Hallervorden-Spatz disease

We describe fluid attenuated inversion recovery sequence MRI and proton MR spectroscopy appearances of the brain in a 7-year old Saudi boy who presented with the clinical features of Hallervorden-Spatz disease to King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia.     

Autophagy, cell death and sustained senescence arrest in B16/F10 melanoma cells and HCT-116 colon carcinoma cells in response to the novel microtubule poison, JG-03-14

Purpose

Previous studies have shown that the novel microtubule poison, JG-03-14, which binds to the colchicine binding site of tubulin, has the capacity to kill breast tumor cells primarily through the promotion of autophagy. The current work was designed to determine whether autophagy was, in fact, the primary mode of action as well as susceptibility to JG-03-14 in two additional tumor cell models, the B16/F10 murine melanoma cell line and the HCT-116 human colon cancer cell line.

Methods

Drug cytotoxicity was monitored based on viable cell number and clonogenic survival. Apoptosis was assessed by DAPI staining, the TUNEL assay and/or FACS analysis. Autophagy was monitored based on staining with acridine orange, redistribution and punctuation of RFP-LC3 and electron microscopy as well as p62 degradation. Senescence was evaluated based on β-galactosidase staining and alterations in cell morphology. Drug effects were also evaluated in a murine model of B16/F10 cells that localizes to the lungs while peripheral neuropathy was assessed by three complementary behavioral assays.

Results

Both HCT-116 colon cancer cells and B16/F10 melanoma cells were sensitive to JG-03-14 in that the drug demonstrated tumor cell killing. However, there was minimal induction of apoptosis. In contrast, there was clear evidence for autophagy and autophagic flux while the residual surviving cells appeared to be in a state of irreversible senescence. Inhibition of drug-induced autophagy in either the melanoma cells or the colon carcinoma cells was only slightly protective as the cells instead died by apoptosis. JG-03-14 reduced the size of tumor nodules in mice lungs; furthermore, the drug did not promote peripheral neuropathy.

Conclusions

Taken together with evidence for its actions as a vascular disrupting agent, these observations support the potential utility of JG-03-14 to effectively treat malignancies that might be resistant to conventional chemotherapy through evasion of apoptosis.     

The prevalence of non-syndromic orofacial clefts and associated congenital heart diseases of a tertiary hospital in Riyadh,Saudi Arabia

BackgroundOrofacial clefts are considered one of the most common birth defects and are frequently associated with other malformations. Congenital heart disease is one of the most prevalent congenital malformation.ObjectiveTo investigate the prevalence of congenital heart diseases associated with non-syndromic orofacial clefts in the Saudi population.MethodsElectronic files of non-syndromic orofacial cleft patients who visited the Oral and Maxillofacial Surgery Department in King Abdulaziz Medical City of Riyadh, Saudi Arabia from January 2015 to December 2018 were retrospectively reviewed. Data were recorded in an excel sheet and analyzed using SPSS via frequency tests.ResultsIn the cleft children identified, the prevalence of non-syndromic orofacial clefts was (77%). Orofacial clefts showed a male predominance (62%). The most common orofacial phenotype was unilateral cleft lip and palate (34%). The prevalence of associated congenital malformations with orofacial clefts was (41%). The most prevalent congenital malformation was congenital heart disease (35%), mainly found in unilateral cleft lip and palate patients (33%). The prevalence of associated congenital heart disease with orofacial clefts was (19%). The most frequent type of congenital heart disease was atrial septal defect (37%).ConclusionThis study highlights the recognition of the associated congenital heart disease with non-syndromic orofacial cleft patients. Global screening protocols designed for newborns with non-syndromic orofacial cleft are needed to eliminate late diagnosis of critical congenital heart diseases which might present operative risks of anesthesia and/or surgical procedures.     

Normative Reference Values and Validity for the 30-Second Chair-Stand Test in Healthy Young Adults

BackgroundClinicians often use physical performance tests (PPT) to measure performance measures in sports since they are easy to administer, portable, and cost-efficient. However, PPT often lack good or known psychometric properties. Perhaps, the 30-second chair-stand test (30CST) would be a good functional test in athletic populations as it has been shown to demonstrate good psychometric properties in older adults.Hypothesis/PurposeThe purpose of this study was to determine normative values for and concurrent, convergent and discriminative validity of 30CST for healthy young adults aged 19-35 years.Study DesignCross-sectionalMethodsEighty-one participants completed this study. All participants performed two trials of 30CST, 5-times sit-to-stand (5xSTS), and lateral step-up test (LSUT). Investigators used the International Physical Activity Questionnaire Leisure Domain (LD-IPAQ) to divide participants into insufficiently or sufficiently active groups based on the weekly metabolic equivalent of task per the Physical Activity Guidelines for Americans.ResultsParticipants (Mean + SD age, 25.1 ± 3.4 years; body height, 1.71 ± 0.09 m; body mass, 72.6 ± 16.1 kg; females 47) performed an average of 33.0±5.4 30CST repetitions. The 30CST performance was negatively associated with 5xSTS (r=-0.79 p=0.01) and positively associated with LSUT performances (r=0.51, p=0.01) when using Pearson correlations. In addition, the sufficiently active group performed significantly greater 30CST repetitions than the insufficiently active group (mean difference = 2.5; p=0.04).ConclusionsIn addition to finding a reference value for 30CST performance in young adults, investigators found that the 30CST displayed concurrent and convergent validity in assessing functional lower extremity (LE) muscle strength and discriminated between those with sufficient and insufficient physical activity levels. Training and rehabilitation professionals could use the 30CST for testing functional LE muscle strength for athletes in pre-season or during rehabilitation. Future investigators should perform studies to determine if 30CST predicts sport performance.Level of EvidenceLevel 2     

Assessment of tear film parameters post-treatment with commercial eyelid cleaning wipes: a pilot study

AIM: To investigate the short-term effects of commercially available eyelid-cleaning wipes on film parameters. METHODS: This study enrolled 48 healthy participants aged 20-35y (both males and females). Clinical assessment included the Ocular Surface Disease Index (OSDI) questionnaire, non-invasive tear break-up time (NITBUT), tear meniscus height (TMH), and lipid layer pattern (LLP). Based on these initial results, participants were categorized as either non-dry eye or dry eye. Participants in each group were randomly allocated to either Blephaclean® or Systane® treatments. Changes in NITBUT, TMH, and LLP levels before and after lid wipe treatment were assessed. RESULTS: The dry eye group exhibited significantly higher OSDI scores and lower NITBUT and TMH levels than in the non-dry eye group (P<0.001). Following the application of eyelid wipes (Systane® wipes), dry eye subjects experienced a significant improvement in NITBUT levels (P=0.0014) compared to the non-dry eye individuals. Although the remaining participants showed a marginal increase in TMH and NITBUT levels, these changes did not achieve statistical significance (P>0.05). Similarly, the LLP levels were significantly improved with Systane® (P<0.001) post-treatment compared to individuals in the non-dry eye group. However, the dry eye subjects showed higher post-treatment LLP levels than the untreated group (P<0.02). CONCLUSION: The short-term effects of Systane® eyelid wipes on tear film parameters suggest their effectiveness in dry eye disease. Nonetheless, further exploration of their long-term impact is essential to justify their cost effectiveness and efficacy in treating both aqueous deficiency and evaporative dryness.     

Angiotensin converting enzyme inhibitors and risk of lung cancer: A systematic review and meta-analysis

Background:We performed a meta-analysis to determine whether a consistent relationship exists between the use of angiotensin converting enzyme inhibitors (ACEIs) and the risk of lung cancer. Accordingly, we summarized and reviewed previously published quantitative studies.Methods:Eligible studies with reference lists published before June 1st, 2019 were obtained from searching several databases. Random effects’ models were used to summarize the overall estimate of the multivariate adjusted odds ratios (ORs) with 95% confidence intervals (CIs)Results:Thirteen observational studies involving 458,686 ACEI users were included in the analysis, Overall, pooled risk ratios indicate that ACEIs use was not a risk factor for lung cancer (RR 0.982, 95% C.I. 0.873 – 1.104; P = .76). There was significant heterogeneity between the studies (Q = 52.54; P < .001; I2 = 86.07). There was no significant association between ACEIs use and lung cancer in studies with over five years of ACEIs exposure (RR 0.95, 95% C.I. 0.75 – 1.20; P = .70); and ≤ 5years of exposure to ACEIs (RR 0.98, 95% C.I. 0.83 – 1.15; P = .77). There were no statistically significant differences in the pooled risk ratio obtained according to the study design (Q = 0.65; P = .723) and the comparator regimen (Q = 3.37; P = .19).Conclusions:The use of ACEIs was not associated with an increased risk of lung cancer. Nevertheless, well-designed observational studies with different ethnic populations are still needed to evaluate the long-term (over 10 years) association between ACEIs use and lung cancer.     

Effect of high-power Nd:YAG laser on the growth of Staphylococcus aureus and Pseudomonas aeruginosa: an experimental study

[Purpose] The aim of this study was to evaluate the effect of high-power Nd:YAG laser on Staphylococcus aureus and Pseudomonas aeruginosa bacterial growth. [Materials and Methods] Seven samples of S. aureus and seven samples of P. aeruginosa were prepared in the microbiology lab, one used as a control sample and the remaining six samples used as experimental samples, which were irradiated by a high-power laser (LASERSIX ME, 15W) with a total dose of 500 and 700 J. The primary measure was the semi-qualitative assessment of turbidity and bacterial count; the turbidity was assessed 24 h after laser application. [Results] There was a significant decrease in turbidity in all experimental samples of S. aureus and P. aeruginosa after 24 h of high-power laser application for 500 and 700 J and a significant decrease in the colony-forming unit (CFU) value in both types, and there were no significant differences in turbidity and CFU when comparing 500 and 700 J. [Conclusion] A high power Nd:YAG laser was found to be an effective modality for inhibition of S. aureus and P. aeruginosa growth.Key words: High-power-laser, Staphylococcus aureus, Pseudomonas aeruginosa