Balance and Gait: Associations With Cognitive Impairment and Dementia in Individuals With Down Syndrome.

BACKGROUND: Atypical aging in Down syndrome (DS) is associated with neuropathological characteristics consistent with Alzheimer disease. Gait abnormalities have been shown to be associated with an increased risk of dementia for the general population. The aim of this study was to determine whether gait disorders are associated with worse cognitive performance and dementia in adults with DS. METHODS: We evaluated 66 individuals with DS (≥20 y of age), divided into 3 groups: stable cognition, prodromal dementia, and dementia (presumed Alzheimer disease). Each individual was evaluated with the Performance-Oriented Mobility Assessment (POMA), Timed Up and Go test, and Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS), in addition to a comprehensive clinical protocol to ascertain the occurrence of medical or psychiatric comorbidities. RESULTS: The score on the POMA-Gait subscale score and body mass index were found to be independent predictors of prodromal dementia and dementia ( P <0.001 for both). With the exception of perception, all cognitive domains correlated with the POMA-Total score ( P <0.05). CONCLUSION: A lower POMA-Gait score increases the chance of prodromal dementia and dementia in adults with DS. Unlike other research, in this study higher body mass index was also found to increase the chance of prodromal dementia and dementia. In those individuals, applying the POMA could facilitate the early diagnosis of dementia, help identify fall risks, and promote the adoption of geriatric interventions focused on improving functional mobility.

Immunological and Some Biological Biomarkers in Patients Infected with Moraxella Catarrhalis.

BACKGROUND: Moraxella catarrhalis is the most common gram-negative bacteria pathogen that affects the human. The current study was carried out to investigate M. catarrhalis infection and how it modulates some biomarkers. METHODS: The samples were collected from 100 patients diagnosed with respiratory tract infections such as pneumonia, otitis media, and tonsillitis. Cultural characteristics were for the colonies cultured on blood and hot blood media. Microscopic method, biochemical tests, and Vitek 2 system was tested and they showed that ten isolates were M. catarrhalis. RESULTS: Out of 10 isolates, 8 isolates (80%) were ß-lactamase-producing. The sensitivity of the isolates was deter-mined against seven antibiotics, and they showed multidrug resistance (MDR). All isolates showed 100% resistance to Ampicillin and Ceftazidime; however, the isolates showed less resistance to Meropenem and Imipenem. Enzyme-linked immunosorbent assay was used to determine the levels of Anti-DNA, IgM, IgG, IL-1ß and hs-CRP in the patient serum. The infected serum with M. catarrhalis showed normal levels of Anti-DNA and IgM compared to control group, while the serum with high levels of IgG, IL-1ß, and hs-CRP were recorded (p < 0.001). CONCLUSIONS: The multi-antibiotic resistance of M. catarrhalis plays an important role in raising pro-inflammatory markers such as IgG, IL-1ß, and hs-CRP levels, which may subsequently affect the respiratory tract.

A membrane-depolarizing toxin substrate of the Staphylococcus aureus type VII secretion system mediates intraspecies competition.

The type VII protein secretion system (T7SS) is conserved across Staphylococcus aureus strains and plays important roles in virulence and interbacterial competition. To date, only one T7SS substrate protein, encoded in a subset of S. aureus genomes, has been functionally characterized. Here, using an unbiased proteomic approach, we identify TspA as a further T7SS substrate. TspA is encoded distantly from the T7SS gene cluster and is found across all S. aureus strains as well as in Listeria and Enterococci. Heterologous expression of TspA from S. aureus strain RN6390 indicates its C-terminal domain is toxic when targeted to the Escherichia coli periplasm and that it depolarizes the cytoplasmic membrane. The membrane-depolarizing activity is alleviated by coproduction of the membrane-bound TsaI immunity protein, which is encoded adjacent to tspA on the S. aureus chromosome. Using a zebrafish hindbrain ventricle infection model, we demonstrate that the T7SS of strain RN6390 promotes bacterial replication in vivo, and deletion of tspA leads to increased bacterial clearance. The toxin domain of TspA is highly polymorphic and S. aureus strains encode multiple tsaI homologs at the tspA locus, suggestive of additional roles in intraspecies competition. In agreement, we demonstrate TspA-dependent growth inhibition of RN6390 by strain COL in the zebrafish infection model that is alleviated by the presence of TsaI homologs.

Bacterial pore-forming toxins.

Pore-forming toxins (PFTs) are widely distributed in both Gram-negative and Gram-positive bacteria. PFTs can act as virulence factors that bacteria utilise in dissemination and host colonisation or, alternatively, they can be employed to compete with rival microbes in polymicrobial niches. PFTs transition from a soluble form to become membrane-embedded by undergoing large conformational changes. Once inserted, they perforate the membrane, causing uncontrolled efflux of ions and/or nutrients and dissipating the protonmotive force (PMF). In some instances, target cells intoxicated by PFTs display additional effects as part of the cellular response to pore formation. Significant progress has been made in the mechanistic description of pore formation for the different PFTs families, but in several cases a complete understanding of pore structure remains lacking. PFTs have evolved recognition mechanisms to bind specific receptors that define their host tropism, although this can be remarkably diverse even within the same family. Here we summarise the salient features of PFTs and highlight where additional research is necessary to fully understand the mechanism of pore formation by members of this diverse group of protein toxins.

Hydroxychloroquine increased cholesterol transfer to high-density lipoprotein in systemic lupus erythematosus: A possible mechanism for the reversal of atherosclerosis in the disease.

INTRODUCTION: The beneficial effect of hydroxychloroquine (HCQ) in decreasing LDL levels on Systemic Lupus Erythematosus (SLE) is well defined. The influence of this drug on HDL levels is still under debate and information about its effect on cholesterol reverse transport is lacking. OBJECTIVE: To evaluate the effects of HCQ on HDL levels and the transfer of lipids to this lipoprotein in SLE. METHODS: Nineteen SLE patients using only HCQ (SLE WITH HCQ), 19 SLE patients without any therapy (SLE WITHOUT THERAPY), and 19 healthy controls (CONTROL) were included. All three groups were premenopausal women age- and gender-matched. Serum lipids and apolipoproteins were determined by commercial kits. An in vitro transfer of four lipids (14C-Phospolipid, 3H-Cholesteryl ester, 3H-Triglyceride, and 14C-Unesterified cholesterol) from a radioactively labeled nanoemulsion donor to HDL was performed in all participants. RESULTS: Groups had comparable mean age, weight, height, BMI(body mass index), and waist circumference (p > .05). Mean HDL levels were higher in SLE WITH HCQ group compared to SLE WITHOUT THERAPY(58.37 ± 14.04 vs 49.79 ± 8.0 mg/dL; p < .05) but lower than CONTROL (58.37 ± 14.04 vs 68.58 ± 9.99 mg/dL; p < .05). Total cholesterol (TC) and LDL levels were also significantly lower in SLE WITH HCQ compared SLE WITHOUT THERAPY(148.16 ± 16.43 vs 167.11 ± 30.18 mg/dL; p < .05, 75.05 ± 22.52 vs 96.05 ± 25.63 mg/dL; p < .05) and CONTROL (148.16 ± 16.43 vs 174.11 ± 23.70 mg/dL; p < .05, 75.05 ± 22.52 vs 88.53 ± 20.24 mg/dL; p < .05). The in vitro lipid transfer to HDL study revealed a significant difference among the three groups (p = .002) with a higher transfer of unesterified cholesterol(UC) in SLE WITH HCQ compared to SLE WITHOUT THERAPY(5.40 ± 1.05% vs. 4.44 ± 1.05%; p < .05). The latter was significantly decreased compared to CONTROL (5.40 ± 1.05% vs. 5.99 ± 1.71%; p < .05).The percentages of transfer of triacylglycerol (4.93 ± 0.69% vs. 4.50 ± 0.69% vs. 5.14 ± 1.01%; p = .054), esterified cholesterol (5.24 ± 0.70% vs. 4.96 ± 0.89% vs. 5.69 ± 1.27%; p = .079), and phospholipid (15.67 ± 1.03% vs. 15.34 ± 1.44% vs. 16.47 ± 1.89%; p = .066) were similar among groups. CONCLUSION: The present study is the first to demonstrate that HCQ promoted a higher transfer of unesterified cholesterol which may account for the increased HDL levels in lupus patients under HCQ. This desirable effect may underlie the reported reduced atherosclerosis in SLE.

Long-term impact of the Tyrnyauz tungsten-molybdenum mining and processing factory waste on environmental pollution and children's population.

We studied the consequences of the long-term impact of remediated tailing ponds from the Tyrnyauz tungsten-molybdenum mining and processing factory on the environmental pollution and children living in the area. For more than 60 years, the factory has been engaged in the development of tungsten-molybdenum deposits by open-pit and mine methods and the enrichment of the extracted ore. More than 252,771 thousand tons of waste accumulated in its dumps and tailings ponds. This 170-hectare tailing pond contains more than 125 million tons of waste with arsenic, tungsten, molybdenum and other metals. To examine the possible accumulation of potentially toxic elements in children's bodies, we determined the content of heavy metals in drinking water and in the hair of children. An exfoliated buccal micronucleus test was used to determine the cytogenetic status of children. We did not find significant differences in the content of heavy metals inherent of a tailing pond in children's hair from polluted area compared to the control zone. In buccal cells of children living in the vicinity of the tailings pond, the total number of cytogenetic abnormalities was increased by 4.1 times, the total index of proliferation by 1.5 times, early destruction of the nucleus by 2 times and apoptosis by 1.2 times compared to the clean zone. Thus, we identified a genotoxic and cytotoxic effect on children living in the vicinity of the tailing ponds, which led to an increase in the number of children belonging to the medium- and high-risk groups. No correlations were found between the content of heavy metals in children's hair and the frequency of cells with cytogenetic abnormalities. Weak positive correlation was found between the content of manganese, zinc and copper in children's hair and the indicators of buccal epithelial cell proliferation.

Heart function in juvenile idiopathic arthritis patients: A biventricular two-dimensional speckle-tracking echocardiography study.

OBJECTIVES: We evaluated cardiac function in juvenile idiopathic arthritis (JIA) patients by 2D speckle-tracking echocardiography (2DSTE) and to assess possible associations with clinical, laboratorial, and treatment data. METHODS: A group of 42 JIA patients and 42 healthy controls were evaluated using both conventional echocardiography and 2DSTE. JIA patients underwent clinical and laboratory assessment. RESULTS: Conventional echocardiography data demonstrated normal left ventricular (LV) ejection fraction in both groups (71 vs. 71%; p = .69). 2DSTE analysis demonstrated that JIA patients presented significantly lower LV global systolic longitudinal strain (LVGLS) (-18.76 vs. -22%; p < .0001), LV systolic strain rate (LVSSR) (1.06 vs. 1.32 s-1; p < .0001), LV diastolic strain rate (LVDSR) (1.58 vs. 1.8 s-1; p < .0137), right ventricular global systolic strain (RVGLS) (-24.1% vs. -27.7%; p = .0002), and right ventricular systolic strain rate (RVSSR) (1.4 vs. 1.8 s-1; p = .0035). JIA patients under biological agents presented higher LVGLS (p = .02) and RVLS (p = .01). We also detected an association between LVGLS and C-reactive protein [CRP; -20% in normal CRP (10/42) vs. -18% in elevated CRP patients (32/42), p = .03]. CONCLUSIONS: JIA patients present different echocardiographic status from healthy patients. Moreover, our data suggest that JIA patients under biological agents present association with better cardiac function as shown by strain analysis.

Phylogeny of Lantana, Lippia, and related genera (Lantaneae: Verbenaceae).

PREMISE: Lantana and Lippia (Verbenaceae) are two large Linnean genera whose classification has been based on associated fruit traits: fleshy vs. dry fruits and one vs. two seed-bearing units. We reconstruct evolutionary relationships and the evolution of the two fruit traits to test the validity of these traits for classification. METHODS: Previous studies of plastid DNA sequences provided limited resolution for this group. Consequently, seven nuclear loci, including ITS, ETS, and five PPR loci, were sequenced for 88 accessions of the Lantana/Lippia clade and three outgroups. RESULTS: Neither Lantana nor Lippia is monophyletic. Burroughsia, Nashia, Phyla, and several Aloysia species are included within the clade comprising Lantana and Lippia. We provide a hypothesis for fruit evolution and biogeographic history in the group and their relevance for classification. CONCLUSIONS: Fleshy fruits evolved multiple times in the Lantana/Lippia clade and thus are not suitable taxonomic characters. Several sections of Lantana and Lippia and the small genera are monophyletic, but Lippia section Zappania is broadly paraphyletic, making circumscription of genera difficult. Lippia sect. Rhodolippia is a polyphyletic group characterized by convergence in showy bracts. Species of Lantana sect. Sarcolippia, previously transferred to Lippia, are not monophyletic. The clade originated and diversified in South America, with at least four expansions into both Central America and the Caribbean and two to Africa. The types species of Lantana and Lippia occur in small sister clades, rendering any taxonomy that retains either genus similar to its current circumscription impossible.

Managing drug-induced QT prolongation in clinical practice.

Many drug therapies are associated with prolongation of the QT interval. This may increase the risk of Torsades de Pointes (TdP), a potentially life-threatening cardiac arrhythmia. As the QT interval varies with a change in heart rate, various formulae can adjust for this, producing a 'corrected QT' (QTc) value. Normal QTc intervals are typically <450 ms for men and <460 ms for women. For every 10 ms increase, there is a ~5% increase in the risk of arrhythmic events. When prescribing drugs associated with QT prolongation, three key factors should be considered: patient-related risk factors (eg, female sex, age >65 years, uncorrected electrolyte disturbances); the potential risk and degree of QT prolongation associated with the proposed drug; and co-prescribed medicines that could increase the risk of QT prolongation. To support clinicians, who are likely to prescribe such medicines in their daily practice, we developed a simple algorithm to help guide clinical management in patients who are at risk of QT prolongation/TdP, those exposed to QT-prolonging medication or have QT prolongation.

Culture-Specific Observations in a Saudi Arabian Digital Home Health Care Program: Focus Group Discussions With Patients and Their Caregivers.

BACKGROUND: There is growing evidence of the need to consider cultural factors in the design and implementation of digital health interventions. However, there is still inadequate knowledge pertaining to the aspects of the Saudi Arabian culture that need to be considered in the design and implementation of digital health programs, especially in the context of home health care services for patients who are chronically and terminally ill. OBJECTIVE: This study aims to explore the specific cultural factors related to patients and their caregivers from the perspective of physicians, nurses, and trainers that have influenced the pilot implementation of Remotely Accessible Healthcare At Home, a connected health program in the Home Health Care department at King Saud University Medical City, Riyadh, Saudi Arabia. METHODS: A qualitative study design was adopted to conduct a focus group discussion in July 2019 using a semistructured interview guide with 3 female and 4 male participants working as nurses, family physicians, and information technologists. Qualitative data obtained were analyzed using a thematic framework analysis. RESULTS: A total of 2 categories emerged from the focus group discussion that influenced the experiences of digital health program intervention: first, culture-related factors including language and communication, cultural views on using cameras during consultation, nonadherence to web-based consultations, and family role and commitment and second, caregiver characteristics in telemedicine that includes their skills and education and electronic literacy. Participants of this study revealed that indirect contact with patients and their family members may work as a barrier to proper communication through the Remotely Accessible Healthcare At Home program. CONCLUSIONS: We recommend exploring the use of interpreters in digital health, creating awareness among the local population regarding privacy in digital health, and actively involving direct family members with the health care providers.

Collaboration during a crisis - the Lighthouse Lab volunteers.

As a group of early-career researchers, we recount our experiences of volunteering at one of the national Lighthouse Labs based at the UK Biocentre in Milton Keynes. We worked together as part of a multidisciplinary team to support the large-scale processing of coronavirus disease 2019 (COVID-19) swabs from across the whole of the UK.

Targeting ROS overgeneration by N-benzyl-2-nitro-1-imidazole-acetamide as a potential therapeutic reposition approach for cancer therapy.

BackgroundWe investigated the role of reactive oxygen species (ROS) in the anticancer mechanism of N-benzyl-2-nitro-1-imidazole-acetamide (BZN), a drug used in Chagas' disease treatment. MethodsBALB/c mice, inoculated with Ehrlich ascites carcinoma (EAC), were treated with BZN or BZN + Nacylcysteine (NAC) or NAC for 9 days. Subsequently, the inhibition of tumor growth and angiogenesis as well as animal survival were evaluated. Apoptosis and the cell cycle were evaluated using fluorescence microscopy and flow cytometry, while oxidative stress was evaluated by measuring TBARS content, DNA damage, calcium influx and ROS generation and antioxidant defenses (CAT, SOD, GPx, GST and GR). Immunoblotting was used to evaluate key death and cell cycle proteins. Results BZN treatment inhibited tumor progression (79%), angiogenesis (2.8-fold) and increased animal survival (29%). Moreover, BZN increased ROS levels (42%), calcium influx (55%), TBARS contents (1.9-fold), SOD (4.4-fold), GPx (17.5-fold) and GST (3-fold) activities and GSH depletion (2.5-fold) also caused DNA fragmentation (7.6-fold), increased cleaved PARP and promoted the trapping of cells in the G1 phase, as corroborated by the reduction in cyclin A and increased CDK2 protein levels. In silico DNA and molecular dynamic simulations showed H-bonds and hydrophobic interactions that were confirmed by circular dichroism. Increased apoptosis (232%), induced by treatment with BZN, was demonstrated by apoptotic cell staining and p53 level. Conclusion The current findings indicate that BZN acts as a tumor growth inhibitor and anti-angiogenic agent by ROS overgeneration, which interact with DNA causing damage and triggering apoptosis.

Androgen deprivation therapy improves the in vitro capacity of high-density lipoprotein (HDL) to receive cholesterol and other lipids in patients with prostate carcinoma.

BACKGROUND: Androgen deprivation therapy (ADT) is widely used in the treatment of testosterone-dependent prostate carcinomas. ADT often increases plasma LDL and HDL cholesterol and triglycerides. The aim was to test whether ADT changes the transfer of lipids to HDL, an important aspect of this metabolism and HDL protective functions, and related parameters. METHODS: Sixteen volunteers with advanced prostate carcinoma submitted to pharmacological ADT or orchiectomy had plasma collected shortly before and after 6 months of ADT. In vitro transfer of lipids to HDL was performed by incubating plasma with donor emulsion containing radioactive lipids by 1 h at 37 °C. After chemical precipitation of apolipoprotein B-containing lipoprotein, the radioactivity of HDL fraction was counted. RESULTS: ADT reduced testosterone to nearly undetectable levels and markedly diminished PSA. ADT increased the body weight but glycemia, triglycerides, LDL and HDL cholesterol, HDL lipid composition and CETP concentration were unchanged. However, ADT increased the plasma unesterified cholesterol concentration (48 ± 12 vs 56 ± 12 mg/dL, p = 0.019) and LCAT concentration (7.15 ± 1.81 vs 8.01 ± 1.55µg/mL, p = 0.020). Transfer of unesterified (7.32 ± 1.09 vs 8.18 ± 1.52%, p < 0.05) and esterified cholesterol (6.15 ± 0.69 vs 6.94 ± 1.29%, p < 0.01) and of triglycerides (6.37 ± 0.43 vs 7.18 ± 0.91%, p < 0.001) to HDL were increased after ADT. Phospholipid transfer was unchanged. CONCLUSION: Increase in transfer of unesterified and esterified cholesterol protects against cardiovascular disease, as shown previously, and increased LCAT favors cholesterol esterification and facilitates the reverse cholesterol transport. Thus, our results suggest that ADT may offer anti-atherosclerosis protection by improving HDL functional properties. This could counteract, at least partially, the eventual worse effects on plasma lipids.

Detecting Infectious Bursal Disease Using a VP1 Gene-Based RT-qPCR Assay Compared to Standard Methods of Virus Isolation, ELISA, and Histopathology.

Infectious bursal disease (IBD) is an immunosuppressive viral disease of chickens, associated with severe economic losses and major threats to poultry production worldwide. Disease prevention programs rely on unequivocal identification of the pathogen, as well as vaccination programs. This study developed a sensitive, one-step, real-time, quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay using a hydrolysis probe system for infectious bursal disease virus (IBDV, VP1 gene) detection and quantification, which was compared to other routinely used diagnostic methods. The assay successfully detected IBD reference viruses and field isolates. The absence of cross-reactivity was detected with negative samples or with other avian viruses in the analytical specificity test. The detection limit of this assay was 70 RNA copies. RT-qPCR was more sensitive in the detection of serially diluted IBDV isolates compared to virus isolation. For clinical samples, the sensitivity and specificity values of RT-qPCR compared to enzyme-linked immunosorbent assay (ELISA) were 97.5% and 100%, respectively, and compared to histopathology, these values were 100% and 93.94%, respectively. RT-qPCR can provide a simple and reliable assay for IBDV surveillance programs and for evaluation of control strategies.

Implementing a connected health intervention for remote patient monitoring in Saudi Arabia and Pakistan: explaining 'the what' and 'the how'.

BACKGROUND: Recent developments in connected health technology provide an opportunity to remotely monitor and provide health care to the patient needing long-term medical care. However, information about how any connected health interventions should be implemented for remote patient monitoring, and how patients should be educated and enabled for active participation in treatment is still not available to a sufficient degree. DISCUSSION: In this paper, we discussed what the components of a connected health intervention, entitled Remotely Accessible Health Care at Home (RAHAH), are, and how this intervention has been implemented in Saudi Arabia and Pakistan. The aim of this intervention is to remotely monitor, treat and educate patients needing long-term medical care. The description of the intervention is presented based on the Template for Intervention Description and Replication (TIDieR) checklist for the transparent, comprehensive and explicit reporting. CONCLUSION: We believe, successful implementation of RAHAH would be crucial to monitor and manage growing chronic care populations more effectively and efficiently in Saudi Arabia and Pakistan.

Insulin stimulus-secretion coupling is triggered by a novel thiazolidinedione/sulfonylurea hybrid in rat pancreatic islets.

New compounds with promising antidiabetic activity were synthesized. For the first time, a portion of the glibenclamide molecule was bound to a part of the core structure of thiazolidinedione to evaluate insulin secretagogue activity. Following studies in our laboratory, 4-{2-[2-(3,4-dichlorophenyl)-4-oxo-1,3-thiazolidin-3-yl]ethyl}benzene-1-sulfonamide (DTEBS) was selected to evaluate glycemia using the glucose tolerance test and insulin secretagogue activity by E.L.I.S.A. The mechanism of action of this compound was studied by 45 Ca2+ influx and whole-cell patch-clamp in rat pancreatic isolated islets. Furthermore, AGE formation in vitro was investigated. We herein show that this novel hybrid compound (DTEBS) exhibits an insulinogenic index and a profile of serum insulin secretion able to maintain glucose homeostasis. Its mechanism of action is mediated by ATP-sensitive potassium channels (KATP) and L-type voltage-dependent calcium channels (VDCC) and by activating protein kinase C and A (PKC and PKA). In addition, the stimulatory action of the compound on calcium influx and insulin secretion indicates that the potentiation of voltage-sensitive K+ currents (Kv) is due to the repolarization phase of the action potential after secretagogue excitation-secretion in pancreatic islets. Furthermore, under these experimental conditions, the compound did not induce toxicity and the in vitro late response of the compound to protein glycation reinforces its use to prevent complications of diabetes. DTEBS exerts an insulin secretagogue effect by triggering KATP, VDCC, and Kv ionic currents, possibly via PKC and PKA pathway signal transduction, in beta-cells. Furthermore, DTEBS may hold potential for delaying the late complications of diabetes.

Mechanism of action of camphoryl-benzene sulfonamide derivative on glucose uptake in adipose tissue.

The aim of the present study was to investigate the mechanism of action of a sulfonamide derivative on glucose uptake in adipose tissue, as well as to characterize the effects of this compound on intestinal disaccharidases and advanced glycation end-products (AGEs) formation. Camphoryl-benzene sulfonamide (CS) was able to stimulate glucose uptake in isolated adipocytes, adipose tissue, and in soleus muscle. The stimulatory effect of the compound (10 µM) on glucose uptake on adipose tissue was blocked by diazoxide, wortmannin, U73122, colchicine, and N-ethylmaleimide. On the other hand, the effects of CS were not blocked by glibenclamide, an inhibitor of the K+ -ATP channel, or even by the inhibitor of protein p38 MAPK, SB 203580. In vivo, this compound reduced intestinal disaccharidase activity, while, in vitro, CS reduced the formation of AGEs at 7, 14, and 28 days of incubation. The stimulatory effect of CS on glucose uptake requires the activation of the K+ -ATP channel, translocation, and fusion of GLUT4 vesicles to the plasma membrane on adipocytes for glucose homeostasis. In addition, the inhibition of disaccharidase activity contributes to the glucose homeostasis in a short-term as well as the remarkable reduction in AGE formation indicates that the CS may prevent of complications of late diabetes.

Oral Mucosa Model for Electrochemotherapy Treatment of Dog Mouth Cancer: Ex Vivo, In Silico, and In Vivo Experiments.

Electrochemotherapy (EQT) is a local cancer treatment well established to cutaneous and subcutaneous tumors. Electric fields are applied to biological tissue in order to improve membrane permeability for cytotoxic drugs. This phenomenon is called electroporation or electropermeabilization. Studies have reported that tissue conductivity is electric field dependent. Electroporation numerical models of biological tissues are essential in treatment planning. Tumors of the mouth are very common in dogs. Inadequate EQT treatment of oral tumor may be caused by significant anatomic variations between dogs and tumor position. Numerical models of oral mucosa and tumor allow the treatment planning and optimization of electrodes for each patient. In this work, oral mucosa conductivity during electroporation was characterized by measuring applied voltage and current of ex vivo rats. This electroporation model was used with a spontaneous canine oral melanoma. The model outcomes of oral tumor EQT is applied in different parts of the oral cavity including near bones and the hard palate. The numerical modeling for treatment planning will help the development of new electrodes and increase the EQT effectiveness.

Cholesteryl ester transfer protein (CETP), HDL capacity of receiving cholesterol and status of inflammatory cytokines in patients with severe heart failure.

BACKGROUND: Heart failure (HF) courses with chronic inflammatory process and alterations in lipid metabolism may aggravate the disease. The aim was to test whether the severity of HF, using brain natriuretic peptide (BNP) as a marker, is associated with alterations in functional aspects of HDL, such as lipid transfer, cholesterol ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT) concentration. METHODS: Twenty-five HF patients in NYHA class I/II and 23 in class III/IV were enrolled. Plasma lipids, apolipoproteins, CETP, LCAT, oxidized-LDL (oxLDL) and paraoxonase-1 (PON-1) activity were determined. Lipid transfer from a donor artificial nanoparticle to HDL was measured by in vitro assay. RESULTS: Total cholesterol (p = 0.049), LDL-C (p = 0.023), non-HDL-C (p = 0.029) and CETP, that promotes lipid transfer among lipoproteins (p = 0.013), were lower in III/IV than in I/II group. Triglycerides, HDL-C, apo A-I, apo B, oxLDL, LCAT, enzyme that catalyzes serum cholesterol esterification, PON-1 activity, and in vitro transfers of cholesterol, triglycerides and phospholipids to HDL, important steps in HDL metabolism, were equal. IL-8 was higher in III/IV (p = 0.025), but TNFα, IL-1ß, IL-6 and MCP-1 were equal. BNP was negatively correlated with CETP (r = - 0.294; p = 0.042) and positively correlated with IL-8 (r = 0.299; p = 0.039). CONCLUSIONS: Our results disclosed the relationship between CETP levels and HF severity, by comparing two HF groups and by correlation analysis. Lower CETP levels may be a marker of HF aggravation and possibly of worse prognosis. Practical applications of this initial finding, as the issue whether CETP could be protective against HF aggravation, should be explored in larger experimental and clinical studies.

Hypertension, mitral valve disease, atrial fibrillation and low education level predict delirium and worst outcome after cardiac surgery in older adults.

BACKGROUND: Delirium is a common complication after cardiac surgery in older adult patients. However, risk factors and the influence of delirium on patient outcomes are not well established. We aimed to determine the incidence, predisposing and triggering factors of delirium following cardiac surgery. METHODS: One hundred seventy-three consecutive patients aged ≥60 years were studied. Patients' characteristics and two cognitive function assessment tests were recorded preoperatively. Perioperative variables were blood transfusion, orotracheal intubation time (OIT), renal dysfunction, and hypoxemia. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit. The composite outcome consisted of death, infection, and perioperative myocardial infarction until hospital discharge or 30 days after surgery, and for up to 18 months. RESULTS: One hundred six patients (61.27%) were men and the age was 69.5 ± 5.8 years. EuroSCORE II index was 4.06 ± 3.86. Hypertension was present in 75.14%, diabetes in 39.88%, and 30.06% were illiterate. Delirium occurred in 59 patients (34.1%). Education level (OR 0.81, 0.71-0.92), hypertension (OR 2.73, 1.16-6.40), and mitral valve disease (OR 2.93, 1.32-6.50) were independent predisposing factors for delirium, and atrial fibrillation after surgery (OR 2.49, 1.20-5.20) represented the potential triggering factor. Delirium (OR 2.35, 1.20-4.58) and OIT ≥ 900 min (OR 2.50; 1.30-4.80) were independently associated with the composite outcome. CONCLUSIONS: In older adult patients submitted to cardiac surgery, delirium is a frequent complication that is associated with worst outcome. Independent risk factors for delirium included education level, hypertension, mitral valve disease, and atrial fibrillation after cardiac surgery.