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1.
Ecol Evol ; 14(6): e11475, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38932972

ABSTRACT

Cyanobacterial blooms in freshwater sources are a global concern, and gaining insight into their causes is crucial for effective resource management and control. In this study, we present a novel computational framework for the causal analysis of cyanobacterial harmful algal blooms (cyanoHABs) in Lake Kinneret. Our framework integrates Convergent Cross Mapping (CCM) and Extended CCM (ECCM) causal networks with Bayesian Network (BN) models. The constructed CCM-ECCM causal networks and BN models unveil significant interactions among factors influencing cyanoHAB formation. These interactions have been validated by domain experts and supported by evidence from peer-reviewed publications. Our findings suggest that Microcystis flos-aquae levels are influenced not only by community structure but also by ammonium, phosphate, oxygen, and temperature levels in the weeks preceding bloom occurrences. We demonstrated a non-parametric computational framework for causal analysis of a multivariate ecosystem. Our framework offers a more comprehensive understanding of the underlying mechanisms driving M. flos-aquae blooms in Lake Kinneret. It captures complex interactions and provides an explainable prediction model. By considering causal relationships, temporal dynamics, and joint probabilities of environmental factors, the proposed framework enhances our understanding of cyanoHABs in Lake Kinneret.

2.
Res Pract Thromb Haemost ; 8(2): 102357, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38550529

ABSTRACT

Background: Since administration of COVID-19 vaccines, there has been growing evidence of thrombotic and thrombocytopenic events following vaccination. However, there remains limited data on long-term management of these adverse hematologic events. Key Clinical Question: We report on 9 patients presenting with thrombocytopenia following COVID-19 vaccination, with 4 subsequently diagnosed with vaccine-induced thrombocytopenia and thrombosis (VITT) and 5 with immune thrombocytopenia. Clinical Approach: A retrospective chart review was completed for adults >18 years of age presenting to a tertiary care center with new-onset thrombocytopenia occurring 4 to 42 days following COVID-19 vaccination. Presenting symptoms, laboratory investigations, and response to treatment are described. Conclusion: Two of 4 patients with VITT developed refractory thrombocytopenia successfully treated with intravenous immunoglobulin, corticosteroids, and plasma exchange therapy. Patients with VITT remained on anticoagulation for at least 9 months due to persistently positive diagnostic tests. Four of 5 patients with immune thrombocytopenia received intravenous immunoglobulin and corticosteroids with good recovery. Patients who received a subsequent COVID-19 mRNA vaccine had no adverse hematologic effects.

3.
Adv Clin Chem ; 114: 151-223, 2023.
Article in English | MEDLINE | ID: mdl-37268332

ABSTRACT

D-dimer containing species are soluble fibrin degradation products derived from plasmin-mediated degradation of cross-linked fibrin, i.e., 'D-dimer'. D-dimer can hence be considered a biomarker of in vivo activation of both coagulation and fibrinolysis, the leading clinical application in daily practice of which is ruling out venous thromboembolism (VTE). D-dimer has been further evaluated for assessing the risk of VTE recurrence and helping define optimal duration of anticoagulation treatment in VTE, for diagnosing disseminated intravascular coagulation (DIC), and for screening those at enhanced risk of VTE. D-dimer assays should however be performed as intended by regulatory agencies, as their use outside these indications might make them a laboratory-developed test (LDT). This narrative review is aimed at: (1) reviewing the definition of D-dimer, (2) discussing preanalytical variables affecting D-dimer measurement, (3) reviewing and comparing the assays performance and some postanalytical variables (e.g., different units and age-adjusted cutoffs), and (4) discussing the interest of D-dimer measurement across different clinical settings, including pregnancy, cancer, and coronavirus disease 2019 (COVID-19).


Subject(s)
COVID-19 , Disseminated Intravascular Coagulation , Venous Thromboembolism , Pregnancy , Female , Humans , Fibrin Fibrinogen Degradation Products/metabolism , Fibrin Fibrinogen Degradation Products/therapeutic use , Venous Thromboembolism/diagnosis , Venous Thromboembolism/drug therapy , COVID-19/diagnosis , Disseminated Intravascular Coagulation/diagnosis , Blood Coagulation Tests
4.
Theriogenology ; 189: 31-41, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35716430

ABSTRACT

Although fetal fluids, amnion (AM) and allantois (AL), have been studied at the end of pregnancy in the bitch, little is known about their composition during gestation. The aim of this study was to characterize and compare the biochemical parameters of fetal fluids collected from healthy pregnant bitches in mid pregnancy. Fetal fluids were collected from 26 pregnant bitches between 35 and 62 days from ovulation based on ultrasonography. A total of 149 samples were analyzed; 94 samples of known origin (61 a.m. and 33 AL) from 17 dams, which included 17 paired samples (AM and AL from the same fetus; 34 samples), and 55 of unknown origin from nine dams. Reference ranges were formulated for 22 biochemical parameters in AM and AL based on the samples of known origin (n = 94). All parameters (creatinine, albumin, GGT and urea) significantly different between AM and AL were included (by mixed model ANOVA) in the analysis and an algorithm to predict the origin of the fluid was developed (by logistic regression). Overall, of the 94 samples, 79 samples (84%) were correctly identified by the algorithm. For the 33 allantois samples, and for the 61 amnion samples, 23 (69.7%) and 56 (91.8%) were correctly identified by the algorithm, respectively. Based on the algorithm, 31 of the unknown samples (58%) were classified as amnion and 22 samples (42%), as allantois fluid. For all the unknown samples, the average certainty was 86% (compared to 81% for the samples whose fluid type was known), showing the degree of precision of the classification.


Subject(s)
Amniotic Fluid , Body Fluids , Allantois , Amniotic Fluid/chemistry , Animals , Body Fluids/chemistry , Dogs , Female , Pregnancy , Urea
5.
J Genet Mutat Disord ; 1(1)2022 Jan.
Article in English | MEDLINE | ID: mdl-35465405

ABSTRACT

Juvenile idiopathic epilepsy (JIE) is a self-limiting neurological disorder with a suspected genetic predisposition affecting young Arabian foals of the Egyptian lineage. The condition is characterized by tonic-clonic seizures with intermittent post-ictal blindness, in which most incidents are sporadic and unrecognized. This study aimed to identify genetic components shared across a local cohort of Arabian foals diagnosed with JIE via a combined whole genome and targeted resequencing approach: Initial whole genome comparisons between a small cohort of nine diagnosed foals (cases) and 27 controls from other horse breeds identified variants uniquely shared amongst the case cohort. Further validation via targeted resequencing of these variants, that pertain to non-intergenic regions, on additional eleven case individuals revealed a single 19bp deletion coupled with a triple-C insertion (Δ19InsCCC) within the TRIM39-RPP21 gene readthrough that was uniquely shared across all case individuals, and absent from three additional Arabian controls. Furthermore, we have confirmed recent findings refuting potential linkage between JIE and other inherited diseases in the Arabian lineage, and refuted the potential linkage between JIE and genes predisposing a similar disorder in human newborns. This is the first study to report a genetic variant to be shared in a sub-population cohort of Arabian foals diagnosed with JIE. Further evaluation of the sensitivity and specificity of the Δ19InsCCC allele within additional cohorts of the Arabian horse is warranted in order to validate its credibility as a marker for JIE, and to ascertain whether it has been introduced into other horse breeds by Arabian ancestry.

6.
Molecules ; 27(7)2022 Mar 22.
Article in English | MEDLINE | ID: mdl-35408443

ABSTRACT

The proton dissociation processes of two tridentate salicylidene aminoguanidine Schiff bases (SISC, Pro-SISC-Me), the solution stability and electrochemical properties of their Cu(II), Fe(II) and Fe(III) complexes were characterized using pH-potentiometry, cyclic voltammetry and UV-visible, 1H NMR and electron paramagnetic resonance spectroscopic methods. The structure of the proline derivative (Pro-SISC-Me) was determined by X-ray crystallography. The conjugation of L-proline to the simplest salicylidene aminoguanidine Schiff base (SISC) increased the water solubility due to its zwitterionic structure in a wide pH range. The formation of mono complexes with both ligands was found in the case of Cu(II) and Fe(II), while bis complexes were also formed with Fe(III). In the complexes these tridentate ligands coordinate via the phenolato O, azomethine N and the amidine N, except the complex [Fe(III)L2]+ of Pro-SISC-Me in which the (O,N) donor atoms of the proline moiety are coordinated beside the phenolato O, confirmed by single crystal X-ray crystallographic analysis. This binding mode yielded a stronger Fe(III) preference for Pro-SISC-Me over Fe(II) in comparison to SISC. This finding is also reflected in the lower redox potential value of the iron-Pro-SISC-Me complexes. The ligands alone were not cytotoxic against human colon cancer cell lines, while complexation of SISC with Cu(II) resulted in moderate activity, unlike the case of its more hydrophilic counterpart.


Subject(s)
Coordination Complexes , Schiff Bases , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Crystallography, X-Ray , Ferric Compounds , Ferrous Compounds , Guanidines , Humans , Ligands , Oxidation-Reduction , Proline , Schiff Bases/chemistry , Schiff Bases/pharmacology
7.
Rev Sci Instrum ; 92(10): 105005, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34717435

ABSTRACT

Low intrinsic noise, high bandwidth, and high accuracy vector magnetometers are key components for many ground or space geophysical applications. Here, we report the design and the test of a 4He vector optically pumped magnetometer specifically dedicated to these needs. It is based on a parametric resonance magnetometer architecture operated in the Earth magnetic field with closed-loop compensation of the three components of the magnetic field. It provides offset-free vector measurements in a ±70 µT range with a DC to 1 kHz bandwidth. We demonstrate a vector sensitivity up to 130 fT/√Hz, which is about ten times better than the best available fluxgate magnetometers currently available for the same targeted applications.

8.
BMC Neurol ; 20(1): 133, 2020 Apr 14.
Article in English | MEDLINE | ID: mdl-32290815

ABSTRACT

BACKGROUND: Cerebral palsy (CP) causes motor, cognitive and sensory impairment at different extents. Many recent rehabilitation developments (therapies) have focused solely on the upper extremities (UE), although the lower extremities (LE) are commonly affected. Hand-arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) applies the concepts of motor skill learning and intensive training to both the UE and LE. It involves constant stimulation of the UE and LE, for several hours each day over a 2-week period. The effects of HABIT-ILE have never been evaluated in a large sample of young children. Furthermore, understanding of functional, neuroplastic and biomechanical changes in infants with CP is lacking. The aim of this study is to carry out a multi-center randomized controlled trial (RCT) to evaluate the effects of HABIT-ILE in pre-school children with unilateral CP on functional, neuroplastic and biomechanical parameters. METHODS: This multi-center, 3-country study will include 50 pre-school children with CP aged 1-4 years. The RCT will compare the effect of 50 h (two weeks) of HABIT-ILE versus usual motor activity, including regular rehabilitation. HABIT-ILE will be delivered in a day-camp setting, with structured activities and functional tasks that will be continuously progressed in terms of difficulty. Assessments will be performed at 3 intervals: baseline (T0), two weeks later and 3 months later. Primary outcomes will be the Assisting Hand Assessment; secondary outcomes include the Melbourne Assessment-2, executive function assessments, questionnaires ACTIVLIM-CP, Pediatric Evaluation of Disability Inventory, Young Children's Participation and Environment Measure, Measure of the Process of Care, Canadian Occupational Performance Measure, as well as neuroimaging and kinematics measures. DISCUSSION: We expect that HABIT-ILE will induce functional, neuroplastic and biomechanical changes as a result of the intense, activity-based rehabilitation process and these changes will impact the whole developmental curve of each child, improving functional ability, activity and participation in the short-, mid- and long-term. Name of the registry: Changes Induced by Early HABIT-ILE in Pre-school Children With Uni- and Bilateral Cerebral Palsy (EarlyHABIT-ILE). TRIAL REGISTRATION: Trial registration number: NCT04020354-Registration date on the International Clinical Trials Registry Platform (ICTRP): November 20th, 2018; Registration date on NIH Clinical Trials Registry: July 16th, 2019.


Subject(s)
Cerebral Palsy/therapy , Physical Therapy Modalities , Cerebral Palsy/physiopathology , Child, Preschool , Disability Evaluation , Hand/physiopathology , Humans , Infant , Lower Extremity/physiopathology , Motor Skills/physiology , Neuronal Plasticity , Secondary Prevention , Surveys and Questionnaires , Upper Extremity/physiopathology
9.
Nanotechnology ; 31(33): 334002, 2020 Aug 14.
Article in English | MEDLINE | ID: mdl-32330924

ABSTRACT

Achieving good quality Ohmic contacts to van der Waals materials is a challenge, since at the interface between metal and van der Waals material different conditions can occur, ranging from the presence of a large energy barrier between the two materials to the metallization of the layered material below the contacts. In black phosphorus (bP), a further challenge is its high reactivity to oxygen and moisture, since the presence of uncontrolled oxidation can substantially change the behavior of the contacts. Here we study three of the most commonly used metals as contacts to bP, chromium, titanium, and nickel, and investigate their influence on contact resistance against the variability between different flakes and different samples. We investigate the gate dependence of the current-voltage characteristics of field-effect transistors fabricated with these metals on bP, observing good linearity in the accumulation regime for all metals investigated. Using the transfer length method, from an analysis of ten devices, both at room temperature and at low temperature, Ni results to provide the lowest contact resistance to bP and minimum scattering between different devices. Moreover, we observe that our best devices approach the quantum limit for contact resistance both for Ni and for Ti contacts.

10.
Thromb Res ; 185: 72-77, 2020 01.
Article in English | MEDLINE | ID: mdl-31775061

ABSTRACT

Direct oral anticoagulants (DOAC)s are often preferred to other anticoagulants as they are more practical and do not require routine laboratory monitoring. Less is known about their use in congenital thrombophilia. Efficacy of DOACs in congenital thrombophilia, effect of DOACs and other anticoagulants on diagnostic tests as well as efficacy and safety of anticoagulant use in this population is still a matter of debate. In this review we intended to analyze the potential pitfalls of testing for thrombophilia in patients using DOACs and vitamin K antagonists (VKA)s as well as to suggest strategies to improve diagnostic accuracy in this setting. We also reviewed the literature for evidence regarding the safety and efficacy of DOACs in patients with congenital thrombophilia. Some evidence was found supporting the use of DOACs in low risk thrombophilia, although evidence for their use in high risk thrombophilia is limited to small series and case reports. Our findings support the generation of better evidence to support DOAC use for congenital thrombophilia, especially in the high risk subgroups.


Subject(s)
Anticoagulants , Thrombophilia , Administration, Oral , Anticoagulants/adverse effects , Humans , Thrombophilia/diagnosis , Thrombophilia/drug therapy
11.
J Inorg Biochem ; 202: 110883, 2020 01.
Article in English | MEDLINE | ID: mdl-31689626

ABSTRACT

Solution chemical properties of two bidentate pyrazolyl thiosemicarbazones 2-((3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazinecarbothioamide (Me-pyrTSC), 2-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)hydrazinecarbothioamide (Ph-pyrTSC), stability of their Cu(II) and Ru(η6-p-cymene) complexes were characterized in aqueous solution (with 30% DMSO) by the combined use of UV-visible spectrophotometry, 1H NMR spectroscopy and electrospray ionization mass spectrometry in addition to their solid phase isolation. The solid phase structures of Me-pyrTSC∙H2O, [Ru(η6-p-cymene)(Me-pyrTSC)Cl]Cl and [Cu(Ph-pyrTSCH-1)2] were determined by single crystal X-ray diffraction. High stability mononuclear Ru(η6-p-cymene) complexes with (N,S) coordination mode are formed in the acidic pH range, and increasing the pH the predominating dinuclear [(Ru(η6-p-cymene))2(L)2]2+ complex with µ2-bridging sulphur donor atoms is formed (where L- is the deprotonated thiosemicarbazone). [CuL]+ and [CuL2] complexes show much higher stability compared to that of complexes of the reference compound benzaldehyde thiosemicarbazone. [CuL2] complexes predominate at neutral pH. Me-pyrTSC and Ph-pyrTSC exhibited moderate cytotoxicity against human colonic adenocarcinoma cell lines (IC50 = 33-76 µM), while their complexation with Ru(η6-p-cymene) (IC50 = 11-24 µM) and especially Cu(II) (IC50 = 3-6 µM) resulted in higher cytotoxicity. Cu(II) complexes of the tested thiosemicarbazones were also cytotoxic in three breast cancer and in a hepatocellular carcinoma cell line. No reactive oxygen species production was detected and the relatively high catalase activity of SUM159 breast cancer cells was decreased upon addition of the ligands and the complexes. In the latter cell line the tested compounds interfered with the glutathione synthesis as they decreased the concentration of this cellular reductant.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Carcinoma, Hepatocellular/drug therapy , Coordination Complexes/chemistry , Liver Neoplasms/drug therapy , Organometallic Compounds/chemistry , Apoptosis , Breast Neoplasms/pathology , Carcinoma, Hepatocellular/pathology , Cell Proliferation , Copper/chemistry , Cymenes/chemistry , Female , Humans , Liver Neoplasms/pathology , Pyrazoles/chemistry , Ruthenium/chemistry , Thiosemicarbazones/chemistry , Tumor Cells, Cultured
12.
Aging Clin Exp Res ; 32(11): 2393-2398, 2020 Nov.
Article in English | MEDLINE | ID: mdl-31776858

ABSTRACT

BACKGROUND: Toxin-producing Clostridium difficile is the most common cause of nosocomial diarrhea in geriatric units. AIM: The purpose of study was to check the impact of intensive staff education on rate of Clostridium difficile-associated disease in hospitalized geriatric patients. METHODS: The sampling frame was all patients suffering from diarrhea checked for Clostridium difficile toxin during the years 2017-2018. Clostridium difficile-positive patients were compared to a similar number of Clostridium difficile toxin-negative patients. The data were compared to our previous study, followed by medical staff's educational program for Clostridium difficile control and prevention. RESULTS: Among 217 patients with diarrhea, 60 (27.6%) were positive for Clostridium difficile toxin. The study group tended to be of older age (p = 0.06), and showed higher rate of functional impairment (p < 0.001) and mortality (p < 0.001) than Clostridium difficile toxin negative patients. The rate of Clostridium difficile toxin-positive patients did not significantly differ between the previous and current studies (20.0% and 27.6%, respectively). CONCLUSIONS AND DISCUSSION: In spite of findings, that patients tended to be older, with high rate of mortality, the rate of Clostridium difficile did not change from the previous study.


Subject(s)
Clostridioides difficile , Clostridium Infections , Cross Infection , Aged , Clostridium Infections/epidemiology , Cross Infection/epidemiology , Diarrhea/epidemiology , Humans
13.
PLoS One ; 14(6): e0217748, 2019.
Article in English | MEDLINE | ID: mdl-31220097

ABSTRACT

BACKGROUND: Thromboprophylaxis for patients with non-surgical isolated lower-limb trauma requiring immobilization is a matter of debate. Our aim was to develop and validate a clinical risk- stratification model based on Trauma, Immobilization and Patients' characteristics (the TIP score). METHODS: The TIP score criteria and the cut-off were selected by a consensus of international experts (n = 27) using the Delphi method. Retrospective validation was performed in a population-based case-control study (MEGA study). The potential score's impact in anticoagulant treatment was assessed in a prospective single-center observational cohort study. FINDINGS: After four successive rounds, 30 items constituting the TIP score were selected: thirteen items for trauma, three for immobilization and 14 for patient characteristics were selected, each rated on a scale of 1 to 3. In the validation database, the TIP score had an AUC of 0·77 (95% CI 0.70 to 0.85). Using the cut-off proposed by the experts (≥5) and assuming a prevalence of 1·8%, the TIP scores had a sensitivity, specificity and negative predictive values of 89·9%, 30·7% and 99·4% respectively. In the prospective cohort, 84·2% (165/196) of all the patients concerned who presented at the emergency department had a low VTE risk not requiring thromboprophylaxis according to their TIP scores. The 3-month rate of symptomatic VTE was 1/196 [95% CI 0.1-2.8] this patient was in the sub-group TIP score ≥5. CONCLUSION: For patients with non-surgical lower-limb trauma and orthopedic immobilization, the TIP score allows an individual VTE risk-assessment and shows promising results in guiding thromboprophylaxis.


Subject(s)
Casts, Surgical/adverse effects , Immobilization/adverse effects , Leg Injuries/complications , Venous Thromboembolism/etiology , Case-Control Studies , Delphi Technique , Humans , Prospective Studies , Reproducibility of Results , Retrospective Studies , Risk Factors , Venous Thromboembolism/prevention & control
14.
J Inorg Biochem ; 195: 91-100, 2019 06.
Article in English | MEDLINE | ID: mdl-30928657

ABSTRACT

Half-sandwich organometallic complexes of curcumin are extensively investigated as anticancer compounds. Speciation studies were performed to explore the solution stability of curcumin complexes formed with [Rh(η5-C5Me5)(H2O)3]2+. Acetylacetone (Hacac), as the simplest ß-diketone ligand bearing (O,O) donor set, was involved for comparison and its Ru(η6­p­cymene), Ru(η6­toluene) complexes were also studied. 1H NMR, UV-visible and pH-potentiometric titrations revealed a clear trend of stability constants of the acac complexes: Ru(η6­p­cymene) > Ru(η6­toluene) > Rh(η5-C5Me5). Despite this order, the highest extent of complex formation is seen for the Rh(η5-C5Me5) complexes at pH 7.4. Formation constant of [Rh(η5-C5Me5)(H2curcumin)(H2O)]+ reveals similar solution stability to that of the acac complex. Additionally, structures of two complexes were determined by X-ray crystallography. The in vitro cytotoxicity of curcumin was not improved by the complexation with these organometallic cations.


Subject(s)
Coordination Complexes/chemistry , Curcumin/analogs & derivatives , Pentanones/chemistry , Rhodium/chemistry , Ruthenium/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Coordination Complexes/metabolism , Coordination Complexes/pharmacology , Humans , Ligands , Molecular Structure , Protein Binding , Serum Albumin, Human/metabolism
15.
Rev Med Interne ; 40(7): 440-444, 2019 Jul.
Article in French | MEDLINE | ID: mdl-30744990

ABSTRACT

The diagnosis of pulmonary embolism (PE) is nowadays based on the sequential use of several diagnostic tests rather than on a single test. These diagnostic strategies are safe and have been prospectively validated. The first step after identifying patients with suspicion of PE is to establish the pre-test clinical probability. Several scores are available in order to make a standardised and reproducible assessment of the clinical probability, and therefore represent precious diagnostic tools. Indeed, clinical probability guides further investigations. Indeed, in patients with a low or an intermediate clinical probability or an "unlikely" probability, PE can be safely ruled out by negative D-dimers in approximately one third of outpatients without additional imaging. In case of positive D-dimers and a high clinical probability or a "likely" clinical probability, CT pulmonary angiography is now the recommended imaging technique. However, lower limb venous compression ultrasound and ventilation/perfusion scans remain useful in patients with contra-indications to CT, mainly those with renal insufficiency. Finally, some novel diagnostic tests seem promising. For example, V/Q SPECT has arisen as a highly accurate test and a potential alternative to CTPA. However, prospective management outcome studies are still lacking and are warranted before its implementation in routine clinical practice.


Subject(s)
Pulmonary Embolism/diagnosis , Computed Tomography Angiography/methods , Diagnosis, Differential , Diagnostic Tests, Routine , Fibrin Fibrinogen Degradation Products/analysis , Humans , Pulmonary Embolism/blood , Pulmonary Embolism/pathology , Radiography, Thoracic/methods , Single Photon Emission Computed Tomography Computed Tomography
16.
Thromb Res ; 176: 79-84, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30780008

ABSTRACT

BACKGROUND: Unprovoked venous thromboembolism (VTE) may be the first manifestation of an underlying cancer. We aimed to assess the period prevalence of occult cancer detection stratified by VTE location (deep vein thrombosis [DVT], pulmonary embolism [PE] or both) and the anatomical relationship between occult cancer and VTE. METHODS: Post-hoc analysis of a systematic review and individual patient data meta-analysis of adults with unprovoked VTE with at least 12 months of follow-up. Cancer types were grouped according to thoracic, abdomino-pelvic, or other locations. RESULTS: A total of 2300 patients were eligible including 1218 with DVT only (53%), 719 with PE only (31%), and 363 with both PE and DVT (16%). The pooled 12-month period prevalence of cancer in DVT only, PE only, and DVT + PE was 5.6% (95% CI, 4.4 to 7.2), 4.3% (95% CI, 2.7 to 6.9), and 5.6% (95% CI, 1.7 to 15.5), respectively. Most occult cancers were located in the abdomen (68.4%). The proportion of patients with an abdomino-pelvic cancer was not different in patients with DVT + PE (81%; 95% CI, 54 to 96) than in those with DVT (68%; 95% CI, 57 to 78) or PE alone (65%; 95% CI, 48 to 79). CONCLUSION: The 12-month prevalence of occult cancer was similar in patients with DVT only, PE only, or both. Most cancers were located in the abdomen, and there was no relationship between VTE type and cancer location.


Subject(s)
Neoplasms/diagnosis , Pulmonary Embolism/complications , Venous Thromboembolism/complications , Humans , Neoplasms/epidemiology , Neoplasms/pathology , Prevalence , Risk Factors
17.
Dalton Trans ; 47(47): 17032-17045, 2018 Dec 04.
Article in English | MEDLINE | ID: mdl-30460942

ABSTRACT

The anticancer activity of 8-hydroxyquinolines relies on complex formation with redox active copper and iron ions. Here we employ UV-visible spectrophotometry and EPR spectroscopy to compare proton dissociation and complex formation processes of the reference compound 8-hydroxyquinoline (Q-1) and three related Mannich bases to reveal possible correlations with biological activity. The studied derivatives harbor a CH2-N moiety at position 7 linked to morpholine (Q-2), piperidine (Q-3), and chlorine and fluorobenzylamino (Q-4) substituents. Solid phase structures of Q-3, Q-4·HCl·H2O, [(Cu(HQ-2)2)2]·(CH3OH)2·Cl4·(H2O)2, [Cu(Q-3)2]·Cl2 and [Cu(HQ-4)2(CH3OH)]·ZnCl4·CH3OH were characterized by single-crystal X-ray diffraction analysis. In addition, the redox properties of the copper and iron complexes were studied by cyclic voltammetry, and the direct reaction with physiologically relevant reductants (glutathione and ascorbic acid) was monitored. In vitro cytotoxicity studies conducted with the human uterine sarcoma MES-SA/Dx5 cell line reveal the significant cytotoxicity of Q-2, Q-3, and Q-4 in the sub- to low micromolar range (IC50 values 0.2-3.3 µM). Correlation analysis of the anticancer activity and the metal binding properties of the compound series indicates that, at physiological pH, weaker copper(ii) and iron(iii) binding results in elevated toxicity (e.g.Q4: pCu = 13.0, pFe = 6.8, IC50 = 0.2 µM vs.Q1: pCu = 15.1, pFe = 13.0 IC50 = 2.5 µM). Although the studied 8-hydroxyquinolines preferentially bind copper(ii) over iron(iii), the cyclic voltammetry data revealed that the more cytotoxic ligands preferentially stabilize the lower oxidation state of the metal ions. A linear relationship between the pKa (OH) and IC50 values of the studied 8-hydroxyquinolines was found. In summary, we identify Q-4 as a potent and selective anticancer candidate with significant toxicity in drug resistant cells.


Subject(s)
Antineoplastic Agents/pharmacology , Copper/chemistry , Ferric Compounds/chemistry , Oxyquinoline/chemistry , Sarcoma/drug therapy , Uterine Neoplasms/drug therapy , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Ascorbic Acid/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Drug Resistance, Neoplasm/drug effects , Female , Glutathione/chemistry , Humans , Inhibitory Concentration 50 , Mannich Bases/chemistry
18.
Curr Oncol ; 25(5): 329-337, 2018 10.
Article in English | MEDLINE | ID: mdl-30464682

ABSTRACT

Management of anticoagulant therapy for the treatment of venous thromboembolism (vte) in cancer patients is complex because of an increased risk of recurrent vte and major bleeding complications in those patients relative to the general population. Subgroups of patients with cancer also show variation in their risk for recurrent vte and adverse bleeding events. Accordingly, a committee of 10 Canadian clinical experts developed the consensus risk- stratification treatment algorithm presented here to provide guidance on tailoring anticoagulant treatment choices for the acute and extended treatment of symptomatic and incidental vte, to prevent recurrent vte, and to minimize the bleeding risk in patients with cancer. During a 1-day live meeting, a systematic review of the literature was performed, and a draft treatment algorithm was developed. The treatment algorithm was refined through the use of a Web-based platform and a series of online teleconferences. Clinicians using this treatment algorithm should consider the bleeding risk, the type of cancer, and the potential for drug-drug interactions in addition to informed patient preference in determining the most appropriate treatment for patients with cancer-associated thrombosis. Anticoagulant therapy should be regularly reassessed as the patient's cancer status and management change over time.


Subject(s)
Anticoagulants/therapeutic use , Neoplasms/drug therapy , Thrombosis/drug therapy , Algorithms , Canada , Consensus , Humans , Neoplasms/complications , Thrombosis/etiology
19.
Oper Dent ; 43(6): E273-E279, 2018.
Article in English | MEDLINE | ID: mdl-30216130

ABSTRACT

OBJECTIVE:: The study aimed to evaluate teaching trends and use of materials in direct posterior restorations during a 13-year period in an Israeli dental school. METHODS:: Data registered in computerized files, relating to posterior restorations performed in the student clinic during the past 13 years (2004-2016), were collected. The restorative materials used (ie, amalgam vs composite), the type of tooth, and the number of surfaces restored were analyzed. RESULTS:: Data analysis included 26,925 restorations performed during 13 years. The number of one-surface composite restorations increased from 54.7% (n=330) to 81.9% (n=873). Two-surface restorations increased from 33.3% (n=254) to 64.3% (n=721). The percentage of amalgam restorations in three-surface restorations decreased from 72.08% to 51.34% (n=173). Analysis of tooth type showed that in 2016, the number of composite restorations performed in premolars reached 80.87% (n=723) and in molars 63.50% (n=1035). The percentage of composite restorations in the mandible and the maxilla was virtually equal. CONCLUSIONS:: A clear trend in favor of composite resin restorations is evident in the 13-year survey and suggests a move toward an amalgam-free era.


Subject(s)
Dental Restoration, Permanent/trends , Dentistry, Operative/education , Education, Dental/trends , Practice Patterns, Dentists'/statistics & numerical data , Bicuspid , Composite Resins/therapeutic use , Dental Amalgam/therapeutic use , Humans , Israel , Molar
20.
Sci Rep ; 8(1): 14284, 2018 09 24.
Article in English | MEDLINE | ID: mdl-30250047

ABSTRACT

Using a temporal-dynamic calibrated Ecosim food web model, we assess the effects of future changes on marine resources and ecosystem conditions of the Israeli Mediterranean continental shelf. This region has been intensely invaded by Indo-Pacific species. The region is exposed to extreme environmental conditions, is subjected to high rates of climate change and has experienced intense fishing pressure. We test the impacts of a new set of fishing regulations currently being implemented, a continued increase in sea temperatures following IPCC projections, and a continued increase in alien species biomass. We first investigate the impacts of the stressors separately, and then we combine them to evaluate their cumulative effects. Our results show overall potential future benefits of fishing effort reductions, and detrimental impacts of increasing sea temperature and increasing biomass of alien species. Cumulative scenarios suggest that the beneficial effects of fisheries reduction may be dampened by the impact of increasing sea temperature and alien species when acting together. These results illustrate the importance of including stressors other than fisheries, such as climate change and biological invasions, in an ecosystem-based management approach. These results support the need for reducing local and regional stressors, such as fishing and biological invasions, in order to promote resilience to sea warming.


Subject(s)
Aquatic Organisms/physiology , Climate Change , Ecosystem , Fisheries , Introduced Species , Oceans and Seas , Biomass , Mediterranean Region , Statistics, Nonparametric
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