Protein phosphorylation regulates several dimensions of cell fate and is substantially dysregulated in pathophysiological instances as evident spatiotemporally via intracellular localizations or compartmentalizations with discrete control by specific kinases and phosphatases. Cardiovascular disease manifests as an intricately complex entity presenting as a derangement of the cardiovascular system. Cardiac or heart failure connotes the pathophysiological state in which deficient cardiac output compromises the body burden and requirements. Protein kinases regulate several pathophysiological processes and are emerging targets for drug lead or discovery. The protein kinases are family members of the serine/threonine phosphatases. Protein kinases covalently modify proteins by attaching phosphate groups from ATP to residues of serine, threonine and/or tyrosine. Protein kinases and phosphatases are pivotal in the regulatory mechanisms in the reversible phosphorylation of diverse effectors whereby discrete signaling molecules regulate cardiac excitation and contraction. Protein phosphorylation is critical for the sustenance of cardiac functionalities. The two major contributory ingredients to progressive myocardium derangement are dysregulation of Ca2+ processes and contemporaneous elevated concentrations of reactive oxygen species, ROS. Certain cardiac abnormalities include cardiac myopathy or hypertrophy due to response in untoward haemodynamic demand with concomitant progressive heart failure. The homeostasis or equilibrium between protein kinases and phosphatases influence cardiac morphology and excitability during pathological and physiological processes of the cardiovascular system. Inasmuch as protein kinases regulate numerous dimensions of normal cellular functions, the pathophysiological dysfunctionality of protein kinase signaling pathways undergirds the molecular aspects of several cardiovascular diseases or disorders as related in this study. These have presented protein kinases as essential and potential targets for drug discovery and heart disease therapy.
Repressive regulation of potassium channel genes by Polycomb group (PcG) proteins contributes to PcG protein-mediated neuroprotection against neuronal ischemic injury, as seen in an ischemic stroke. Here we asked the question whether Trithorax group (TrxG) proteins, the antagonistic partners of PcG proteins (i.e, epigenetic activators targeting the same genes) may also regulate potassium channels. Results of patch-clamp studies on cultured neuronal cells showed that inhibition of TrxG protein MLL-1 led to an increase in potassium channel activity, an unexpected effect for a presumed gene activator. In contrast, decreased sodium currents were observed with MLL-1 inhibition. Increased or decreased levels of potassium channel protein Kv2.1 or sodium channel protein Nav1.2, respectively, were seen with MLL-1 inhibition, as determined by immunocytochemistry. These results, for the first time, demonstrate an involvement of TrxG protein MLL-1 in regulating neuronal ion channels, potentially repressing potassium channel genes.
Familial dysautonomia is a rare autosomal recessive neurodegenerative disease affecting cells of the autonomic nervous system. Patients with this disease are insensitive to pain but their autonomic nervous system is still activated with noxious stimuli. This report details a case of a patient with familial dysautonomia who underwent right ankle open reduction and internal fixation for a bimalleolar right ankle fracture. The patients preoperative and intraoperative course were uneventful but shortly after handoff to the intensive care unit, the patient experienced an autonomic crisis. Management of these patients is complex, requiring maintenance of physiologic homeostasis as well as preventing hemodynamic instability caused by noxious stimuli. Any deviations from baseline may cause an autonomic crisis, as happened in our patient. Herein, we detail the perioperative management of a patient with familial dysautonomia in further detail.
Flow cytometry (FCM) is a unique technique that allows rapid quantitative measurement of multiple parameters on a large number of cells at the individual level. FCM is based on immunolabelling with fluorochrome-conjugated antibodies, leading to high sensitivity and precision while time effective sample preparation. FCM can be performed on tissue following enzymatic or mechanical dissociation. The expression of epithelial antigens and cytokeratin isoforms help in distinguishing tumor cells from adjacent epithelial cells and from tumor infiltrating leukocytes. Tumor phenotypes can be characterized on expression intensity, aberrancies and presence of tumor-associated antigens as well as their cell proliferation rate and eventual heteroploidy. FCM can measure quantitative expression of hormone or growth factor receptors, immunoregulatory proteins to guide adjuvant therapy. Expression of adhesion molecules tells on tumor’s capacity for tissue invasion and metastasis seeding. Tumor heterogeneity can be explored quantitatively and rare, potentially emerging, clones with poor prognosis can be detected. FCM is easily applicable on fine needle aspiration and in any tumor related biological fluids. FCM can also be used to detect circulating tumor cells (CTC) to assess metastatic potential at diagnosis or during treatment. Detecting CTC could allow early detection of tumors before they are clinically expressed although some difficulties still need to be solved. It thus appears that FCM should be in the pathologist tool box to improve cancer diagnosis, classification and prognosis evaluation as well as in orientating personalized adjuvant therapy and immunotherapy. More developments are still required to better known tumor phenotypes and their potential invasiveness
We report a case of a right gluteal mass from the sacroiliac joint to the knee of an infant girl. Biopsy showed histopathological features similar to infantile fibrosarcoma (IFS). However, unlike most IFS, no ETV6-NTRK3 fusion gene abnormality was detected. Molecular analysis with TruSight RNA Pan-Cancer Panel detected the presence of KIAA1549-BRAF translocation and an oncogenic NF2p.Q459* SNV with potential clinical significance. A review revealed that the combination of this patient’s tumor site with the presence of a KIAA1549-BRAF translocation abnormality and an accompanying single nucleotide variant has not been previously described. The detection of this translocation abnormality raises the possibility that the spindle cell tumors in infants with an absence of the ETV6-NTRK3 fusion gene abnormality might have a distinct pathogenetic mechanism different from the previously known IFS and congenital mesoblastic nephroma. Furthermore, the discovery of BRAF translocation and its aberrant signaling of the mitogen-activated protein kinase (MAPK) pathway in this tumor contributes to the promise of clinical benefit of using the MEKi trametinib for the treatment of progressive disease that is refractory to conventional chemotherapy.
Development of genetic profiles from the biological mixtures has remained challenging, although modern-day technologies may help forensic scientists to attain a reliable genetic profile in the identification of the accused.
In the case of rape, vaginal swab exhibits usually contain epithelial cells of victims and sperm cells of accused, such samples are more challenging when there is more than one contributor. In such cases, separation of distinct cells from a mixture that includes blood cells, epithelial cells and sperm cells for their single genetic profile is important.
In the last ten decades several new techniques were developed and invented for the separation of single cell from the biological mixture that includes differential lysis, laser micro-dissection, cell sorting (FACS), sieve-based filtration, (vi) micro-fluidic devices or immunomagnetic beads cell separation of fresh samples, and the magnetic activated cell sorting (MACS).
Out of them, some techniques have been commonly applied for cell separation in forensic biology. Each technique has its own limitation. Some recent studies showed, magnetic activated cell sorting (MACS), laser capture microdissection (LCM), DEPArray technology and fluorescence activated cell sorting (FACS) has proved to be effective in separation of single cell from cell mixtures.
Therefore, in this review we have evaluated these four alternative methods and their potential application in the modern-day over the others for the separation of a single cell from the mixture. In this review we also discuss the advantage of these methods and their modern–day applicability and acceptance in the forensic world.
Introduction: Cancer treatment and prognosis depend heavily on early detection. Survival in the early stages is excellent for almost all types of cancer. Unfortunately, in Saudi Arabia, a large number of cancer patients present with advanced disease, resulting in a poor prognosis. There are three levels of delay in the management of cancer patients. The first level is the time between the first cancer-related symptoms and the presentation to the health facility, the second level is from the presentation to the diagnosis, and the third level is between the diagnosis and the treatment. This study aims to determine if there is a delay, at what level and to study the factors causing such delays.Materials and methods: Two hundred cancer patients who presented to the Armed Forces Hospital Southern Region, Oncology Department, were interviewed from January 1st to June 30th, 2018. The interviews were conducted by trained physicians familiar with the questionnaire’s contents. The questionnaire consisted of four sections: a demographic section and three more sections to identify factors causing the delay at the three levels from the patients’ perspectives. All data were analyzed using the SPSS version 20.0.Results: The mean patient age was 63 years. A total of 112 patients were female and 88 were male. The most common cancer type was breast cancer (27.5%). Among the patients, 61% were illiterate and 25.5% had elementary school degrees, 86% expressed little or no general medical knowledge about cancer. More women than men paid attention to cancer symptoms (70% vs. 54%). 75% of the patients presented to the first health facility after 2 months from the first appearance of symptoms (level 1 delay). Only 2% of the patients presented within one week. 50% of the patients received a diagnosis after visiting two health facilities. All patients were diagnosed at hospitals. 40% of patients used alternative medicines, 70% of whom thought this was the cause of their delayed presentations. 67% had their diagnosis confirmed within one month (level 2 delay), and 66% started their definitive treatment within one month (level 3 delay). 75% of the patients blame themselves for the delay. Educational level (p = 0.03), knowledge about cancer (p < 0.01), and the use of complementary and alternative medicines (CAM) (p = 0.01) were significantly associated with delayed presentation of patients to the health facility. Conclusion: There is a delay in the presentation of cancer patients (level 1) in the southern part of Saudi Arabia. Educational level, knowledge of cancer symptoms, and use of complementary and alternative medicines are the main causes. There were no delays in diagnosis and start of treatment (level 2,3).
Strobilurin is a group of natural products and their synthetic analogs have been widely used to control and prevent fungal diseases. Strobilurins were firstly isolated in 1977 from the mycelium of Strobilurus tenacellus, a saprobic Basidiomycete fungus causing wood-rotting on forest trees. This group of pesticides was designed to manage fungal pathogens classes such as Ascomycetes, Basidiomycetes, and Oomycetes. Also, Strobilurin commercialized included derivatives such as are azoxystrobin, kresoxim-methyl, picoxystrobin, fluoxastrobin, oryzastrobin, dimoxystrobin, pyraclostrobin and trifloxystrobin. This group is a part of the larger group of QoI inhibitors, which act to inhibit the respiratory chain at the level of Complex III. Strobilurins group control an unusually wide array of fungal diseases, included water molds, downy mildews, powdery mildews, leaf spotting and rusts. This group are used on cereals, field crops, fruits, tree nuts, vegetables, turfgrasses and ornamentals. Also, Strobilurins found to enhance the plant growth in some cases.
Tina Katamea, Olivier Mukuku, Patient Dinanga Nzala, Bénédicte Malonda Nsasi, Charles Wembonyama Mpoy, Oscar Numbi Luboya and Stanis Okitotsho Wembonyama*
Introduction: Despite advances in the management of sickle cell disease (SCD), gaps still exist in the knowledge of healthcare professionals (HCPs) about the disease. The objective of this study was to assess the knowledge of HCPs about SCD.
Methods: This is a cross-sectional study involving 465 HCPs (physicians and nurses) who responded to the DFConhecimento instrument questionnaire. Performance was tested in terms of average score and proportion of correct response for each questionnaire item topic.
Results: The average score for respondents was 4.6 ± 1.9 out of a total of 13 points. Proportions of professionals who responded well were greater than 58% in three topics (Neonatal screening program, Sickle cell conditions, and Sickle cell anemia genotype). In the other topics, rates of good response ranged from 11.6% to 46.0%. There was a statistical association between best performance and medical title: physicians were more knowledgeable than nurses (OR = 6.26; 95% CI: 2.69-14.56).
Conclusion: This study highlighted that knowledge of SCD among HCPs is very inadequate. This lack of sufficient information on SCD from HCPs indicates the need to develop continuing education programs.
Non-alcoholic fatty liver disease (NAFLD) is a condition that is associated with cirrhosis and hepatocellular carcinoma, and is increasing in prevalence worldwide. Sleep disruptions are commonly seen in NAFLD, and the disease process is associated with sleep disorders, including obstructive sleep apnea, circadian rhythm disorders, and insufficient sleep. The intermittent hypoxia seen in obstructive sleep apnea may contribute to fibrotic changes in the liver.A major component of this linkage may be related to gut microbiome changes. One notable change is increase in Bacteroidetes/Firmicutes ratio, and decrease in flora that ferment fiber into anti-inflammatory short-chain fatty acids. Several therapeutic options exist for NAFLD that target both sleep and NAFLD, including non-pharmacological factors, such as lifestyle modification (mainly diet and exercise). Pharmacological options include melatonin, Vitamin E, thiazolidinediones, and fecal microbiota transplantation.Core tipThe pathogenesis of non-alcoholic fatty liver disease is closely tied to sleep and circadian rhythm abnormalities, through shared inflammatory pathways and altered metabolism. This review explores the pathogenesis of NAFLD in the context of sleep and circadian abnormalities. The associated inflammatory response is linked to changes in gut-microbiome interactions that contribute to the disease process. Understanding of this linkage has implications for various therapies for disease mitigation.
The involvement of bile duct in lymphoma is considered to be very rare and is usually a sequela of a disseminated disease [1]. In contrast to secondary involvement, primary non-Hodgkin’s lymphoma arising from the bile duct is extremely rare and presents with obstructive jaundice [2,3]. Non-Hodgkin’s lymphoma (NHL) accounts for 1% - 2% of all cases of malignant biliary obstruction [4]. Hepatobiliary involvement by malignant lymphoma is usually a secondary manifestation of systemic lymphoma. The first case of Non-Hodgkin lymphoma arising from bile duct was described by Nguyen in 1982 [5]. Most common extra nodal involvement of NHL is abdomen. Although, involvement of the stomach, pancreas or common bile duct is not common [6]. We present to you a case of 31year old male who presented to us with obstructive jaundice and was later diagnosed as Diffuse Large B-Cell lymphoma.
A micellar thin-layer chromatography method for the quantitative determination and validation of coumarin in Meliloti herba and its ethanolic extracts was developed and validated. For achieving good determination, the mobile phase of 5 x 10-4 mol/L Tween-80 in a mixture propanol-2 – water (5:95 v/v) was used. Densitometric determination was carried out at 275 nm. The calibration curve was linear in the range of 0.1-2.5 μg per band. The proposed method is simple, rapid, precise and accurate; replacing hazardous solvents by greener ones correspond to the modern requirements in “Green chemistry” concepts. The obtained data can be used for the routine analysis of coumarin in medical plant and extracts.
Oral lichen planus (OLP) is an autoimmune chronic inflammatory disease. The potential risk of malignant transformation in OLP remains controversial. The aim of the present study was to review original clinical studies published in indexed databases, which assessed the potential risk cofactors which were implicated in the malignant transformation of oral lichen planus. We focused our search to include most of the studies that reported malignant transformation of oral lichen planus using different combinations of the following key indexing terms: oral lichen planus, malignant transformation, smoking, alcohol, chronic inflammation, candida, human papillomavirus (HPV), hepatitis C virus (HCV) and immunosuppression. The animal studies were excluded from our study. Despite a dearth of studies on this topic we have identified consumption of tobacco and/or alcohol, the presence of erosive and/or atrophic areas, infection with candida, HCV, HPV, and immunosuppression as significant cofactors. Patients with OLP with these risk co-factors are at risk of malignant transformation should, therefore be followed up for an extensive period or even for life.
COVID-19 is a disease that is caused by SARS-CoV-2 and very speedily spreading all over the world. The blood group’s effect on COVID-19 is not clear. The main aim of this article is to determine the relationship between sensitivity of COVID-19 and ABO blood group. For this study we have observed that the individuals with blood group A are at higher risk of getting COVID-19 because they contain the higher concentration of Angiotensin-converting enzyme-2 that provide the site to virus for entry. But in other blood groups the natural Anti A antibodies block the interaction between host receptor and virus and disturb their interaction. Certain studies show that the infectivity and mortality rate in covid patients is not affected by AB blood group system. But according to research, increased ventilator usage, ICU stay was observed in critically ill patients with AB blood group than of other blood groups. O blood group has proved to be protective against SARS-CoV-2 due to the presence of both anti-A and anti-B antibodies as they prevent the binding of the spike protein S of the virus with the ACE2 receptors which are present on the surface of cells. Moreover, furin also plays a major role in penetration of virus in the host cells. Furin is required for the activation of the spike protein S of the virus and due to the low efficiency of furin cleavage in blood group O it is protected from SARS-CoV-2 and other chronic diseases. Mortality rate of covid 19 depends upon the environmental factors, number of people living in the area and also some economic factors. The different strains of COVID-19 effect the different people differently and as the time passes the strain of COVID-19 has changed and thus according to this the mortality rate of different provinces and areas varies due to environmental factors. Pregnant women have no any kind of transportation of covid to their fetuses but mostly patients of blood group A are being affected by COVID-19 and hence their fetuses are somehow effected. And those pregnant women having blood group O does not have any risk of COVID-19 of severe stages.
The fungal pathogen, Nothophaeocryptopus gaeumannii, occurs wherever Douglas-fir is found but disease damage is believed to be limited to the Coast Range and is of no concern outside the coastal fog zone (Shaw, et al., 2011). However, knowledge remains limited on the history and spatial distribution of Swiss Needle Cast (SNC) impacts in the Pacific Northwest (PNW). We reconstructed the history of SNC impacts on mature Douglas-fir trees based on tree ringwidth chronologies from the west slope of the Coast Range to the high Cascades of Oregon. Our findings show that SNC impacts on growth occur wherever Douglas-fir is found in western Oregon and is not limited to the coastal fog zone. The spatiotemporal patterns of growth impact from SNC disease were synchronous across the region, displayed periodicities of 25-30 years, strongly correlated with winter and summer temperatures and summer precipitation, and matched the patterns of enriched cellulosic stable carbon isotope indicative of physiological stress. While winter and summer temperature and summer precipitation influenced pathogen dynamics at all sites, the primary climatic factor of these three limiting factors varied spatially by location, topography, and elevation. In the 20th century, SNC impacts at low- to mid-elevations were least severe during the warm phase of the Pacific Decadal Oscillation (PDO, 1924-1945) and most severe in 1984-1986, following the cool phase of the PDO (1945-1977). At high elevations on the west slope of the Cascade Mountains, SNC impacts were the greatest in the 1990s and 2000s, a period of warmer winter temperatures associated with climate change. Warmer winters will likely continue to increase SNC severity at higher elevations, north along the coast from northern Oregon to British Columbia, and inland where low winter temperatures currently limit growth of the pathogen. Surprisingly, tree-ring records of ancient Douglas-fir logs dated ~53K radioactive years B.P. from Eddyville, OR displayed 7.5- and 20-year periodicities of low growth, similar to those found in modern day coastal Douglas-fir tree-ring records which we interpret as being due to cyclic fluctuations in SNC severity. Our findings indicate that SNC has persisted for as long as its host, and as a result of changing climate, may become a significant forest health problem in areas of the PNW beyond the coastal fog zone.
For a long time there was no explanation of a study which had revealed that people with schizoaffective disorders and in particular suicidal attempts rarely get cancer. But now, we can assume that there are diseases that are “mirrored” because they occur with reverse/feedback pathophysiological mechanisms so that they are, in fact, antagonists.
Retrorectal cystic hamartomas (HCR) (“tailgut cyst” in English-language literature) are congenital cystic tumors derived from vestiges of the hindgut. Its incidence is low, being more frequent in adult women. They are variable in size, uni or multiloculated. They can be lined with several types of epithelia (squamous, transitional, mucinous,...) in a same cyst and can contain mucus. Lesions usually present during adulthood due to pain, discomfort, rectal bleeding, infection, or malignant transformation. The incidence of malignancy is low, being adenocarcinoma and neuroendocrine the most frequent tumors associated to HCR. We present a case of HCR associated with squamous cell carcinoma and discuss aspects of the treatment.
Malignant pericardial effusion is a usual and crucial exacerbation in malignancies. In some cases, pericardial effusion may be the first manifestation of the disease. Neoplastic pericarditis is extremely rare in thyroid cancer. Hereby, we describe the case of a 54-year-old man submitted to the hospital for chest pain and dyspnea. Clinical and radiological examinations were suggestive of pericardial effusion and mediastinal lymphadenopathy. The patient underwent pericardial drainage and surgical biopsy of a paratracheal lymph node. Pericardial biopsies were also taken. Histology study was compatible with metastatic papillary thyroid carcinoma with “signet-ring” cell morphology. Extended study of thyroid gland and function was performed and he was referred to oncologists for further treatment. Clinical presentation and histology are discussed emphasizing the rare correlation between pericardial pathology and metastatic thyroid carcinomas as the first diagnosis. Histopathologic findings of “signet-ring” cell morphology are very challenging for a differential diagnosis between thyroid carcinoma and other metastatic adenocarcinomas.
Aims: To examine patient satisfaction of an outpatient operative hysteroscopy performed by both doctors and nurse hysteroscopists. Secondly, compare satisfaction, complications, and failure rate of these procedures performed by doctors and nurse hysteroscopists.Methods: In this retrospective study, the charts of 80 women who attended the service over one year were examined. Women were included if either an endometrial polyp or submucosal leiomyoma required removal using an endoscopic morcellator. All women had signed a consent form for the procedure. Results: In total 67/80 (84%) patients were satisfied with the service. Nurse hysteroscopists completed most procedures 59/80 (74%). Satisfaction ratings were not recorded for 13/80 (16%) consultations, completed by doctors. There was no difference in satisfaction and complication rates between doctors and nurse hysteroscopists. A total of five patients required repeat endoscopic morcellation, three completed by doctors and two completed by nurse hysteroscopists. For this group, satisfaction and complication ratings did not change.Conclusion: High patient satisfaction and low complication rates were found. Nurse hysteroscopists performed more procedures, providing a safe and useful service. Few patients required repeat morcellation procedures.
Specific receptors for atrial natriuretic peptide (ANP) located in intra-ovarian tissues are suggested to be involved in ovarian functions such as oocyte maturation and follicle development. However, the characteristics and modulation of its receptor in relation to ovarian folliculogenesis are not well defined. This study examined the properties of ANP receptors in the ovary using quantitative receptor autoradiography. In the pig ovary, the highest binding sites for 125I-ANP(1-28) were localized in the granulosa cell layer of the follicles as well as cumulus oophorous. The binding sites for 125I-ANP(1-28) on theca layer of the ovarian follicles were mainly localized in the external layer, but none was observed in the internal layer. Specific binding of 125I-ANP(1-28) was not found clearly in atretic follicles. In the corpus luteum, the binding site was not observed. Analysis of the competitive inhibition of the binding of 125I-ANP(1-28) to the granulosa and theca externa layers in various preovulatory follicles by increasing concentrations of unlabeled ANP(1-28)was consistent with a single high affinity for 125I-ANP(1-28). The maximal binding capacities of 125I-ANP(1-28) in granulosa layer were significantly increased in proportion to the development of ovarian follicles. However, no significant difference of binding capacities of 125I-ANP(1-28) was observed in theca externa layer. The binding affinities of 125I-ANP(1-28) in granulosa and theca externa layers were not different from each other. Especially, the correlation between specific binding of 125I-ANP(1-28) and follicle diameter. A significant correlation was revealed between specific binding of 125I-ANP(1-28) and follicle diameter (R = 0.88, p < 0.0001) in granulosa layer, however, less relationship was detected in theca externa layer (R = 0.50, p < 0.0001). Therefore, these results indicate that the biological ANP receptors exist in granulosa and the theca externa layers of the pig ovary, and suggest that the ANP receptors in granulosa layer may be related to the regulatory function of the ovarian follicullogenesis including oocyte maturation.
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BS, PharmD., MBA, CPHIMS, FHIMSS, Adjunct Professor, Global Healthcare Management, MCPHS University, Chief Strategy Offi cer, MedicaSoft, Senior Advisor, National Health IT (NHIT) Collaborative for Underserved, New York HIMSS, National Liaison, Health 2.0 Boston, Past Chair, Chair Innovation, USA
Helen Figge
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Department of Agricultural Economics, Agribusiness and Extension, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Akowuah Jones Asafo
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University of Port Harcourt Teaching Hospital, Nigeria
Dr. Elizabeth A Awoyesuku
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Department of Biotechnology, Uttaranchal college of Applied and Life Sciences, Uttaranchal University, Dehradun, Uttarakhand, India
Archna Dhasmana
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University of Jacqmar, Inc., USA
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Assistant Professor, UCLAS Uttaranchal University, Dehradun, India
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