Innovative approaches for mycotoxin detection in various food categories.

Mycotoxins (MTs), produced by filamentous fungi, represent a severe hazard to the health of humans and food safety, affecting the quality of various agricultural products. They can contaminate a wide range of foods, during any processing phase before or after harvest. Animals and humans who consume MTs-contaminated food or feed may experience acute or chronic poisoning, which may result in serious pathological consequences. Accordingly, developing rapid, easy, and accurate methods of MTs detection in food becomes highly urgent and critical as a quality control and to guarantee food safety and lower health hazards. In this review, we highlighted and discussed innovative approaches like biosensors, fluorescent polarization, capillary electrophoresis, infrared spectroscopy, and electronic noses for MT identification pointing out current challenges and future directions. The limitations, current challenges, and future directions of conventional detection methods versus innovative methods have also been highlighted and discussed.

Evaluation of ELISA and immunoaffinity fluorometric analytical tools of four mycotoxins in various food categories.

Mycotoxins (MTs) are secondary toxic metabolites that can contaminate food, impacting quality and safety, leading to various negative health effects and serious pathological consequences conferring urgent need to evaluate and validate the currently standard methods used in their analysis. Therefore, this study was aimed to validate ELISA and VICAM immunoaffinity fluorometric, the two common methods used to monitor the level of MTs according to the Egyptian Organization for Standardization and Quality Control. A total of 246 food samples were collected and tested for Aflatoxins (196 samples), Ochratoxin A (139), Zearalenone (70), and Deoxynivalenol (100) using both analytical methods. Results showed that aflatoxins exceeded limits in 42.9, 100, and 13.3% of oily seeds, dried fruits, and chili and spices, respectively. For ochratoxin A, 3.9% of Gramineae and 8% of spices and chili (locally sourced) exceeded the limits, while 17.6% of imported pasta and noodles exceeded the limits for deoxynivalenol. Significant differences for the aflatoxins and ochratoxin A detection among different categories of chocolate, dried fruits, and oily seeds (p-value < 0.05). No zearalenone contamination was detected in the exported, imported, and locally sourced categories. No deoxynivalenol contamination was detected in the tested Gramineae category. In contrast, for pasta and noodles, the imported samples exhibited the highest contamination rate (above the upper limit of 750 µg/kg) with 17.6% of the samples testing positive for deoxynivalenol with no significant difference among different sample categories of Gramineae, pasta, and noodles (p-value > 0.05). In conclusion, our study found no significant differences between the ELISA and immunoaffinity fluorometric analysis in the detection of the respective MTs in various food categories and therefore, they can substitute each other whenever necessary. However, significant differences were observed among different food categories, particularly the local and imported ones, highlighting the urgent need for strict and appropriate control measures to minimize the risk of MTs adverse effects.

Insight into Genetic Mutations of SZT2: Is It a Syndrome?

BACKGROUND: The seizure threshold 2 (SZT2) gene encodes a protein of unknown function, which is widely expressed, confers a low seizure threshold, and enhances epileptogenesis. It also comprises the KICSTOR protein complex, which inhibits the mTORC1 pathway. A pathogenic variant in the SZT2 gene could result in hyperactive mTORC1 signaling, which can lead to several neurological disorders. AIM OF THE STUDY: To review every reported case and present two novel cases to expand the current knowledge and understanding of the mutation. METHODS: Whole exome sequencing (WES) was used to identify the novel cases and present their clinical and radiological findings. A detailed revision of the literature was conducted to illustrate and compare findings. The clinical, genetical, neuroimaging, and electrophysiological data were extracted. RESULTS: The study included 16 female patients and 13 male patients in addition to the 2 novel male cases. Eighteen patients had heterozygous mutations; others were homozygous. The majority presented with facial dysmorphism (n = 22). Seizures were noted as the predominant hallmark (n = 26). Developmental delay and hypotonia were reported in 27 and 15 patients, respectively. The majority of patients had multifocal epileptiform discharges on the electroencephalogram (EEG) and short and thick corpus callosum on the magnetic resonance imaging (MRI). CONCLUSION: Several promising features are becoming strongly linked to patients with SZT2 mutations. High variability among the cases was observed. Developmental delay and facial dysmorphism can be investigated as potential hallmarks; aiding clinicians in diagnosing the condition and optimizing management plans.

Shared thoughts and practices on some modifiable cancer risk factors.

OBJECTIVE: Numerous cancer-causing factors are inversely correlated with health literacy. The current study's objective was to evaluate the Saudi community's knowledge, attitude, and behavior regarding certain carcinogens. SUBJECTS AND METHODS: To perform this descriptive study, a cross-sectional survey was carried out in Hail City, Northern Saudi Arabia, between September 2020 and November 2020. In the city of Hail, about 450 volunteers have expressed interest in taking part in the study. RESULTS: A total of 165 individuals smoked cigarettes and drank alcohol, respectively (67%) and 42 (9%). Negative attitudes toward cigarette smoking, alcohol consumption, radiation exposure, genetic predisposition, some viruses, some bacterial infection, some parasites, and fungi were 85/450 (19%), 209/450 (46.4%), 206/450 (45.8%), 322/450 (71.6%), 297/450 (66%), 375/450 (83.3%), 403/450 (89.6%), and 405/450 (90%), in that order. CONCLUSIONS: Some cancer-causing substances are widely used in the Saudi community. Lack of understanding and a negative attitude toward some carcinogens are widespread, necessitating immediate interventions at the community and health affairs levels.

Personal caution about some cancer-related lifestyle habits in Northern Saudi Arabia.

OBJECTIVE: The present study aimed at assessing community familiarity with cancer-related lifestyle habits in Northern Saudi Arabia. SUBJECTS AND METHODS: This descriptive cross-sectional study involved a community-based sample of 442 civilians living in Hail, Northern Saudi Arabia. Data were collected during the period between October and November 2020. Data were randomly collected from different public gathering places regardless of age or sex. RESULTS: Higher nescience percentages were associated with physical inactivity followed by obesity and fast food, representing 328/390 (84%), 311/390 (80%), and 263/390 (67%), respectively. CONCLUSIONS: Northern Saudi Arabia has a high negative attitude toward cancer risk factors, necessitating the implementation of community-based health education and cancer awareness programs. Level of education and age have no significant role in the level of cancer awareness.

A new exploration toward adamantane derivatives as potential anti-MDR agents: Design, synthesis, antimicrobial, and radiosterilization activity as potential topoisomerase IV and DNA gyrase inhibitors.

Developing novel antimicrobial agents has become a necessitate due to the increasing rate of microbial resistance to antibiotics. All the newly adamantane derivatives were evaluated for their antimicrobial activities against six MDR clinical pathogenic isolates. The results exhibited that 13 compounds have from potent to good activity. Among those, five derivatives (6, 7, 9, 14a, and 14b) displayed the potent activities against the different isolates tested (MIC < 0.25 µg/ml with bacteria and <8 µg/ml with fungi) compared with Ciprofloxacin (CIP) and Fluconazole (FCA). Additionally, the potent adamantanes showed bactericidal and fungicidal effects based on (MBCs and MFCs) and the time-kill assay. The most active adamantane derivatives 7 and 14b exhibited a synergistic effect of ΣFIC ≤ 0.5 with CIP and FCA against the bacterial and fungal isolates. Moreover, no antagonistic effect appeared for the tested derivatives. Additionally, the interaction of DNA gyrase and topoisomerase IV enzymes with the compounds 6, 7, 9, 14a, and 14b exhibited potent antimicrobial activity using in vitro biochemical assays and gel-based DNA-supercoiling inhibition method. The activity of DNA gyrase and topoisomerase IV enzymes showed inhibitory activity (IC50 ) of 6.20 µM and 9.40 µM with compound 7 and 10.14 µM and 13.28 µM with compound 14b, respectively. Surprisingly, exposing compound 7 to gamma irradiation sterilized and increased its activity. Finally, the in-silico analysis predicted that the most active derivatives had good drug-likeness and safe properties. Besides, molecular docking and quantum chemical studies revealed several important interactions inside the active sites and showed the structural features necessary for activity.

Development of adamantane scaffold containing 1,3,4-thiadiazole derivatives: Design, synthesis, anti-proliferative activity and molecular docking study targeting EGFR.

A new series of 1,3,4-thiadiazolo-adamantane derivatives were synthesized through molecular hybridization approach, then used as starting material to synthesize chloro and cyano acetamide-thiadiazole derivatives 2, 3. The newly designed compounds 1-3 were treated with different reagents to design 5-adamantyl thiadiazole derivatives 4-17 and evaluate their in vitro anti-proliferative activity against three cancer cell lines (MCF-7, HepG-2 and A549). Doxorubicin was used as a positive control. The most promising compounds 5, 6, 10a, 10b, 14b, 14c, and 17 showed up-regulation for BAX and down-regulation of Bcl-2, these findings proved their role as hopeful apoptotic inducers. In addition, the inhibitory activity against both wild EGFRWT and mutant EGFRL858R-TK for these derivatives revealed that compounds 5, 14c, and 17 have IC50 value ranging from 85 nM to 71.5 nM against wild EGFRWT and 37.85-41.19 nM against the mutant type, Lapatinib was used as a reference standard with IC50 values of 31.8 nM and 39.53 nM, respectively. The most potent derivatives were subjected to further evaluation against double mutant EGFR L858R/T790M and showed good IC50 values between (0.27-0.78 nM) compared to Lapatinib (0.18 nM) and Erlotinib (0.21 nM). Among them, thiazolo-thiadiazole adamantane derivative 17 exhibited the strongest inhibitory activity to the EGFR. Molecular docking studies were performed inside the active site of EGFR (1M17), and binding energy scores ranged between (-19.19 to -22.07 Kcal/mol) compared to Erlotinib (-19.10 Kcal/mol). Furthermore, oral bioavailability beside some pharmacokinetics properties of these derivatives were also investigated in this research work.

The Impact of Pediatric Epilepsy on Children and Families: A Multicenter Cross-Sectional Study.

BACKGROUND AND OBJECTIVES: Epilepsy is considered one of the most prevalent causes of morbidity in children. The aim of this study is to determine how epilepsy impacts the lives of children with epilepsy and their families. METHODS: A translated version of the "Impact of Pediatric Epilepsy Scale" (IPES) questionnaire was completed by the 80 mothers of children with epilepsy, recruited at three hospitals in Jeddah, Saudi Arabia This is a validated self-administered questionnaire used to assess the impact of epilepsy on the lives of the child and family, as well as the quality of life (QoL) of the child. RESULTS: The mean age of children epilepsy was 6.32 years (SD = 3.22). The mean IPES score was 6.28 (SD = 8.42) and the mean child's QoL was 2.85 (SD= 0.83). 87.5% of the mothers rated their child's QoL as low. IPES score was significantly associated with cause of seizure (ß=0.259; 95%-CI= 0.263 - 10.334; p = 0.039). Child's QoL was significantly associated with frequency of seizure (ß=0.251; 95%-CI= 0.016 - 0.568; p= 0.039) and child's nationality (ß=-0.270; 95%-CI -0.252, -0.013; p= 0.031). CONCLUSIONS: Pediatric epilepsy may have a greater impact on the lives of the child and the family when it is not comorbid with cerebral palsy. Quality of life tends to be lower for non-Saudi children, and children with more frequent seizures. Therefore, these groups may need more support in managing the impact that epilepsy has on their daily functioning and quality of life.

Primary wound closure of diabetic foot ulcers by debridement and stitching.

OBJECTIVE: The role of stitching in healing diabetic foot ulcers (DFUs) has little attention, with few reports published on the technique. This study aimed to report on the role of stitching in healing of neuropathic DFUs. METHOD: This comparative study was between patients with diabetes with neuropathic foot ulcers who had undergone wound stitching and those on conventional wound care. The study was carried in Jabir Abu Eliz Diabetic Center Khartoum (JADC) during between January 1 2011 and January 1 2013. All patients presented with neuropathic diabetic septic foot on the plantar aspect or extending up the leg were included. Initial surgical sharp debridement under intravenous broad spectrum antibiotics was performed and oral antibiotics were given 3 days later after the results of the bacterial culture were received. Regular wound debridement was performed with the aim of pairing the wound edges for stitching. Primary closure was performed when the wound was clean from any necrotic tissues and partial closure when the wound was still oozy to secure drainage and avoid splaying of the wound edges. All patients were using either crutches or wheel chair initially until any sepsis cleared and then proper off-loading by shoes purpose made in our centre. RESULTS: A 160 patients with neuropathic DFUs that needed debridement and frequent dressing changes as outpatients were included. Both groups had the same tap water wound dressing either daily, every other day or every two days according to the wound progress. Absorbent dressings and negative pressure wound therapy (NPWT) were unavailable. Half of the patients (n=80) had debridement, frequent dressing change using tap water throughout the period of study (group 1) while the rest (n=80) in addition to wound debridement underwent stitching of their wounds (group 2). Complete healing was achieved in 46 patients in Group 1 (57.5%) compared with 19 patients (23%) in group 2 (p=0.001). The average number of dressings used was 19 in stitch group compared with 30 in the non-stitch group (p=0.000). The average duration of healing in stitch group was 2.9 months compared with 5.7 months in non-stitch group (p=0.000). CONCLUSION: Stitching of neuropathic DFUs reduced the duration of wound healing and the frequency of wound dressing change.

Validated liquid chromatographic-fluorescence method for the quantitation of darifenacin in mice plasma and its application to a pharmacokinetic study.

A highly selective, sensitive, and rapid high-performance liquid chromatography (HPLC) method has been developed and validated for the quantification of darifenacin in mouse plasma. Bisoprolol was used as an internal standard (IS). Darifenacin and the IS were extracted using the deproteinisation technique, followed by injection of an aliquot of the supernatant into the chromatographic system. The chromatographic separation was achieved on a reversed phase C18 column with a mobile phase of acetonitrile: 0.1% diethyl amine (pH 3.5) (60:40, v/v) pumped at a flow rate of 1.0 mL min(-1). The analytes were detected at 210 and 314 nm for excitation and emission, respectively. The assay exhibited a linear range of 100-3000 ng mL(-1), with a lower detection limit of 35 ng mL(-1). The method was statistically validated for linearity, accuracy, precision, selectivity and stability according to the FDA guidelines. The intra- and inter-assay coefficients of variation did not exceed 13.5% from the nominal concentration. The accuracy for darifenacin was within ±15% of the theoretical value. The assay was successfully applied in a pharmacokinetic study.

Ultrastructural alterations in the gills of Labeo rohita fingerlings exposed to thermal extremes.

This study aimed to determine the cellular alterations in the gill of Labeo rohita exposed to lethal temperature maxima (LTM ax ) and lethal temperature minima (LTM in ) by means of transmission electron microscopy (TEM). Acclimation of advanced fingerlings of L. rohita was carried out at 26°C for 30 days. Acclimated fish were subjected to a constant rate of increase or decrease in temperature (0.3°C/min) until the LTM ax and LTM in values were reached. Dissected gills were processed for TEM, both at the end of acclimation period at ambient temperature (26°C) and at lethal temperatures. Results indicated that at ambient temperature, the gill tissues appeared normal. However, significant changes were observed at lethal temperatures. The gill tissues at lethal temperature maxima showed severely damaged lamellae, with more vacuolated space. At lethal temperature minima, gill tissues showed increased density of mitochondria. Our prima-facie report indicated that L. rohita exposed to lethal temperatures exhibited marked ultrastructural changes in the gills.

Preparing for the Objective Structured Clinical Examination (OSCE). Guide for students and residents.

The objective structured clinical examination (OSCE) has become an accepted method for evaluating clinical competence. Limited references are available for students and residents to help them prepare adequately for such examinations. In this review an outline on how to prepare, approach, and behave during the OSCE is presented. Students should prepare by repeated practice keeping in mind that the exam is usually divided into history and physical examination stations. Candidates should pay close attention to all given instructions and rules of the exam. During the encounter, proper interaction, and good communication with the patient and family are critical for a successful exam. At the end of the OSCE, candidates should avoid rushing the patient or asking for their mark. To conclude, careful preparation for the OSCE is needed to improve the likelihood of a successful outcome.

Primary stabbing "ice-pick" headache.

Primary stabbing "ice-pick" headache is rarely reported in children. It is characterized by transient, sharp stabbing pain that occurs within a localized area of the scalp for seconds. Five children were diagnosed according to the International Classification of Headache Disorders Diagnostic Criteria, Second Edition. Ages at diagnosis ranged from 6-16 years (mean age, 9.8 years), with signs lasting for 3-12 months (mean, 6.5 months) before assessment. All children presented with recurrent daily to monthly headaches that were very brief, lasting for seconds. The headache was orbital in one child, temporal in one child, and occipital in three children. Three children manifested other associated migraine headache types, and two had a positive family history of migraine. Amitriptyline was prescribed to two patients because of headache frequency and severity. The signs gradually subsided in all patients during follow-up of 3 months to 5 years (mean, 27 months). Primary stabbing headache may occasionally occur in children with features different from those encountered in adults. The headache is less frequent and often occipital in location. Its signs respond well to amitriptyline. However, larger prospective pediatric studies are needed to describe this syndrome further.

Shuddering attacks are not related to essential tremor.

Shuddering attacks are benign shivering movements occurring in young children. The etiology is unknown; however, a relationship to essential tremor has been postulated. A series of 12 consecutive children were identified over a 6-year period ending January 1, 2007. Shuddering attacks were diagnosed based on descriptive history and videotape review. Their referral diagnosis was epilepsy in 7 (58%) and movement disorder in 5 (42%). The referring physician never suspected the diagnosis. The age of onset ranged from 8 months to 2 years (mean 13 months). Family history was negative for essential tremor. None had epileptiform discharges on electroencephalography (EEG). All children were followed for 2 to 8 years (mean 6.3). Complete remission was noted by 3 to 7 years (mean 5.6) of age, and none had subsequent tremor during follow-up. In conclusion, shuddering attacks are frequently misdiagnosed leading to unnecessary investigations or treatment. No association with essential tremor was found neither in the child nor in the family.

Severe proximal myopathy with remarkable recovery after vitamin D treatment.

BACKGROUND: Osteomalacia is an uncommon cause of muscle weakness. Our objectives were to describe features of myopathy associated with Vitamin D deficiency and examine the contributing factors leading to osteomalacic myopathy in our region. METHODS: Patients identified retrospectively for the six year period ending in December 2006 with the diagnosis of osteomalacia and/or Vitamin D deficiency associated proximal muscle weakness were included. They were followed in three major centers in western Saudi Arabia. Clinical, biochemical, radiological, and electrophysiological findings were collected before and after Vitamin D treatment by chart review. RESULTS: Forty seven female patients aged 13-46 years (mean 23.5, SD 4.5) were included. All were veiled and covered heavily when outside the house for social and cultural reasons. Only eight (17%) had adequate varied diet with daily milk ingestion. All patients presented with progressive proximal muscle weakness lasting 6-24 months (mean 14) prior to our evaluation. The weakness was severe in six (13%) patients leading to wheel chair bound states. Associated musculoskeletal pain involving the back, hips, or lower limbs was common (66%). Osteomalcia was the referral diagnosis in only 11 patients and the remaining 36 (77%) patients were misdiagnosed. All patients had metabolic and radiological profiles suggestive of osteomalacia. Remarkable recovery was documented in all patients following oral cholecalciferol and calcium supplementation. CONCLUSIONS: Vitamin D deficiency is an important treatable cause of osteomalacic myopathy in Saudi Arabia. The diagnosis is frequently delayed or missed. Screening for Vitamin D deficiency in patients with acquired myopathy is needed to identify this treatable disorder.

Pregabalin: preliminary experience in intractable childhood epilepsy.

Pregabalin is a new antiepileptic drug that acts at presynaptic calcium channels, modulating neurotransmitter release. We report on treating consecutive children with severe drug-resistant epilepsy in a prospective, open-label, add-on trial. Nineteen children (63% male) aged 4-15 years (mean, 9.7; S.D., 2.9) were included. Most (74%) had daily seizures that failed multiple drugs (mean, 5). Epilepsy was symptomatic in 58%, and 74% exhibited associated cognitive deficits. Seizures were mixed in nine (47%), and four (21%) manifested Lennox-Gastaut syndrome. Pregabalin was maintained at 150-300 mg/day. On pregabalin, one (6%) child became seizure-free, and seven (37%) had >50% seizure reduction. The percentage of children with daily seizures was reduced from 74% before pregabalin to 37% afterward (P < 0.002). Side effects were evident in six (32%) with somnolence, weight gain, dizziness, or behavioral change. The drug was withdrawn in five (26%) children for lack of efficacy, and in two (11%) for worsening of myoclonic epilepsy. We conclude that pregabalin is a useful addition in the treatment of refractory childhood epilepsy. The drug should be used with caution in myoclonic epilepsy. Controlled studies are needed to establish long-term efficacy and tolerability.

Seizure semiology: value in identifying seizure origin.

The diagnosis of epilepsy depends upon a number of factors, particularly detailed and accurate seizure history, or semiology. Other diagnostic data, consisting of electroencephalography, video-monitoring of the seizures, and magnetic resonance imaging, are important in any comprehensive epilepsy program, particularly with respect to lateralizing and localizing the seizure focus, if such a focus exists, and with respect to determining the type of seizure or seizure syndrome. The aim of this review is to present a survey of important semiologic characteristics of various seizures that provide the historian with observations, which help to lateralize and localize epileptic zones. Clinical semiology is the starting point of understanding a seizure disorder and making the diagnosis of epilepsy. While it may not provide unequivocal evidence of localization of the epileptic focus, nevertheless it usually directs subsequent investigations, whose concordance is necessary for the ultimate localization.

Neurological examination of difficult and poorly cooperative children.

Many physicians consider examining the nervous system as one of the most difficult parts of the physical examination. Difficult and poorly cooperative children remain the most challenging group to examine accurately and completely. In this situation, the physician becomes less confident about the neurological findings and clinical evaluation. Several factors are predictive of difficult behavior during the evaluation, including anxiety when meeting unfamiliar people, short time to adjust to the medical situation, previous hospitalization, fear of injections, and parental anxiety. Limited neurological literature addresses the issues relating to the examination of difficult and poorly cooperative children. In this review, some practical tips and techniques are presented that can be used to improve the likelihood of obtaining accurate information about the neurological status of young and difficult children. Certainly, repeated examinations and experience play an important role; however, solid knowledge, strong communication skills, accurate observational skills, and use of proper techniques are crucial for eliciting and interpreting neurological signs in difficult children. Finally, a patient and empathetic physician and supportive guiding parents are needed for a successful neurological assessment.

Distribution and population dynamics of ticks (Acari: Ixodidae) infesting sheep in Sennar State, Sudan.

A cross-sectional survey of ticks infesting sheep was conducted in Sennar State, Sudan. A total body collection of ticks was carried out at five localities Sennar town, Singa, Dinder, Abu Naama and Um Banein on two types of Desert sheep (Watish and Ashgar) on two farms at each locality at two monthly intervals for one year starting July 2002 to May 2003. Four tick genera and eight species were identified. They were Amblyomma lepidum, Hyalomma anatolicum anatolicum, Hyalomma truncatum, Rhipicephalus (Boophilus) decoloratus, Rhipicephalus camicasi, Rhipicephalus evertsi evertsi, Rhipicephalus guilhoni and Rhipicephalus muhsamae. A significant (P < or = 0.05) seasonal pattern of activity was observed for A. lepidum and R. guilhoni with peak activity occurring during rainy seasons. The highest mean number of ticks (7.26 +/- 0.58) was recorded at Abu Naama, while the lowest mean (3.61 +/- 0.31) was recorded in Sennar. Watish type sheep carried significantly (P < or = 0.05) more ticks than Ashgar type.