MDM4 Isoform Expression in Melanoma Supports an Oncogenic Role for MDM4-A.

The p53 tumor suppressor integrates upstream signals such as DNA damage and active oncogenes to initiate cell cycle arrest or apoptosis. This response is critical to halting inappropriate growth signals. As such, p53 activity is lost in cancer. In melanoma, however, the p53 gene is intact in a reported 94% of human cases. Rather than direct mutation, p53 is held inactive through interaction with inhibitory proteins. Here, we examine the expression of the two primary inhibitors of p53, MDM2 and MDM4, in genomic databases and biopsy specimens. We find that MDM4 is frequently overexpressed. Moreover, changes in splicing of MDM4 occur frequently and early in melanomagenesis. These changes in splicing must be considered in the design of therapeutic inhibitors of the MDM2/4 proteins for melanoma.

Measuring the appropriateness of carbamazepine and valproic acid prescribing and utilization using a newly implemented online system in the Tabuk Region of Saudi Arabia.

Epilepsy is a common neurologic disorder, which is efficiently treated with carbamazepine and valproic acid. Moreover, Saudi Ministry of Health implemented a new E-system for Poison Control Centers called Awtar to enhance technology utilization in ensuring patients' satisfaction and to improve treatment outcomes. Therefore, we conducted this study to assess appropriateness of indication of requests and therapeutic levels of carbamazepine and valproic acid in Tabuk area, North West Saudi Arabia. This is a retrospective observational study conducted in Poison Control & Forensic Chemistry Center, Tabuk, Saudi Arabia. Patients' data were obtained for years 2018 and 2019. The blood levels of carbamazepine and valproic acid were measured by Therapeutic Drug Monitoring (TDM) Unit. We selected patients treated with either valproic acid or carbamazepine alone without any history of drug allergy. Data of 264 patients were extracted from Awtar E-system. Serum carbamazepine levels were within therapeutic range in 114 patients (75.50%), above-therapeutic range in 13 patients (8.61%) and sub-therapeutic levels in 24 patients (15.89%). Regarding serum valproic acid, it is within therapeutic range in 62 patients (54.87%), above-therapeutic range in 11 patients (9.73%) and sub-therapeutic levels in 40 patients (35.40%). In conclusion, this study gives information about partial appropriateness of usage of carbamazepine and low level of appropriateness of valproic acid. However, more efforts are needed to improve results of appropriateness of indication of antiepileptic drugs.

Effect of transcranial direct current stimulation on the number of smoked cigarettes in tobacco smokers.

BACKGROUND: Recent studies reported that transcranial direct current stimulation (tDCS) applied over the dorsolateral prefrontal cortex (DLPFC) reduced craving and cigarette smoking. We aimed to evaluate whether 3 sessions of tDCS over the DLPFC modulate cigarette smoking which is a critical factor in tobacco smokers. METHODS: In a double-blinded, sham-controlled, parallel experimental study, 22 participants who wished to quit smoking received tDCS with the cathodal over the right DLPFC and anodal over the left DLPFC based on the 10-20 EEG international system (F4, F3) at an intensity of 1.5 mA for 20 minutes during three consecutive days. For sham stimulation, the electrodes placement was the same as for the active stimulation. RESULTS: For the short time interval (8 days after the end of the tDCS regimen), the number of smoked cigarettes was reduced similarly in the active and sham groups (p < 0.001). Also, at the long time-interval (4 months after the end of the tDCS regimen) as compared to pre-tDCS, there was no significant difference in the number of smoked cigarettes in the active (p = 0.806) or the sham (p = 0.573) groups. Overall, there were no statistically significant differences between the active and sham tDCS groups on cigarette smoking. CONCLUSION: These findings suggested that 3 sessions of tDCS over the right and left DLPFC may reduce number of smoked cigarettes for short-time period but might not be significantly more effective than sham to decrease cigarette smoking.

High-power blue superluminescent diode for high CRI lighting and high-speed visible light communication.

We demonstrated a high-power (474 mW) blue superluminescent diode (SLD) on c-plane GaN-substrate for speckle-free solid-state lighting (SSL), and high-speed visible light communication (VLC) link. The device, emitting at 442 nm, showed a large spectral bandwidth of 6.5 nm at an optical power of 105 mW. By integrating a YAG-phosphor-plate to the SLD, a CRI of 85.1 and CCT of 3392 K were measured, thus suitable for solid-state lighting. The SLD shows a relatively large 3-dB modulation bandwidth of >400 MHz, while a record high data rate of 1.45 Gigabit-per-second (Gbps) link has been achieved below forward-error correction (FEC) limit under non-return-to-zero on-off keying (NRZ-OOK) modulation scheme. Our results suggest that SLD is a promising alternative for simultaneous speckle-free white lighting and Gbps data communication dual functionalities.

Effect of Smoking on Cognitive Functioning in Young Saudi Adults.

BACKGROUND Smoking is the predominant form of tobacco consumption and is growing worldwide, particularly in the younger generation in the Middle-East. We aimed to determine the effects of tobacco smoking on cognitive functions among young Saudi adults. MATERIAL AND METHODS We recruited a group of cigarette smokers (N=22) and a group of controls (non-smokers) (N=30) from apparently healthy male volunteers aged 18-29 years. Cognitive function was assessed by using the Cambridge Neuropsychological Automated Battery (CANTAB). The cognitive functions outcome variables were the response time (attention-switching task [AST]), and the percentage of correct response (pattern recognition memory [PRM] task). Clinical, demographic, blood markers (brain-derived neurotrophic factor (BDNF) and apolipoprotein E) were assessed between groups. RESULTS The 2 groups were matched for age and educational status. In comparison to the control group, smokers showed significant cognitive impairments in AST-Latency (p=0.001), AST-Congruent (p=0.001), and AST-Incongruent condition (p=0.001). There was not significant difference in BDNF APOE serum level between the 2 groups. CONCLUSIONS These results indicate that attention and alertness were significantly impaired in smokers compared to non-smokers.

Ultrabroad linewidth orange-emitting nanowires LED for high CRI laser-based white lighting and gigahertz communications.

Group-III-nitride laser diode (LD)-based solid-state lighting device has been demonstrated to be droop-free compared to light-emitting diodes (LEDs), and highly energy-efficient compared to that of the traditional incandescent and fluorescent white light systems. The YAG:Ce3+ phosphor used in LD-based solid-state lighting, however, is associated with rapid degradation issue. An alternate phosphor/LD architecture, which is capable of sustaining high temperature, high power density, while still intensity- and bandwidth-tunable for high color-quality remained unexplored. In this paper, we present for the first time, the proof-of-concept of the generation of high-quality white light using an InGaN-based orange nanowires (NWs) LED grown on silicon, in conjunction with a blue LD, and in place of the compound-phosphor. By changing the relative intensities of the ultrabroad linewidth orange and narrow-linewidth blue components, our LED/LD device architecture achieved correlated color temperature (CCT) ranging from 3000 K to above 6000K with color rendering index (CRI) values reaching 83.1, a value unsurpassed by the YAG-phosphor/blue-LD counterpart. The white-light wireless communications was implemented using the blue LD through on-off keying (OOK) modulation to obtain a data rate of 1.06 Gbps. We therefore achieved the best of both worlds when orange-emitting NWs LED are utilized as "active-phosphor", while blue LD is used for both color mixing and optical wireless communications.

Comparison of 22G reverse-beveled versus standard needle for endoscopic ultrasound-guided sampling of solid pancreatic lesions.

OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) using standard needles has a high diagnostic value in the evaluation of solid pancreatic masses. Fenestrated needles have been developed to improve the quality of EUS-guided tissue sampling by providing core biopsies (FNB). METHODS: Patients with solid pancreatic masses of >2 cm were prospectively included in our study and randomized to receive EUS sampling, using either a standard 22G FNA or a 22G Procore® FNB needle. The main study endpoint was the number of needle passes required to obtain a diagnosis in more than 90% of cases. RESULTS: We included 100 patients (male = 63, female = 37; mean age = 68.4 years) in our study. We found that 88% of the lesions were malignant, with a mean size of 32 mm. A sample adequate for diagnosis was obtained in more than 90% of cases after the second needle pass in the FNB group, versus the third needle pass in the FNA group. Slide cellularity and presence of tissue microfragments were significantly higher in the FNB group. Sensitivity for the diagnosis of malignancy was 88.4% versus 97.8% for the EUS-FNA and EUS-FNB group, respectively, while specificity for both techniques was 100%. No complications were recorded. CONCLUSIONS: Although the accuracy of both needle types for proving malignancy was similar, a lower number of passes was required with the FNB needles to achieve the same contributive sample rate as with the FNA needles. FNB also improved the histopathological quality of specimens, suggesting an overall superiority of FNB sampling.

Diagnostic impact of routine colonoscopy following acute diverticulitis: A multicenter study in 808 patients and controls.

BACKGROUND: The diagnosis of acute diverticulitis is mainly based on clinical, biological and computed tomography (CT)-scan findings. Elective colonoscopy is recommended after medical treatment, to rule out another diagnosis and to detect associated conditions; however, the relevance of this recommendation has been questioned. PATIENTS AND METHODS: Between January 2005 and December 2011, we retrospectively identified in three referral centers the consecutive patients whom underwent a colonoscopy after the medical treatment of a CT scan-proven acute diverticulitis episode. We excluded from the analysis patients with haematochezia or recent change in bowel habits. Sex and age-matched asymptomatic patients undergoing a screening colonoscopy were chosen as a control group. We collected and compared the results of colonoscopy and histological findings in both groups. RESULTS: We matched 404 patients whom underwent a colonoscopy after an episode of acute diverticulitis with 404 control patients. Their mean age was 60.9 years, with 59% being women. Colorectal adenoma, advanced adenoma and cancer detection rates in acute diverticulitis patients were 12.1%, 2.7% and 0.25%, respectively; versus 14.6% (p = 0.35), 6.7% (p = 0.01) and 0.25% respectively, in control patients. CONCLUSIONS: Diagnosis rates for adenomas and for colorectal cancer during a colonoscopy scheduled after acute diverticulitis were similar than those of control patients undergoing a screening colonoscopy, while the detection rate of advanced adenomas was lower. We suggest that colonoscopy should be indicated only in selected patients, i.e. those presenting with reasonable doubt on initial CT-scan, those with alarm symptoms, and those with identified risk factors for colorectal cancer.

Obscure gastrointestinal bleeding: preliminary comparison of 64-section CT enteroclysis with video capsule endoscopy.

OBJECTIVE: To retrospectively compare the diagnostic capabilities of 64-section CT enteroclysis with those of video capsule endoscopy (VCE) to elucidate the cause of obscure gastrointestinal bleeding. METHODS: Thirty-two patients who had 64-section CT enteroclysis and VCE because of obscure gastrointestinal bleeding were included. Imaging findings were compared with those obtained at double balloon endoscopy, surgery and histopathological analysis, which were used as a standard of reference. RESULTS: Concordant findings were found in 22 patients (22/32; 69%), including normal findings (n=13), tumours (n=7), lymphangiectasia (n=1) and inflammation (n=1), and discrepancies in 10 patients (10/32; 31%), including ulcers (n=3), angioectasias (n=2), tumours (n=2) and normal findings (n=3). No statistical difference in the proportions of abnormal findings between 64-section CT enteroclysis (11/32; 34%) and VCE (17/32, 53%) (P=0.207) was found. However, 64-section CT enteroclysis helped identify tumours not detected at VCE (n=2) and definitely excluded suspected tumours (n=3) because of bulges at VCE. Conversely, VCE showed ulcers (n=3) and angioectasias (n=2) which were not visible at 64-section CT enteroclysis. CONCLUSION: Our results suggest that 64-section CT enteroclysis and VCE have similar overall diagnostic yields in patients with obscure gastrointestinal bleeding. However, the two techniques are complementary in this specific population.