Vitamin D Deficiency in Children and Adolescents in Saudi Arabia: A Systematic Review.

Vitamin D deficiency is a globally recognized health concern, with particular prominence in specific geographies and demographics. Saudi Arabia, with its unique climatic conditions and cultural practices, has been under scrutiny regarding the prevalence of this deficiency, especially among children and adolescents. This systematic review aimed to assess the prevalence of vitamin D deficiency among children and adolescents in Saudi Arabia by compiling and analyzing various studies to offer a comprehensive view of the situation. The comprehensive web search encompassed a range of databases, including Google Scholar and PubMed, to gather studies published between 2012 and 2023. An analysis was conducted on seven studies, totaling 2,429 participants, with each study focusing on various aspects, regions, and cohorts within Saudi Arabia. These studies employed different methodologies, ranging from cross-sectional surveys to randomized clinical trials. The review unveiled an alarming prevalence of vitamin D deficiency in the studied population. On average, around 81.1% of children and adolescents showcased inadequate vitamin D levels. Specific vulnerable groups, such as those with Type 1 diabetes mellitus or asthma, had pronounced deficiencies. Factors influencing these levels ranged from dietary habits, sun exposure, physical activity, and socioeconomic parameters. The compelling evidence from the studies underscores a consistent health issue among the pediatric population in Saudi Arabia that the overwhelming majority of Saudi children and adolescents lack adequate vitamin D. Addressing this widespread deficiency needs a multifaceted approach. Implementing policies that support vitamin D food fortification, encouraging routine screenings, and launching public awareness campaigns about safe sun exposure and diet can play a transformative role in this health crisis.

Antitumor Effect of Bleomycin Nanoaerosol in Murine Carcinoma Model.

Bleomycin, which is widely used as an antitumor agent, possesses serious adverse effects such as pulmonary toxicity. Local nanoaerosol deposition for lung cancer treatment is a promising alternative to drug delivery to lung lesions. The aim of this work is to test the hypothesis that bleomycin nanoaerosol can be effectively used to treat multiple lung metastases. To obtain bleomycin nanoaerosol, an aerosol generator based on electrospray of a solution of a nonvolatile substance with gas-phase neutralization of charged aerosol particles was used. Lung metastases in murine Lewis lung carcinoma and B16 melanoma animal models were counted. The effect of inhaled bleomycin nanoparticles on the number and volume of metastases, as well as pulmonary side effects, was investigated. Using a mouse exposure chamber, the dose-dependent effect of inhaled bleomycin on tumor volume was evaluated in comparison with intraperitoneal administration. Bleomycin nanoaerosol reduced the volume of metastases and produced a higher antitumor effect at much lower doses. It has been established that long-term exposure to nanoaerosol with a low dose of bleomycin is capable of suppressing cancer cell growth. The treatment was well tolerated. In the lungs, minor changes were found in the form of focal-diffuse infiltration of the lung parenchyma.

Antiproliferative, proapoptotic, and tumor-suppressing effects of the novel anticancer agent alsevirone in prostate cancer cells and xenografts.

The aim of this study was to explore the mechanisms of action of alsevirone in prostate cancer (PC) in vitro and in vivo: CYP17A1 inhibition, cytotoxic, apoptotic, and antitumor effects in comparison with abiraterone. The CYP17A1-inhibitory activity was investigated in rat testicular microsomes using high-performance liquid chromatography. Testosterone levels were evaluated using enzyme-linked immunoassay. IC50 values were calculated for PC3, DU-145, LNCaP, and 22Rv1 cells using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test. The antitumor effect in vivo was studied in DU-145 and 22Rv1 subcutaneous xenografts in Balb/c nude mice. Alsevirone reduced the CYP17A1-inhibitory activity by 98% ± 0.2%. A statistically significant reduction in the testosterone concentration in murine blood was recorded after the 7th administration of 300 mg/kg alsevirone at 0.31 ± 0.03 ng/ml (p < .001) versus 0.98 ± 0.22 ng/ml (p = .392) after abiraterone administration and 1.52 ± 0.49 ng/ml in control animals. Alsevirone was more cytotoxic than abiraterone in DU-145, LNCaP, and 22Rv1 cells, with IC50 values of 23.80 ± 1.18 versus 151.43 ± 23.70 µM, 22.87 ± 0.54 versus 28.80 ± 1.61 µM, and 35.86 ± 5.63 versus 109.87 ± 35.15 µM, respectively. Alsevirone and abiraterone significantly increased annexin V-positive, caspase 3/7-positive, and activated Bcl-2-positive cells. In 22Rv1 xenografts, alsevirone 300 mg/kg × 10/24 h per os inhibited tumor growth: on Day 9 of treatment, tumor growth inhibition = 59% (p = .022). Thus, alsevirone demonstrated significant antitumor activity associated with CYP17A1 inhibition, apoptosis in PC cells, and testosterone reduction.

Novel Copper-Containing Cytotoxic Agents Based on 2-Thioxoimidazolones.

A series of 73 ligands and 73 of their Cu+2 and Cu+1 copper complexes with different geometries, oxidation states of the metal, and redox activities were synthesized and characterized. The aim of the study was to establish the structure-activity relationship within a series of analogues with different substituents at the N(3) position, which govern the redox potentials of the Cu+2/Cu+1 redox couples, ROS generation ability, and intracellular accumulation. Possible cytotoxicity mechanisms, such as DNA damage, DNA intercalation, telomerase inhibition, and apoptosis induction, have been investigated. ROS formation in MCF-7 cells and three-dimensional (3D) spheroids was proven using the Pt-nanoelectrode. Drug accumulation and ROS formation at 40-60 µm spheroid depths were found to be the key factors for the drug efficacy in the 3D tumor model, governed by the Cu+2/Cu+1 redox potential. A nontoxic in vivo single-dose evaluation for two binuclear mixed-valence Cu+1/Cu+2 redox-active coordination compounds, 72k and 61k, was conducted.

Characterization of Neopestalotiopsis Species Associated with Mango Grey Leaf Spot Disease in Sinaloa, Mexico.

Mango is one of the most popular and nutritious fruits in the world and Mexico is the world's largest exporter. There are many diseases that directly affect fruit yield and quality. During the period 2016-2017, leaves with grey leaf spots were collected from 28 commercial mango orchards distributed in two main production areas in Sinaloa State of Mexico, and 50 Neopestalotiopsis isolates were obtained. Fungal identification of 20 representative isolates was performed using morphological characterization and phylogenetic analysis based on the internal transcribed spacer (ITS) region of ribosomal DNA, part of the translation elongation factor 1-alpha (TEF) and the ß-tubulin (TUB) genes. Phylogenetic analysis indicated that the 20 isolates from this study formed four consistent groups, however, overall tree topologies do not consistently provide a stable and sufficient resolution. Therefore, even though morphological and phylogenetic separation is evident, these isolates were not assigned to any new taxa and were tentatively placed into four clades (clades A-D). Pathogenicity tests on detached mango leaves of cv. Kent showed that the 20 isolates that belong to the four Neopestalotiopsis clades from this study and induce lesions on mango leaves. This is the first report of species of Neopestalotiopsis causing mango grey leaf spot disease in Mexico.

In Silico Approach to Investigate the Structural and Functional Attributes of Familial Hypercholesterolemia Variants Reported in the Saudi Population.

Familial hypercholesterolemia (FH) is a metabolic disorder that leads primarily to premature cardiovascular diseases, the main cause of mortality in Saudi Arabia (SA). FH is underreported and underdiagnosed in SA with statistical evidence of high expected prevalence in such a consanguineous community. Lacking knowledge of which and how these alterations are actually impacting lipid metabolism is one of the main reasons why FH is insufficiently diagnosed in the region. The aim of this study was to develop a fast prediction approach using an integrated bioinformatics method for future screening of the potential causative variants from national registries. A total of 21 variants were detected with majority rate in LDLR (81%). Variants were classified based on the type of mutation. Missense variants resulting in amino acid changes, c.1429G>A (p.D477N), c.1474G>A (p.D492N), c.1731G>T (p.W577C), and c.1783C>T (p.R595W) in LDLR gene, in addition to c.9835A>G (p.S3279G) in APOB, were shown to be deleterious by concordant analysis. Furthermore, functional interaction deformities showed a significant loss and gain of energies in the mutated proteins. These findings will help in distinguishing the most harmful mutations needed to be screened for clinically diagnosed FH patients in SA. Such computational research is necessary to avoid time consumption and the usage of expensive biological experiments. This can be a fast track to facilitate the future filtering and screening of causative mutations from national registries.

Modes of ever marijuana use among adult tobacco users and non-tobacco users-Styles 2014.

BACKGROUND: Tobacco and marijuana use are related behaviors; therefore, it is important to identify how users consume marijuana, and how it varies with tobacco use status. We estimated the modes of ever marijuana use among current, former, and never adult tobacco users. METHODS: Weighted data were analyzed for 4181 adults from 2014 Styles, an online consumer panel survey of US adults, to estimate proportions for modes of ever marijuana use. Differences in modes of ever marijuana use between categories of tobacco use status were assessed (p-value <0.05). RESULTS: More than half of current (56.6%) and former tobacco users (50.9%) had ever used marijuana, whereas only 13.0% of never tobacco users had ever used marijuana. Among ever marijuana users, joint use was the most common mode of use among current (86.4%), former (92.5%), and never (79.8%) tobacco users. Similarly, other modes of marijuana use were significantly higher in current and former tobacco users compared to never tobacco users. CONCLUSIONS: Prevalence of all modes of ever marijuana use was higher in current and former tobacco users. These findings underscore the importance of considering the relationship between marijuana and tobacco use when developing programs and policies aimed at preventing and reducing marijuana use.

Combined treatment, based on lysomustine administration with mesenchymal stem cells expressing cytosine deaminase therapy, leads to pronounced murine Lewis lung carcinoma growth inhibition.

BACKGROUND: The combination of stem cell-based gene therapy with chemotherapy comprises an advantageous strategy that results in a reduction of system toxicity effects and an improvement in the general efficacy of treatment. In the present study, we estimated the efficacy of adipose tissue-derived mesenchymal stem cells (AT-MSCs) expressing cytosine deaminase (CDA) combined with lysomustine chemotherapy in mice bearing late stage Lewis lung carcinoma (LLC). METHODS: Adipose tissue-derived mesenchymal stem cells were transfected with non-insert plasmid construct transiently expressing fused cytosine deaminase-uracil phosphoribosyltransferase protein (CDA/UPRT) or the same construct fused with Herpes Simplex Virus Type1 tegument protein VP22 (CDA/UPRT/VP22). Systemic administration of 5-fluorocytosine (5FC) and lysomustine was implemented after a single intratumoral injection of transfected AT-MSCs. RESULTS: We demonstrated that direct intratumoral transplantation of AT-MSCs expressing CDA/UPRT or CDA/UPRT/VP22 followed by systemic administration of 5FC resulted in a significant tumor growth inhibition. There was a 56% reduction in tumor volume in mice treated by AT-MSCs-CDA/UPRT + 5FC or with AT-MSCs-CDA/UPRT/VP22 + 5FC compared to control animals grafted with lung carcinoma alone. Transplantation of AT-MSCs-CDA/UPRT + 5FC and AT-MSCs-CDA/UPRT/VP22 + 5FC prolonged the life span of mice bearing LLC by 27% and 31%, respectively. Co-administration of lysomustine and AT-MSCs-CDA/UPRT + 5FC led to tumor growth inhibition (by 86%) and life span extension (by 60%) compared to the control group. CONCLUSIONS: Our data indicate that a combination CDA/UPRT-expressing AT-MSCs with lysomustine has a superior antitumor effect in the murine lung carcinoma model compared to monotherapies with transfected AT-MSCs or lysomustine alone, possibly because of a synergistic effect of the combination therapy. Copyright © 2016 John Wiley & Sons, Ltd.

CD146 is a novel marker for highly tumorigenic cells and a potential therapeutic target in malignant rhabdoid tumor.

Malignant rhabdoid tumor (MRT) is a rare, highly aggressive pediatric malignancy that primarily develops during infancy and early childhood. Despite the existing standard of intensive multimodal therapy, the prognosis of patients with MRT is dismal; therefore, a greater understanding of the biology of this disease is required to establish novel therapies. In this study, we identified a highly tumorigenic sub-population in MRT, based on the expression of CD146 (also known as melanoma cell adhesion molecule), a cell adhesion molecule expressed by neural crest cells and various derivatives. CD146+ cells isolated from four MRT cell lines by cell sorting exhibited enhanced self-renewal and invasive potential in vitro. In a xenograft model using immunodeficient NOD/Shi-scid IL-2Rγ-null mice, purified CD146+ cells obtained from MRT cell lines or a primary tumor exhibited the exclusive ability to form tumors in vivo. Blocking of CD146-related mechanisms, either by short hairpin RNA knockdown or treatment with a polyclonal antibody against CD146, effectively suppressed tumor growth of MRT cells both in vitro and in vivo via induction of apoptosis by inactivating Akt. Furthermore, CD146 positivity in immunohistological analysis of 11 MRT patient samples was associated with poor patient outcomes. These results suggest that CD146 defines a distinct sub-population in MRT with high tumorigenic capacity and that this marker represents a promising therapeutic target.

In vitro expansion of CD34(+)CD38(-) cells under stimulation with hematopoietic growth factors on AGM-S3 cells in juvenile myelomonocytic leukemia.

Using serum-containing culture, we examined whether AGM-S3 stromal cells, alone or in combination with hematopoietic growth factor(s), stimulated the proliferation of CD34(+) cells from patients with juvenile myelomonocytic leukemia (JMML). AGM-S3 cells in concert with stem cell factor plus thrombopoietin increased the numbers of peripheral blood CD34(+) cells to approximately 20-fold of the input value after 2 weeks in nine JMML patients with either PTPN11 mutations or RAS mutations, who received allogeneic hematopoietic transplantation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) also augmented the proliferation of JMML CD34(+) cells on AGM-S3 cells. The expansion potential of CD34(+) cells was markedly low in four patients who achieved spontaneous hematological improvement. A large proportion of day-14-cultured CD34(+) cells were negative for CD38 and cryopreservable. Cultured JMML CD34(+)CD38(-) cells expressed CD117, CD116, c-mpl, CD123, CD90, but not CXCR4, and formed GM and erythroid colonies. Day-7-cultured CD34(+) cells from two of three JMML patients injected intrafemorally into immunodeficient mice stimulated with human GM-CSF after transplantation displayed significant hematopoietic reconstitution. The abilities of OP9 cells and MS-5 cells were one-third and one-tenth, respectively, of the value obtained with AGM-S3 cells. Our culture system may provide a useful tool for elucidating leukemogenesis and for therapeutic approaches in JMML.

Effects of virtual body motion on visually-induced motion sickness.

To reduce possibilities of visually-induced motion sickness caused by animations, video games and movies, we need to develop an evaluation method of visually-induced motion sickness. Our previous results have shown that virtual roll motion had the most effective for producing the sickness. In the present study, we focused on the effectivity of image types, such as random dots and ordinary scene, and also the effectivity of virtual rotation speed on the sickness. In the first experiment, we confirmed our former results that virtual roll motion produced the highest score relating motion sickness, regardless of image types. In the second experiment, virtual rotation speed of 30 to 60 deg/s gave the highest scores regardless of the rotation types, yawing, pitching and rolling. We concluded that moving images simulating nonreciprocating rolling has robust effects on the sickness. Moreover, we speculated that the effect of rotation speed is determined by inconsistency of visual and nonvisual information, but not by retinal image speed.

Use of infrared TV cameras built into head-mounted display to measure torsional eye movements.

PURPOSE: The head-mounted display (HMD) has produced conflict between visual and vestibular stimuli because the HMD image does not move with the head motion of the wearer. The HMD can show binocular parallax three-dimensional (3D) images, in which vergence and accommodation conflict. Thus, the HMD may affect the normal visual/vestibular functions. We attempted to develop a system that makes possible the measurement of torsional eye movements, vergence eye movements, and pupillary responses of the HMD wearer. METHODS: Our apparatus is composed of two infrared CCD cameras installed in the HMD. Iris images produced by these cameras are analyzed by a personal computer using free software. Further, a third camera fixed on the HMD projects an image of the view as the subject sees it, via video tape recorder or frame memory to the HMD. Images can be stored, replayed, or frozen. RESULTS: Our system can measure torsional eye movement with 0.20 degrees resolution every 1/30 (or 1/60) seconds even though the pupil size alternates during measurement. Binocular eye movement and pupillary response are also measured. CONCLUSION: A system was developed which can be used for assessment of the effect of 3D HMD on the visual system. A third camera coupled with HMD can control visual stimulus independently of head motion (vestibular stimulus).

Closed-loop and open-loop accommodative vergence eye movements.

We examined accommodative vergence eye movements under conditions in which feedback about retinal-image slip was and was not present (i.e. closed-loop and open-loop conditions). We found that (a) in both conditions the two eyes started to move at the same time; (b) in the open-loop condition, vergence continued in both eyes; and (c) in the closed-loop condition, vergence continued in the occluded eye only, and the magnitude and velocity exceeded that of the occluded eye in the open-loop condition by a factor of two.

Transformation of the visual-line value in binocular vision: stimuli on corresponding points can be seen in two different directions.

We examined Wheatstone's (1838 Philosophical Transactions of the Royal Society of London 128 371-394) claim that images falling on retinally corresponding points can be seen in two different directions, in violation of Hering's law of identical visual direction. Our analyses showed that random-dot stereograms contain stimulus elements that are conceptually equivalent to the line stimuli in the stereogram from which Wheatstone made his claim. Our experiment demonstrated that two lines embedded in a random-dot stereogram appeared in two different directions when they stimulated retinally corresponding points, if the disparity gradient value of the lines was infinity relative to adjacent elements. To ensure that the two lines stimulated corresponding points, observers made vergence eye movements while maintaining the perception of the two lines in two different directions.

Methodological caveats for monitoring binocular eye position with nonius stimuli.

Three experiments, using two sets of Nonius lines placed in a random-dot stereogram, indicated that Nonius alignment does not always reflect binocular eye position and, thus, a caveat is necessary when Nonius alignment is used to monitor binocular eye position. We found that: (a) two Nonius lines with visual line values that differed by up to 7.6 min of arc can appear aligned; (b) the two lines of each of the two Nonius sets continued to appear aligned despite a change in vergence angle of 5.9 min of arc; and (c) the Nonius alignment reflected eye position better, when the binocular dots near the Nonius lines were eliminated.

How is motion disparity integrated with binocular disparity in depth perception?

Two experiments presented motion disparity conflicting with binocular disparity to examine how these cues determined apparent depth order (convex, concave) and depth magnitude. In each experiment, 8 subjects estimated the depth order and depth magnitude. The first experiment showed the following. (1) The visual system used one of these cues exclusively in selecting a depth order for each display. (2) The visual system integrated the depth magnitude information from these cues by a weighted additive fashion if it selected the binocular disparity in depth order perception and if the depth magnitude specified by motion disparity was small relative to that specified by binocular disparity. (3) The visual system ignored the depth magnitude information of binocular disparity if it selected the motion disparity in depth order perception. The second experiment showed that these three points were consistent whether the subject's head movement or object movement generated motion disparity.

The contribution of color to depth perceived from motion parallax.

Perceived depth was measured in a colored stimulus while stimulus movement yoked to head displacement simulated a depth of 1 cm. Velocity judgments were also made for similar stimuli moving at the same average speed but without head movement. Both measures decreased to a minimum of about 30-40% of the veridical values when the stimuli were equiluminous. Perceived depth and speed also decreased for a monochromatic stimulus as a function of luminance contrast but much more abruptly than for the chromatic stimuli. The results indicate that equiluminous color stimuli contribute to the perception of depth from motion parallax and that the contribution is not mediated by residual luminance.

Tactile pattern recognition by graphic display: importance of 3-D information for haptic perception of familiar objects.

Haptic recognition of familiar objects by the early blind, the late blind, and the sighted was investigated with two-dimensional (2-D) and three-dimensional (3-D) stimuli produced by small tactor-pins. The 2-D stimulus was an outline of an object that was depicted by raising tactor-pins to 1.5 mm. The 3-D stimulus was a relief that was produced by raising the tactors up to 10 mm, corresponding to the height of the object. Mean recognition times for correct answers to the 3-D stimuli were faster than those for the 2-D stimuli, in all three subject groups. No statistically significant differences in percentage of correct responses between the 2-D and the 3-D stimuli were found for the late-blind and sighted groups, but the early-blind group demonstrated a significant difference. In addition, the haptic legibility for the quality of depiction of the object, without regard to whether or not the stimulus was understood, was measured. The haptic legibility of the 3-D stimuli was significantly higher than that of the 2-D stimuli for all the groups. These results suggest that 3-D presentation seems to promise a way to overcome the limitations of 2-D graphic display.

[A study of microdensitometric evaluation of opacity of maxillary sinuses in patients with nasal allergy].

The opacity of the maxillary sinuses on X-ray film in Waters' view in patients with nasal allergy was evaluated by a microdensitometer. The patients with nasal allergy were diagnosed with the positive results of the following; 1) eosinophilia in nasal secretion, 2) nasal provocation test, 3) intradermal skin test or radioallergosorbent test (RAST). The ratio of density of the maxillary sinuses and orbits was determined by a microdensitometer, and the ratio of the average degree of the opacity of the maxillary sinus to that of the ipsilateral orbit was designated as the M/O ratio. The normal range of the M/O ratio was set over the mean value -2 standard deviations in the normal group. The results are followings. 1) The abnormal shadows in the maxillary sinuses were found out to be 36.9% in patients with nasal allergy. 2) Patients under 15 years old had significantly higher incidence of abnormal shadows, especially in the bilateral sinuses compared with patients over 15 years old. 3) Polyps in the maxillary sinus were recognized in 5.0% of all the sinuses. 4) There were no significant differences for the incidence of abnormal shadow among the patients with nasal allergy caused by different antigens.

The effect of middle ear effusions from children on in vitro ciliary activity.

In an attempt to clarify the effect of middle ear effusions (MEEs) on ciliary activity, the ciliary beat frequency (CBF) of nasal epithelium from normal subjects was determined following incubation in Hanks' solution containing effusions from pediatric otitis media with effusion. Both serous and mucoid types of effusions increased CBF 15 min after incubation. The mucoid type of effusion was then found to decrease CBF 6 h after incubation. Since the pH and osmotic pressure of the solution containing the effusions were within the physiological ranges for normal ciliary beating, our findings show that MEEs can influence CBF in vitro.