ligands-stimulated-PBMCs from ANC/non-ANC-patients and TLR-signaling-molecules (non-ANC-patients) were measured. PBMCs were used to assess gene expression levels by TaqMan-Low-Density-Array.     

The utility of PAX8 in comparison with PAX5 immunohistochemical staining in the diagnosis of Hodgkin lymphoma

BackgroundHodgkin's lymphoma (HL) is among the most prevalent lymphomas worldwide. PAX5 has a great value in separating this entity from other T cell lymphoma; however, it is weakly expressed in neoplastic cells. Polyclonal PAX8 was positive in a variety of lymphoid neoplasms in several previous studies and the staining paralleled that of PAX5 but monoclonal PAX8 was negative in the same neoplasms. The aim of this study was to compare immunohistochemical patterns of monoclonal PAX8 with PAX5 in Classical and NLPHL samples.Material and methodsThis retrospective study was conducted on 89 formalin-fixed paraffin embedded blocks from HL patients (69 Classical and 20 NLPHL) admitted to Imam Khomeini and Dr. Shariati hospitals, Tehran, Iran during 2016–2020. Diagnoses were confirmed by reviewing previous immunohistochemistry (IHC) studies, including PAX5. All samples were stained for PAX8 (clone MRQ-50). Expression intensity scoring was made for both antibodies in neoplastic and background cells based on nuclear staining percentage.ResultsPAX8 was positive in neoplastic and background B lymphocytes of all classical and NLPHL samples. PAX8 Expression intensity was significantly higher in neoplastic and background cells compared to PAX5 in classical HL samples (P = 0.001). PAX5 expression intensity in neoplastic cells was significantly higher in NLPHL samples compared to classical HL (P = 0.040); however, no significant difference in PAX8 expression between neoplastic cells of NLPHL and HL was seen. PAX8 expression intensity was not significantly correlated with gender, histologic subtype, tumor location, and relapse.ConclusionsPAX8 monoclonal antibody (clone MRQ-50) showed strong nuclear reactivity in neoplastic and background cells of classical HL and NLPHL samples. Therefore, this marker can be utilized as a valuable alternative for PAX5 in differentiating HL from other T cell lymphoma in challenging cases.     

Cerebrospinal fluid from patients with multiple system atrophy promotes in vitro α-synuclein fibril formation

The aggregation of α-synuclein (αS) in the central nervous system (CNS) is the hallmark of multiple system atrophy (MSA) and Lewy body diseases including Parkinson's disease (PD) and dementia with Lewy bodies (DLB) (α-synucleinopathies). To test the hypothesis that patients with α-synucleinopathies have a CNS environment favorable for αS aggregation, we examined the influence of cerebrospinal fluid (CSF) from patients with MSA (n = 20), DLB (n = 8), and PD (n = 10) on in vitro αS fibril (fαS) formation at pH 7.5 and 37 °C using fluorescence spectroscopy with thioflavin S, compared with those with hereditary spinocerebellar ataxia (hSCA) (n = 16), and tension-type headache (n = 7). CSF from MSA patients (MSA-CSF) promoted fαS formation more strongly than PD-, hSCA-, or headache-CSF. By electron microscopic analyses, the width of fαS formed in MSA-CSF was significantly greater than others. MSA may have a CSF environment particularly favorable for fαS formation.     

Interaction between immunoglobulin allotypes and NK receptor genes in diabetes post-hepatitis C virus infection

Genetic interactions between natural killer (NK) cells immunoglobulin-like receptor (KIR) genes and immunoglobulin allotypes have been previously reported in type 2 diabetes mellitus (DM) patients. Puerto Rican Americans with a history of intravenous drug use who developed DM following HCV infection (n = 32) were compared to individuals infected with HCV without diabetes (n = 121) and to DM non-infected individuals (n = 95). Subjects were genotyped for KIRs and immunoglobulin allotypes. We found interactions of immunoglobulin allotypes KM3/KM3 with NK inhibitory receptors 2DL3/2DL3, 2DL1 in the absence of 2DS4 associated with susceptibility to DM in HCV infected individuals. These data suggest the possibility that a subset of patients with HCV could have an immune-mediated component contributing to the development of DM.     

Searching for an immunogenetic factor that will illuminate susceptibility to non-tuberculous mycobacterial disease

The incidence of pulmonary non-tuberculous mycobacteria (NTM) disease in otherwise healthy adults is increasing as the population ages. The organisms are ubiquitous so susceptibility probably reflects a deficiency in a protective immune response. Here we investigate if singlenucleotide polymorphisms (SNP) affecting cytokines, chemokines and their receptors associate with pulmonary NTM disease. Samples from NTM patients (n = 79) and healthy controls (n = 188) were genotyped using TaqMan probes. Of the 16 SNPs assessed, IL28B-rs8099917^*TG (rs8099917; P = 0.01, OR = 2.2), TNFA-1031^*CC (rs1799964; p = 0.02, OR = 0.48) and IL10-1082^*AA (rs1800896; P = 0.001, OR = 0.33) were significantly associated with NTM disease. IL28B-rs8099917 and IL10-1082 have been associated with perturbations of the Th1/Th2 balance, whilst TNFA-1031^*CC associates with sensory neuropathy in HIV patients. IL10-1082 warrants further investigation because we observed high production of IL-10 in blood mononuclear cells from NTM patients.     

Histamine excites rat lateral vestibular nuclear neurons through activation of post-synaptic H2 receptors

Through whole-cell patch recordings in brainstem slices, the effects of histamine on neuronal activity of the lateral vestibular nucleus (LVN) were investigated. Bath application of histamine elicited a concentration-dependent excitation of both spontaneous firing (n = 19) and silent (n = 7) LVN neurons. Moreover, histamine induced a stable inward current in the LVN neurons (n = 5) and the histamine-induced depolarization of membrane potential persisted in the presence of tetrodotoxin (n = 4), indicating a direct post-synaptic effect of the histamine on the LVN neurons. Selective histamine H2 receptor antagonist ranitidine effectively blocked the histamine-evoked excitatory responses on the LVN neurons (n = 4), but selective histamine H1 receptor antagonist triprolidine did not (n = 4). In addition, selective histamine H2 receptor agonist dimaprit (n = 3) rather than 2-pyridylethylamine (n = 4), a selective histamine H1 receptor agonist, mimicked the excitatory action of histamine on LVN neurons. The results demonstrate that histamine excites the LVN neurons via post-synaptic histamine H2 receptors and suggest that the central histaminergic projection arising from the hypothalamus may modulate LVN neurons activity and actively influence the vestibular reflexes and functions.     

Genetic variants of FOXP3 influence graft survival in kidney transplant patients

FOXP3⁺ regulatory T cells (T_reg) play a role in controlling alloreactivity. It has been shown that short (GT)_n dinucleotide repeats (?(GT)₁₅; S) in the promoter region of the FOXP3 gene enhance the promoter activity when compared to long (GT)_n repeats (?(GT)₁₆; L). The present study retrospectively investigated the influence of this (GT)_n FOXP3 gene polymorphism on renal allograft survival. A total of 599 consecutive first-time kidney transplant patients (median follow-up time 7.7 years) were subdivided according to their FOXP3 genotype into the S-genotype group (SG) and the L-genotype group (LG). The SG was superior to the LG in both general graft survival censored for death (logrank test, p = 0.013) and graft survival following acute rejection (p = 0.021). Multivariate analysis defined the (GT)_n FOXP3 dinucleotide repeat polymorphism as an independent factor and confirmed an advantage for the SG in renal allograft survival (HR = 0.67, 95% CI 0.48–0.94, p = 0.02). This gene association study identified a beneficial effect of FOXP3 genetic variants on graft survival in kidney transplant patients.     

Peer educator vs. respiratory therapist support: Which form of support better maintains health and functional outcomes following pulmonary rehabilitation?

Objective

This study examined if ongoing support delivered by telephone following pulmonary rehabilitation (PR) assisted chronic obstructive pulmonary disease (COPD) patients to maintain health outcomes.

Methods

Phase one (n = 79) compared post-rehabilitation telephone-based support delivered by peers compared to usual care (UC). The second phase (n = 168) compared post-rehabilitation support from peer educators, respiratory therapists (RT), or UC. Primary outcome variables were St. George's Respiratory Questionnaire (SGRQ) total score and the six minute walk test (6MWT). Measures were obtained at baseline, immediately following PR, and six-months post PR.

Results

Six-month follow-up data for phase one was collected for 66 COPD patients (n = 35 peer support, n = 31 UC) and 142 for phase two (n = 42 peer support, n = 52 RT support, n = 48 UC). Per-protocol and intention to treat (ITT) analysis in both phases found no significant group by time differences for SGRQ or 6MWT.

Conclusion

Providing peer or RT support via telephone following PR was not more effective than UC for maintaining health outcomes.

Practice implications

There are concerns with using peers to provide ongoing support to COPD patients. Additionally, COPD patients require a higher level of care than telephone support can provide.     

Defining the human immunodeficiency virus type 1 transmission genetic bottleneck in a region with multiple circulating subtypes and recombinant forms

The Mbeya region of Tanzania has a genetically complex HIV epidemic with multiple subtypes and recombinant forms circulating, together with a high frequency of dual infections with more than one subtype. This study aimed to determine whether this impacted the HIV-1 transmission bottleneck. A total of 210 env sequences from 22 participants were generated from recently infected women from Mbeya using the single genome amplification approach. Participants were infected with subtypes C (n = 9), A (n = 4), or D (n = 1), and recombinants AC (n = 4), CD (n = 2), AD (n = 1), or ACD (n = 1). Sixteen participants (73%) were infected with a single variant; five (23%) with multiple variants; and one (4%) was dually infected. Thus the frequency of single variant infections was similar to cohorts located in genetically restricted subtype B or C epidemics, suggesting that multiple circulating subtypes and unique recombinant forms do not have a significant impact on the transmission bottleneck.     

Can interactive skills-based seminars with standardized patients enhance clinicians’ prevention skills? Measuring the impact of a CME program

Objective

Communication skills are crucial for high-risk behavior screening and counseling. Practicing physicians have limited opportunities to improve these skills. This paper assesses the impact of a continuing medical education (CME) program for Student Health Center clinicians that targeted communication skills, screening practices and patient satisfaction.

Methods

Program evaluation included pre- and post-objective structured clinical examinations (OSCE's), chart review, and provider and patient satisfaction surveys. Data were analyzed using paired t-tests and ranked sum tests.

Results

OSCE scores (n = 15) revealed significant improvements in communication skills overall (p = 0.004) and within specific domains (data gathering: p = 0.003; rapport building: p = 0.01; patient education: p = 0.02), but no change in case-specific knowledge (p = 0.1). Participants (n = 14) reported high satisfaction with program methods (mean = 4.6/5) and content (mean = 4.7/5), 70% planning to alter their clinical practice. Chart audits (pre = 96, post = 103) showed increased screening for smoking (RR 1.65, p = 0.03), depressed mood (RR 1.40, p = 0.04), anhedonia (RR 1.47, p = 0.01), sexual activity (RR 1.73, p = 0.002) and drinking (RR 1.77, p = 0.04). Sampling of satisfaction among participants’ patients (pre n = 689, post n = 383) detected no increase in already high baseline satisfaction.

Conclusion

This curriculum improved clinicians’ relevant skills and screening behavior.

Practice implications

Skills-oriented CME can improve clinicians’ communication skills and screening and counseling practices.