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Fulltext Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction

den Hoed J, de Boer E, Voisin N, Dingemans AJM, Guex N, Wiel L, et al.

Am J Hum Genet, 2021 02 04;108(2):346-356.
PMID: 33513338 DOI: 10.1016/j.ajhg.2021.01.007

Whereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene, SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carrying SATB1 variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression, and a severe phenotype. In contrast, variants predicted to result in haploinsufficiency are associated with a milder clinical presentation. A similarly mild phenotype is observed for individuals with premature protein truncating variants that escape nonsense-mediated decay, which are transcriptionally active but mislocalized in the cell. Our results suggest that in-depth mutation-specific genotype-phenotype studies are essential to capture full disease complexity and to explain phenotypic variability.
Impact of Ramadan-focused diabetes education on hypoglycemia risk and metabolic control for patients with type 2 diabetes mellitus: A systematic review

Tourkmani AM, Abdelhay O, Alharbi TJ, Bin Rsheed AM, Azmi Hassali M, Alrasheedy AA, et al.

Int J Clin Pract, 2021 Mar;75(3):e13817.
PMID: 33159361 DOI: 10.1111/ijcp.13817

BACKGROUND: Ramadan fasting is regarded as a form of worship amongst Muslims. However, patients with a high risk of diabetic complications are advised to avoid fasting, as the practice is associated with significant impacts on several health factors for type 2 diabetic patients, including glycaemic control. Thus, a lack of focused education before Ramadan may result in negative health outcomes.
AIM: To evaluate the impact of a Ramadan-focused diabetes education programme on hypoglycaemic risk and other clinical and metabolic parameters.
METHODS: A systematic literature search was performed using Scopus, PubMed, Embase, and Google Scholar to identify relevant studies meeting the inclusion criteria from inception. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and guidelines were followed when performing the search and identification of appropriate studies.
RESULTS: Seventeen studies were included in this systemic review; five of them met the criteria to compile for a meta-analysis. The included studies were with various study designs, including randomised controlled trials, quasi-experimental and non-randomised studies. Overall, the results revealed a significant reduction of hypoglycemia risk (81% reduction) for fasting patients in intervention groups who received Ramadan-focused education compared with patients receiving conventional care (OR 0.19, 95% CI: 0.08-0.46). Moreover, HbA1c significantly improved amongst patients who received a Ramadan-focused diabetes education intervention, compared with those receiving conventional care.
CONCLUSION: Ramadan-focused diabetes education had a significant impact on hypoglycemia and glycaemic control, with no significant effect on body weight, blood lipids or blood pressure.
Fulltext Central Composite Designed Fast Dissolving Tablets for Improved Solubility of the Loaded Drug Ondansetron Hydrochloride

Thalluri C, Amin R, Mandhadi JR, Gacem A, Emran TB, Dey BK, et al.

Biomed Res Int, 2022;2022:2467574.
PMID: 36046453 DOI: 10.1155/2022/2467574

Ondansetron tablets that are directly compressed using crospovidone and croscarmellose as a synthetic super disintegrant are the subject of this investigation. A central composite, response surface, randomly quadratic, nonblock (version 13.0.9.0) 32 factorial design is used to optimize the formulation (two-factor three-level). To make things even more complicated, nine different formulation batches (designated as F1-F9) were created. There were three levels of crospovidone and croscarmellose (+1, 0, -1). In addition to that, pre- and postcompressional parameters were evaluated, and all evaluated parameters were found to be within acceptable range. Among all postcompressional parameter dispersion and disintegration time, in vitro drug release experiments (to quantify the amount of medication released from the tablet) and their percentage prediction error were shown to have a significant influence on three dependent variables. Various pre- and postcompression characteristics of each active component were tested in vitro. Bulk density, tap density, angle of repose, Carr's index, and the Hausner ratio were all included in this analysis, as were many others. This tablet's hardness and friability were also assessed along with its dimension and weight variations. Additional stability studies may be conducted using the best batch of the product. For this study, we utilised the Design-Expert software to select the formulation F6, which had dispersion times of 17.67 ± 0.03 seconds, disintegration times of 120.12 ± 0.55 seconds, and percentage drug release measurements of 99.25 ± 0.36 within 30 minutes. Predicted values and experimental data had a strong correlation. Fast dissolving pills of ondansetron hydrochloride may be created by compressing the tablets directly.
Exploring the interaction between the antiallergic drug, tranilast and human serum albumin: Insights from calorimetric, spectroscopic and modeling studies

Tayyab S, Zaroog MS, Feroz SR, Mohamad SB, Malek SN

Int J Pharm, 2015 Aug 1;491(1-2):352-8.
PMID: 26142245 DOI: 10.1016/j.ijpharm.2015.06.042

The interaction of tranilast (TRN), an antiallergic drug with the main drug transporter in human circulation, human serum albumin (HSA) was studied using isothermal titration calorimetry (ITC), fluorescence spectroscopy and in silico docking methods. ITC data revealed the binding constant and stoichiometry of binding as (3.21 ± 0.23) × 10(6)M(-1) and 0.80 ± 0.08, respectively, at 25°C. The values of the standard enthalpy change (ΔH°) and the standard entropy change (ΔS°) for the interaction were found as -25.2 ± 5.1 kJ mol(-1) and 46.9 ± 5.4 J mol(-1)K(-1), respectively. Both thermodynamic data and modeling results suggested the involvement of hydrogen bonding, hydrophobic and van der Waals forces in the complex formation. Three-dimensional fluorescence data of TRN-HSA complex demonstrated significant changes in the microenvironment around the protein fluorophores upon drug binding. Competitive drug displacement results as well as modeling data concluded the preferred binding site of TRN as Sudlow's site I on HSA.
MXenes and MXene-based materials for removal of pharmaceutical compounds from wastewater: Critical review

Tawalbeh M, Mohammed S, Al-Othman A, Yusuf M, Mofijur M, Kamyab H

Environ Res, 2023 Jul 01;228:115919.
PMID: 37072081 DOI: 10.1016/j.envres.2023.115919

The rapid increase in the global population and its ever-rising standards of living are imposing a huge burden on global resources. Apart from the rising energy needs, the demand for freshwater is correspondingly increasing. A population of around 3.8 billion people will face water scarcity by 2030, as per the reports of the World Water Council. This may be due to global climate change and the deficiency in the treatment of wastewater. Conventional wastewater treatment technologies fail to completely remove several emerging contaminants, especially those containing pharmaceutical compounds. Hence, leading to an increase in the concentration of harmful chemicals in the human food chain and the proliferation of several diseases. MXenes are transition metal carbide/nitride ceramics that primarily structure the leading 2D material group. MXenes act as novel nanomaterials for wastewater treatment due to their high surface area, excellent adsorption properties, and unique physicochemical properties, such as high electrical conductivity and hydrophilicity. MXenes are highly hydrophilic and covered with active functional groups (i.e., hydroxyl, oxygen, fluorine, etc.), which makes them efficient adsorbents for a wide range of species and promising candidates for environmental remediation and water treatment. This work concludes that the scaling up process of MXene-based materials for water treatment is currently of high cost. The up-to-date applications are still limited because MXenes are currently produced mainly in the laboratory with limited yield. It is recommended to direct research efforts towards lower synthesis cost procedures coupled with the use of more environmentally friendly materials to avoid secondary contamination.
Fulltext Saffron (Crocus sativus L.): As an Antidepressant

Siddiqui MJ, Saleh MSM, Basharuddin SNBB, Zamri SHB, Mohd Najib MHB, Che Ibrahim MZB, et al.

J Pharm Bioallied Sci, 2018 12 21;10(4):173-180.
PMID: 30568374 DOI: 10.4103/JPBS.JPBS_83_18

Saffron, Crocus sativus (Iridaceae), is a perennial herb, which earned its popularity as both medicine and spice. It is an inhabitant of different mountainous regions of Asia Minor to Greece, Western Asia, Egypt, and India. The benefits of saffron as an antidepressant are well-documented. Almost 150 volatile and nonvolatile compounds are obtained from the chemical analysis of this plant. Fewer than 50 constituents elucidated and identified so far showed phytochemical characteristics. The major bioactive compounds identified are safranal, crocin, and picrocrocin, which are responsible for its aroma as well as its bitter taste. This review is an attempt to encompass the methods of analysis and pharmacodynamic and pharmacokinetic properties of saffron followed by its efficacious and safe potential.
Fulltext Efficacy of Three Types of Plaque Control Methods During Fixed Orthodontic Treatment: A Randomized Controlled Trial

Shilpa M, Jain J, Shahid F, Gufran K, Sam G, Khan MS

J Pharm Bioallied Sci, 2019 May;11(Suppl 2):S246-S251.
PMID: 31198346 DOI: 10.4103/JPBS.JPBS_1_19

Aim: The aim of this study was to evaluate and compare the efficacy of three types of plaque control methods among 13- to 35-year-old subjects receiving fixed orthodontic treatment in Coorg Institute of Dental Sciences, Virajpet, Coorg district, Karnataka, India.
Materials and Methods: A total of 111 subjects who fulfilled the inclusion and exclusion criteria were randomly included in the study. The subjects were recalled after 1 month of the commencement of fixed orthodontic treatment for the recording of baseline data including plaque index (PI), gingival index (GI), and modified papillary bleeding index (MPBI). After recording of the baseline data, the subjects were randomly allocated into each of the intervention groups, i.e., group A (manual tooth brush), group B (powered tooth brush), and group C (manual tooth brush combined with mouthwash) by lottery method. Further, all the subjects were recalled after 1 and 2 months for recording the data.
Results: Regarding plaque levels, it was seen that there was a highly statistically significant difference between the three groups (P = 0.001), with the manual tooth brush combined with chlorhexidine mouthwash group recording the lowest mean PI score of 0.5 ± 0.39. A comparison of the mean GI scores among the groups at the end of 2 months shows a highly statistically significant difference (P = 0.001). The mean MPBI scores at the end of 2 months were highly statistically significant among the three groups (P = 0.001), with the group C recording the lowest mean MPBI score of 0.3 ± 0.3.
Conclusion: The powered tooth brush group subjects exhibited significantly lesser PI, GI, and MPBI scores than the manual tooth brush group at the end of 2 months, whereas the manual tooth brush combined with chlorhexidine mouth wash group subjects showed maximum improvement, having significantly lesser PI and GI scores than the powered tooth brush group.
Fulltext COVID-19 Vaccine Acceptance among Social Media Users: A Content Analysis, Multi-Continent Study

Shaaban R, Ghazy RM, Elsherif F, Ali N, Yakoub Y, Aly MO, et al.

Int J Environ Res Public Health, 2022 May 08;19(9).
PMID: 35565132 DOI: 10.3390/ijerph19095737

Vaccine hesitancy (VH) is defined as a delayed in acceptance or refusal of vaccines despite availability of vaccination services. This multinational study examined user interaction with social media about COVID-19 vaccination. The study analyzed social media comments in 24 countries from five continents. In total, 5856 responses were analyzed; 83.5% of comments were from Facebook, while 16.5% were from Twitter. In Facebook, the overall vaccine acceptance was 40.3%; the lowest acceptance rates were evident in Jordan (8.5%), Oman (15.0%), Senegal (20.0%) and Morocco (20.7%) and the continental acceptance rate was the lowest in North America 22.6%. In Twitter, the overall acceptance rate was (41.5%); the lowest acceptance rate was found in Oman (14.3%), followed by USA (20.5%), and UK (23.3%) and the continental acceptance rate was the lowest in North America (20.5%), and Europe (29.7%). The differences in vaccine acceptance across countries and continents in Facebook and Twitter were statistically significant. Regarding the tone of the comments, in Facebook, countries that had the highest number of serious tone comments were Sweden (90.9%), USA (61.3%), and Thailand (58.8%). At continent level, serious comments were the highest in Asia (58.4%), followed by Africa (46.2%) and South America (46.2%). In Twitter, the highest serious tone was reported in Egypt (72.2%) while at continental level, the highest proportion of serious comments was observed in Asia (59.7%), followed by Europe (46.5%). The differences in tone across countries and continents in Facebook and Twitter and were statistically significant. There was a significant association between the tone and the position of comments. We concluded that the overall vaccine acceptance in social media was relatively low and varied across the studied countries and continents. Consequently, more in-depth studies are required to address causes of such VH and combat infodemics.
Effect of Different Carriers on In Vitro and In Vivo Drug Release Behavior of Aceclofenac Proniosomes

Sammour RMF, Chatterjee B, Taher M, Saleh MSM, Shahiwala A

Curr Drug Deliv, 2021;18(9):1272-1279.
PMID: 33605859 DOI: 10.2174/1567201818666210219105509

BACKGROUND: Improved bioavailability of Aceclofenac (ACE) may be achieved through proniosomes, which are considered as one of the most effective drug delivery systems and are expected to represent a valuable approach for the development of better oral dosage form as compared to the existing product. However, the carrier in this system plays a vital role in controlling the drug release and modulating drug dissolution. Accordingly, a comparative study on different carriers can give a clear idea about the selection of carriers to prepare ACE proniosomes.
OBJECTIVE: This study aims to evaluate the role of maltodextrin, glucose, and mannitol as carriers for in vitro and in vivo performance of Aceclofenac (ACE) proniosomes.
METHODS: Three formulations of proniosomes were prepared by the slurry method using the 100 mg ACE, 500 mg span 60, 250 mg cholesterol with 1300mg of different carriers, i.e., glucose (FN1), maltodextrin (FN2), and mannitol (FN3). In vitro drug release studies were conducted by the USP paddle method, while in vivo studies were performed in albino rats. Pure ACE was used as a reference in all the tests. Lastly, the results were analyzed using the High-Pressure Liquid Chromatography (HPLC) method, and data were evaluated using further kinetic and statistical tools.
RESULTS: No significant differences (p > 0.05) in entrapment efficiency (%EE) of FN1, FN2, and FN3 (82 ± 0.5%, 84 ± 0.66%, and 84 ± 0.34% respectively) were observed and formulations were used for further in vitro and in vivo evaluations. During in vitro drug release studies, the dissolved drug was found to be 42% for the pure drug, while 70%, 17%, and 30% for FN1, FN2, and FN3, respectively, at 15 min. After 24 hrs, the pure drug showed a maximum of 50% release while 94%, 80%, and 79% drug release were observed after 24 hr for FN1, FN2, and FN3, respectively. The in vivo study conducted on albino rats showed a higher Cmax and AUC of FN1 and FN2 in comparison with the pure ACE. Moreover, the relative oral bioavailability of proniosomes with maltodextrin and glucose as carriers compared to the pure drug was 183% and 112%, respectively. Mannitol- based formulation exhibited low bioavailability (53.7%) that may be attributed to its osmotic behavior.
CONCLUSION: These findings confirm that a carrier plays a significant role in determining in vitro and in vivo performance of proniosomes and careful selection of carrier is an important aspect of proniosomes optimization.
GC-MS analysis of metabolites from soxhlet extraction, ultrasound-assisted extraction and supercritical fluid extraction of Salacca zalacca flesh and its alpha-glucosidase inhibitory activity

Saleh MSM, Bukhari DAM, Siddiqui MJA, Kasmuri AR, Murugesu S, Khatib A

Nat Prod Res, 2020 May;34(9):1341-1344.
PMID: 30678487 DOI: 10.1080/14786419.2018.1560295

Different extraction processes were employed to extract bioactive metabolites from Salacca zalacca flesh by a range of aqueous and organic solvents. The highest extraction yield was obtained by 50% ethanol extract of SE (73.18 ± 4.35%), whereas SFE_1 showed the lowest yield (0.42 ± 0.08%). All extracts were evaluated for in vitro α-glucosidase inhibitory activity, measured by their IC50 values in comparison to that of quercetin, the positive control (IC50 = 2.7 ± 0.7 μg/mL). The lowest α-glucosidase inhibitory activity was indicated by water extract of SE (IC50 = 724.3 ± 42.9 μg/mL) and the highest activity was demonstrated by 60% ethanol extract by UAE (IC50 = 16.2 ± 2.4 μg/mL). All extracts were analysed by GC-MS and identified metabolites like carbohydrates, fatty acids, organic acids, phenolic acids, sterols and alkane-based compounds etcetera that may possess the potential as α-glucosidase inhibitor and may attribute to the α-glucosidase inhibitory activity.
Fulltext UPLC-MS-Based Metabolomics Profiling for α-Glucosidase Inhibiting Property of Parkia speciosa Pods

Saleh MSM, Jalil J, Mustafa NH, Ramli FF, Asmadi AY, Kamisah Y

Life (Basel), 2021 Jan 22;11(2).
PMID: 33499128 DOI: 10.3390/life11020078

Parkia speciosa is a food plant that grows indigenously in Southeast Asia. A great deal of interest has been paid to this plant due to its traditional uses in the treatment of several diseases. The pods contain many beneficial secondary metabolites with potential applications in medicine and cosmetics. However, studies on their phytochemical properties are still lacking. Therefore, the present study was undertaken to profile the bioactive compounds of P. speciosa pods collected from six different regions of Malaysia through ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) and α-glucosidase inhibitory potential. This study applied metabolomics to elucidate the differences between P. speciosa populations found naturally in the different locations and to characterize potential α-glucosidase inhibitors from P. speciosa pods. P. speciosa collected from different regions of Malaysia showed good α-glucosidase inhibitory activity, with a median inhibitory concentration (IC50) of 0.45-0.76 μg/mL. The samples from the northern and northeastern parts of Peninsular Malaysia showed the highest activity. Using UHPLC-QTOF-MS/MS analysis, 25 metabolites were identified in the pods of P. speciosa. The findings unveiled that the pods of P. speciosa collected from different locations exhibit different levels of α-glucosidase inhibitory activity. The pods are a natural source of potent antidiabetic bioactive compounds.
Modulation of metabolic alterations of obese diabetic rats upon treatment with Salacca zalacca fruits extract using 1H NMR-based metabolomics

Saleh MSM, Siddiqui MJ, Mediani A, Ahmed QU, Mat So'ad SZ, Saidi-Besbes S, et al.

Food Res Int, 2020 11;137:109547.
PMID: 33233172 DOI: 10.1016/j.foodres.2020.109547

Fruit of salak (Salacca zalacca) is traditionally used and commercialized as an antidiabetic agent. However, the scientific evidence to prove this traditional use is lacking. This research was aimed to evaluate the metabolic changes of obese-diabetic (OBDC) rats treated with S. zalacca fruit extract using proton-nuclear magnetic resonance (1H NMR)-based metabolomics approach. This research presents the first report on the in vitro antidiabetic effect of S. zalacca fruits extract using this approach. The obtained results indicated that the administration of 400 mg/kg bw of 60% ethanolic S. zalacca extract for 6 weeks significantly decreased the blood glucose level and normalized the blood lipid profile of the OBDC rats. The potential biomarkers in urine were 2-oxoglutarate, alanine, leucine, succinate 3-hydroxybutyrate, taurine, betaine, allantoin, acetate, dimethylamine, creatine, creatinine, glucose, phenyl-acetylglycine, and hippurate. Based on the data obtained, the 60% ethanolic extract could not fully improved the metabolic complications of diabetic rats. The extract of S. zalacca fruit was able to decrease the ketones bodies as 3-hydroxybutyrate and acetoacetate. It also improved energy metabolism, involving glucose, acetate, lactate, 2-hydroxybutyrate, 2-oxoglutarate, citrate, and succinate. Moreover, it decreased metabolites from gut microflora, including choline. This extract had significant effect on amino acid metabolism, metabolites from gut microflora, bile acid metabolism and creatine. The result can further support the traditional claims of S. zalacca fruits in management of diabetes. This finding might be valuable in understanding the molecular mechanism and pharmacological properties of this medicinal plant for managing diabetes mellitus.
Fulltext Genus Parkia: Phytochemical, Medicinal Uses, and Pharmacological Properties

Saleh MSM, Jalil J, Zainalabidin S, Asmadi AY, Mustafa NH, Kamisah Y

Int J Mol Sci, 2021 Jan 09;22(2).
PMID: 33435507 DOI: 10.3390/ijms22020618

The genus Parkia (Fabaceae, Subfamily, Mimosoideae) comprises about 34 species of mostly evergreen trees widely distributed across neotropics, Asia, and Africa. This review aims to provide an overview of the current status of the species from the genus Parkia in terms of its relationship between its phytochemistry and medical uses. Comprehensive information on Parkia species was retrieved from electronic databases, which were Web of Science, ScienceDirect, PubMed, and Google Scholar. This review identified nine species from genus Parkia with properties of medicinal use. They are used traditionally to treat several ailments, such as diabetes, diarrhea, wounds, hypertension, cough, chronic piles, conjunctivitis, and measles. The most common species studied are P. biglobosa, P. speciosa, P. javanica, P. bicolor, P. biglandulosa, P. filicoidea, and P. clappertoniana. A considerable number of secondary metabolites, such as terpenoids, phenolic acids, flavonoids (aglycone and glycosides), and numerous volatile compounds have been identified in this genus, which are responsible for their diverse pharmacological activities. Their extracts, pure compounds and seed lectins have been reported for their anticancer, antimicrobial, antihypertensive, antiulcer, antidiabetic, anti-inflammatory, antioxidant, antimalarial, hepatoprotective, and antidiarrheal activities. The information gathered in this review might be of help for future studies in terms of the current knowledge on the link between the phytochemical components and medicinal uses. This could facilitate more discoveries on its potentials particularly in the pharmacological characteristics and potential to be developed into modern medicines.
Fulltext Correlation of FT-IR Fingerprint and α-Glucosidase Inhibitory Activity of Salak (Salacca zalacca) Fruit Extracts Utilizing Orthogonal Partial Least Square

Saleh MSM, Siddiqui MJ, Mat So'ad SZ, Roheem FO, Saidi-Besbes S, Khatib A

Molecules, 2018 06 13;23(6).
PMID: 29899270 DOI: 10.3390/molecules23061434

Salak fruit (Salacca zalacca), commonly known as snake fruit, is used indigenously as food and for medicinal applications in Southeast Asia. This study was conducted to evaluate the α-glucosidase inhibitory activity of salak fruit extracts in correlation to its Fourier transform infrared spectroscopy (FT-IR) fingerprint, utilizing orthogonal partial least square. This calibration model was applied to develop a rapid analytical method tool for quality control of this fruit. A total of 36 extracts prepared with different solvent ratios of ethanol⁻water (100, 80, 60, 40.20, 0% v/v) and their α-glucosidase inhibitory activities determined. The FT-IR spectra of ethanol⁻water extracts measured in the region of 400 and 4000 cm−1 at a resolution of 4 cm−1. Multivariate analysis with a combination of orthogonal partial least-squares (OPLS) algorithm was used to correlate the bioactivity of the samples with the FT-IR spectral data. The OPLS biplot model identified several functional groups (C⁻H, C=O, C⁻N, N⁻H, C⁻O, and C=C) which actively induced α-glucosidase inhibitory activity.
Fulltext Prevalence and risk estimates of Cryptosporidium oocysts infection associated with consumption of raw-eaten vegetables in Maiduguri metropolis LGAs, Northeast Nigeria

Saidu AS, Mohammed S, Adamu SG, Sadiq MA, Tijjani AO, Musa HI, et al.

Sci Rep, 2023 Dec 27;13(1):23079.
PMID: 38155194 DOI: 10.1038/s41598-023-49451-0

Cryptosporidium is one of the most important protozoan parasitic pathogens, and it is a common cause of diarrhoea in humans, domestic animals, and wild vertebrates and has serious public health threats. A cross-sectional study was designed to determine the prevalence of Cryptosporidium oocysts in raw-eaten vegetables in Maiduguri Metropolitan Council (MMC) and Jere Local Government Areas (LGAs). A total of 400 samples were collected from four (4) different locations, namely Tashan Bama, Gomboru, and Monday Markets (n = 100), while fifty (n = 50) each from 202-Vegetable-Vendors and Unimaid Commercials. A total of 16 visits were conducted in all the sampling areas (twenty-five samples per visit). The Cryptosporidium oocysts were detected using the Modified Ziehl-Neelsen Staining Technique. The locations, sources, and types of raw-eaten vegetables were also assessed. The oocysts were confirmed (100×) as bright pink spherules. Data generated were analyzed using IBM-SPSS V23.0, and p ≤ 0.05 was considered significant. Out of the total samples (n = 400) analyzed, cabbage appeared to have the highest number of 10 (12.5%) of Cryptosporidium oocysts detected, while Tomato and garden egg had 9 (11.3%) and 1 (1.2%), respectively. There was a statistically significant association (χ2 = 12.5, P = 0.014) between the presence of Cryptosporidium oocysts in raw-eaten vegetables and vegetable types. Among the sources of the vegetables sampled, Alau had the highest number of Cryptosporidium oocysts, 15 (12.5%), followed by Kilari-Abdullahi and Zabarmari sources with 4 (10.0%) and 4 (5.0%), respectively. However, Jetete appeared to have the least number 2 (2.5%) of oocysts, and there was a statistically significant association (χ2= 10.4, P = 0.034) between the presence of Cryptosporidium oocysts and the sources of vegetables and fruits. The study concludes that the raw-eaten vegetables sampled from Maiduguri Metropolis were contaminated with Cryptosporidium oocysts. The study recommends that all raw-eaten vegetables should be from cleaned sources and washed before consumption. Consumers should be enlightened on the hygienic measures in the food chain in line with the Hazard Analysis and Critical Control Points (HACCP) principles.
Determination of rare earth elements concentration at different depth profile of Precambrian pegmatites using instrumental neutron activation analysis

Sadiq Aliyu A, Musa Y, Liman MS, Abba HT, Chaanda MS, Ngene NC, et al.

Appl Radiat Isot, 2018 Jan;131:36-40.
PMID: 29107886 DOI: 10.1016/j.apradiso.2017.10.046

The Keffi area hosts abundant pegmatite bodies as a result of the surrounding granitic intrusions. Keffi is part of areas that are geologically classified as North Central Basement Complex. Data on the mineralogy and mineralogical zonation of the Keffi pegmatite are scanty. Hence the need to understand the geology and mineralogical zonation of Keffi pegmatites especially at different depth profiles is relevant as a study of the elemental composition of the pegmatite is essential for the estimation of its economic viability. Here, the relative standardization method of instrumental neutron activation analysis (INAA) has been used to investigate the vertical deviations of the elemental concentrations of rare earth elements (REEs) at different depth profile of Keffi pegmatite. This study adopted the following metrics in investigating the vertical variations of REEs concentrations. Namely, the total contents of rare earth elements (∑REE); ratio of light to heavy rare earth elements (LREE/HREE), which defines the enrichment or depletion of REEs; europium anomaly (Eu/Sm); La/Lu ratio relative to chondritic meteorites. The study showed no significant variations in the total content of rare elements between the vertical depth profiles (100-250m). However, higher total concentrations of REEs (~ 92.65ppm) were recorded at the upper depth of the pegmatite and the europium anomaly was consistently negative at all the depth profiles suggesting that the Keffi pegmatite is enriched with light REEs.
Fulltext Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015

Roth GA, Johnson C, Abajobir A, Abd-Allah F, Abera SF, Abyu G, et al.

J Am Coll Cardiol, 2017 Jul 04;70(1):1-25.
PMID: 28527533 DOI: 10.1016/j.jacc.2017.04.052

BACKGROUND: The burden of cardiovascular diseases (CVDs) remains unclear in many regions of the world.
OBJECTIVES: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden.
METHODS: CVD mortality was estimated from vital registration and verbal autopsy data. CVD prevalence was estimated using modeling software and data from health surveys, prospective cohorts, health system administrative data, and registries. Years lived with disability (YLD) were estimated by multiplying prevalence by disability weights. Years of life lost (YLL) were estimated by multiplying age-specific CVD deaths by a reference life expectancy. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility.
RESULTS: In 2015, there were an estimated 422.7 million cases of CVD (95% uncertainty interval: 415.53 to 427.87 million cases) and 17.92 million CVD deaths (95% uncertainty interval: 17.59 to 18.28 million CVD deaths). Declines in the age-standardized CVD death rate occurred between 1990 and 2015 in all high-income and some middle-income countries. Ischemic heart disease was the leading cause of CVD health lost globally, as well as in each world region, followed by stroke. As SDI increased beyond 0.25, the highest CVD mortality shifted from women to men. CVD mortality decreased sharply for both sexes in countries with an SDI >0.75.
CONCLUSIONS: CVDs remain a major cause of health loss for all regions of the world. Sociodemographic change over the past 25 years has been associated with dramatic declines in CVD in regions with very high SDI, but only a gradual decrease or no change in most regions. Future updates of the GBD study can be used to guide policymakers who are focused on reducing the overall burden of noncommunicable disease and achieving specific global health targets for CVD.
Fulltext RAC1 Missense Mutations in Developmental Disorders with Diverse Phenotypes

Reijnders MRF, Ansor NM, Kousi M, Yue WW, Tan PL, Clarkson K, et al.

Am J Hum Genet, 2017 Sep 07;101(3):466-477.
PMID: 28886345 DOI: 10.1016/j.ajhg.2017.08.007

RAC1 is a widely studied Rho GTPase, a class of molecules that modulate numerous cellular functions essential for normal development. RAC1 is highly conserved across species and is under strict mutational constraint. We report seven individuals with distinct de novo missense RAC1 mutations and varying degrees of developmental delay, brain malformations, and additional phenotypes. Four individuals, each harboring one of c.53G>A (p.Cys18Tyr), c.116A>G (p.Asn39Ser), c.218C>T (p.Pro73Leu), and c.470G>A (p.Cys157Tyr) variants, were microcephalic, with head circumferences between -2.5 to -5 SD. In contrast, two individuals with c.151G>A (p.Val51Met) and c.151G>C (p.Val51Leu) alleles were macrocephalic with head circumferences of +4.16 and +4.5 SD. One individual harboring a c.190T>G (p.Tyr64Asp) allele had head circumference in the normal range. Collectively, we observed an extraordinary spread of ∼10 SD of head circumferences orchestrated by distinct mutations in the same gene. In silico modeling, mouse fibroblasts spreading assays, and in vivo overexpression assays using zebrafish as a surrogate model demonstrated that the p.Cys18Tyr and p.Asn39Ser RAC1 variants function as dominant-negative alleles and result in microcephaly, reduced neuronal proliferation, and cerebellar abnormalities in vivo. Conversely, the p.Tyr64Asp substitution is constitutively active. The remaining mutations are probably weakly dominant negative or their effects are context dependent. These findings highlight the importance of RAC1 in neuronal development. Along with TRIO and HACE1, a sub-category of rare developmental disorders is emerging with RAC1 as the central player. We show that ultra-rare disorders caused by private, non-recurrent missense mutations that result in varying phenotypes are challenging to dissect, but can be delineated through focused international collaboration.
Fulltext Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations

Rambhatla A, Shah R, Ziouziou I, Kothari P, Salvio G, Gul M, et al.

World J Mens Health, 2024 Apr 04.
PMID: 38606867 DOI: 10.5534/wjmh.230339

PURPOSE: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA.
MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process.
RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit.
CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.
Fulltext A Comprehensive Review on the Current Vaccines and Their Efficacies to Combat SARS-CoV-2 Variants

Rabaan AA, Mutair AA, Hajissa K, Alfaraj AH, Al-Jishi JM, Alhajri M, et al.

Vaccines (Basel), 2022 Oct 02;10(10).
PMID: 36298520 DOI: 10.3390/vaccines10101655

Since the first case of Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, SARS-CoV-2 infection has affected many individuals worldwide. Eventually, some highly infectious mutants-caused by frequent genetic recombination-have been reported for SARS-CoV-2 that can potentially escape from the immune responses and induce long-term immunity, linked with a high mortality rate. In addition, several reports stated that vaccines designed for the SARS-CoV-2 wild-type variant have mixed responses against the variants of concern (VOCs) and variants of interest (VOIs) in the human population. These results advocate the designing and development of a panvaccine with the potential to neutralize all the possible emerging variants of SARS-CoV-2. In this context, recent discoveries suggest the design of SARS-CoV-2 panvaccines using nanotechnology, siRNA, antibodies or CRISPR-Cas platforms. Thereof, the present comprehensive review summarizes the current vaccine design approaches against SARS-CoV-2 infection, the role of genetic mutations in the emergence of new viral variants, the efficacy of existing vaccines in limiting the infection of emerging SARS-CoV-2 variants, and efforts or challenges in designing SARS panvaccines.

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