Mental health and COVID-19: The impact of a virtual course for family caregivers of adults with intellectual and developmental disabilities.

BACKGROUND: The COVID-19 pandemic has significantly impacted family caregivers of adults with intellectual and developmental disabilities (IDD). This study evaluated a virtual course for family caregivers from across Canada, focused on supporting the mental health and well-being of adults with IDD and their families. The evaluation examined the feasibility and acceptability of the course, as well as the impact of the intervention on participants' overall health and well-being. METHODS: The 6-week virtual course, informed by a parallel Extension for Community Healthcare Outcomes (ECHO) course for service providers, combined didactic instruction with applied activities. A total of 126 family caregiver course participants consented to be part of the research evaluation delivered over three cycles between October 2020 and April 2021. Attendance was measured at each weekly session. Satisfaction was assessed weekly and post-program. Learning, self-efficacy, and well-being were assessed pre- and post-course, and again at follow-up (8 weeks post-course). Mixed-effects models assessed changes between and within individuals across time. RESULTS: Participants had consistent attendance, low-dropout rates, and reported high satisfaction, with 93% of participants reporting that their expectations for the course were met. Compared with pre-course, participants reported improved self-efficacy and well-being post-course, which were maintained at follow-up. CONCLUSIONS: An interactive and applied virtual education course delivered to a large group of family caregivers of adults with IDD was both feasible and acceptable. It positively impacted participants' well-being by offering much needed mental health support and creating a peer-led community of practice.

Improvement of Ejection Fraction in Patients undergoing Coronary Artery Bypass Grafting with Impaired Left Ventricular Function.

Background Myocardial revascularization surgery has shown better long term survival expectancy compared to medical therapy in patient with impaired left ventricular function. Objective To evaluate the change in ejection fraction after 90 days in patients who underwent coronary artery bypass surgery and had preoperative left ventricular ejection fraction of less than and equal to 45% in a single cardiac center of Nepal over the period of 2 years. Method Out of 82 eligible patients during 2 years, 3 patients expired in immediate postoperatively and 24 patients had loss of 90 days' follow up. So, they were excluded from the study. Total 55 patients were taken for the study for whom statistical analysis was done to compare preoperative ejection fraction with post-operative 90 days' ejection fraction. Result Single vessel disease was present in 2(3.6%) patients, double vessel disease in 7(12.7%) patients and triple vessel disease in 46(83.6%) of the patients. In 2(3.6%) patients 2 grafts, in 18(32.7%) patients 3 grafts, in 33(60%) patients 4 grafts and in 2(3.6%) patients 5 grafts were placed for revascularization. The mean left ventricular EF in preoperative patients was 37.12±5.69% which improved to 45.80±10.00% in postoperative follow up at 90 days which was statistically significant (p=0.000). Conclusion Surgical revascularization of myocardium in preoperatively impaired left ventricular function patients helps improve left ventricular ejection fraction postoperatively. So we suggest surgical revascularization in patient with low ejection fraction for improvement of myocardial function. Hence improve survival rate in these patients.

Impact of antagonistic crustaceans on the population of Aedes aegypti L. larvae under laboratory conditions.

BACKGROUND & OBJECTIVES: Dengue and chikungunya are two mosquito-borne viral diseases transmitted by Aedes mosquito species and are a great public health concern in India. The present study was aimed to check the influence of antagonistic crustaceans, especially Mesocyclops aspericornis and Daphnia magna on Ae. aegypti L. mosquito population. METHOD: Variable ratios of these crustaceans (Aedes: Mesocyclops: Daphnia) against Ae. aegypti larvae were tested by putting them in plastic beakers having dechlorinated water along with yeast stock solution provided as food, and kept in BOD incubator at a temperature of 26 ±1°C. RESULTS: Out of all tested concentrations, 1:1:3 where the number of D. magna was thrice the number of Mesocyclops and Aedes; larvae showed a significant delay of 5-6 days in the developmental period. Maximum reduction in the emergence of females was recorded in the ratio 1:1:3, i.e. only 6.5 ± 0.47 females emerged when Daphnia used thrice the number of Aedes larvae. Body size of both males and females emerged from treated sets was found to be significantly reduced. The longevity of adults was also reduced from 8-17 days to 5-8 days in the case of males and from 14-26 days to 5-9 days in females. INTERPRETATION & CONCLUSION: Among variable ratios tested under laboratory conditions, 1:1:2 and 1:1:3 ratios were found to be the effective ratios that greatly reduced the development duration, survivorship of larvae, and the number of larvae emerging into adulthood. Thus, antagonistic crustaceans specifically Mesocyclops and Daphnia can be used as biocontrol agents for the sustainable control of container breeding mosquitoes.

Calcium channel blockers and the incidence of breast and prostate cancer: A meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Breast cancer (BCa) and prostate cancer (PCa), both hormone-dependent cancers, are the second leading cause of death in both women and men, respectively. Calcium channel blockers (CCBs) have been thought to increase the risk of cancer by inhibiting calcium signal-mediated apoptosis, but the evidence for this association remains inconclusive. We have reviewed pertinent literature and pooled data to establish a consensus on the relationship of CCB use and the incidence of these two cancers. METHODS: PubMed was used to conduct a search for English articles from inception to April 2016. Relevant data including study design, number of total participants and CCB users, total cases of BCa and PCa, age (mean and/or range), follow-up period and statistical outcomes were retrieved. Quality assessment was carried out using Newcastle Ottawa system, with the selection of high-quality studies. Summary effects were obtained using random- and mixed-effects models, followed by sensitivity analysis, and testing for publication bias. RESULTS AND DISCUSSION: This meta-analysis includes 11 relevant studies for BCa and 6 for PCa. The odds ratio (OR) association between BCa and CCB use was 1.14 (95%CI: 1.02, 1.27, P = .02). The OR association between PCa and CCB use was 1.12 (95%CI .94-1.35, P = .21). WHAT IS NEW AND CONCLUSION: Although a statistically significant association between CCB use and incidence of BCa does exist, the limitations of the individual studies restrict the clinical application of this relationship. Our meta-regression model does newly identify a 9-year latency period of CCB use and a significantly increased risk of BCa. No significant association exists between CCB use and the incidence of PCa. Our meta-regression shows CCB may have a protective effect upon PCa incidence among older populations.

Exposure of bovine oocytes and embryos to elevated non-esterified fatty acid concentrations: integration of epigenetic and transcriptomic signatures in resultant blastocysts.

BACKGROUND: Metabolic stress associated with negative energy balance in high producing dairy cattle and obesity in women is a risk factor for decreased fertility. Non-esterified fatty acids (NEFA) are involved in this pathogenesis as they jeopardize oocyte and embryo development. Growing evidence indicates that maternal metabolic disorders can disturb epigenetic programming, such as DNA methylation, in the offspring. Oocyte maturation and early embryo development coincide with methylation changes and both are sensitive to adverse environments. Therefore, we investigated whether elevated NEFA concentrations affect establishment and maintenance of DNA methylation in oocytes and embryos, subsequently altering transcriptomic profiles and developmental competence of resultant blastocysts. RESULTS: Bovine oocytes and embryos were exposed to different NEFA concentrations in separate experiments. In the first experiment, oocytes were matured in vitro for 24 h in medium containing: 1) physiological ("BASAL") concentrations of oleic (OA), palmitic (PA) and stearic (SA) acid or 2) pathophysiological ("HIGH COMBI") concentrations of OA, PA and SA. In the second experiment, zygotes were cultivated in vitro for 6.5 days under BASAL or HIGH COMBI conditions. Developmental competence was evaluated by assessing cleavage and blastocyst rate. Overall gene expression and DNA methylation of resultant blastocysts were analyzed using microarray. DNA methylation data were re-evaluated by pyrosequencing. HIGH COMBI-exposed oocytes and embryos displayed a lower competence to develop into blastocysts compared to BASAL-exposed counterparts (19.3% compared to 23.2% and 18.2% compared to 25.3%, respectively) (P < 0.05). HIGH COMBI-exposed oocytes and embryos resulted in blastocysts with altered DNA methylation and transcriptomic fingerprints, compared to BASAL-exposed counterparts. Differences in gene expression and methylation were more pronounced after exposure during culture compared to maturation suggesting that zygotes are more susceptible to adverse environments. Main gene networks affected were related to lipid and carbohydrate metabolism, cell death, immune response and metabolic disorders. CONCLUSIONS: Overall, high variation in methylation between blastocysts made it difficult to draw conclusions concerning methylation of individual genes, although a clear overview of affected pathways was obtained. This may offer clues regarding the high rate of embryonic loss and metabolic diseases during later life observed in offspring from mothers displaying lipolytic disorders.

Effect of antibiotic on survival and development of Spodoptera litura (Lepidoptera: Noctuidae) and its gut microbial diversity.

Addition of antibiotics to artificial diets of insects is a key component in the rearing of insects in the laboratory. In the present study an antimicrobial agent, streptomycin sulphate was tested for its influence on survival and fitness of Spodoptera litura (Fabricus) (Lepidoptera: Noctuidae) as well as its gut microbial diversity. The antibiotic did not adversely affect the survival of S. litura. Faster growth of larvae was recorded on diet amended with different concentrations of streptomycin sulphate (0.03, 0.07 and 0.15%) as compared to diet without streptomycin sulphate. The overall activity of various digestives enzymes increased on S+ diet while the activity of detoxifying enzymes significantly decreased. In addition, alteration in microbial diversity was found in the gut of S. litura larvae fed on diet supplemented with antibiotic (S+) and without antibiotic (S-).

Effect of Ubiquinol on Serum Reproductive Hormones of Amenorrhic Patients.

In neuroendocrine system the increase in oxidative status is produced by a glucocorticoid-dependent and transcriptional increase in pro-oxidative drive, with concurrent inhibition of the antioxidant defense system, ultimately leading to increased neuronal cell death. Functional hypothalamic disturbances and neuroendocirne aberrations have both short and long term consequences for reproductive health. Understandably, an impaired or diminished hypothalamic-pituitary-ovarian axis leads to anovulation and hypoestrogenism. Anovulation is directly linked to the neurohormonal and hormonal background of Functional Hypothalamic Amenorrhea. Impairment of pulsatile Gonadotropin Releasing Hormone secretion causes the impairment of pulsatile Lutenizing Hormone (LH) and Follicle Stimulating Hormone (FSH) secretion. The importance of oxidative stress in various pituitary disorders suggesting a possible clinical usefulness of antioxidant molecules like the lipophilic antioxidant Ubiquinol. Coenzyme Q10 or Ubiquinol is an essential part of the cell energy-producing system of mitochondria. However, it is also a powerful lipophilic antioxidant, protecting lipoproteins and cell membranes from autooxidation. Due to these unique actions Ubiquinol is used in clinical practice as an antioxidants for neurodegenerative diseases. So to identify the role of Ubiquinol on reproductive hormones FSH and LH, we have included 50 infertile patients of age group of 20-40, which are mostly amenorrhic. Out of 50 only 30 patients were in continuous follow up after supplementing them with 150 mg of Ubiquinol every day for 4 months. The hormonal levels were estimated by Enzyme Linked Immuno Sorbent Assay technique at follicular phase. The result suggests that FSH concentration is increased up to three times (from 3.10 ± 2.70 to 10.09 ± 6.93) but remains within the normal limit (P < 0.05). LH values were found doubled (P < 0.05) than its normal range (from 14.83 ± 10.48 to 27.85 ± 22.30). The Prolactin values were decreased while Progesterone values were high but not in the significant range (P > 0.05). The supplementation of 150 mg of Ubiquinol may reduce the oxidative stress in neuroendocrine system which further improves the function of diminished HPA axis. Hence increased level of FSH and LH may be due to reduced oxidative stress by Ubiquinol.

Studies on cocktails of 31-kDa, 36-kDa and 51-kDa antigens of Leishmania donovani along with saponin against murine visceral leishmaniasis.

A substantial number of antigens of Leishmania donovani have been described in the past. However, identifying candidate antigens is not enough. Appropriate antigen delivery to induce the right type of immune response against leishmaniasis (i.e. induction of a strong antigen-specific Th1 type of immune response) is another crucial component of an effective vaccine. Therefore, 'cocktail' vaccines are proposed based on the assumption that such cocktails will show enhanced efficacy. Studies have been carried out on LD31 and LD51 polypeptides from L. donovani promastigotes, which have proven to be potential vaccine candidates. This study was designed to check the protective efficacy of various cocktails of low molecular weight antigens alone and along with saponin as adjuvant. Mice were sacrificed on different post-challenge days for evaluation of parasite load and other immunological parameters. Protective efficacy of different vaccine formulations was revealed by significant decline in parasite burden and increased DTH Delayed Type Hypersenstivity responses. The antibody response was of IgG type with elevated IgG2a and decreased production of IgG1, whereas cytokine levels pointed towards the generation of protective Th1 type of immune response. Among all vaccine formulations, cocktail of 31+51+saponin was found to be highly immunogenic and imparted maximum protection.

Primary tracheobronchial amyloidosis: coronal CT scan may provide clues for early diagnosis.

Primary tracheobronchial amyloidosis (PTBA) is a localized form of amyloidosis. The clinical signs of this condition are non-specific and diagnosis before bronchoscopic examination with multiple biopsies is uncommon. We present three cases of PTBA and compare findings between the thoracic imaging and fiberoptic bronchoscopy. Radiographic findings often had uncharacteristic features. The relatively specific coronal section CT preceded findings in transverse sections, and showed an irregular mucosal surface with diffuse prominent nodes and/or calcification of the tracheobronchus, which we called the "wavy path sign". In conclusion, coronal CT scan can provide ample clues for the early diagnosis of PTBA.

Hematological Parameters and RBC TBARS Level of Q 10 Supplemented Tribal Sickle Cell Patients: A Hospital Based Study.

The study has been undertaken as number of sickle cell patients in Chhattisgarh tribal population is 23.7 %. The Co enzyme Q10 is a strong antioxidant and energy producing compound. The patients were divided into three groups group A homozygous (SS), group B heterozygous (AS) and group C controls for TBARS study. The age group is 10-55 years and 200 mg of CoQ10 was given to A and B groups. The hematological parameters, C reactive protein as well as RBC TBARS level were performed by usual and standard techniques. The results were obtained as 25.37 % increased RBC level in group A and 23.24 % in group B. The increased hemoglobin level was observed as 16.73 % in group A and 10.7 % in group B. In case of WBC it was observed increased 24.38 % in group A and 12.0 % in group B. C-reactive protein was observed 7.8 times decreased in group A and 1.54 times in group B. The RBC TBARS level was also found decreased 48 % in group A and 51 % in group B as compared to group C. During the supplementation of coenzyme Q10 the pain caused by vaso-occlusive events has reduced. This significant increase in hematological parameters as well as decreased C-reactive protein and TBARS level suggest that the Q10 should be included in the diet of sickle cell patients.

Serum Magnesium Level and It's Relation in Predicting Adverse In-Hospital Outcome in Patients with First Attack of Myocardial Infarction.

Acute myocardial infarction (AMI) patients characterize a large proportion of admissions in coronary care unit and their management and risk stratification is of immense importance. Hypomagnesemia is a long-term risk factor for incident of both myocardial infarction and arrhythmia. We assessed whether serum magnesium levels at admission is associated with arrhythmias and in-hospital mortality in patients with acute myocardial infarction (AMI). The aim of the study was to evaluate the prognostic implications of serum magnesium level in patients with acute myocardial infarction. This cross-sectional observational study was conducted in the department of cardiology in Mymensingh Medical College Hospital from October 2017 to March 2019. Total 259 acute myocardial infarction patients were included considering inclusion and exclusion criteria. The sample population was divided into two groups: Group-I: Patients with acute myocardial infarction with serum magnesium ≥1.82mg/dl. Group-II: Patients with acute myocardial infarction with serum magnesium <1.82mg/dl. Serum magnesium level was measured on admission, and the incidence of in-hospital major cardiac events was assessed. In this study mean serum magnesium level of Group-I, Group-II were 2.21±0.14mg/dl, 1.60±0.15mg/dl respectively. It was statistically significant (p<0.05). In-hospital outcomes of the study group revealed that low risk group patients were uneventful outcome during hospitalization period, they had no any complication. In Group-I patient, 9(4.8%) were developed arrhythmias, 26(13.9%) were developed heart failure, 9(4.8%) were developed cardiogenic shock and 3(1.6%) were died and in Group-II patient, 44(61.10%) developed arrhythmias, 9(12.50%) were developed heart failure, 7(9.7%) were developed cardiogenic shock and 12(16.7%) were died out of them which was statistically significant (p<0.05). Mean duration of hospital stay of the study population according serum magnesium level was in Group-I, 4.27±0.68 days, in Group-II, 5.84±1.05 days which was statistically significant (p<0.05). In conclusion patient with serum magnesium level less than 1.82mg/dl increased the risk of in-hospital arrhythmia and death.

The relationship between physical activity, structural deformity, and spinal mobility in adolescent idiopathic scoliosis patients.

PURPOSE: Adolescent idiopathic scoliosis (AIS) patients experience structural spinal deformity, but the impact of AIS on physical activity is not widely studied. Reports of physical activity levels between children with AIS and their peers are mixed. This study sought to characterize the relationship between spinal deformity, spinal range of motion, and self-reported physical activity in AIS patients. METHODS: Patients aged 11-21 completed self-reported measures of physical activity using the HSS Pedi-FABS and PROMIS Physical Activity questionnaires. Radiographic measures were obtained from standing biplanar radiographic imaging. Surface topographic (ST) imaging data was obtained using a whole-body ST scanning system. Hierarchical linear regression models analyzed the relationship between physical activity, ST, and radiographic deformity while controlling for age and BMI. RESULTS: 149 patients with AIS (mean age 14.5 ± 2.0 years, mean Cobb angle 39.7° ± 18.9°) were included. In the hierarchical regression predicting physical activity from Cobb angle, no factors were significant predictors of physical activity. When predicting physical activity from ST ROM measurements, age and BMI served as covariates. No covariates or ST ROM measurements were significant predictors of physical activity levels for either activity measure. CONCLUSIONS: Physical activity levels of patients with AIS were not predicted by levels of radiographic deformity or surface topographic range of motion. Although patients may experience severe structural deformity and range of motion limitations, these factors do not appear to be associated with decreased physical activity level utilizing validated patient activity questionnaires. LEVEL OF EVIDENCE: Level II.

The UHRF1 protein is a key regulator of retrotransposable elements and innate immune response to viral RNA in human cells.

While epigenetic mechanisms such as DNA methylation and histone modification are known to be important for gene suppression, relatively little is still understood about the interplay between these systems. The UHRF1 protein can interact with both DNA methylation and repressive chromatin marks, but its primary function in humans has been unclear. To determine what that was, we first established stable UHRF1 knockdowns (KD) in normal, immortalized human fibroblasts using targeting shRNA, since CRISPR knockouts (KO) were lethal. Although these showed a loss of DNA methylation across the whole genome, transcriptional changes were dominated by the activation of genes involved in innate immune signalling, consistent with the presence of viral RNA from retrotransposable elements (REs). We confirmed using mechanistic approaches that 1) REs were demethylated and transcriptionally activated; 2) this was accompanied by activation of interferons and interferon-stimulated genes and 3) the pathway was conserved across other adult cell types. Restoring UHRF1 in either transient or stable KD systems could abrogate RE reactivation and the interferon response. Notably, UHRF1 itself could also re-impose RE suppression independent of DNA methylation, but not if the protein contained point mutations affecting histone 3 with trimethylated lysine 9 (H3K9me3) binding. Our results therefore show for the first time that UHRF1 can act as a key regulator of retrotransposon silencing independent of DNA methylation.

Acute aortic intramural hematoma presenting with painless recurrent syncope.

A patient presented with recurrent syncope due to transient severe hypotension. The patient's history, physical examination, and initial baseline investigation did not suggest a cardiovascular cause. After fluid resuscitation, a raised jugular venous pulse was noted. Bedside transthoracic echocardiogram showed a pericardial effusion and a proximally dilated aorta. Computed tomography of the thorax confirmed these findings and also demonstrated an intramural hematoma of the proximal aortic wall.The patient was transferred to a cardiothoracic center, where he was at first treated medically. He then developed sudden cardiogenic shock due to pericardial tamponade and was successfully operated on.It is important to recognize an acute intramural hematoma of the proximal aortic wall as a cardiothoracic emergency. This condition can present atypically, but nevertheless warrants urgent surgical intervention, equal to type A aortic dissection. Echocardiography can help in making the diagnosis.

Label-free quantitative proteomics reveals molecular correlates of altered biomechanical properties in molar incisor hypomineralization (MIH): an in vitro study.

PURPOSE: Molar-incisor hypomineralization (MIH) is a qualitative developmental defect of enamel that affects first permanent molars with or without affecting permanent incisors. We aimed to carry out a quantitative proteomics-based study to compare and evaluate proteins in sound and MIH-affected enamel. MATERIALS AND METHODS: Ten blocks each of the MIH-affected enamel and sound enamel were processed and prepared for LC-MS/MS analysis. Label-free quantitation was carried out to evaluate the differentially expressed proteins in the two groups of samples. RESULTS: A significant increase in the number of proteins in MIH-affected enamel (50.3 ± 29.6) was observed compared to the sound enamel (21.4 ± 3.2). While proteins like collagens, α1-anti-trypsin, kallikrein-4 (KLK4), matrix metalloprotease-20 (MMP-20), alpha-2-macroglobulin, and alpha-2-HS-glycoprotein were upregulated in sound enamel, there was over-expression of albumin, calcium-binding proteins, anti-thrombin III, and dentin sialophosphoprotein (DSPP), along with proteins implicated in stress response and inflammatory processes in MIH. CONCLUSION: We propose that altered biomechanical properties of the enamel in MIH samples arise due to (i) down-regulation of proteins contributing to collagen biosynthesis and fibril formation; (ii) an overall imbalance in required levels of proteases (KLK4 and MMP-20) and anti-proteases (anti-thrombin-III which inhibits KLK-4), essential for optimal mineralization; (iii) very low levels of alpha-2-macroglobulin with important consequences in enamel mineralization and amelogenesis; and (iv) increased albumin in MIH, preventing proper growth of hydroxyapatite crystals. Increased inflammatory component was also seen in MIH; however, whether inflammation is a cause or consequence of the poor mineralization process needs to be assessed.

Association of Body Mass Index with Angiographic Severity of Coronary Artery disease in patients with Acute Coronary Syndrome.

Coronary artery disease (CAD) is the leading cause of death in developed and developing countries. Associated co-morbidities like diabetes, hypertension and obesity are making the situation worse. WHO enlisted obesity as an epidemic which also affects a great number of young population. Some recent studies showed the presence of an apparent paradoxical relationship between obesity and cardiovascular prognosis in certain subsets of patents. As BMI is an established marker of obesity; an attempt has been made to assess relationship between BMI and angiographic severity of coronary artery disease in Acute Coronary Syndrome (ACS) patients of Bangladeshi origin. To assess the association between body mass index and angiographic severity of coronary artery disease in patients with acute coronary syndrome; this cross sectional analytical study was conducted in the Department of Cardiology, Mymensingh Medical College Hospital (MMCH) and Bangabandhu Sheikh Mujib Medical University (BSMMU) from December 2016 to February 2018 among purposively selected 65 patients. Relevant ethical issues were taken into consideration. Coronary angiogram was done in the same index hospitalization period. After coronary angiogram performed patients were grouped into two groups according to their BMI. Patients with BMI <25kg/m² as Group I and those ≥25kg/m² as Group II. Angiographic severity of coronary artery disease was assessed by vessel score and Syntax score. Mean age of Group I was 54.45±10.42 years, while in Group II it was 50.76±8.89 years reflecting the early presentation of higher BMI patients. Male to female ratio was 12:1. Mean BMI of Group I and Group II was 22.56±1.59 and 28.67±2.64 respectively. In Group I, 10(25.0%) had single vessel lesion, 15(37.5%) had double vessel lesion and 14(35.0%) had triple vessel lesion, while in Group II, 6(24.0%) had single vessel lesion, 12(48.0%) had double vessel lesion and 5(20.0%) had triple vessel lesion. Mean Syntax score of Group I and Group II was 13.18±8.45 and 10.42±7.14 respectively. Patients in the increasing BMI class had a higher prevalence of diabetes, hypertension and dyslipidaemia. A negative correlation was observed between BMI and angiographic severity (Vessel score, Syntax score and HRCA e.g. LM disease) of CAD indicating that patients with higher BMI had a lower coronary artery disease (CAD) severity than their normal BMI counterparts. Patients with high BMI have a lower CAD severity than usually expected. After adjustment for co-morbidities, BMI was not found as an independent predictor of severity of coronary artery disease.

Mimicry of the a determinant of hepatitis B surface antigen by an antiidiotypic antibody. I. Evaluation in hepatitis B surface antigen responder and nonresponder strains.

B and T cell responses of several strains of mice, immunized with a monoclonal antiidiotype (anti-Id) that mimics the a determinant of hepatitis B surface antigen (HBsAg), were studied to determine if the immune response to the anti-Id was regulated by H-2-linked immune response genes as has been previously observed for HBsAg. We report that immunization with anti-Id could elicit HBsAg-specific antibodies in mice of the H-2d,q, or f haplotype and in an outbred wild mouse strain (Mus spretus), thus circumventing the H-2 haplotype restriction pattern observed when immunizing with HBsAg in H-2f mice. Purified lymph node T cells from mice of the H-2d or q haplotype and M. spretus that were primed in vivo with HBsAg or anti-Id could be stimulated in vitro with either HBsAg or anti-Id but not with an irrelevant antibody of the same subclass as the anti-Id. However, purified lymph node T cells from H-2f mice that were primed in vivo with the anti-Id could only be stimulated in vitro with anti-Id. No in vitro stimulation whatsoever was observed in H-2f mice immunized with HBsAg. The effect of processing and presentation of the anti-Id by antigen-presenting cells (APC) was studied in mice of the H-2d haplotype. Stimulation of purified lymph node T cells by HBsAg and anti-Id was shown to be strictly dependent on APC and restricted by major histocompatibility complex class II antigens at the I-A locus. Treatment of APC with paraformaldehyde or chloroquine abrogated the T cell response to all antigens except for a nine-amino acid synthetic peptide representing a partial analogue of the group a determinant of HBsAg S(139-147). The significance of these results is discussed in the context of understanding the mechanism of mimicry elicited by the anti-Id.

Label-free sensing of exosomal MCT1 and CD147 for tracking metabolic reprogramming and malignant progression in glioma.

Malignant glioma is a fatal brain tumor whose pathological progression is closely associated with glycolytic reprogramming, leading to the high expression of monocarboxylate transporter 1 (MCT1) and its ancillary protein, cluster of differentiation 147 (CD147) for enhancing lactate efflux. In particular, malignant glioma cells (GMs) release tremendous number of exosomes, nanovesicles of 30 to 200 nm in size, promoting tumor progression by the transport of pro-oncogenic molecules to neighboring cells. In the present study, we found that hypoxia-induced malignant GMs strongly enhanced MCT1 and CD147 expression, playing a crucial role in promoting calcium-dependent exosome release. Furthermore, it was first identified that hypoxic GMs-derived exosomes contained significantly high levels of MCT1 and CD147, which could be quantitatively detected by noninvasive localized surface plasmon resonance and atomic force microscopy biosensors, demonstrating that they could be precise surrogate biomarkers for tracking parent GMs' metabolic reprogramming and malignant progression as liquid biopsies.