Molecular Imaging of Acute Graft-Versus-Host Disease.

Noninvasive molecular imaging of acute graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation has great potential to detect GvHD at the early stages, aid in grading of the disease, monitor treatment response, and guide therapeutic decisions. Although the specificity of currently available tracers appears insufficient for clinical GvHD diagnosis, recently, several preclinical studies have identified promising new imaging agents targeting one or more biologic processes involved in GvHD pathogenesis, ranging from T-cell activation to tissue damage. In this review, we summarize the different approaches reported to date for noninvasive detection of GvHD using molecular imaging with a specific focus on the use of PET. We discuss possible applications of molecular imaging for the detection of GvHD in the clinical setting, as well as some of the predictable challenges that are faced during clinical translation of these approaches.

PET Imaging of Innate Immune Activation Using 11C Radiotracers Targeting GPR84.

Chronic innate immune activation is a key hallmark of many neurological diseases and is known to result in the upregulation of GPR84 in myeloid cells (macrophages, microglia, and monocytes). As such, GPR84 can potentially serve as a sensor of proinflammatory innate immune responses. To assess the utility of GPR84 as an imaging biomarker, we synthesized 11C-MGX-10S and 11C-MGX-11Svia carbon-11 alkylation for use as positron emission tomography (PET) tracers targeting this receptor. In vitro experiments demonstrated significantly higher binding of both radiotracers to hGPR84-HEK293 cells than that of parental control HEK293 cells. Co-incubation with the GPR84 antagonist GLPG1205 reduced the binding of both radiotracers by >90%, demonstrating their high specificity for GPR84 in vitro. In vivo assessment of each radiotracer via PET imaging of healthy mice illustrated the superior brain uptake and pharmacokinetics of 11C-MGX-10S compared to 11C-MGX-11S. Subsequent use of 11C-MGX-10S to image a well-established mouse model of systemic and neuro-inflammation revealed a high PET signal in affected tissues, including the brain, liver, lung, and spleen. In vivo specificity of 11C-MGX-10S for GPR84 was confirmed by the administration of GLPG1205 followed by radiotracer injection. When compared with 11C-DPA-713-an existing radiotracer used to image innate immune activation in clinical research studies-11C-MGX-10S has multiple advantages, including its higher binding signal in inflamed tissues in the CNS and periphery and low background signal in healthy saline-treated subjects. The pronounced uptake of 11C-MGX-10S during inflammation, its high specificity for GPR84, and suitable pharmacokinetics strongly support further investigation of 11C-MGX-10S for imaging GPR84-positive myeloid cells associated with innate immune activation in animal models of inflammatory diseases and human neuropathology.

Development and Initial Assessment of [18F]OP-801: a Novel Hydroxyl Dendrimer PET Tracer for Preclinical Imaging of Innate Immune Activation in the Whole Body and Brain.

PURPOSE: Innate immune activation plays a critical role in the onset and progression of many diseases. While positron emission tomography (PET) imaging provides a non-invasive means to visualize and quantify such immune responses, most available tracers are not specific for innate immune cells. To address this need, we developed [18F]OP-801 by radiolabeling a novel hydroxyl dendrimer that is selectively taken up by reactive macrophages/microglia and evaluated its ability to detect innate immune activation in mice following lipopolysaccharide (LPS) challenge. PROCEDURES: OP-801 was radiolabeled in two steps: [18F]fluorination of a tosyl precursor to yield [18F]3-fluoropropylazide, followed by a copper-catalyzed click reaction. After purification and stability testing, [18F]OP-801 (150-250 µCi) was intravenously injected into female C57BL/6 mice 24 h after intraperitoneal administration of LPS (10 mg/kg, n=14) or saline (n=6). Upon completing dynamic PET/CT imaging, mice were perfused, and radioactivity was measured in tissues of interest via gamma counting or autoradiography. RESULTS: [18F]OP-801 was produced with >95% radiochemical purity, 12-52 µCi/µg specific activity, and 4.3±1.5% decay-corrected yield. Ex vivo metabolite analysis of plasma samples (n=4) demonstrated high stability in mice (97±3% intact tracer >120 min post-injection). PET/CT images of mice following LPS challenge revealed higher signal in organs known to be inflamed in this context, including the liver, lung, and spleen. Gamma counting confirmed PET findings, showing significantly elevated signal in the same tissues compared to saline-injected mice: the liver (p=0.009), lung (p=0.030), and spleen (p=0.004). Brain PET/CT images (summed 50-60 min) revealed linearly increasing [18F]OP-801 uptake in the whole brain that significantly correlated with murine sepsis score (r=0.85, p<0.0001). Specifically, tracer uptake was significantly higher in the brain stem, cortex, olfactory bulb, white matter, and ventricles of LPS-treated mice compared to saline-treated mice (p<0.05). CONCLUSION: [18F]OP-801 is a promising new PET tracer for sensitive and specific detection of activated macrophages and microglia that warrants further investigation.

Clinical Radiosynthesis and Translation of [18F]OP-801: A Novel Radiotracer for Imaging Reactive Microglia and Macrophages.

Positron emission tomography (PET) is a powerful tool for studying neuroinflammatory diseases; however, current PET biomarkers of neuroinflammation possess significant limitations. We recently reported a promising dendrimer PET tracer ([18F]OP-801), which is selectively taken up by reactive microglia and macrophages. Here, we describe further important characterization of [18F]OP-801 in addition to optimization and validation of a two-step clinical radiosynthesis. [18F]OP-801 was found to be stable in human plasma for 90 min post incubation, and human dose estimates were calculated for 24 organs of interest; kidneys and urinary bladder wall without bladder voiding were identified as receiving the highest absorbed dose. Following optimization detailed herein, automated radiosynthesis and quality control (QC) analyses of [18F]OP-801 were performed in triplicate in suitable radiochemical yield (6.89 ± 2.23% decay corrected), specific activity (37.49 ± 15.49 GBq/mg), and radiochemical purity for clinical imaging. Importantly, imaging mice with tracer (prepared using optimized methods) 24 h following the intraperitoneal injection of liposaccharide resulted in the robust brain PET signal. Cumulatively, these data enable clinical translation of [18F]OP-801 for imaging reactive microglia and macrophages in humans. Data from three validation runs of the clinical manufacturing and QC were submitted to the Food and Drug Administration (FDA) as part of a Drug Master File (DMF). Subsequent FDA approval to proceed was obtained, and a phase 1/2 clinical trial (NCT05395624) for first-in-human imaging in healthy controls and patients with amyotrophic lateral sclerosis is underway.

PET imaging of TREM1 identifies CNS-infiltrating myeloid cells in a mouse model of multiple sclerosis.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) that causes substantial morbidity and diminished quality of life. Evidence highlights the central role of myeloid lineage cells in the initiation and progression of MS. However, existing imaging strategies for detecting myeloid cells in the CNS cannot distinguish between beneficial and harmful immune responses. Thus, imaging strategies that specifically identify myeloid cells and their activation states are critical for MS disease staging and monitoring of therapeutic responses. We hypothesized that positron emission tomography (PET) imaging of triggering receptor expressed on myeloid cells 1 (TREM1) could be used to monitor deleterious innate immune responses and disease progression in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. We first validated TREM1 as a specific marker of proinflammatory, CNS-infiltrating, peripheral myeloid cells in mice with EAE. We show that the 64Cu-radiolabeled TREM1 antibody-based PET tracer monitored active disease with 14- to 17-fold higher sensitivity than translocator protein 18 kDa (TSPO)-PET imaging, the established approach for detecting neuroinflammation in vivo. We illustrate the therapeutic potential of attenuating TREM1 signaling both genetically and pharmacologically in the EAE mice and show that TREM1-PET imaging detected responses to an FDA-approved MS therapy with siponimod (BAF312) in these animals. Last, we observed TREM1+ cells in clinical brain biopsy samples from two treatment-naïve patients with MS but not in healthy control brain tissue. Thus, TREM1-PET imaging has potential for aiding in the diagnosis of MS and monitoring of therapeutic responses to drug treatment.

Assessment of Serum Total Cholesterol in Adult Male Hypertensive Bangladeshi People.

Hypertension is a most common health problem worldwide and its incidence seems to be increasing on global scale. The objective of the study was to assess the relationship of serum Total Cholesterol with hypertensive patients in order to compare this parameter with normotensive subjects. This analytical type of cross sectional study was carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh, Bangladesh from July 2017 to June 2018. A total number of 120 male subjects, age ranged from 30-65 years was included in this study. Among them, sixty (60) hypertensive subjects were taken as study group (Group II) and sixty (60) age matched normotensive male subjects were taken as control group (Group I). Data were expressed as mean±SD and statistical significance of difference among the group was calculated by unpaired students' 't' test. In this study we found that serum total cholesterol was significant in study group (229.62±17.49mg/dl) in comparison with control group (166.32±18.04mg/dl). Therefore, by this study we recommended that routine estimation of these parameters is important for prevention of complication related to hypertension for leading a healthy life.

Highly Excretable Gold Supraclusters for Translatable In Vivo Raman Imaging of Tumors.

Raman spectroscopy provides excellent specificity for in vivo preclinical imaging through a readout of fingerprint-like spectra. To achieve sufficient sensitivity for in vivo Raman imaging, metallic gold nanoparticles larger than 10 nm were employed to amplify Raman signals via surface-enhanced Raman scattering (SERS). However, the inability to excrete such large gold nanoparticles has restricted the translation of Raman imaging. Here we present Raman-active metallic gold supraclusters that are biodegradable and excretable as nanoclusters. Although the small size of the gold nanocluster building blocks compromises the electromagnetic field enhancement effect, the supraclusters exhibit bright and prominent Raman scattering comparable to that of large gold nanoparticle-based SERS nanotags due to high loading of NIR-resonant Raman dyes and much suppressed fluorescence background by metallic supraclusters. The bright Raman scattering of the supraclusters was pH-responsive, and we successfully performed in vivo Raman imaging of acidic tumors in mice. Furthermore, in contrast to large gold nanoparticles that remain in the liver and spleen over 4 months, the supraclusters dissociated into small nanoclusters, and 73% of the administered dose to mice was excreted during the same period. The highly excretable Raman supraclusters demonstrated here offer great potential for clinical applications of in vivo Raman imaging.

Study on Serum Calcium Level in Patients with Chronic Kidney Disease.

Patients often present with chronic kidney disease (CKD) complicated with hypocalcaemia. Lower serum calcium is independently associated with chronic kidney disease. Aim of this study was to assess of serum calcium level in chronic kidney diseased patients in order to compare this parameter with healthy subjects. This analytical type of cross-sectional study was carried out in the Physiology department, Mymensingh Medical College, Mymensingh, Bangladesh from July 2018 to June 2019. A total number of 200 subjects, age range 30-70 year were included in this study. Among 200 subjects, 100 healthy were taken as control group (Group I) and 100 chronic kidney diseased patients were taken as study group (Group II). Control group (Group I) subdivided into male healthy subject (Group IA) and female healthy subject (Group IB). Also study group (Group II) subdivided into male chronic kidney diseased patient (Group IIA) and female chronic kidney diseased patient (Group IIB). The results were calculated and analyzed by using SPSS version-21. Expression of data as mean±SE and statistical significance of difference among the group was calculated by unpaired student's 't' test. In this study we found that mean±SE serum calcium of Group IA and Group IIA were 9.60±0.09mg/dl & 8.04±0.03mg/dl respectively. The mean±SE serum calcium of Group IB and Group IIB were 9.38±0.096mg/dl & 8.19±0.05mg/dl respectively. Serum calcium was significantly decreased in study groups in comparison with control groups (p<0.001). By this study we therefore recommended that routine estimation of this parameter is important for prevention of complication related to chronic kidney disease for leading a healthy life.

ICOS immunoPET enables visualization of activated T cells and early diagnosis of murine acute gastrointestinal GvHD.

Allogeneic hematopoietic cell transplantation (HCT) is a well-established and potentially curative treatment for a broad range of hematological diseases, bone marrow failure states, and genetic disorders. Acute graft-versus-host disease (GvHD), mediated by donor T cells attacking host tissues, still represents a major cause of morbidity and mortality following allogeneic HCT. Current approaches to diagnosis of gastrointestinal acute GvHD rely on clinical and pathological criteria that manifest at late stages of disease. New strategies allowing for GvHD prediction and diagnosis, prior to symptom onset, are urgently needed. Noninvasive antibody-based positron emission tomography (PET) (immunoPET) imaging of T-cell activation post-allogeneic HCT is a promising strategy toward this goal. In this work, we identified inducible T-cell costimulator (ICOS) as a potential immunoPET target for imaging activated T cells during GvHD. We demonstrate that the use of the Zirconium-89-deferoxamine-ICOS monoclonal antibody PET tracer allows in vivo visualization of donor T-cell activation in target tissues, namely the intestinal tract, in a murine model of acute GvHD. Importantly, we demonstrate that the Zirconium-89-deferoxamine-ICOS monoclonal antibody PET tracer does not affect GvHD pathogenesis or the graft-versus-tumor (GvT) effect of the transplant procedure. Our data identify ICOS immunoPET as a promising strategy for early GvHD diagnosis prior to the appearance of clinical symptoms.

Multiparameter Longitudinal Imaging of Immune Cell Activity in Chimeric Antigen Receptor T Cell and Checkpoint Blockade Therapies.

Longitudinal multimodal imaging presents unique opportunities for noninvasive surveillance and prediction of treatment response to cancer immunotherapy. In this work we first designed a novel granzyme B activated self-assembly small molecule, G-SNAT, for the assessment of cytotoxic T lymphocyte mediated cancer cell killing. G-SNAT was found to specifically detect the activity of granzyme B within the cytotoxic granules of activated T cells and engaged cancer cells in vitro. In lymphoma tumor-bearing mice, the retention of cyanine 5 labeled G-SNAT-Cy5 correlated to CAR T cell mediated granzyme B exocytosis and tumor eradication. In colorectal tumor-bearing transgenic mice with hematopoietic cells expressing firefly luciferase, longitudinal bioluminescence and fluorescence imaging revealed that after combination treatment of anti-PD-1 and anti-CTLA-4, the dynamics of immune cell trafficking, tumor infiltration, and cytotoxic activity predicted the therapeutic outcome before tumor shrinkage was evident. These results support further development of G-SNAT for imaging early immune response to checkpoint blockade and CAR T-cell therapy in patients and highlight the utility of multimodality imaging for improved mechanistic insights into cancer immunotherapy.

Correlation Study between COPD and Heart Failure in Elderly Patient.

Heart failure and chronic obstructive pulmonary disease (COPD) are acquiring significant morbidity and mortality and the amalgamation presents many diagnostic challenges. Assessment of cardiac and pulmonary function by echocardiography and pulmonary function tests should be executed in all patients with cautious explanation to avoid misdiagnosis and wrong treatment. Both conditions share overlapping pathophysiological processes. Both functional status and quality of life are greatly influenced by these and associated with high morbidity and mortality rates leading to increase the health-care costs. Although both diseases have been studied extensively, information about the correlation between heart failure and COPD is lacking. Classifying the reason of breathing symptoms among people with both the diseases can be demanding. Therefore it is plausible that a considerable proportion of patients with a diagnosis of COPD have associated heart failure, which ruins unrecognized by primary care physicians or pulmonologists. This study's aim was to assess the relationship between chronic obstructive pulmonary disease and heart failure among elderly patients with chronic cough and dyspnea. This study was done in 100 patient's ≥40 years with a GP (general physician) diagnosis of COPD. Descriptive cross sectional study was carried out in the Department of Medicine, Shaheed Ziaur Rahman Medical College Hospital, Bogra, Bangladesh from November 2011 to April 2012. A total of 100 cases of chronic cough with breathlessness coming into out patient department and admitted into Department of Medicine of Shaheed Ziaur Rahman Medical College Hospital, Bogra, Bangladesh were included according to inclusion and exclusion criteria. Informed written consent was taken from the participants and data was collected by a questionnaire and relevant investigations were done. Data were analyzed with SPSS software and were expressed as mean±SE and significance level of differences among the group was calculated by unpaired student's 't' test. In this study among 100 participating patients with a diagnosis of COPD by their physician, in 24(24%) patients had previously unrecognized heart failure. Pearson Correlation study showed that there is significant positive correlation between FEV1/FVC and Left Ventricular Diastolic Dysfunction and there is also significant positive correlation between FEV1/FVC and Total Left Ventricular Dysfunction. By this study we recommend that evaluation and assessment of cardiac status is very important in elderly patients with COPD.

Visualizing T-Cell Responses: The T-Cell PET Imaging Toolbox.

T lymphocytes are key mediators of the adaptive immune response. Inappropriate or imbalanced T-cell responses are underlying factors in cancer progression, allergy, and other immune disorders. Monitoring the spatiotemporal dynamics of T cells and their functional status has the potential to provide unique biologic insights into health and disease. Noninvasive PET imaging represents an ideal whole-body modality for achieving this goal. With the appropriate PET imaging probes, T-cell dynamics can be monitored in vivo with high specificity and sensitivity. Herein, we provide a comprehensive overview of the applications of this state-of-the-art T-cell PET imaging toolbox and the potential it has to improve the clinical management of cancer immunotherapy and T-cell-driven diseases. We also discuss future directions and prospects for clinical translation.

Neurovascular, Muscle, and Skin Changes on [18F]FDG PET/MRI in Complex Regional Pain Syndrome of the Foot: A Prospective Clinical Study.

OBJECTIVE: The goal of this study is to demonstrate the feasibility of simultaneous [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) for noninvasive visualization of muscular, neurovascular, and skin changes secondary to complex regional pain syndrome (CRPS). SUBJECTS: Seven adult patients with CRPS of the foot and seven healthy adult controls participated in our [18F]FDG PET/MRI study. METHODS: All participants received whole-body PET/MRI scans 1 hour after the injection of 370MBq [18F]FDG. Resulting PET/MRI images were reviewed by two radiologists. Metabolic and anatomic abnormalities identified, were grouped into muscular, neurovascular, and skin lesions. The [18F]FDG uptake of each lesion was compared with that of corresponding areas in controls using a Mann-Whitney U-test. RESULTS: On PET images, muscular abnormalities were found in five patients, neurovascular abnormalities in four patients, and skin abnormalities in two patients. However, on MRI images, no muscular abnormalities were detected. Neurovascular abnormalities and skin abnormalities in the affected limb were identified on MRI in one and two patients, respectively. The difference in [18F]FDG uptake between the patients and the controls was significant in muscle (P = .018) and neurovascular bundle (P = .0005). CONCLUSIONS: The increased uptake of [18F]FDG in the symptomatic areas likely reflects the increased metabolism due to the inflammatory response causing pain. Therefore, our approach combining metabolic [18F]FDG PET and anatomic MR imaging may offer noninvasive monitoring of the distribution and progression of inflammatory changes associated with CRPS.

Correlation between Fasting Serum Glucose and Serum Zinc Level in Patients with Type-2 Diabetes Mellitus.

Type-2 diabetes mellitus accounts for 90-95% of all diabetes. There is a Correlation between Fasting Serum Glucose and Serum Zinc level in patients with Type-2 Diabetes Mellitus. This study was done to assess the relationship of Fasting Serum Glucose and Serum Zinc in type-2 diabetic patients in order to compare this parameter with healthy subjects. This analytical type of cross sectional study was carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh, Bangladesh from July 2018 to June 2019. A total number of 140 subjects, age ranged from 35-65 years was included in this study. Among them, seventy (70) type-2 diabetic patients were taken as study group (Group II) and seventy (70) ages matched healthy subjects were taken as control group (Group I). Group I again subdivided into control group male (Group IA) and control group female (Group IB). Group II also subdivided into study group male (Group IIA) and study group female (Group IIB). Pearson correlation coefficient test is done to correlate the relationship between fasting serum glucose (FSG) and serum zinc. In this study we found that serum zinc level was decreased in study groups in comparison with control groups. Therefore, by this study we recommended that routine estimation of this parameter is important for prevention of complication related to diabetes for leading a healthy life.

A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2-Induced Glycolytic Reprogramming in Glioblastoma.

PURPOSE: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel PET tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and patients with GBM. EXPERIMENTAL DESIGN: [18F]DASA-23 was synthesized with a molar activity of 100.47 ± 29.58 GBq/µmol and radiochemical purity >95%. We performed initial testing of [18F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next, we produced [18F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers and a pilot cohort of patients with glioma. RESULTS: In mouse imaging studies, [18F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio of 3.6 ± 0.5. In human volunteers, [18F]DASA-23 crossed the intact blood-brain barrier and was rapidly cleared. In patients with GBM, [18F]DASA-23 successfully outlined tumors visible on contrast-enhanced MRI. The uptake of [18F]DASA-23 was markedly elevated in GBMs compared with normal brain, and it identified a metabolic nonresponder within 1 week of treatment initiation. CONCLUSIONS: We developed and translated [18F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [18F]DASA-23 to assess its utility for imaging therapy-induced normalization of aberrant cancer metabolism.

A miniaturized optoelectronic biosensor for real-time point-of-care total protein analysis.

A miniaturized optoelectronic sensor is demonstrated that measures total protein concentration in serum and urine with sensitivity and accuracy comparable to gold-standard methods. The sensor is comprised of a vertical cavity surface emitting laser (VCSEL), photodetector and other custom optical components and electronics that can be hybrid packaged into a portable, handheld form factor. In conjunction, a custom fluorescence assay has been developed based on the protein-induced fluorescence enhancement (PIFE) phenomenon, enabling real-time sensor response to changes in protein concentration. Methods are described for the following:•Standard curves: Used to determine the sensitivity, dynamic range, and linearity of the VCSEL biosensor/PIFE assay system in buffer as well as in human blood and urine samples.•Comparison of VCSEL biosensor performance with a benchtop fluorimetric microplate reader.•Accuracy of the VCSEL biosensor/PIFE assay system: Evaluated by comparing sensor measurements with gold-standard clinical laboratory measurements of total protein in serum and urine samples from patients with diabetes.

Minicircles for a two-step blood biomarker and PET imaging early cancer detection strategy.

Early cancer detection can dramatically increase treatment options and survival rates for patients, yet detection of early-stage tumors remains difficult. Here, we demonstrate a two-step strategy to detect and locate cancerous lesions by delivering tumor-activatable minicircle (MC) plasmids encoding a combination of blood-based and imaging reporter genes to tumor cells. We genetically engineered the MCs, under the control of the pan-tumor-specific Survivin promoter, to encode: 1) Gaussia Luciferase (GLuc), a secreted biomarker that can be easily assayed in blood samples; and 2) Herpes Simplex Virus Type 1 Thymidine Kinase mutant (HSV-1 sr39TK), a PET reporter gene that can be used for highly sensitive and quantitative imaging of the tumor location. We evaluated two methods of MC delivery, complexing the MCs with the chemical transfection reagent jetPEI or encapsulating the MCs in extracellular vesicles (EVs) derived from a human cervical cancer HeLa cell line. MCs delivered by EVs or jetPEI yielded significant expression of the reporter genes in cell culture versus MCs delivered without a transfection reagent. Secreted GLuc correlated with HSV-1 sr39TK expression with R2 = 0.9676. MC complexation with jetPEI delivered a larger mass of MC for enhanced transfection, which was crucial for in vivo animal studies, where delivery of MCs via jetPEI resulted in GLuc and HSV-1 sr39TK expression at significantly higher levels than controls. To the best of our knowledge, this is the first report of the PET reporter gene HSV-1 sr39TK delivered via a tumor-activatable MC to tumor cells for an early cancer detection strategy. This work explores solutions to endogenous blood-based biomarker and molecular imaging limitations of early cancer detection strategies and elucidates the delivery capabilities and limitations of EVs.

Study on Body Mass Index, Serum C-Reactive Protein and Their Association with Cardiovascular Risk Factors in Postmenopausal Women.

Menopause is the natural process of ageing when women pass from reproductive to non -reproductive phase with the cessation of cyclical ovarian functions. After menopause women are usually troubled by increasing weight and waist circumference caused by obesity and androidal fat redistribution. With the increase in life expectancy resulting in women living one half to one third of their lives after menopause, the high incidence of overweight and obesity in women have become important public health concerns. In postmenopausal women, elevated C-reactive protein (CRP) is one of the most significant predictors of cardiovascular disease and heart attack risk. In middle aged women, the risk of a coronary event rises dramatically after onset of menopause corresponding to decreased levels of circulating endogenous estrogens. Both body mass index (BMI) and serum CRP are significantly higher among postmenopausal women as compared with reproductive aged women. To assess the BMI and serum CRP level changes in healthy postmenopausal women in order to compare this parameter with healthy reproductive aged women. This comparative study was carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh, Bangladesh from July, 2018 to June, 2019. Two hundred healthy women (100 female were postmenopausal as study group and 100 female were reproductive aged women as control group) aged between 25 to 65 years were enrolled in this study. BMI was calculated as weight in kilogram divided by the height in meter square. Serum CRP by CRP-Latex Test (Slide agglutination procedure). Data were expressed as mean±SD and statistical significance of difference among the group was calculated by unpaired students' 't' test. The mean value ±SD of BMI and serum CRP level was higher in postmenopausal group in comparison to the reproductive women group. This study concludes, BMI and Serum C-Reactive protein level increased in postmenopausal women.

Evaluation of Change of Peak Expiratory Flow Rate (PEFR) in Male Chronic Obstructive Pulmonary Diseased (COPD) Patients.

Chronic obstructive pulmonary disease (COPD) is a major public health problem which causes high health care utilizations, poor health-related quality of life, and substantial cost burden and deaths in worldwide. This study was done to evaluate the changes of peak expiratory flow rate (PEFR) in COPD patients in comparison to healthy person. This analytical type of cross sectional study was carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh, Bangladesh from July 2018 to June 2019. A total number of 160 male subjects, age ranged from 30-70 years was included in this study. Among them, eighty (80) male COPD subjects were taken as study group (Group II) and eighty (80) age matched male healthy subjects were taken as control group (Group I). PEFR was assessed by peak flow meter. Data were expressed as mean ±SD and statistical significance of difference among the group was calculated by unpaired students' 't' test. The mean ±SD of PEFR of Group I and Group II were 432.75±30.23 L/min & 203.5±20.81 L/min respectively. The mean ±SD of PEFR significantly lower in study group in comparison with control group. Patients with COPD with greater changes in PEFR causes more frequent hospitalization and increased mortality and morbidity due to COPD related complications. So, assessment of this parameter is important for early detection and prevention of complications related to COPD for leading a healthy life.

Unrecognized Heart Failure in Elderly Patient with COPD.

Both of heart failure and chronic obstructive pulmonary diseases are in the elderly. They have an important impact on quality of life and functional status, show high morbidity and mortality rates and lead to extensive health-care costs. Although both diseases have been studied extensively, information about the prevalence of heart failure in stable chronic obstructive pulmonary disease (COPD) patients is lacking. For people who have both the diseases, identifying the cause of breathing symptoms can be challenging. It seems therefore plausible that a considerable proportion of patients with a diagnosis of COPD have concomitant heart failure, which remains unrecognized by primary care physicians or pulmonologists. The main aim of this study was to assess the prevalence of heart failure in patients with a diagnosis of chronic obstructive pulmonary disease. The prevalence of previously unknown heart failure was assessed in 100 patients ≥40 years with a GP (General physician) diagnosis of COPD, in a stable phase of their disease. This descriptive cross sectional study was carried out in the Department of Medicine, Shaheed Ziaur Rahman Medical College hospital, Bogra, Bangladesh from November 2011 to April 2012. A total of 100 cases of chronic breathlessness coming into out patient department and admitted into Department of Medicine of Shaheed Ziaur Rahman Medical College Hospital, Bogra were included based on inclusion & exclusion criteria. After taking informed written consent data was collected by a questionnaire and relevant investigations were done. Then collected data was analyzed and were expressed as mean ±SE and statistical significance of difference among the group was calculated by unpaired students 't' test. In this study we founded among 100 participating patients with a diagnosis of COPD by their physician, in 24 (24%) patients had previously unrecognized heart failure. Therefore, by this study we recommend that evaluation and assessment of cardiac status is very important in elderly patients with COPD.