Exploring the synergistic effects of indole acetic acid (IAA) and compost in the phytostabilization of nickel (Ni) in cauliflower rhizosphere.

Heavy metals (HMs) contamination, owing to their potential links to various chronic diseases, poses a global threat to agriculture, environment, and human health. Nickel (Ni) is an essential element however, at higher concentration, it is highly phytotoxic, and affects major plant functions. Beneficial roles of plant growth regulators (PGRs) and organic amendments in mitigating the adverse impacts of HM on plant growth has gained the attention of scientific community worldwide. Here, we performed a greenhouse study to investigate the effect of indole-3-acetic acid (IAA @ 10- 5 M) and compost (1% w/w) individually and in combination in sustaining cauliflower growth and yield under Ni stress. In our results, combined application proved significantly better than individual applications in alleviating the adverse effects of Ni on cauliflower as it increased various plant attributes such as plant height (49%), root length (76%), curd height and diameter (68 and 134%), leaf area (75%), transpiration rate (36%), stomatal conductance (104%), water use efficiency (143%), flavonoid and phenolic contents (212 and 133%), soluble sugars and protein contents (202 and 199%), SPAD value (78%), chlorophyll 'a and b' (219 and 208%), carotenoid (335%), and NPK uptake (191, 79 and 92%) as compared to the control. Co-application of IAA and compost reduced Ni-induced electrolyte leakage (64%) and improved the antioxidant activities, including APX (55%), CAT (30%), SOD (43%), POD (55%), while reducing MDA and H2O2 contents (77 and 52%) compared to the control. The combined application also reduced Ni uptake in roots, shoots, and curd by 51, 78 and 72% respectively along with an increased relative production index (78%) as compared to the control. Hence, synergistic application of IAA and compost can mitigate Ni induced adverse impacts on cauliflower growth by immobilizing it in the soil.

Unveiling the sweetness: evaluating yield and quality attributes of early generation sweet corn (Zea mays subsp. sachharata) inbred lines through morphological, biochemical and marker-based approaches.

BACKGROUND: Sweet corn is gaining tremendous demand worldwide due to urbanization and changing consumer preferences. However, genetic improvement in this crop is being limited by narrow genetic base and other undesirable agronomic traits that hinder the development of superior cultivars. The main requirement in this direction is the development of potentially promising parental lines. One of the most important strategies in this direction is to develop such lines from hybrid-oriented source germplasm which may provide diverse base material with desirable biochemical and agro-morphological attributes. METHODS AND RESULTS: The study was undertaken to carry out morphological and biochemical evaluation of 80 early generation inbred lines (S2) of sweet corn that were developed from a cross between two single cross sweet corn hybrids (Mithas and Sugar-75). Moreover, validation of favourable recessive alleles for sugar content was carried out using SSR markers. The 80 sweet corn inbreds evaluated for phenotypic characterization showed wide range of variability with respect to different traits studied. The highest content of total carotenoids was found in the inbred S27 (34 µg g-1) followed by the inbred S65 (31.1 µg g-1). The highest content for total sugars was found in S60 (8.54%) followed by S14 (8.34%). Molecular characterization of 80 inbred lines led to the identification of seven inbreds viz., S21, S28, S47, S48, S49, S53, and S54, carrying the alleles specific to the sugary gene (su1) with respect to the markers umc2061 and bnlg1937. Comparing the results of scatter plot for biochemical and morphological traits, it was revealed that inbreds S9, S23, S27 and S36 contain high levels of total sugars and total carotenoids along with moderate values for amylose and yield attributing traits. CONCLUSION: The inbred lines identified with desirable biochemical and agro-morphological attributes in the study could be utilized as source of favourable alleles in sweet corn breeding programmes after further validation for disease resistance and other agronomic traits. Consequently, the study will not only enhance the genetic base of sweet corn germplasm but also has the potential to develop high-yielding hybrids with improved quality. The inbreds possessing su1 gene on the basis of umc2061 and bnlg1937 markers were also found to possess high sugar content. This indicates the potential of these lines as desirable candidates for breeding programs aimed at improving sweet corn yield and quality. These findings also demonstrate the effectiveness of the molecular markers in facilitating marker-assisted selection for important traits in sweet corn breeding.

Emicizumab Prophylaxis in Patients with Severe Hemophilia A: Insights from A Resource Limited Country.

METHODS: In this prospective study, severe HA patients were recruited from January 2022 to June 2023. Inhibitor positive and inhibitor negative patients with annual bleeding rate (ABR) 8 or greater and past histories of bleeding like intra-cranial, intra-abdominal, and pseudo-tumors were included. Emicizumab loading dose was 3 mg/kg in the first 4 weeks, and the maintenance dose was started at week 5 at 6 mg/kg/month. Patients' detailed bleeding history and demographics were recorded. The five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) was used to evaluate patients' HRQoL. Furthermore, Hemophilia Joint Health Score (HJHS) and Functional Independence score in Hemophilia (FISH) were applied for the assessment of joints at different time points. Results were analyzed by SPSS version 21. RESULTS: A total of 36 HA male patients with the mean age of 19.7 ± 14.42 years were recruited in the study; among them, 19 patients were inhibitor positive, while 17 were negative. Patients clinically presented with bleeding symptoms which included: hemarthrosis 95%, GI bleeding 13.8%, and bruises and gums bleeding 13.8%. Significant reduction was observed in the bleeding episodes after the therapeutic intervention, and joints assessment and Euro-Quality-of-life Visual Analog Scale showed a significant improvement in health after treatment. Similarly, there was a remarkable reduction in bleeding episodes and improved quality of life among HA patients. The ABR decreased from 53.6% episodes per year prior to treatment to 2.4% during Emicizumab therapy. Prior to initiating Emicizumab therapy, participants exhibited an average FISH score of 16 and HJHS score of 10, indicating moderate limitations due to joint-related issues. After treatment, the mean FISH score improved to 9 and HJHS score to 4 reflecting a substantial enhancement in participants' ability to perform daily activities (P < 0.057). CONCLUSION: Our results showed that HA patients on prophylactic treatment with Emicizumab were less restricted and had improved quality of life due to marked decrease in bleeding episodes which resulted in improved health and social lives. In addition, it was well tolerated, and no participant discontinued treatment because of adverse events.

Factors associated with maternal health services utilization in Pakistan: Evidence from Pakistan maternal mortality survey, 2019.

BACKGROUND: This study investigates the factors associated with maternal health services utilization in Pakistan using two outcome indicators, ideal antenatal care (IANC), defined as the pregnant woman receiving all the essential services included in standard antenatal care, and skilled birth attendance (SBA). METHODS: This study used the Pakistan Maternal Mortality Survey 2019 data. The study utilized binary logistic regression models to investigate the adjusted association between the outcome variables, separately for IANC and SBA, and the independent variables, education, wealth, parity, and residence. RESULTS: Wealth showed a positive association with utilization of IANC (adjusted odds ratio [AOR] = 11.48, 95% CI = 7.76, 16.99) and SBA (AOR = 4.37, 95% CI = 3.30,5. 80). Maternal age was associated only with IANC for women aged 35 or more years (AOR = 1.31, 95% CI = 1.06, 1.62). Increased likelihood of utilization of IANC and SBA services was also observed for women with formal education. Women who had 3-5 previous live births had higher odds of using IANC and SBA than women who had 1-2 or more than five previous live births. Urban residency was not correlated with either IANC or SBA. CONCLUSION: When compared to the wealthy and educated quintile, women in the lower wealth quintile and those without any formal education were less likely to utilize ANC and SBA services. A comprehensive and multipronged approach from the health and education sectors is needed to improve maternal health in Pakistan.

Efficacy and Safety of Therapeutic Hypothermia as an Adjuvant Therapy for Percutaneous Coronary Intervention in Acute Myocardial Infarction: A Systematic Review and Meta-Analysis.

The study aims to compare the use of hypothermia in patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI) with control. We systematically searched four electronic databases until March 2022. The inclusion criteria were any study design that compared hypothermia in patients with MI undergoing PCI with control. The risk of bias assessment of the included randomized controlled trials was conducted through Cochrane Tool, while the quality of the included cohort studies was assessed by the NIH tool. The meta-analysis was performed on RevMan. A total of 19 studies were entered. Regarding the mortality, there were nonsignificant differences between hypothermia and control (odds ratio [OR] = 1.06, 95% confidence interval [CI] 0.75 to 1.50, p = 0.73). There was also no significant difference between the control and hypothermia in recurrent MI (OR = 1.21, 95% CI 0.64 to 2.30, p = 0.56). On the other hand, the analysis showed a significant favor for hypothermia over the control infarct size (mean difference = -1.76, 95% CI -3.04 to -0.47, p = 0.007), but a significant favor for the control over hypothermia in the overall bleeding complications (OR = 1.88, 95% CI 1.11 to 3.18, p = 0.02). Compared with the control, hypothermia reduced the infarct size of the heart, but this finding was not consistent across studies. However, the control had lower rates of bleeding problems. The other outcomes, such as death and the incidence of recurrent MI, were similar between the two groups.

Screening for orthostatic hypotension in the geriatric population in a real-world primary care setting reduces prescribed antihypertensive medications.

BACKGROUND: To determine if outpatient screening for orthostatic hypotension (OH) in the geriatric population results in fewer prescribed antihypertensive medications and if a relationship exists between OH and specific pharmacologic classes of antihypertensive medications. MATERIALS AND METHODS: Patients ≥ 65 years were screened for OH, defined as a decrease in systolic blood pressure (SBP) ≥ 20 mm Hg or a decrease in diastolic blood pressure (DBP) ≥ 10 mm Hg after standing for 3 minutes. Sitting blood pressure (BP) was measured after patients had been seated quietly in an exam room. Patients then stood for approximately 3 minutes at which time standing BP was recorded. RESULTS: OH prevalence was 18%. Standing DBP was significantly different between the two groups (70 mmHg ± 18, 80 mmHg ± 13, P  = 0.007). Compared to patients without OH, patients with OH were more likely to have been previously prescribed beta-blockers (56% vs. 32%, P  = 0.056) and potassium-sparing diuretics (11% vs. 1%, P  = 0.026). Physicians discontinued an antihypertensive medication more often in patients who screened positive for OH than in to those who did not (17% vs. 4%, P  = 0.037). Calcium channel blockers were the most frequently discontinued class of medication. CONCLUSION: Asymptomatic OH is prevalent in geriatric patients. Screening for OH may lead to de-escalation of antihypertensive regimen and a reduction in polypharmacy. Positive screening for OH was associated with de-prescribing of antihypertensive medications. Prior use of beta-blockers and potassium-sparing diuretics was most largely associated with OH.

Mycophenolate Mofetil-Induced Colonic Injury Manifesting Endoscopically As Ischemic Colitis.

Mycophenolate mofetil (MMOF) is a commonly used immunosuppressive prodrug in kidney transplant patients. However, it is not without side effects. The most common of these is diarrhea which inadvertently leads to colonoscopic and endoscopic evaluation when all other workup returns negative. Colonoscopies often show diffuse ulcers and colitis changes depending on the degree of diarrhea. In rare situations, MMOF-induced ischemic colitis may occur on gross endoscopy. We describe an unusual phenomenon of an adult male status post renal transplant with histopathologically diagnosed MMOF-induced colitis who developed gross endoscopic findings concerning ischemic colitis. Our case highlights the importance of recognizing that MMOF-induced colonic changes can rarely mimic ischemic colitis. With this in mind, we aim for gastroenterologists to better understand the varying endoscopic colonic findings of this immunosuppressive drug.

Gene expression of near-isogenic lines (NILs) carrying blast resistance genes Pi9 and Pi54 in the background of rice cultivar Mushk Budji.

BACKGROUND: Kashmir valley, India is a homeland to rice landraces like Zag, Nunbeoul, Qadirbeigh, Kawkadur, Kamad, Mushk Budji, etc., generally characterized by short grains, aroma, earliness and cold tolerance. Mushk Budji is a commercially important speciality rice known for its taste and aroma, nonetheless, is extremely vulnerable to blast disease. Through the use of the marker-assisted backcrossing (MABC) approach, a set of 24 Near-isogenic lines (NILs) was created, and the lines with the highest background genome recovery were chosen. The expression analysis was carried out for the component genes and other eight pathway genes related to blast resistance. RESULTS: The major blast resistance genes Pi9 (from IRBL-9W) and Pi54 (from DHMAS 70Q 164-1b) were incorporated following simultaneous-but-step-wise MABC. The NILs harbouring genes Pi9 + Pi54, Pi9 and Pi54 expressed resistance to isolate (Mo-nwi-kash-32) under controlled and natural field conditions. The loci controlling ETI (effector triggered immunity) included the gene Pi9 and showed 61.18 and 60.27 fold change in relative gene expression in Pi54 + Pi9 and Pi9 carrying NILs against RP Mushk Budji. Pi54 was up regulated and showed 41 and 21 fold change in relative gene expression for NIL-Pi54 + Pi9 and NIL-Pi54, respectively. Among the pathway genes, LOC_Os01g60600 (WRKY 108) recorded 8 and 7.5 fold up regulation in Pi9 and Pi54 NILs. CONCLUSION: The NILs showed recurrent parent genome recovery (RPG) per cent of 81.67 to 92.54 and were on par in performance to recurrent parent Mushk Budji. The lines were utilized to study the expression of the loci controlling WRKYs, peroxidases and chitinases that confer overall ETI response.

HIV-Positive Patient With Non-Percutaneous Coronary Intervention (PCI)-Amenable Left Coronary Artery Aneurysms Presenting With ST-Elevation Myocardial Infarction (STEMI).

Human immunodeficiency virus (HIV) was first reported in the early 1980s and a once untreatable and fatal disease has since allowed individuals to live healthy lives with the advent of novel antiviral medications. While the life expectancy of an HIV-positive individual has dramatically increased, a myriad of HIV-related complications such as pneumocystis pneumonia, candidiasis, renal disease, anxiety/depression, and cardiovascular disease have dramatically decreased. However, these patients are still prone to complex medical problems. In this case report, we aim to highlight a rare, complicated case of an HIV-positive patient with coronary artery aneurysms complicated by an ST-elevation myocardial infarction (STEMI).

Methodology for development of single cell dendritic spine (SCDS) synaptic tagging and capture model using Virtual Cell (VCell).

Single cell dendritic spine modelling methodology has been adopted to explain structural plasticity and respective change in the neuronal volume previously. However, the single cell dendrite methodology has not been employed previously to explain one of the important aspects of memory allocation i.e., Synaptic tagging and Capture (STC) hypothesis. It is difficult to relate the physical properties of STC pathways to structural changes and synaptic strength. We create a mathematical model based on earlier reported synaptic tagging networks. We built the model using Virtual Cell (VCell) software and used it to interpret experimental data and investigate the behavior and characteristics of known Synaptic tagging candidates.•We investigate processes associated with synaptic tagging candidates and compare them to the assumptions based on the STC hypothesis.•We assess the behavior of several reported synaptic tagging candidates against the requirements outlined in the synaptic tagging hypothesis.

A multifarious exploration of synaptic tagging and capture hypothesis in synaptic plasticity: Development of an integrated mathematical model and computational experiments.

The synaptic tagging and capture (STC) hypothesis not only explain the integration and association of synaptic activities, but also the formation of learning and memory. The synaptic pathways involved in the synaptic tagging and capture phenomenon are called STC pathways. The STC hypothesis provides a potential explanation of the neuronal and synaptic processes underlying the synaptic consolidation of memories. Several mechanisms and molecules have been proposed to explain the process of memory allocation and synaptic tags, respectively. However, a clear link between the STC hypothesis and memory allocation is still missing because the encoding of memories in neural circuits is mainly associated with strongly recurrently connected groups of neurons. To explore the mechanisms of potential synaptic tagging candidates and their involvement in the process of memory allocation, we develop a mathematical model for a single dendritic spine based on five essential criteria of a synaptic tag. By developing a mathematical model, we attempt to understand the roles of the potentially critical molecular networks underlying the STC and the essential attributes of a synaptic tag. We include essential memory molecules in the STC model that have been identified in earlier studies as crucial for STC pathways. CaMKII activation is critical for the setting of the initial tag; however, coordinated activities with other kinases and the biochemical pathways are necessary for the tag to be stable. PKA modulates NMDAR-mediated Ca2+ signalling. Similarly, PKA and ERK crosstalk is essential for Ca2+ - mediated protein synthesis during l-LTP. Our theoretical model explains the quantitative contribution of Tags and protein synthesis during l-LTP in synaptic strength.

Sphingosine Kinase 1 Deficiency in Smooth Muscle Cells Protects against Hypoxia-Mediated Pulmonary Hypertension via YAP1 Signaling.

Sphingosine kinase 1 (SPHK1) and the sphingosine-1-phosphate (S1P) signaling pathway have been shown to play a role in pulmonary arterial hypertension (PAH). S1P is an important stimulus for pulmonary artery smooth muscle cell (PASMC) proliferation and pulmonary vascular remodeling. We aimed to examine the specific roles of SPHK1 in PASMCs during pulmonary hypertension (PH) progression. We generated smooth muscle cell-specific, Sphk1-deficient (Sphk1f/f TaglnCre+) mice and isolated Sphk1-deficient PASMCs from SPHK1 knockout mice. We demonstrated that Sphk1f/f TaglnCre+ mice are protected from hypoxia or hypoxia/Sugen-mediated PH, and pulmonary vascular remodeling and that Sphk1-deficient PASMCs are less proliferative compared with ones isolated from wild-type (WT) siblings. S1P or hypoxia activated yes-associated protein 1 (YAP1) signaling by enhancing its translocation to the nucleus, which was dependent on SPHK1 enzymatic activity. Further, verteporfin, a pharmacologic YAP1 inhibitor, attenuated the S1P-mediated proliferation of hPASMCs, hypoxia-mediated PH, and pulmonary vascular remodeling in mice and hypoxia/Sugen-mediated severe PH in rats. Smooth muscle cell-specific SPHK1 plays an essential role in PH via YAP1 signaling, and YAP1 inhibition may have therapeutic potential in treating PH.

A retrospective observational study of biomarker levels and severity assessment in pediatric community-acquired pneumonia.

METHODS: A retrospective chart review was conducted on children (aged 60 days to 18 years) diagnosed with CAP, and admitted to a regional, tertiary hospital (Charleston, WV, USA) for 3 years (2015-2018). Patients were stratified into 2 severity cohorts, mild (no ICU care), and moderate/severe (required ICU care). Biomarker values were then compared between the severity cohorts and area under the curve (AUC), and cut-off values and performance characteristics were calculated. RESULTS: A total of 108 patients met inclusion criteria with 46% having moderate/severe CAP. Elevated levels of CRP (51.7 mg/L in mild vs. 104.8 mg/L in moderate/severe, P = .003, PCT (0.29 ng/ml in mild vs. 4.02 ng/mL in moderate/severe, P = .001) and band counts (8% in mild vs. 15% moderate/severe, P = .009) were associated with increased pneumonia severity. In predicting moderate/severe CAP, PCT had the highest AUC of 0.77 (P = .001) followed by bands AUC of 0.69 (P = .009) and CRP AUC of 0.67 (P = .003). Cut-off for PCT of 0.55 ng/mL had a sensitivity of 83% and a specificity of 65%. Cut-off level of 53.1 mg/L for CRP had a sensitivity of 79% and specificity of 52%. Cut off level of 12.5% bands had a sensitivity of 61% and specificity of 71%. In a multivariable model controlled for patient demographics and other biomarker levels, only PCT levels significantly predicted moderate/severe CAP (adjusted odds ratio: 1.40 [95% CI, 1.14-1.73], P = .002). CONCLUSION: Biomarkers, in particular PCT, obtained early in hospitalization may perform as possible predictors for CAP severity in children and be beneficial in guiding CAP management. However, biomarkers in pneumonia should not drive severity assessment or patient management independent of clinical presentation.

Glomerular Filtration Rate Estimation With Commonly Used Methods Among Healthy Live Kidney Donors of South Punjab, Pakistan.

Background Accurate estimation of the donor's glomerular filtration rate (GFR) is crucial for not only ensuring the medical appropriateness of the donor but also for the prediction of future allograft performance. The aim of this study was to compare the GFR estimation formulas and 24-hour urine creatinine clearance with diethylene triamine pentaacetic acid (DTPA) renal scan GFR. Methods This cross-sectional study was done at the Department of Nephro Urology Dialysis & Renal Transplantation, Bahawal Victoria Hospital, Quaid e Azam Medical College, Bahawalpur, Pakistan from September 2018 to September 2021. A total of 92 potential healthy live-related kidney donors of both genders, aged 18 to 60 years having body mass index below 35 kg/m2 were included. GFR was calculated with modification of diet in renal disease (MDRD), Cockcroft-Gault (CG), chronic kidney disease epidemiology (CKD-EPI) equations as well as by 24-hour urine creatinine clearance. DTPA renal scan was done to record GFR findings. GFR was compared using analysis of variance (ANOVA) among different methods. Results Out of a total of 92 individuals, 49 (53.3%) were male and 43 (46.7%) female. Mean age and BMI were noted to be 34.62±10.57 years and 24.40±2.71 kg/m2, respectively. Statistically significant differences existed between various methods of GFR estimation (p<0.001). Mean GFR as per DTPA renal scan findings was noted to be 97.32±9.39 ml/min/1.73 m2. Difference of 31.48±20.81, 27.37±21.1, 23.38±6.38, 15.52±37.52 was noted in estimated GFR (ml/min/1.73 m2) with CG formula, MDRD formula, EPI-CKD formula and 24-hour urine creatinine clearance respectively when compared with DTPA renal scan findings. The highest proportion of patients was seen with normal GFR with DTPA renal scan findings as 83 (90.2%) individuals while 24-hour urine creatinine clearance observed these to be 59 (64.1%), CG EPI-CKD formula 44 (47.8%), MDRD formula 39 (42.4%) and 40 (43.5%) with CG formula. Conclusion None of the GFR estimation methods resulted in similar findings. With reference to the DTPA renal scan, 24-hour urine creatinine clearance was the closest GFR estimation followed by CKD-EPI and MDRD equations.

Thrombosis of Bilateral Profunda Femoris, Anterior Tibial, and Tibioperoneal Arteries in a Patient With COVID-19 Infection.

COVID-19, also known as severe acute respiratory distress syndrome coronavirus 2, mostly affects the respiratory system causing acute respiratory syndrome. It not only targets lungs but also causes vascular endothelial disruption, which can lead to arterial or venous thrombosis causing ischemia, which increases the morbidity and mortality in some patients, if not recognized and treated in a timely manner. We present an interesting case of a patient recovering from COVID-19 pneumonia , who developed bilateral foot ischemia due to thrombosis of bilateral profunda femoris, bilateral anterior tibial, and tibioperoneal arteries. A 44-year-old gentleman presented to the emergency department complaining of severe bilateral foot pain, which progressively got worse. Upon examination he had blue toes bilaterally with absent dorsalis pedis and posterior tibial pulse. CT angiogram was performed, which showed severe multilevel lower limb arterial occlusions involving bilateral profunda femoris, bilateral anterior tibial, and tibioperoneal arteries. The patient was initially thrombolyzed and later underwent thrombectomy with the assistance of interventional radiologist. Hospital course was uneventful, and the patient was discharged on warfarin following complete resolution of symptoms.

Abdominal Pain Caused by Occlusion of the Celiac Trunk and Superior Mesenteric Artery in Addition to Irritable Bowel Syndrome: Case Series and Literature Review.

Irritable bowel syndrome (IBS) is a benign condition of the gastrointestinal tract causing abdominal pain, bloating, diarrhea, and/or constipation. Symptoms of IBS usually improve on passing flatus and defecation. There is no known identifiable underlying pathology; however, several risk factors are known to contribute to the development of IBS, which include a stressful lifestyle and certain foods such as bread, coffee, alcohol, pasta, and chocolates. Intestinal bacteria may also contribute to symptoms of IBS. IBS is diagnosed clinically and treated with various medications to control the symptoms. On the other hand, celiac and mesenteric artery thrombosis (CAMAT) is a condition that may cause significantly higher mortality and morbidity if not recognized early. CAMAT leads to the blockage of major blood vessels to the intestine and several abdominal viscera leading to abdominal pain, nausea, sweating, and, in some cases, symptoms of shock. CAMAT is most likely caused by thrombosis; however, occasionally, embolisms from distant sources in patients with atrial fibrillation can also contribute to the development of CAMAT. CAMAT is usually diagnosed with a computed tomography angiogram (CTA) and treated either surgically or medically with anticoagulants. Vascular thrombus in the thoracic and abdominal region causing ischemia of the stomach and abdominal pain in patients with a history of IBS can easily be missed and cause grave complications with high morbidity and mortality. We present two cases who were initially diagnosed and treated for IBS and later diagnosed with serious intra-abdominal pathology of CAMAT thrombosis. The first case is of a 55-year-old female who was previously diagnosed with IBS and was treated with mebeverine 200mg twice daily and esomeprazole 20mg once daily for 10 weeks. Her pain continued to get worse and she presented to the emergency department by ambulance. She underwent CTA, which showed occlusion of the celiac trunk and superior mesenteric artery causing liver and splenic infarcts. The patient received heparin and underwent a thrombectomy and embolectomy of the superior mesenteric and celiac arteries. No significant abnormality was found in the blood results. Thrombophilia screening was negative. The patient was discharged on warfarin. The second case is of a 53-year-old man who was also initially diagnosed with IBS and was treated with mebeverine 200mg twice daily for eight weeks before presenting to the emergency department with worsening abdominal pain. He underwent a CTA with contrast, which showed occlusion of the common hepatic artery and stenosis of the splenic artery leading to multiple splenic infarcts. No significant abnormality was found in blood test. Thrombophilia screening was negative. He was treated with new anticoagulant medication, dabigatran 150 mg orally twice daily. Both patients were managed with successful outcomes and were discharged home on anticoagulants. There was no recurrence of symptoms at three-month follow-up. These cases highlight that a secondary cause of symptoms such as vascular thrombosis must be sought for patients who fail to improve with conservative management of IBS.

Cigarette Smoke and Nicotine-Containing Electronic-Cigarette Vapor Downregulate Lung WWOX Expression, Which Is Associated with Increased Severity of Murine Acute Respiratory Distress Syndrome.

A history of chronic cigarette smoking is known to increase risk for acute respiratory distress syndrome (ARDS), but the corresponding risks associated with chronic e-cigarette use are largely unknown. The chromosomal fragile site gene, WWOX, is highly susceptible to genotoxic stress from environmental exposures and thus an interesting candidate gene for the study of exposure-related lung disease. Lungs harvested from current versus former/never-smokers exhibited a 47% decrease in WWOX mRNA levels. Exposure to nicotine-containing e-cigarette vapor resulted in an average 57% decrease in WWOX mRNA levels relative to vehicle-treated controls. In separate studies, endothelial (EC)-specific WWOX knockout (KO) versus WWOX flox control mice were examined under ARDS-producing conditions. EC WWOX KO mice exhibited significantly greater levels of vascular leak and histologic lung injury. ECs were isolated from digested lungs of untreated EC WWOX KO mice using sorting by flow cytometry for CD31+ CD45-cells. These were grown in culture, confirmed to be WWOX deficient by RT-PCR and Western blotting, and analyzed by electric cell impedance sensing as well as an FITC dextran transwell assay for their barrier properties during methicillin-resistant Staphylococcus aureus or LPS exposure. WWOX KO ECs demonstrated significantly greater declines in barrier function relative to cells from WWOX flox controls during either methicillin-resistant S. aureus or LPS treatment as measured by both electric cell impedance sensing and the transwell assay. The increased risk for ARDS observed in chronic smokers may be mechanistically linked, at least in part, to lung WWOX downregulation, and this phenomenon may also manifest in the near future in chronic users of e-cigarettes.

Functional repertoire of protein kinases and phosphatases in synaptic plasticity and associated neurological disorders.

Protein phosphorylation and dephosphorylation are two essential and vital cellular mechanisms that regulate many receptors and enzymes through kinases and phosphatases. Ca2+- dependent kinases and phosphatases are responsible for controlling neuronal processing; balance is achieved through opposition. During molecular mechanisms of learning and memory, kinases generally modulate positively while phosphatases modulate negatively. This review outlines some of the critical physiological and structural aspects of kinases and phosphatases involved in maintaining postsynaptic structural plasticity. It also explores the link between neuronal disorders and the deregulation of phosphatases and kinases.

Feasibility of Repurposing Clioquinol for Cancer Therapy.

BACKGROUND: Cancer is a prevalent disease in the world and is becoming more widespread as time goes on. Advanced and more effective chemotherapeutics need to be developed for the treatment of cancer to keep up with this prevalence. Repurposing drugs is an alternative to discover new chemotherapeutics. Clioquinol is currently being studied for reposition as an anti-cancer drug. OBJECTIVE: This study aimed to summarize the anti-cancer effects of clioquinol and its derivatives through a detailed literature and patent review and to review their potential re-uses in cancer treatment. METHODS: Research articles were collected through a PubMed database search using the keywords "Clioquinol" and "Cancer." The keywords "Clioquinol Derivatives" and "Clioquinol Analogues" were also used on a PubMed database search to gather research articles on clioquinol derivatives. Patents were gathered through a Google Patents database search using the keywords "Clioquinol" and "Cancer." RESULTS: Clioquinol acts as a copper and zinc ionophore, a proteasome inhibitor, an anti-angiogenesis agent, and is an inhibitor of key signal transduction pathways responsible for its growth-inhibitory activity and cytotoxicity in cancer cells preclinically. A clinical trial conducted by Schimmer et al., resulted in poor outcomes that prompted studies on alternative clioquinol-based applications, such as new combinations, new delivery methods, or new clioquinol-derived analogues. In addition, numerous patents claim alternative uses of clioquinol for cancer therapy. CONCLUSION: Clioquinol exhibits anti-cancer activities in many cancer types, preclinically. Low therapeutic efficacy in a clinical trial has prompted new studies that aim to discover more effective clioquinol- based cancer therapies.

Repurposing Disulfiram as An Anti-Cancer Agent: Updated Review on Literature and Patents.

BACKGROUND: Despite years of success of most anti-cancer drugs, one of the major clinical problems is inherent and acquired resistance to these drugs. Overcoming the drug resistance or developing new drugs would offer promising strategies in cancer treatment. Disulfiram, a drug currently used in the treatment of chronic alcoholism, has been found to have anti-cancer activity. OBJECTIVE: To summarize the anti-cancer effects of Disulfiram through a thorough patent review. METHODS: This article reviews molecular mechanisms and recent patents of Disulfiram in cancer therapy. RESULTS: Several anti-cancer mechanisms of Disulfiram have been proposed, including triggering oxidative stress by the generation of reactive oxygen species, inhibition of the superoxide dismutase activity, suppression of the ubiquitin-proteasome system, and activation of the mitogen-activated protein kinase pathway. In addition, Disulfiram can reverse the resistance to chemotherapeutic drugs by inhibiting the P-glycoprotein multidrug efflux pump and suppressing the activation of NF-kB, both of which play an important role in the development of drug resistance. Furthermore, Disulfiram has been found to reduce angiogenesis because of its metal chelating properties as well as its ability to inactivate Cu/Zn superoxide dismutase and matrix metalloproteinases. Disulfiram has also been shown to inhibit the proteasomes, DNA topoisomerases, DNA methyltransferase, glutathione S-transferase P1, and O6- methylguanine DNA methyltransferase, a DNA repair protein highly expressed in brain tumors. The patents described in this review demonstrate that Disulfiram is useful as an anti-cancer drug. CONCLUSION: For years the FDA-approved, well-tolerated, inexpensive, orally-administered drug Disulfiram was used in the treatment of chronic alcoholism, but it has recently demonstrated anti-cancer effects in a range of solid and hematological malignancies. Its combination with copper at clinically relevant concentrations might overcome the resistance of many anti-cancer drugs in vitro, in vivo, and in patients.