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BackgroundGermline mutations in CDH1 are associated with hereditary diffuse gastric cancer; lobular breast cancer also occurs excessively in families with such condition.MethodTo determine if CDH1 is a susceptibility gene for lobular breast cancer in women without a family history of diffuse gastric cancer, germline DNA was analysed for the presence of CDH1 mutations in 318 women with lobular breast cancer who were diagnosed before the age of 45 years or had a family history of breast cancer and were not known, or known not, to be carriers of germline mutations in BRCA1 or BRCA2. Cases were ascertained through breast cancer registries and high-risk cancer genetic clinics (Breast Cancer Family Registry, the kConFab and a consortium of breast cancer genetics clinics in the United States and Spain). Additionally, Multiplex Ligation-dependent Probe Amplification was performed for 134 cases to detect large deletions.ResultsNo truncating mutations and no large deletions were detected. Six non-synonymous variants were found in seven families. Four (4/318 or 1.3%) are considered to be potentially pathogenic through in vitro and in silico analysis.ConclusionPotentially pathogenic germline CDH1 mutations in women with early-onset or familial lobular breast cancer are at most infrequent.

Accurate prognosis and diagnosis are crucial for selecting and planning lung cancer treatments. As a result of the rapid development of medical imaging technology, the use of computed tomography (CT) scans in pathology is becoming standard practice. An intricate interplay of requirements and obstacles characterizes computer-assisted diagnosis, which relies on the precise and effective analysis of pathology images. In recent years, pathology image analysis tasks such as tumor region identification, prognosis prediction, tumor microenvironment characterization, and metastasis detection have witnessed the considerable potential of artificial intelligence, especially deep learning techniques. In this context, an artificial intelligence (AI)-based methodology for lung cancer diagnosis is proposed in this research work. As a first processing step, filtering using the Butterworth smooth filter algorithm was applied to the input images from the LUNA 16 lung cancer dataset to remove noise without significantly degrading the image quality. Next, we performed the bi-level feature selection step using the Chaotic Crow Search Algorithm and Random Forest (CCSA-RF) approach to select features such as diameter, margin, spiculation, lobulation, subtlety, and malignancy. Next, the Feature Extraction step was performed using the Multi-space Image Reconstruction (MIR) method with Grey Level Co-occurrence Matrix (GLCM). Next, the Lung Tumor Severity Classification (LTSC) was implemented by using the Sparse Convolutional Neural Network (SCNN) approach with a Probabilistic Neural Network (PNN). The developed method can detect benign, normal, and malignant lung cancer images using the PNN algorithm, which reduces complexity and efficiently provides classification results. Performance parameters, namely accuracy, precision, F-score, sensitivity, and specificity, were determined to evaluate the effectiveness of the implemented hybrid method and compare it with other solutions already present in the literature.

Purpose: To investigate best corrected visual acuity (BCVA), subretinal fluid (SRF) absorption time or ellipsoid zone (EZ) restoration time and various variables in patients with persistent SRF after successful primary repair of rhegmatogenous retinal detachment (RRD)., Methods: This retrospective multicenter study allowed independent analysis of the healing pattern by two observers based on composite of serial cross-sectional macular optical coherence tomography (OCT) scans. Univariate and multivariate analyses were implemented., Results: One hundred and three cases had persistent SRF after pars plana vitrectomy, scleral buckling, or pneumatic retinopexy. By univariate analysis, SRF resolution time correlated positively with the number of retinal breaks ( p  < 0.001) and with increased myopia ( p  = 0.011). Using multivariate analysis, final BCVA (log MAR) correlated positively with age, duration of RRD, initial BCVA (OR = 3.28; [95%CI = 1.44-7.47]; p  = 0.015), and SRF resolution time (OR = 0.46 [95%CI 0.21-1.05]; p  = 0.049). EZ restoration time was longer with increasing number of retinal tears (OR = 0.67; [95%CI 0.29-1.52]; p  = 0.030), worse final BCVA, and presence of macula-off RRD (OR = 0.26; [95%CI 0.08-0.88]; p  = 0.056). SRF resolution time correlated marginally with prone position., Conclusions: Residual posterior SRF is more common in eyes with multiple breaks or in myopic eyes. Final BCVA is better in younger subjects and in eyes with shorter duration of RRD. Persistent SRF is a self-limited disorder with a mean resolution of 11.2 months with good visual prognosis improving from a mean baseline logMAR of 1.08 to 0.25 at one year., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The aim of this study is to transform optical coherence tomography angiography (OCTA) scans into innovative OCTA graphs, serving as novel biomarkers representing the macular vasculature., Patients and Methods: The study included 90 healthy subjects and 39 subjects with various abnormalities (29 with diabetic retinopathy, 5 with age-related macular degeneration, and 5 with choroid neovascularization). OCTA 5µm macular coronal views (MCVs) were generated for each subject, followed by blood vessel segmentation and skeleton processing. Subsequently, the blood vessel density index, blood vessel skeleton index, and blood vessel tortuosity index were computed. The graphs of each metric were plotted against the axial axes of the OCTA B-scan, representing the integrity of vasculature at successive 5µm macular depths., Results: The results revealed two significant findings. First, the B-scans from OCTA can be transformed into OCTA graphs, yielding three specific OCTA graphs in this study. These graphs provide new biomarkers for assessing the integrity of deep vascular complex (DVC) and superficial vascular complex (SVC) within the macula. Second, a statistically significant difference was observed between normal (n=90) and abnormal (n=39) subjects, with a t -test p-value significantly lower than 0.001. The Mann-Whitney u -test also yielded significant difference but only between the 90 normal and 29 DR subjects., Conclusion: The novel OCTA graphs offer a unique representation of the macula's SVC and DVC, suggesting their potential in aiding physicians in the diagnosis of eye health within OCTA clinics. Further research is warranted to finalize the shape of these newly derived OCTA graphs and establish their clinical relevance and utility., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Al-Hinnawi et al.)

Purpose: To study the anatomic outcome of leaving vitreous cortex remnants (VCR) during pars plana vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD)., Methods: The study comprised patients with RRD who had PPV by a single surgeon between January 2019 and December 2020 and followed for 6 months. After intravitreal injection of triamcinolone acetonide, the topographic pattern of VCR at the periphery (p) and macula (m) was divided into 2 types by extent: complete or 4 quadrants (pVCR4Q), and   between 2 and 4 quadrants ≥2 quadrants (pVCR>2Q), or by location >1 inferior retinal quadrant (pVCR>1InfQ), and at the macula (mVCR). Anatomical failure or retinal re-detachment within 6 months after surgery was the primary outcome measures. The occurrence of grade C proliferative vitreoretinopathy (PVR) and epiretinal membrane (ERM) were used as secondary outcome indicators., Results: A 6-month prospective follow-up was performed on 103 patients. pVCR4Q was detected in 31 eyes, pVCR>2Q in 40 eyes, pVCR>1InfQ in 40 eyes and mVCR in 54 eyes. Recurrent RRD developed in 9 (8.7%) eyes, PVR grade C in 6 (5.8%) eyes and ERM in 11 (10.7%) eyes. According to multivariate regression analysis, the existence of any type of VCR did not correlate with anatomical failure, PVR or ERM., Conclusion: The initial success rate of PPV and the growth of PVR or ERM do not appear to be impacted by keeping VCR., Competing Interests: None of the authors had any financial/conflicting interests to disclose., (© 2023 Assi et al.)

Colorectal cancer (CRC) is ranked as the third most prevalent and the second deadliest cancer worldwide. In the Middle East and North Africa (MENA) region, the number of CRC cases increased over the past decades and will nearly double by 2030. The lack of clear MENA guidelines for the management of patients with CRC represents a step backwards in the fight against this burden. Therefore a panel of 24 MENA experts in the field of gastrointestinal oncology developed, using a Delphi process, the first consensus recommendations for the management of patients with advanced CRC. Forty-seven different statements were formulated in the areas of epidemiology, screening, biomarkers and treatment. These recommendations will guide, standardize and unify the management of this cancer in the MENA region.

Background: Contextual processing dysfunction in patients with schizophrenia (SCZ) is not uniform and task-dependent. In SCZ, studies on the rod and frame test (RFT), which evaluates contextual modulation of verticality perception, are sparse. A main study that utilized a two-alternative forced choice design for judging rod verticality reported equivalent strength of RFT contextual modulation in healthy controls and SCZ. The current study aims to uncover any potential differences in contextual modulation between controls and SCZ with an adjustment method on a computerized RFT., Materials and Methods: A total of 17 healthy controls and 15 SCZ aligned an oriented rod to their perceived vertical with a computer mouse under four randomized frame presentations: absent frame, non-tilted (Frame 0° ), or tilted by 18 degrees leftward (Frame -18° ) or rightward (Frame +18° ). Rod deviation error was assigned a negative or positive value when aligned leftward or rightward, respectively, of 0°. Signed and absolute errors, the rod and frame effect (RFE), and intra-individual variability (inconsistency) were used for analysis., Results: There was no group difference in rod alignment errors or derived measures, except that SCZ displayed greater inconsistency in rod alignment, compared to controls. The negative symptom scale (PANSS-N) scores correlated positively with the variability measure and with unsigned Frame -18° error., Conclusions: Only the variability measure was sensitive enough to distinguish between controls and SCZ. SCZ with more severe negative symptoms had larger variability in rod alignment, probably reflecting a state of indifference. The larger deviation errors only with a leftward tilted frame, as PANSS-N scores increased, may indicate a lateralized attentional abnormality that is correlated with severity of symptoms in SCZ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Razzak, Jahrami, Husni, Ali and Bagust.)

Diabetic foot ulcer (DFU) is one of the slowest healing wounds that hurt the human body. Many studies from developed countries are concerned about materials, procedures, and equipment that accelerate the healing time. In Sweden, the diabetic foot management costs around 24965$/patient. In this review, we would evaluate the healing time of DFUs during what is considered one of the worst humanitarian crisis of the 21st century. 1747 DFUs were studied from the main diabetic foot clinic in Damascus (2014-2019). We predicted many variables that could prolong the healing time. The cost according to these variables was also reported. The SINBAD Classification was performed to grade the severity of ulcers. We noticed that the median healing time for DFUs was 8 weeks. Almost half of these ulcers healed between 3 and 12 weeks. The time of healing for men was significantly longer than that for women. While the presence of infection doubled the median time of healing, the presence of peripheral artery disease doubled the mean of the direct health care cost. The location of the ulcer acted as another independent risk factor. In conclusion, DFUs face many barriers to heal during a crisis.The environment with resource-poor settings should be added to the traditional risk factors that delay the healing of DFUs for months or even years. More studies from disaster are as are needed to evaluate low-cost materials that could be cost effective in applying standard care of the diabetic foot., (© 2021 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Objectives: To determine the patient-related factors that contribute to intraoperative corticocapsular adhesions (CCA) during phacoemulsification cataract extraction (PCE)., Methods: Prospective, single surgeon, multi-year study of consecutive patients undergoing PCE was performed. At the conclusion of each procedure, the surgeon recorded the CCA and perceived surgeon stress score. Patient variables included gender, age, diabetes mellitus, intake of oral alpha blockers, floppy iris, laterality, pseudo-exfoliation, and intraocular lens power., Results: During the 10-year study, 1097 eyes underwent surgery and CCA was diagnosed intraoperatively in 41 eyes. On multi-variable analysis, the following patient characteristics were associated with intraoperative CCA: diabetes mellitus (p = 0.002), age >80 years (p = 0.002), presence of posterior capsular cataract (p = 0.046), severe nuclear sclerosis (p = 0.004), and absence of pseudo-exfoliation (p = 0.043)., Conclusion: Diabetes mellitus, advanced age and posterior subcapsular cataract are associated with CCA necessitating generous repetitive hydrodissection., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: The daily life management of patients with Alzheimer's disease (AD) constitutes a significant and rapidly expanding health-care responsibility. In this study, an innovative prototype of a wireless-sensing smart wearable medical device (SWMD) is proposed as a multi-functions solution for Alzheimer patients. The SWMD is aimed to assemble three main biomedical engineering advances: 1) use of a Wi-Fi microcontroller, 2) simultaneous monitoring of a set of vital biomarkers, and 3) cautions of fall down conditions, in addition to GPS location indicator., Methods: The SWMD employs a Wi-Fi controller that is incorporated with electronic circuits to monitor three vital signals (temperature, heart rate, and oxygen saturation), fall down conditions in three directions (X, Y, and Z axis), and GPS location. The SWMD was connected to the Firebase Service (database hosted on the Internet Cloud). The proposed device was tested on 13 normal volunteers. The left side, right side, forward, and backward fall down conditions were assessed. The prototype's functions during daily activity such as rising hand, sitting down or standing up, and walking conditions were also assessed., Results: The three assembled functions were all successfully incorporated to build the SWDM device as a suggested solution offering real-time alerts during daily activity to AD patients. The Bland-Altman statistical test showed no significant difference (p-value >0.05) between the SWMD biomarkers' acquisition and the reference methods. The gyro/accelerator sensor yielded 93% sensitivity in fall down detection and 95% specificity during daily activities. The GPS yielded correct positioning of the SWDM holder, while the internet cloud allowed saving and managing all vital biomarkers daily., Conclusion: The SWMD is a possible solution for daily life support for AD patients. It incorporates three functions in one single device, GPS location indicator, monitoring set of biomarkers, and fall down alert, which are all controlled via a Wi-Fi micro controller on-line connected to Internet Cloud. It successfully would allow the management of the daily records as well as the real-time alerts to remote persons., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Al-Naami et al.)

Global high demand for Pacific white shrimp Penaeus vannamei has led to intensified cultivation and a wide range of disease problems, including bacterial diseases due to vibrios. Three presumptive luminescent Vibrio harveyi strains (Vh5, Vh8 and Vh10) were isolated from the hepatopancreas (Vh5) and haemolymph (Vh8 and Vh10) of diseased growout Pacific white shrimp from a farm in Setiu, Terengganu, Malaysia, using Vibrio harveyi agar (VHA) differential medium. All three strains were identified as V. harveyi by biochemical characteristics. 16S rRNA gene-based phylogenetic analyses by neighbour-joining, maximum likelihood and maximum parsimony methods showed all three strains in the V. harveyi cluster. All three strains were β-haemolytic and positive for motility, biofilm formation and extracellular products (caseinase, gelatinase, lipase, DNase, amylase and chitinase). Vh10 was subjected to pathogenicity test in Pacific white shrimp by immersion challenge and determined to have a LC 50 of 6.0 × 10 8 CFU mL -1 after 168 h of exposure. Antibiotic susceptibility tests showed that all strains were resistant to oxytetracycline (OXT30), oleandomycin (OL15), amoxicillin (AML25), ampicillin (AMP10) and colistin sulphate (CT25) but sensitive to doxycycline (DO30), flumequine (UB30), oxolinic acid (OA2), chloramphenicol (C30), florfenicol (FFC30), nitrofurantoin (F5) and fosfomycin (FOS50). Each strain was also resistant to a slightly different combination of eight other antibiotics, with an overall multiple antibiotic resistance (MAR) index of 0.40, suggesting prior history of heavy exposure to the antibiotics. Vh10 infection resulted in pale or discoloured hepatopancreas, empty guts, reddening, necrosis and luminescence of uropods, as well as melanised lesions in tail muscle. Histopathological examination showed necrosis of intertubular connective tissue and tubule, sloughing of epithelial cells in hepatopancreatic tubule, haemocytic infiltration, massive vacuolation and loss of hepatopancreatic tubule structure., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To determine the patient-related factors that contribute to surgeon stress during phacoemulsification cataract extraction (PCE) performed under unassisted topical anesthesia., Methods: This is a prospective study of perceived surgeon stress during phacoemulsification by a single surgeon of consecutive patients undergoing PCE. At the conclusion of each procedure, the surgeon recorded the perceived stress according to the following three indices: surgeon score, qualitative score (yes or no), and total score (sum of itemized causes of stress). Patient variables included in the analysis included gender, age, diabetes mellitus, morbid obesity, intake of oral alpha blockers, floppy iris, laterality, pseudo-exfoliation, intraocular lens power, and initial visual acuity., Results: During the 10-year study, 1097 eyes underwent surgery. The following patient variables were seen frequently: floppy iris syndrome (92), pseudo-exfoliation (72), and morbid obesity (36). Surgeon identified stress was reported after 250 procedures. On multivariable analysis, the following patient characteristics were associated with surgeon stress: age >80 years; morbid obesity; floppy iris syndrome; severe nuclear sclerosis; and poor baseline distance corrected visual acuity., Conclusion: Several ocular and systemic patient-related characteristics contribute to surgeon stress during PCE., Competing Interests: Michael W. Stewart, MD: Consultant – Alkahest, Bayer; Institutional Research Support – Allergan, Regeneron. The authors report no other conflicts of interest in this work., (© 2020 Mansour et al.)

Background: Chemotherapy-induced peripheral neuropathy (CIPN) affects 30% to 40% of patients with cancer with long-lasting disability. Scrambler therapy (ST) appeared to benefit patients in uncontrolled trials, so we performed a randomized sham-controlled Phase II trial of ST., Methods: The primary end point was "average pain" after 28 days on the Numeric Rating Scale. Each received ten 30-minute sessions of ST on the dermatomes above the painful areas, or sham treatment on the back, typically at L3-5 where the nerve roots would enter the spinal cord. Outcomes included the Brief Pain Inventory (BPI)-CIPN and the EORTC CIPN-20 scale. Patients were evaluated before treatment (day 0), day 10, and days 28, 60, and 90., Results: Data regarding pain as a primary outcome were collected for 33 of the 35 patients. There were no significant differences between the sham and the "real" ST group at day 10, 28, 60, or 90, for average pain, the BPI, or EORTC CIPN-20. Individual responses were noted during the ST treatment on the real arm, but most dissipated by day 30. There was improvement in the sensory subscale of the CIPN-20 at 2 months in the "real" group ( P = .14). All "real" patients wanted to continue treatment if available., Discussion: We observed no difference between sham and real ST CIPN treatment. Potential reasons include at least the following: ST does not work; the sham treatment had some effect; small sample size with heterogeneous patients; misplaced electrodes on an area of nonpainful but damaged nerves; or a combination of these factors.

The development of efficacious and safe drugs for the treatment of neurological diseases related to glutamate toxicity has been a focus in neuropharmacological research. Specifically, discovering antagonists to modulate the activity and kinetics of AMPA receptors, which are the fastest ligand-gated ion channels involved in excitatory neurotransmission in response to glutamate. Thus, the current study investigated novel curcumin derivatives on the biophysical properties of AMPA receptors, specifically on the homomeric GluA2 and the heteromeric GluA2/A3 subunits and assessed for inhibitory actions. The biophysical parameter (i.e., desensitization, deactivation, and peak currents) were measured by using whole-cell patch clamp electrophysiology with and without the administration of the derivatives onto HEK293 cells. CR-NN, CR-NNPh, CR-MeNH, and CR-NO of the tested derivatives showed inhibition on all AMPA receptors up to 6 folds. Moreover, the inhibitory derivatives also increased desensitization and deactivation, which further intensifies the compounds' neuroprotective effects. However, CR-PhCl, CR-PhF, and CR-PhBr did not show any significant changes on the peak current, deactivation or desensitization rates. By comparison to other discovered and widely used antagonist, the prepared curcumin derivatives are not selective to a specific AMPA subunit, instead implement its effect in the same way between all types of AMPA receptors. Additionally, the obtained results provide derivatives that not only noncompetitively inhibit AMPARs but also decrease its biophysical kinetics, specifically desensitization and deactivation rates. Hence, to potentially serve as a new AMPAR inhibitor with therapeutic potential, the current study provides compounds that are non-selective and non-competitive antagonist, which also effect the desensitization and deactivation rates of the receptor., Competing Interests: The authors have declared that no competing interests exist.

Nurses play an integral role in high-quality patient care. Thus, their skills in providing end-of-life care should be assessed and continually enhanced. Education intended to improve end-of-life skills must address the affective/emotional component of nursing care. Evidence demonstrates that emotional engagement and resilience among health care providers are correlated with improved quality outcomes and, conversely, that burnout and stress negatively affect patient safety. Addressing the emotional needs of health care providers is critical to improving quality throughout the health care system. An evidence-based workshop was implemented among direct care staff on a hospital-based palliative care unit, with the goal of fostering emotional engagement to improve staff perceptions and attitudes about caring for patients at or near the end of life. Although perceptions about quality of death were not affected by this intervention, there was a significant improvement in attitudes about end-of-life nursing care. Qualitative feedback also reflected appreciation for small group discussions and opportunities to debrief with peers away from the unit. This intervention reflected the value of emotional engagement in educational efforts to improve end-of-life nursing care.

Purpose: The primary objective was to assess the effect of general anaesthesia versus regional anaesthesia in a single exposure before the age of 2 years on the development of long-term behavioural changes in children., Methods: The study was conducted between January 2014 and March 2015. Medical records of eligible children were reviewed. Then, parents of children who were included in the study were contacted and asked to visit the Outpatient Department to fill the Eyberg Child Behaviour Inventory questionnaire to measure behavioural changes in children. Children who were exposed to regional or general anaesthesia for surgery between January 2002 and December 2006 were included. Data collected were age and weight at the time of the first anaesthesia exposure and surgery duration. Chi-square test, t-test and multivariate analysis were used., Results: In total, 394 children were exposed to anaesthesia before the age of 2 years. Among the 168 patients who were exposed to general anaesthesia, 44 children (26.2%) developed behavioural abnormalities compared to 12 out of 226 patients (5.3%) who were exposed to regional anaesthesia (P-value<0.0001). Exposure to anaesthesia before age of 2 years increases the risk of developing behavioural disorder when surgery is accompanied by general anaesthesia, younger age at time of exposure, and longer surgery duration (P-value<0.0001, 0.001, 0.038 respectively)., Conclusion: Regional anaesthesia showed much lesser effect on children's behaviour compared to general anaesthesia. The incidence of behavioural disorder is increased with the use of general anaesthesia, younger age of the patient at time of exposure, and longer surgery duration., (Copyright © 2018 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Curcumin is a natural polyphenol that has a broad spectrum of therapeutic characters, including neuroprotective actions against various neurological diseases. However, the molecular mechanism behind its neuroprotective properties remains obscure. The current study investigated the neuroprotective properties of 7 different curcumin derivatives on the gating biophysical properties of AMPA receptors, specifically on the calcium-permeable homomeric GluA1 and calcium impermeable heteromeric GluA1/A2 subunits. Due to the association between excessive activation of AMPARs and neurotoxicity linked to numerous pathologies, we aim to target and manipulate the kinetics of AMPARs through these derivatives. The current study used patch-clamp electrophysiology to measure the whole-cell currents in the presence and absence of the curcumin derivatives onto HEK293 cells expressing AMPA subunits. Our results showed that some of the curcumin derivatives showed an inhibitory effect and altered the gating biophysical properties, namely, deactivation and desensitization. In the presence of those derivatives, the peak current measured was significantly reduced, and the desensitization and deactivation rates decreased as well, achieving slower kinetics of the receptor and depressing its activity. These results suggest that the two most promising derivatives have inhibitory actions and act as allosteric modulators. Many neurological diseases like epilepsy, ALS, and strokes are associated with overactivation of AMPA receptors. We can potentially synthesize a more potent neuroprotective drug to treat those neurological diseases, by understanding the most stable chemical interaction between the derivative and the receptor underlying the reported neuronal depressive properties., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Lavandula dentata L. and Origanum syriacum L. essential oils have numerous health benefits and properties, such as possessing common components with a variant degree of depressive actions in the central nervous system. We investigated the depressive property of these oils on AMPA receptors, which are responsible for most of the fast-excitatory neurotransmission in the CNS and play a critical role in synaptic plasticity. Since excessive activation of AMPARs has been linked to neurotoxicity leading to various pathologies, we hypothesize that these oils have a neuroprotective role by acting directly on the kinetics of AMPARs. Using Gas Chromatography-Mass Spectrometry (GC/MS) and patch-clamp electrophysiology, the essential oils of L. dentata flowers and O. syriacum leaves were characterized and the whole cell currents were measured with and without the administration of the oils onto HEK293 cells. The current study results showed that the biophysical properties of AMPA receptor subunits showed a decrease in desensitization rate of GluA1 and GluA2 homomers, using O. syriacum , while administering L. dentata oil decreased the desensitization rate of GluA1 and GluA2 homomers, as well as GluA1/2 heteromers. As for the deactivation rate, both oils slowed the deactivation kinetics of all AMPA receptor subunits. Intriguingly, between the two oils, the effect of desensitization and deactivation was of a greater significance for L. dentata oil than O. syriacum . Our data suggest that the two oils contain components that are essential to identify, as those active components underlie the oils' neuronal depressive properties reported, and to extract them to synthesize a potent neuroprotective drug to treat neurological diseases potentially.

Background: Transcatheter closure of patent foramen ovale (PFO) after cryptogenic stroke has long been a contentious issue. Herein, we pool aggregate data examining safety and efficacy of transcatheter closure of PFO compared with medical therapy following initial cryptogenic stroke., Methods: We searched for randomized clinical trials (RCT) that compared device closure with medical management and reported on subsequent stroke and adverse events. Stroke was considered as the primary efficacy endpoint, whereas bleeding and atrial fibrillation were considered primary safety endpoints. Data were pooled by the random effects model and I2 was used to assess heterogeneity., Results: A total of 5 RCT investigating 3630 patients met inclusion criteria. Pooled analysis revealed that device closure compared to medical management was associated with a significant reduction in stroke (RR=0.3, 95% CI=0.02-0.57). There was, however, a significant increase in atrial arrhythmias with device therapy (RR=4.8, 95% CI=2.2-10.7). We found no increase in bleeding (RR=0.80, 95% CI=0.5-1.4), death (RR=0.76, 95% CI=0.3-1.99) or "any adverse events" (RR=1.02, 95% CI=0.85-1.23) with device therapy. Sub-group analysis revealed that device closure significantly reduced the incidence of the composite primary endpoint among patients who had moderate to large shunt sizes (RR=0.22, 95% CI=0.02-0.42)., Conclusions: Transcatheter closure is associated with a significant reduction in the risk of stroke compared to medical management at the expense of an increased risk of atrial arrhythmias., (Copyright © 2018. Published by Elsevier Inc.)

The confinement of liquid mixtures in porous channels provides new insight into fluid ordering at the nanoscale. In this study, we address a phenomenon of microphase separation, which appears as a novel fascinating confinement effect for fully miscible binary liquids. We investigate the structure of tert-butanol-toluene mixtures confined in the straight and mono-dispersed cylindrical nanochannels of SBA-15 mesoporous silicates (D = 8.3 nm). Small angle neutron scattering experiments on samples with carefully designed isotopic compositions are performed to systematically vary the scattering length density of the different compounds and assess the radial concentration profile of the confined phases. The resulting modulation of the Bragg reflections of SBA-15 is compared with the predictions from different core-shell models, highlighting a molecular-scale phase-separated tubular structure with the tert-butanol forming a layer at the pore surface, surrounding a toluene-rich core. The present structural study suggests that the microphase separation phenomenon in confinement, which so far had only been reported for a smaller pore size (D = 3.65 nm) and a unique mixture composition, must be considered as a general phenomenon. It also highlights the strength of neutron scattering method with isotopic substitution, which is a unique experimental approach to reveal this phenomenon.

Drug-induced seizures are rare causes of hospital admissions (Coleman, 2004). Various classes of drugs are reported to induce seizures either directly, due to their epileptogenic potential or due to drug withdrawal effect, or indirectly, due to systemic and CNS-related side effects (Thundiyil et al., 2011). Midwakh is commonly used among young Emiratis. However, its CNS-related adverse effects are not well studied. We report seven consecutive patients with a history of seizures provoked by smoking midwakh and a negative workup for epilepsy. Six of these patients had no further seizures after they had agreed to discontinue smoking midwakh., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A 40-year-old male presented with headache, complete loss of vision in the right eye and decreased vision of the left eye. On examination, fundoscopy revealed secondary optic atrophy in the right eye and pale temporal disc in the left eye. MRI brain revealed a soft tissue mass arising from sphenoid sinus, eroding the overlying bone and extending into the sellar and parasellar regions up to the third ventricle. The MRI scan favoured the diagnosis of craniopharyngioma, most likely, while CT scan showed sellar floor erosion and calcification which favoured a pituitary lesion. The mass was also compressing the optic apparatus. The patient underwent excision biopsy through subfrontal approach. The histopathology report revealed it to be a chondrosarcoma. Chondrosarcoma is a rare malignant mesenchymal tumour of cartilageproducing cells; only 7% tend to involve craniocervical region. Maximal surgical resection followed by proton radiation therapy have clinically shown promising outcome.

A bilateral filter (BF) is a non-linear filter that has been proved to de-noise images without overrunning edges. Multi-slice computerized tomography (CT) may employ a BF to participate in dose reduction. This paper quantifies the role of the BF in achieving this objective on 1/2-dose CT. Two sets of CT images are acquired for the chest-pelvis at two different radiation doses. The BF was applied on the 1/2-dose CT images by use of various window sizes. Each time, a set of values of the BF range was fixed while the BF domain was modified. The goal was to observe the behavior of the BF on 1/2-dose CT images in comparison with full-dose CT images. The comparison was carried out by use of four co-occurrence matrix descriptors. Additionally, the peak signal-to-noise ratio (PSNR) and the mean square error (MSE) were reported. The study was applied to the sagittal, coronal, and axial CT views. The results showed that the impact of applying a BF varies among different CT views. The BF can retrieve only part of the signal being lost due to reduction of the radiation dose by one half. Yet, the BF improves the appearance of the 1/2-dose chest-pelvis CT examination. Thus, the BF can contribute to a 50% dose reduction. A procedure for employing the BF on CT machines is proposed. The results also showed that texture descriptors are similar to the PSNR and MSE in providing quantities for assessing medical image quality.

Unlabelled: This study aims at (1) Assessing trends in maternal mortality in kuwait (2) Define strategies for prevention., Methods: Retrospective analysis of maternal deaths that occurred among, 55,979 live births at a tertiary hospital, between 1980 and 2009., Results: There were 14 maternal deaths, and 55,979 live births, giving a maternal mortality rate of 25 per 100,000 live birth. In terms of decades maternal mortality declined from 54.8 in 1980-90 to 28.4 in 1990-2000 and continued to decline to 12.2 in 2000-2009. Thromboembolism (28.6%), Obstetric haemorrhage (21.5%) and Eclampsia (14.3%) were the leading causes of direct deaths. Cardiac disease is the most common cause of indirect deaths (14.3%) followed by H1N1 pneumonia 7.1%. Eclampsia contributed to 40% of deaths, only in the 1980s. Thromboembolism caused 28.6% of deaths, 50% of which were in the last 9 years. Indirect deaths from cardiomyopathies (66.7%) gained prominence in the 1990s. No deaths from puerperal sepsis were reported after the 1980s (14.3%)., Conclusions: Maternal mortality rates are decreasing significantly (p<0.01) at our institution over the last 29 years. Obstetric haemorrhage and thromboembolism remain important causes of maternal mortality. Substandard care was identified in 70% of Direct and 55% of indirect deaths.

Background: Premature mortality and disparities in morbidity observed in African-American men may be associated with factors in their social, economic, and built environments that may be especially influential during the transition to adulthood., Objective: To have young, African-American men from Los Angeles County identify and prioritize factors associated with their transition to manhood using photovoice methodology and pile-sorting exercises., Design: Qualitative study using community-based participatory research (CBPR) and photovoice, Participants: Twelve African-American men, ages 16-26 years, from Los Angeles County, California., Approach: We used CBPR principles to form a community advisory board (CAB) whose members defined goals for the partnered project, developed the protocols, and participated in data collection and analysis. Participants were given digital cameras to take 50-300 photographs over three months. Pile-sorting techniques were used to facilitate participants' identification and discussion of the themes in their photos and selected photos of the group. Pile-sorts of group photographs were analyzed using multidimensional scaling and hierarchical cluster analysis to systematically compare participants' themes and identify patterns of associations between sorted photographs. Sub-themes and related quotes were also elicited from the pile-sorting transcripts. The CAB and several study participants met periodically to develop dissemination strategies and design interventions informed by study findings., Key Results: Four dominant themes emerged during analysis: 1) Struggles face during the transition to manhood, 2) Sources of social support, 3) Role of sports, and 4) Views on Los Angeles lifestyle. The project led to the formation of a young men's group and community events featuring participants., Conclusions: CBPR and photovoice are effective methods to engage young, African-American men to identify and discuss factors affecting their transition to manhood, contextualize research findings, and participate in intervention development.

Objective: To identify the risk factors and study the incidence, indications and complications of emergency peripartum hysterectomy (EPH)., Materials and Methods: This was a retrospective case-control study. The cases consisted of all women who underwent EPH between January 1983 and January 2011. Two controls per case were randomly selected from the remaining deliveries by using a random number table. Case records were retrieved from the medical records., Results: Among 150,993 deliveries, there were 59 EPHs (cases), giving a rate of 0.390 per 1,000. Of the 59 cases, only 56 were analysed because 3 files were unavailable. These women were older (mean age 36 ± 5.7 vs. 22 ± 5.3 years, p < 0.01) and had delivered more than 1 child (p = 0.02). Thirty-seven (66%) cases had had previous caesarean sections (CSs) and the number of CSs in this group was greater than in the controls (21%, p < 0.01). More index cases had a history of atonic postpartum haemorrhage (46 vs. 4%, p < 0.001) and placenta praevia (34 vs. 4%, p < 0.01). More cases than controls were delivered by CS (73 vs. 29%; p = 0.003). The leading indications for EPH were haemorrhage due to uterine atony and placenta praevia. Independent risk factors were older age, multiparity, history of one or more CSs and placenta praevia. There were 2 maternal deaths from coagulopathy following massive obstetric haemorrhage. The main complications of EPH were febrile morbidity: 12 (21%), wound infection: 8 (14%) and bladder or ureteric injury: 8 (14%)., Conclusions: CSs, especially repeat CSs in women with placenta praevia and persistent uterine atony, significantly increased the risks of peripartum hysterectomy., (Copyright © 2011 S. Karger AG, Basel.)

The objective was to test the effect of nicotinic acid on apolipoprotein A-I (apo A-I) gene expression in hepatic (HepG2) and intestinal (Caco-2) cell lines. HepG2 and Caco-2 cells were treated with 0.1, 0.3, 1.0, 3.0, and 10 mmol/L of nicotinic acid; and apo A-I concentrations in conditioned media were measured with Western blots. Relative apo A-I messenger RNA (mRNA) levels, normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA, were measured with quantitative real-time polymerase chain reaction method. The nicotinic acid response element in the apo A-I promoter was identified using a series of apo A-I reporter plasmids containing deletion constructs of the promoter. In other experiments, HepG2 cells were also transfected with the apo A-I reporter plasmid and the hepatocyte nuclear factors 3α and β expression plasmids. The apo A-I levels in conditioned media from HepG2 cells, apo A-I mRNA levels, and apo A-I promoter activity increased significantly following treatment with 1.0, 3.0, and 10 mmol/L nicotinic acid. Nicotinic acid-induced promoter activity required a region of the apo A-I gene located between -170 and -186 base pairs. Exogenous overexpression of the hepatocyte nuclear factors 3α and β had no additive effect on apo A-I promoter. Apolipoprotein A-I concentrations in conditioned media and the apo A-I promoter activity were also significantly increased in Caco-2 intestinal cells. Nicotinic acid may increase apo A-I protein synthesis in the liver and small intestine. Induction of apo A-I gene by nicotinic acid requires a nicotinic acid responsive element in the apo A-I promoter.

Aims: Ligands for the vitamin D receptor (VDR) regulate apolipoprotein A-I (apo A-I) gene expression in a tissue-specific manner. The vitamin D metabolite 24, 25-dihydroxycholecalciferol (24, 25-(OH)(2)D(3)) has been shown to possess unique biological effects. To determine if 24, 25-(OH)(2)D(3) modulates apo A-I gene expression, HepG2 hepatocytes and Caco-2 intestinal cells were treated with 24, 25-(OH)(2)D(3) or its precursor 25-OHD(3)., Main Methods: Apo A-I protein levels and mRNA levels were measured by Western and Northern blotting, respectively. Changes in apo A-I promoter activity were measured using the chlorampenicol acetytransferase assay., Key Findings: Treatment with 24, 25-(OH)(2)D(3), but not 25-OHD(3), inhibited apo A-I secretion in HepG2 and Caco-2 cells and apo A-I mRNA levels and apo A-I promoter activity in HepG2 cells. To determine if 24, 25-(OH)(2)D(3) represses apo A-I gene expression through site A, the nuclear receptor binding element that is essential for VDRs effects on apo A-I gene expression, HepG2 cells were transfected with plasmids containing or lacking site A. While the site A-containing plasmid was suppressed by 24, 25-(OH)(2)D(3), the plasmid lacking site A was not. Likewise, treatment with 24, 25-(OH)(2)D(3) suppressed reporter gene expression in cells transfected with a plasmid containing site A in front of a heterologous promoter. Finally, antisense-mediated VDR depletion failed to reverse the silencing effects of 24, 25-(OH)(2)D(3) on apo A-I expression., Significance: These results suggest that the vitamin D metabolite 24, 25-(OH)(2)D(3) is an endogenous regulator of apo A-I synthesis through a VDR-independent signaling mechanism., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: Hyperglycemia-induced endothelial cell dysfunction in vascular disease can occur due to increased oxidative stress and a concomitant increase in endoplasmic reticulum (ER) stress. To investigate whether these cellular stresses are independent or causally linked, we determined whether or not specific glycolytic intermediates that induce oxidative stress also induce ER stress., Methods: Human umbilical vein endothelial cells were treated with dextrose, partially metabolizable (e.g., fructose and galactose) and non-metabolizable sugars (e.g., 3-O-methyglucose), and various intermediates of the glycolytic and tricarboxylic acid pathways. Activation of the unfolded protein response and subsequent generation of ER stress was measured by the ER stress-responsive alkaline phosphatase method, and superoxide (SO) generation was measured using the hydro-ethidene-fluorescence method. The mitochondrial origin of the SO and the generation of ER stress by dextrose and the intermediate metabolites were confirmed with experiments using allopurinol and diphenyleneiodonium chloride to block SO generation by xanthine oxidase and nicotinamide adenosine dinucleotide phosphate oxidase, respectively., Results: Although ER stress could be induced by glycolytic intermediates up to and including pyruvate, the SO generation occurred in the presence of glycolytic and mitochondrial metabolites., Conclusion: Although the mitochondria are the site of signals generated by dextrose to initiate oxidative stress, the dextrose-induced ER stress, unlike SO generation, does not require pyruvate oxidation in the mitochondria., (Published by Elsevier Inc.)

Aim: Hyperglycemia-induced endothelial cell dysfunction can be the result of increased oxidative stress and concomitant increase in endoplasmic reticulum (ER) stress. To test the extent of coupling between these two stresses, the effect of antioxidant vitamins on glucose-induced oxidative stress and ER stress in endothelial cells were studied., Methods: Human umbilical vein endothelial cells (HUVEC) were treated with physiological (5.5mM) or supra-physiological (27.5mM) dextrose concentrations, and ER stress and oxidative stress were measured. Additional experiments were carried out in HUVEC over-expressing exogenous glucose transporter-1 (Glut-1) and treated with 5.5mM dextrose., Results: Supra-physiological dextrose concentrations increased both ER stress and oxidative stress. However, while oxidative stress could be effectively inhibited with alpha-tocopherol and ascorbic acid, these antioxidants had no effect on ER stress. Increasing intracellular glucose levels by exogenous expression of Glut-1 in endothelial cells also increased oxidative stress and ER stress. Whereas the oxidative stress in these cells was reduced with alpha-tocopherol and ascorbic acid and dimethylsulfoxide, the ER stress could not be ameliorated with alpha-tocopherol and ascorbic acid., Conclusions: These results indicate that ER stress can be uncoupled from oxidative stress and antioxidants can ameliorate the latter without altering the ER stress induced by hyperglycemia., (Published by Elsevier Ireland Ltd.)

Background: The purpose of the current study was to characterize the outcomes of patients with metastatic triple-negative breast cancers, including the risk and clinical consequences of central nervous system (CNS) recurrence., Methods: Using pharmacy and pathology records, a study group of 116 patients who were treated for metastatic triple-negative breast cancer at Dana-Farber Cancer Institute between January 2000 and June 2006 was identified., Results: The median survival from time of metastatic diagnosis was 13.3 months. Sixteen patients (14%) were diagnosed with CNS involvement at the time of initial metastatic diagnosis; overall, 46% of patients were diagnosed with CNS metastases before death. The median survival after a diagnosis of CNS metastasis was 4.9 months. The age-adjusted and race-adjusted rate of death for patients whose first presentation included a CNS metastasis was 3.4 times (95% confidence interval, 1.9-6.1 times) that of patients without a CNS lesion at the time of first metastatic presentation. Of the 53 patients who developed brain metastases, only 3 patients were judged to have stable or responsive systemic disease in the face of progressive CNS disease at the last follow-up before death., Conclusions: Triple-negative breast cancer is associated with poor survival after recurrence. CNS recurrence is common, but death as a direct consequence of CNS progression in the setting of controlled systemic disease is uncommon. Thus, it does not appear that the high rate of CNS involvement is because of a sanctuary effect, but rather is due to the lack of effective therapies in general for this aggressive subtype of breast cancer. New treatment strategies are needed.

In prodrug-activated ("suicide") gene therapy, tumor cells are transfected with the gene for an enzyme that converts an inactive prodrug, such as ganciclovir (GCV), to a toxic compound. Transfected cells are killed on administration of GCV, as also are untransfected "bystander" cells. The ability of the dendritic cell stimulatory cytokine Flt3 ligand (Flt3-L) to modulate prodrug-activated gene therapy has been investigated. Transfectants of the murine colon carcinoma MC26 were generated expressing soluble (FLS) and membrane-bound forms of Flt3-L. They were inoculated together with wild-type MC26 cells and cells expressing herpes simplex virus-1 (HSV1) thymidine kinase into BALB/c mice, which were then administered GCV. Expression of Flt3-L or FLS prevented regrowth of tumor in most mice, which was comparable to the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), while tumors recurred in all mice receiving "suicide" gene therapy alone. Recurring tumor cells were resistant to direct killing by GCV but sensitive to "bystander" killing in vitro. Mice without tumor recurrence were rechallenged with unmodified MC26 cells. Of those mice given transfectants expressing GM-CSF, Flt3-L, or FLS, approximately 50% were immune to rechallenge. These mice also showed cytotoxic and proliferative responses to MC26 cells. These experiments show that both soluble and membrane-bound forms of Flt3-L were able to induce a protective immune response to colon carcinoma cells in a fashion similar to GM-CSF.