Mechanoresponsive ETS1 causes endothelial dysfunction and arterialization in varicose veins via NOTCH4/DLL4 signaling.

Varicose veins are the most common venous disorder in humans and are characterized by hemodynamic instability due to valvular insufficiency and orthostatic lifestyle factors. It is unclear how changes in biomechanical signals cause aberrant remodeling of the vein wall. Our previous studies suggest that Notch signaling is implicated in varicose vein arterialization. In the arterial system, mechanoresponsive ETS1 is a transcriptional activator of the endothelial Notch, but its involvement in sensing disrupted venous flow and varicose vein formation has not been investigated. Here, we use human varicose veins and cultured human venous endothelial cells to show that disturbed venous shear stress activates ETS1-NOTCH4/DLL4 signaling. Notch components were highly expressed in the neointima, whereas ETS1 was upregulated in all histological layers of varicose veins. In vitro microfluidic flow-based studies demonstrate that even minute changes in venous flow patterns enhance ETS1-NOTCH4/DLL4 signaling. Uniform venous shear stress, albeit an inherently low-flow system, does not induce ETS1 and Notch proteins. ETS1 activation under altered flow was mediated primarily by MEK1/2 and, to a lesser extent, by MEK5 but was independent of p38 MAP kinase. Endothelial cell-specific ETS1 knockdown prevented disturbed flow-induced NOTCH4/DLL4 expression. TK216, an inhibitor of ETS-family, prevented the acquisition of arterial molecular identity and loss of endothelial integrity in cells exposed to the ensuing altered shear stress. We conclude that ETS1 senses blood flow disturbances and may promote venous remodeling by inducing endothelial dysfunction. Targeting ETS1 rather than downstream Notch proteins could be an effective and safe strategy to develop varicose vein therapies.

Variation of Mid shaft Antero-posterior and Transverse Diameter of Femur in Bangladeshi People.

Femoral morphometric variation is a dynamic system for different region, which is influenced by geographical, physiological and environmental factors, due to the adaptation, functional and remodeling responses of bones. This descriptive cross-sectional study was conducted on 150 (64 right and 86 left) fully ossified dry human femur of Bangladeshi people to find out the variation of mid shaft antero-posterior and transverse diameter of femur. Sample was collected in the Department of Anatomy, Mymensingh Medical College (MMC), Bangladesh from January 2019 to December 2019. All samples were assessed to eliminate fractured, pathologically damaged and remodeled bones. The diameters were measured with the help of digital Vernier slide calipers. The mean±SD mid shaft antero-posterior diameter of right and left femur were 25.03±2.86 mm and 25.54±2.65mm respectively. The mean±SD transverse diameter of right and left femur was 24.24±2.43mm and 24.54±2.38mm respectively. The knowledge of variations in the parameters of dry femora will help the orthopedicians for the treatment and management of femoral shaft fracture. These data also provide information about mid shaft diameter of femur of Bangladeshi people and to compare these data to those from various other races. Thus it could contribute for the design of well-fitting prosthesis which suits the Bangladeshi population. This value may be considered while making a best-fit femoral prosthesis.

Effectiveness of education and attitudes toward different types of deceased donor kidneys: Survey analysis of single-center experience.

Background: We lack data on the effectiveness of education and the patient's attitude toward different deceased donor kidney types. A prospective study was performed to evaluate patient attitudes, baseline knowledge, and effectiveness of our kidney transplant education process. We also analyzed the knowledge retention of our waitlist patients. Design: We prospectively surveyed a patient cohort using a paired analysis pre and post education with initial evaluation visit. Knowledge retention among waitlist patients was assessed with annual waitlist visit. Results: One hundred four patients received paired surveys to assess the baseline knowledge and effectiveness of education. Forty-three patients received a single survey with their annual waitlist evaluation to assess knowledge retention. Paired survey showed mixed results, with no statistically significant improvement in the kidney donor profile index domain. Significant improvement was seen in the hepatitis C virus-positive donor domain and the Public Health Service (PHS) increased-risk donor domain. For the waitlist cohort, overall knowledge retention ranged from excellent to fair, with a decline in knowledge for the PHS increased-risk donor domain. Conclusion: Our study suggests that the education intervention regarding different deceased donor kidney types is effective overall and transplant candidates retain the knowledge while waiting for transplant.

Oscillatory shear stress modulates Notch-mediated endothelial mesenchymal plasticity in cerebral arteriovenous malformations.

BACKGROUND: Cerebral arteriovenous malformations (cAVM) are a significant cause of intracranial hemorrhagic stroke and brain damage. The arteriovenous junctions in AVM nidus are known to have hemodynamic disturbances such as altered shear stress, which could lead to endothelial dysfunction. The molecular mechanisms coupling shear stress and endothelial dysfunction in cAVMs are poorly understood. We speculated that disturbed blood flow in artery-vein junctions activates Notch receptors and promotes endothelial mesenchymal plasticity during cAVM formation. METHODS: We investigated the expression profile of endothelial mesenchymal transition (EndMT) and cell adhesion markers, as well as activated Notch receptors, in 18 human cAVM samples and 15 control brain tissues, by quantitative real-time PCR (qRT-PCR) and immunohistochemical evaluation. Employing a combination of a microfluidic system, qRT-PCR, immunofluorescence, as well as invasion and inhibitor assays, the effects of various shear stress conditions on Notch-induced EndMT and invasive potential of human cerebral microvascular endothelial cells (hCMEC/d3) were analyzed. RESULTS: We found evidence for EndMT and enhanced expression of activated Notch intracellular domain (NICD3 and NICD4) in human AVM nidus samples. The expression of transmembrane adhesion receptor integrin α9/ß1 is significantly reduced in cAVM nidal vessels. Cell-cell adhesion proteins such as VE-cadherin and N-cadherin were differentially expressed in AVM nidus compared with control brain tissues. Using well-characterized hCMECs, we show that altered fluid shear stress steers Notch3 nuclear translocation and promotes SNAI1/2 expression and nuclear localization. Oscillatory flow downregulates integrin α9/ß1 and VE-cadherin expression, while N-cadherin expression and endothelial cell invasiveness are augmented. Gamma-secretase inhibitor RO4929097, and to a lesser level DAPT, prevent the mesenchymal transition and invasiveness of cerebral microvascular endothelial cells exposed to oscillatory fluid flow. CONCLUSIONS: Our study provides, for the first time, evidence for the role of oscillatory shear stress in mediating the EndMT process and dysregulated expression of cell adhesion molecules, especially multifunctional integrin α9/ß1 in human cAVM nidus. Concomitantly, our findings indicate the potential use of small-molecular inhibitors such as RO4929097 in the less-invasive therapeutic management of cAVMs.

An Observational Study of Fixed Drug Eruption in A Tertiary Care Hospital in Bangladesh.

Fixed drug eruption (FDE) is a distinctive pattern of cutaneous adverse drug reaction. Characteristically the eruption recurs at the same site on re exposure to the offending agent. Aim of this study was to evaluate and identification of the various offending drugs causing FDE which may help the physician to limit the associate complication regarding the drug. This observational cross sectional study was conducted from 1st June 2021 to 31st May 2022 in the department of Dermatology & Venereology of Mymensingh Medical College Hospital after taking approval from institutional ethical committee. A detailed history with clinical evaluation were done for all patients with FDE and thereby recorded in a pre designed proforma. Analysis of data was done using Microsoft Excel 2010 Spread sheet. Out of 65 cases 36(55.38%) were male and 29(44.6%) were female. Majority of cases were found in the age group of 31 to 40 years. The most common group of drug causing FDE was NSAID (52.31%) followed by antimicrobials (44.61%) and anti epileptics (3.07%). Ibuprofen (20.0%) was the most common offending drug followed by doxycycline (18.46%), diclofenac and fluconazole (13.84%), naproxen (9.23%), ciprofloxacin (7.69%), paracetamol (6.15%), metronidazole (4.61%), carbamazepine (3.07%) and aspirin (3.07%) respectively. Extremities (43.07%) were the most frequently involved site followed by trunk (29.23%) and face (10.77%). Generalized FDE found in 16.92% cases. Although FDE are very common the offending drugs show some regional variation as a result of changing trends of pharmacotherapy.

Direct Correlation of Soluble HLA and HLA-Containing Exosomes and Inverse Correlation of Tolerance Marker-Containing Exosomes With Antibody-Mediated Rejection After Simultaneous Liver-Kidney Transplantation: A Case Study.

There is a lower incidence of antibody-mediated rejection (AMR) after simultaneous liver-kidney transplantation (SLKT) than after kidney-only transplantation. It has been suggested that soluble human leukocyte antigen (sHLA) produced by the liver protects the kidney from AMR. However, this hypothesis has not been tested after SLKT. We present a case of SLKT with 2 donor-specific antibodies (DSAs) (DR53, 12,364 mean fluorescence intensity [MFI]; DQ7, 1253 MFI) that displayed a decrease by day 7 (DR53, 2747 MFI; DQ7, 107 MFI). On day 351, the patient was diagnosed with kidney AMR associated with high levels of DSA (DR53, 18,542 MFI; DQ7, 22,007 MFI) that persisted until day 531. High levels of sHLA-DR/DQ and HLA-DR/DQ-containing exosomes were also detected on day 398. Consequently, the patient underwent treatment with plasmapheresis, intravenous immunoglobulin, prednisone, and rituximab. On day 752, biopsy results were negative for AMR. Moderate levels of DSA (DR53, 9798 MFI; DQ7, 1271 MFI), and baseline levels of sHLA-DR/DQ and HLA-DR/DQ-containing exosomes were observed. Increases in CD4+CD25+FOXP3+ regulatory T cell marker-containing exosomes (CD73, programmed death-ligand 1) were observed on day 752 compared to day 398. These data show a direct correlation between sHLA and HLA-containing exosomes and an inverse correlation between tolerance marker-containing exosomes and kidney AMR after SLKT.

Development and Validation of a Kidney-Transplant Specific Measure of Treatment Burden.

BACKGROUND: Treatment burden refers to the work involved in managing one's health and its impact on well-being and has been associated with nonadherence in patients with chronic illnesses. No kidney transplant (KT)-specific measure of treatment burden exists. The aim of this study was to develop a KT-specific supplement to the Patient Experience with Treatment and Self-Management (PETS), a general measure of treatment burden. METHODS: After drafting and pretesting KT-specific survey items, we conducted a cross-sectional survey study involving KT recipients from Mayo Clinic in Minnesota, Arizona, and Florida. Exploratory factor analysis (EFA) was used to identify domains for scaling the KT-specific supplement. Construct and known-groups validity were determined. RESULTS: Survey respondents (n = 167) had a mean age of 61 years (range 22-86) and received a KT on average 4.0 years ago. Three KT-specific scales were identified (transplant function, self-management, adverse effects). Higher scores on the KT-specific scales were correlated with higher PETS treatment burden, worse physical and mental health, and lower self-efficacy (p < 0.0001). Patients taking more medications reported higher transplant self-management burden. CONCLUSIONS: We developed a KT-specific supplement to the PETS general measure of treatment burden. Scores may help providers identify recipients at risk for nonadherence.

A Multifaceted Intervention to Improve Medication Adherence in Kidney Transplant Recipients: An Exploratory Analysis of the Fidelity of the TAKE IT Trial.

BACKGROUND: Inadequate adherence to prescribed immunosuppressive medication regimens among kidney transplant recipients is common, yet interventions are needed to support patients in sustaining adequate adherence to prescribed regimens and achieving optimal transplant outcomes. OBJECTIVE: We examined the preliminary fidelity of a transplant center-based, multifaceted adherence monitoring strategy known as TAKE IT. METHODS: The TAKE IT strategy includes: (1) routine, online, monthly patient self-report adherence assessments; (2) care alerts directed to nurses; (3) quarterly reports monitoring tacrolimus values and adherence trends; (4) support tools tailored to specific adherence concerns. A 2-arm, patient-randomized trial is underway at two large transplant centers (N=449). To evaluate the initial fidelity of TAKE IT, we investigated patient uptake of monthly adherence assessments during the course of a 3-month period, whether any disparities emerged, and the nature of any reported adherence concerns. RESULTS: Among 202 patients randomized and exposed to TAKE IT for 3-months or more, 81% (164/202) completed an adherence assessment, 73% (148/202) completed at least two, and 57% (116/202) completed all monthly assessments. Overall, 50% (82/164) of kidney transplant recipients reported at least one adherence concern over the 3-month assessment period. The most common barriers were classified as regimen-related (eg, regimen complexity), cognitive (eg, forgetfulness), and medical (eg, side effects). Higher-income participants were more likely to complete all surveys compared to lower-income participants (P=.01). CONCLUSIONS: TAKE IT demonstrated 81% (164/202) completion of an adherence assessment, 73% (148/202) completion of at least two, and 57% (116/202) completion of all monthly assessments during this brief, initial observation period. Among those that did respond to the online assessments, the majority demonstrated sustained engagement. Additional monitoring modalities could also be offered to meet patient preferences to ensure all patients' medication use can be properly monitored. TRIAL REGISTRATION: ClinicalTrials.gov NCT03104868; https://clinicaltrials.gov/ct2/show/NCT03104868.

Number and Diameter of White Pulp of Spleen in Different Age and Sex Groups of Bangladeshi People.

Spleen is a haemo-lymph organ and belongs to the reticuloendothelial system of human body, develops from mesodermal proliferation between the two leaves of dorsal mesogastrium. The microscopic structure of spleen is variable depending on the developmental stage of the organ, and the age and immune status of the individual. In our country, we depend on foreign data which came from the subjects of different races and from the individuals under different geographic conditions. So the study was carried out to minimize the dependency on foreign standards and to identify the diameter of white pulp in different age and sex of the Bangladeshi individuals with a view to establish local data bank related to spleen of Bangladeshi people. This cross-sectional descriptive study was performed on 65 postmortem human spleens (34 of male and 31 of female) to find out the number and diameter of white pulp of spleen of Bangladeshi people by purposive sampling technique. And done in Autopsy laboratory of the Department of Forensic Medicine of Mymensingh Medical College, Bangladesh from 16th October 2016 to 15th January 2017. The samples were divided into three age groups including Group A (5-20 years), Group B (21-40 years) and Group C (41-60 years). Dissection was performed according to standard autopsy techniques. For statistical analysis, unpaired student 't' test was done. The mean±SD number of white pulp of male spleen was greater than female spleen in Group A, B and C but mean±SD diameter of white pulp of female spleen was found greater than male spleen in all groups. Comparison of number of white pulp between sexes showed that statistically there was no significant difference within all the age groups at p>0.05 level. No age change was evident in diameter of white pulp but in between sexes, diameter is greater in females than males. Mean difference of diameter of white pulp between sexes showed no significant difference within the age groups at p>0.05.

Age Related Changes in the Purkinje Cells in Human Cerebellar Cortex in Bangladeshi People.

This study was done to see the changes in the number of Purkinje cells per square mm in different age groups of Bangladeshi people. This cross-sectional descriptive type of study was done on total 40 postmortem human cerebellums, in the Department of Anatomy, Mymensingh Medical College, Bangladesh from July 2016 to June 2017. The specimens were collected from morgue in the department of Forensic Medicine, Mymensingh Medical College, by purposive sampling technique. All the specimens were grouped into four categories: Group A (20 to 29 years), Group B (30 to 39 years), Group C (40 to 49 years) and Group D (50 to 59 years). Paraffin blocks of cerebellum were cut at 4-5µm thickness and stained with routine "Haematoxylin and Eosin" (H & E) stain. Estimation of number of Purkinje cell was done by using the counting circle and examined under the light microscope. In the present study, the mean±SD number of Purkinje cell was found 128.67±25.15 per sq mm in Group A, 136.53±34.45 in Group B per sq mm, 135.55±29.44 per sq mm in Group C, 127.69±35.31 per sq mm in Group D.

Molecular Biomarkers and Drug Targets in Brain Arteriovenous and Cavernous Malformations: Where Are We?

Vascular malformations of the brain (VMB) comprise abnormal development of blood vessels. A small fraction of VMBs causes hemorrhages with neurological morbidity and risk of mortality in patients. Most often, they are symptomatically silent and are detected at advanced stages of disease progression. The most common forms of VMBs are arteriovenous and cavernous malformations in the brain. Radiopathological features of these diseases are complex with high phenotypic variability. Early detection of these malformations followed by preclusion of severe neurological deficits such as hemorrhage and stroke is crucial in the clinical management of patients with VMBs. The technological advances in high-throughput omics platforms have currently infused a zest in translational research in VMBs. Besides finding novel biomarkers and therapeutic targets, these studies have withal contributed significantly to the understanding of the etiopathogenesis of VMBs. Here we discuss the recent advances in predictive and prognostic biomarker research in sporadic and familial arteriovenous malformations as well as cerebral cavernous malformations. Furthermore, we analyze the clinical applicability of protein and noncoding RNA-based molecular-targeted therapies which may have a potentially key role in disease management.

Three-Jaw Chuck Pinch Strength and its Correlation with Hand Depth in Electronics Technicians.

The three jaw chuck pinch is a variety of pinch technique where thumb opposes both middle and index fingers. Pinch strength is generally influenced by the health status and level of physical activity of a person. The present study was conducted to measure the correlation of three-jaw chuck pinch strength with hand depth in electronics technicians working in Dhaka Metropolitan City. The data obtained from the study may be used as a base line for other professions as well as for research in our country. This cross sectional, analytical study was carried out in the department of Anatomy, Dhaka Medical College, Dhaka, Bangladesh from July 2015 to June 2016 on 100 adults male electronics technicians and 100 adult sedentary workers. Electronics technicians were considered as case group and sedentary workers were considered as control group. Case group was further subdivided according to their working experiences. Study subjects were selected by convenient purposive sampling technique. Hand depth was measured by digital slide calipers and pinch gauge was used to measure the three-jaw chuck pinch strength. The mean three-jaw chuck pinch strength was significantly higher (p<0.05) in case group than in the control group. Significant difference were also observed between case group and control group in the mean hand depth (p<0.05). Mean hand depth was greater in case group than that of control group. Three-jaw chuck pinch strength showed significant positive correlation with hand depth in case group. Case group was further subdivided according to their working experiences, the mean three-jaw chuck pinch strength and hand depth was significantly higher (p<0.05) in more working experience group than in less working experience group. Three-jaw chuck pinch strength showed significant positive correlation with hand depth.

Correlation between Length of Ala and Transverse Diameter of First Sacral Vertebral Body in both Sexes.

Sacrum is a triangular bone formed by the fusion of five sacral vertebrae. It is situated near the lower end of the spinal column, where it joins both hip bones to form the posterio superior wall of the pelvic cavity. It is an important bone for identification of sex in human skeletal system. This cross sectional and descriptive study was done among 150 (59 male and 91 female) fully ossified dry human sacrum in Mymensingh Medical College, Mymensingh, Bangladesh from January 2017 to December 2017. The sex of sacrum was determined by previously measured different parameters. Sample collection was done by purposive sampling technique from anatomy department of Mymensingh Medical College and Community Based Medical College of Bangladesh, Mymensingh. The parameters included the length of ala and transverse diameter of first sacral vertebral body which were measured by digital vernier slide caliper and was expressed in mm. In present study the mean length of ala in male and female were 29.21±6.30mm and 30.77±5.56mm respectively. The mean transverse diameter of first sacral vertebral body in male and female were 48.10±4.83mm and 44.05±6.16mm respectively. Comparison of both length of ala and transverse diameter of first sacral vertebral body was done between male and female by unpaired student 't' test which was statistically significant. There was positive correlation between these two parameters and the differences were statistically highly significant in both sexes.

Heat shock proteins-driven stress granule dynamics: yet another avenue for cell survival.

Heat shock proteins (HSPs) are evolutionary conserved 'stress-response' proteins that facilitate cell survival against various adverse conditions. HSP-mediated cytoprotection was hitherto reported to occur principally in two ways. Firstly, HSPs interact directly or indirectly with apoptosis signaling components and suppress apoptosis. Secondly, through chaperon activity, HSPs suppress proteotoxicity and maintain protein-homeostasis. Recent studies highlight the interaction of HSPs with cytoplasmic stress granules (SGs). SGs are conserved cytoplasmic mRNPs granules that aid in cell survival under stressful conditions. We primarily aim to describe the distinct cell survival strategy mediated by HSPs as the crucial regulators of SGs assembly and disassembly. Based on the growing evidence, HSPs and associated co-chaperones act as important determinants of SG assembly, composition and dissolution. Under cellular stress, as a 'stress-coping mechanism', the formation of SGs reprograms protein translation machinery and modulates signaling pathways indispensable for cell survival. Besides their role in suppressing apoptosis, HSPs also regulate protein-homeostasis by their chaperone activity as well as by their tight regulation of SG dynamics. The intricate molecular signaling in and around the nexus of HSPs-SGs and its importance in diseases has to be unearthed. These studies have significant implications in the management of chronic diseases such as cancer and neurodegenerative diseases where SGs possess pathological functions.

A Postmortem Study of Length & Depth of the Central Sulcus in Different Age & Sex Groups of Bangladeshi People.

The central sulcus (CS) is a prominent landmark of the brain, separating the parietal lobe from the frontal lobe and the primary motor cortex from the primary somatosensory cortex. Variations in the morphology of the central sulcus are seen with respect to the length and depth of the central sulcus. This study was done to establish a normal standard of length and depth of central sulcus in different age and sex groups of Bangladeshi people. Interhemispheric age and gender differences of the central sulcus were done by cross sectional descriptive study which was performed into four categories- Group A (20 to 29 years), Group B (30 to 39 years), Group C (40 to 49 years) and Group D (50 years & above). The specimens were collected from morgue in the department of Forensic Medicine, Mymensingh Medical College, Bangladesh by purposive sampling technique. The length of central sulcus was measured by using thread and the depth was measured by using wooden stick at middle of the upper, middle and lower third of the central sulcus in superolateral surface. The mean length of central sulcus was 10.51±0.529cm to 9.78±0.996cm in male and 10.27±0.786cm to 8.83±0.379cm in female. Depth of the central sulcus was 1.333±0.100cm to 1.029±0.125cm in male and 1.173±0.144cm to 1.01±0.200cm in female. The difference in mean length & depth of the central sulcus for both left and right hemisphere between male and female was statistically non significant in all age groups. In present study the length and depth of the central sulcus showed gradual decreasing values with advancing age. Knowledge of morphometry of central sulcus is not only important during neurosurgery of brain but also holds tremendous significance in diagnosis and management of diseases of the cerebral cortex. The present study will help to increase the information pool on the length and depth of the central sulcus of Bangladeshi people which will minimize the dependency on foreign standards.

Variation of Length of Calcarine Sulcus in Different Age & Sex Groups of Bangladeshi People.

Calcarine sulcus, one of the major sulcus of occipital lobe of cerebral hemisphere which is intimately related with visual function. The detailed anatomy of this lobe is essential for the surgeons and radiologists for clinical investigation & surgery. The aim of the present study was to identify the variation of this sulcus of the occipital lobe. This study was done to establish a normal standard in length of calcarine sulcus in different age & sex groups of Bangladeshi people. Inter-hemispheric age and gender differences of this sulcus was done by cross sectional descriptive study which was performed into four categories: Group A (20 to 29 years), Group B (30 to 39 years), Group C (40 to 49 years) and Group D (50 years & above). The specimens were collected from morgue in the department of Forensic Medicine, Mymensingh Medical College, Mymensingh, Bangladesh by purposive sampling technique. The length of calcarine sulcus was measured by using thread. The mean length of calcarine sulcus was lowest to highest values 7.07±0.616cm to 7.86±0.792cm in male and 6.53±0.808cm to 7.62±0.806cm in female. The mean difference of the length of right calcarine sulcus between group A & D was statistically significant at p<0.05, but not significant in any other age & sex groups for both left and right hemisphere. In present study, the length of the calcarine sulcus showed gradual decreasing values with advancing age. For proper planning of neurosurgical procedures and radiological representation of visual functional areas, detailed knowledge on the variation of this sulcus is essential. Proper knowledge of calcarine sulcus can permit safer access to deep structures and reduce operative complications. The present study will also help to increase the information pool on the length of the calcarine sulcus of Bangladeshi people which will minimize the dependency on foreign standards.

Transplant regimen adherence for kidney recipients by engaging information technologies (TAKE IT): Rationale and methods for a randomized controlled trial of a strategy to promote medication adherence among transplant recipients.

BACKGROUND: Several studies report a high prevalence of non-adherence to prescribed immunosuppressive (IS) medications among kidney transplant recipients (KTRs), yet few interventions have been effective for helping patients sustain appropriate post-transplant adherence. We describe a multifaceted, evidence-based, medication adherence monitoring strategy ('TAKE IT') that leverages available transplant center resources to identify potential medication non-adherence and other concerns earlier to prevent complications that could result from inadequate IS adherence. METHODS: The TAKE IT strategy includes: 1) medication adherence mobile application; 2) routine, online patient self-reported adherence assessments; 3) care alert notifications via the electronic health record (EHR) directed to transplant coordinators; 4) quarterly adherence reports to monitor IS values and summarize adherence trends; 5) deployment of adherence support tools tailored to specific adherence concerns. To test the TAKE IT intervention, we will conduct a two-arm, patient-randomized controlled trial at two large, diverse transplant centers (Northwestern University, Mayo Clinic, AZ) with planned recruitment of 450 KTRs (n = 225 per site) within 2 years of transplantation and 2 years of follow-up. Study assessments will take place at baseline, 6 weeks, 6, 12, 18 and 24 months. The primary effectiveness outcome is medication adherence via pill count, secondary outcomes include self-reported adherence and clinical outcomes. Process outcomes and cost-effectiveness will also be examined. CONCLUSION: The TAKE IT trial presents an innovative approach to monitoring and optimizing medication adherence among a population taking complex medication regimens. This trial seeks to evaluate the effectiveness and feasibility of this strategy compared to usual care.

Neurovascular inflammation in the pathogenesis of brain arteriovenous malformations.

Brain arteriovenous malformations (bAVM) arise as congenital or sporadic focal lesions with a significant risk for intracerebral hemorrhage (ICH). A wide range of interindividual differences is present in the onset, progression, and severity of bAVM. A growing body of gene expression and polymorphism-based research studies support the involvement of localized inflammation in bAVM disease progression and rupture. In this review article, we analyze the altered responses of neural, vascular, and immune cell types that contribute to the inflammatory process, which exacerbates the pathophysiological progression of vascular dysmorphogenesis in bAVM lesions. The cumulative effect of inflammation in bAVM development is orchestrated by various genetic moderators and inflammatory mediators. We also discuss the potential therapies for the treatment of brain AVM by targeting the inflammatory processes and mediators. Elucidating the precise role of inflammation in the bAVM growth and hemorrhage would open novel avenues for noninvasive and effectual causal therapy that may complement the current therapeutic strategies.

Hemodynamics mediated epigenetic regulators in the pathogenesis of vascular diseases.

Endothelium of blood vessels is continuously exposed to various hemodynamic forces. Flow-mediated epigenetic plasticity regulates vascular endothelial function. Recent studies have highlighted the significant role of mechanosensing-related epigenetics in localized endothelial dysfunction and the regional susceptibility for lesions in vascular diseases. In this article, we review the epigenetic mechanisms such as DNA de/methylation, histone modifications, as well as non-coding RNAs in promoting endothelial dysfunction in major arterial and venous diseases, consequent to hemodynamic alterations. We also discuss the current challenges and future prospects for the use of mechanoepigenetic mediators as biomarkers of early stages of vascular diseases and dysregulated mechanosensing-related epigenetic regulators as therapeutic targets in various vascular diseases.

Length of Umbilical Cord in Different Gestational Age Groups of Healthy Pregnant Mother of Bangladesh.

This cross sectional descriptive study was performed on 80 human placenta and umbilical cord to find out the variation in length of umbilical cord of healthy Bangladeshi mother in relation to different gestational age. This study was conducted in the Department of Anatomy, Mymensingh Medical College, Mymensingh, from January to December 2018. The specimens were collected from the Department of Gynaecology and Obstetrics, Mymensingh Medical College Hospital, Mymensingh, Bangladesh by purposive sampling technique. According to gestational age the collected samples were divided into three groups. They were Group A (28 to 36 weeks), Group B (37 to 40 weeks) and Group C (above 40 weeks) and examined morphologically by fine dissection method. The length of umbilical cord was measured with the help of flexible tape in cm. For statistical analysis, differences of length between age groups were analyzed by using unpaired student 't' test. The mean±SD length of umbilical cord was 56.15±7.61cm in Group A, 62.54±8.78cm in Group B and 68.54±10.53cm in Group C. It was also observed that the mean length of the umbilical cord was increased with increase of gestational age. The mean difference of length of umbilical cord between Groups A and C was statistically highly significant (p<0.001), difference between Groups A and B was statistically moderately significant (p<0.01) but the difference between Groups B and C was statistically significant (p<0.05). This study was done to provide information about the length of umbilical cord in different gestational ages of healthy pregnancies.