Screening for Antibiotic Resistance Genes in Bacteria and the Presence of Heavy Metals in the Upstream and Downstream Areas of the Wadi Hanifah Valley in Riyadh, Saudi Arabia.

Valley surface water is considered a focal public health concern owing to the presence of multi-drug-resistant bacteria. The distribution of antimicrobial resistance (AMR) bacteria in the surface water is affected by the presence of multiple factors, including antibiotics coming from wastewater discharge or other contaminant sources such as pharmaceuticals, biocides, and heavy metals. Furthermore, there is evidence suggesting that high levels of antibiotic resistance genes (ARGs) can be transferred within bacterial communities under the influence of heavy metal stress. Hence, the primary aim of this study is to investigate the presence of heavy metals and bacterial ARGs in upstream as well as downstream locations of Wadi Hanifah Valley in Riyadh, Saudi Arabia. Sample collection was conducted at eighteen surface water sites within the valley in total. The selection of ARGs was associated with the most common antibiotics, including ß-lactam, tetracycline, erythromycin, gentamicin, sulphonamide, chloramphenicol, vancomycin, trimethoprim, and colistin antibiotics, which were detected qualitatively using polymerase chain reaction (PCR) technology. The tested antibiotic resistance genes (ARGs) included (blaNDM-1 (for the antibiotic class Beta-lactamases), mecA (methicillin-resistant Staphylococcus aureus), tet(M) and tet(B) (for the antibiotic class Tetracycline), ampC (for the antibiotic class Beta-lactamases), vanA (for the antibiotic class vancomycin), mcr-1 (for the antibiotic class colistin), erm(B) (for the antibiotic class erythromycin), aac6'-Ie-aph2-Ia (for the antibiotic class Gentamicin), sulII (for the antibiotic class sulphonamide), catII (for the antibiotic class Chlorophincol), and dfrA1 (for the antibiotic class trimethoprim). Moreover, an assessment of the levels of heavy metals such as lithium (Li), beryllium (Be), chromium (Cr), cobalt (Co), arsenic (As), cadmium (Cd), tin (Sn), mercury (Hg), and lead (Pb) was conducted by using inductively coupled plasma mass spectrometry (ICPMS). According to our findings, the concentrations of sulphonamide, erythromycin, and chloramphenicol ARGs (erm(B), sulII, and catII) were observed to be the most elevated. Conversely, two ARGs, namely mecA and mcr-1, were not detected in the samples. Moreover, our data illustrated a significant rise in ARGs in the bacteria of water samples from the upstream sites as compared with the water samples from the downstream sites of Wadi Hanifah Valley. The mean concentration of Li, Be, Cr, Co, As, Cd, Sn, Hg, and Pb in the water samples was estimated to be 37.25 µg/L, 0.02 µg/L, 0.56 µg/L,0.32 µg/L, 0.93 µg/L, 0.01 µg/L, 200.4 µg/L, 0.027 µg/L, and 0.26 µg/L, respectively, for the selected 18 sites. Furthermore, it was revealed that the concentrations of the screened heavy metals in the water samples collected from various sites did not surpass the maximum limits set by the World Health Organization (WHO). In conclusion, this study offers a concise overview of the presence of heavy metals and ARGs in water samples obtained from the Wadi Hanifah Valley in Riyadh, KSA. Such findings will contribute to the ongoing monitoring and future risk assessment of ARGs spread in surface water.

Prevalence of Steroid-Induced Hyperglycemia in King Abdulaziz Specialist Hospital, Taif City, Saudi Arabia.

Background Hyperglycemia is a common side effect of high-dose steroid therapy in hospitalized patients. Objectives To assess the prevalence of hyperglycemia among hospitalized patients receiving steroid therapy. Methods A retrospective study was conducted among 245 patients. The inclusion criteria were patients undergoing steroid therapy and admitted to a single tertiary care hospital due to medical complications or exacerbation of the diseases they were suffering from. Data encompassing patient demographics, admission, discharge dates, comorbidities, medication histories, laboratory results (including blood glucose levels), and documented corticosteroid administrations were meticulously gathered from electronic health records (EHRs). A logistic regression model analysis was done to predict the risk factors of poor glycemic control among hospitalized patients. Results The prevalence of hyperglycemia among the patients who were on steroid therapy was 34.2%. About 70.7% of the patients who required insulin at the time of admission required >17 units, and the insulin requirement was significantly higher among patients who received dexamethasone compared to other steroids (p<0.05). Older age (>65 years) was found to be independently associated with poor glycemic control (p<0.05). Conclusion The study revealed that almost one-third of patients on steroid therapy had hyperglycemia. Monitoring of patients for hyperglycemia after beginning high-dose steroid therapy should be done.

The Potency of Goat Milk in Reducing the Induced Neurotoxic Effects of Valproic Acid in Rat Pups as a Rodent Model of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a progressively prevalent neurodevelopmental disorder with substantial clinical heterogeneity. Despite the considerable interest in dietary interventions, no consensus has been reached regarding the optimal nutritional therapy. The present study aimed to investigate the possible positive effect of goat's milk (GM) compared to cow's milk (CM) on ASD autistic features in a valproic acid (VPA; 600 mg/kg)-induced white albino rat model of autism. All tests were conducted on rats that were divided into four groups (n = 15/group): control with goat milk (GM) treatment, control with cow milk (CM) treatment, autistic with goat milk (GM) treatment, and autistic with cow milk treatment. The casein levels were also measured in GM and CM. Social behavior was assessed by three-chambered sociability to test social interaction after the intervention. After 15 days of intervention, selected biomarkers, such as glutathione (GSH), thiobarbituric acid reactive substance (TBARS), interleukin-6 (IL-6), neurotransmitter dopamine (DA), serotonin (5-hydroxytryptamine, 5-HT), and glutamate (GLU), were measured in blood serum and brain homogenates. The results showed a significant positive effect on social interaction in the VPA rat ASD model fed GM. Blood serum and brain samples showed a positive increase in TBARS in the VPA rat model fed GM, but brain and serum serotonin levels were lower in both VPA-GM and VPA-CM groups. Dopamine in serum was also lower in the VPA-CM group than in the VPA-GM group. IL-6 levels were slightly lower in the VPA-GM group than in the VPA-CM group. In comparison with cow's milk, goat's milk was effective in ameliorating the neurotoxic effects of VPA. Goat's milk may be considered a suitable source of dairy for children diagnosed with ASD. Autistic children with allergies to cow's milk could possibly convert to goat's milk. Nevertheless, more in-depth studies and clinical trials are recommended.

Different Alterations in Gut Microbiota between Bifidobacterium longum and Fecal Microbiota Transplantation Treatments in Propionic Acid Rat Model of Autism.

Autism spectrum disorders (ASD) consist of a range of neurodevelopmental conditions accompanied by dysbiosis of gut microbiota. Therefore, a number of microbiota manipulation strategies were developed to restore their balance. However, a comprehensive comparison of the various methods on gut microbiota is still lacking. Here, we evaluated the effect of Bifidobacterium (BF) treatment and fecal microbiota transplantation (FT) on gut microbiota in a propionic acid (PPA) rat model of autism using 16S rRNA sequencing. Following PPA treatment, gut microbiota showed depletion of Bacteroidia and Akkermansia accompanied by a concomitant increase of Streptococcus, Lachnospiraceae, and Paraeggerthella. The dysbiosis was predicted to cause increased levels of porphyrin metabolism and impairments of acyl-CoA thioesterase and ubiquinone biosynthesis. On the contrary, BF and FT treatments resulted in a distinct increase of Clostridium, Bifidobacterium, Marvinbryantia, Butyricicoccus, and Dorea. The taxa in BF group positively correlated with vitamin B12 and flagella biosynthesis, while FT mainly enriched flagella biosynthesis. In contrast, BF and FT treatments negatively correlated with succinate biosynthesis, pyruvate metabolism, nitrogen metabolism, beta-Lactam resistance, and peptidoglycan biosynthesis. Therefore, the present study demonstrated that BF and FT treatments restored the PPA-induced dysbiosis in a treatment-specific manner.

The Efficacy of Fecal Transplantation and Bifidobacterium Supplementation in Ameliorating Propionic Acid-Induced Behavioral and Biochemical Autistic Features in Juvenile Male Rats.

Gut microbiota plays a major role in neurological disorders, including autism. Modulation of the gut microbiota through fecal microbiota transplantation (FMT) or probiotic administration, such as Bifidobacteria, is suggested to alleviate autistic symptoms; however, their effects on the brain are not fully examined. We tested both approaches in a propionic acid (PPA) rodent model of autism as treatment strategies. Autism was induced in Sprague-Dawley rats by administering PPA orally (250 mg/kg) for 3 days. Animals were later treated with either saline, FMT, or Bifidobacteria for 22 days. Control animals were treated with saline throughout the study. Social behavior and selected brain biochemical markers related to stress hormones, inflammation, and oxidative stress were assessed. PPA treatment induced social impairments, which was rescued by the treatments. In the brain, Bifidobacteria treatment increased oxytocin relative to control and PPA groups. Moreover, Bifidobacteria treatment rescued the PPA-induced increase in IFN-γ levels. Both treatments increased GST levels, which was diminished by the PPA treatment. These findings indicate the potential of gut microbiota-targeted therapeutics in ameliorating behavioral deficit and underlying neural biochemistry.

Fecal Transplant and Bifidobacterium Treatments Modulate Gut Clostridium Bacteria and Rescue Social Impairment and Hippocampal BDNF Expression in a Rodent Model of Autism.

Autism is associated with gastrointestinal dysfunction and gut microbiota dysbiosis, including an overall increase in Clostridium. Modulation of the gut microbiota is suggested to improve autistic symptoms. In this study, we explored the implementation of two different interventions that target the microbiota in a rodent model of autism and their effects on social behavior: the levels of different fecal Clostridium spp., and hippocampal transcript levels. Autism was induced in young Sprague Dawley male rats using oral gavage of propionic acid (PPA) for three days, while controls received saline. PPA-treated animals were divided to receive either saline, fecal transplant from healthy donor rats, or Bifidobacterium for 22 days, while controls continued to receive saline. We found that PPA attenuated social interaction in animals, which was rescued by the two interventions. PPA-treated animals had a significantly increased abundance of fecal C. perfringens with a concomitant decrease in Clostridium cluster IV, and exhibited high hippocampal Bdnf expression compared to controls. Fecal microbiota transplantation or Bifidobacterium treatment restored the balance of fecal Clostridium spp. and normalized the level of Bdnf expression. These findings highlight the involvement of the gut-brain axis in the etiology of autism and propose possible interventions in a preclinical model of autism.

The role of sex-differentiated variations in stress hormones, antioxidants, and neuroimmune responses in relation to social interaction impairment in a rodent model of autism.

Males are more likely to develop autism as a neurodevelopmental disorder than females, but the mechanisms underlying male susceptibility are not fully understood. In this paper, we used a well-characterized propionic acid (PPA) rodent model of autism to study sex differences in stress hormones, antioxidants' status, and the neuroimmune response that may contribute to the preponderance of autism in males. Sprague Dawley rats of both sexes were divided into a saline-treated group as controls and PPA-treated groups, receiving 250 mg/kg of PPA per day for three days. Animals' social behavior was examined using the three-chamber social test. Hormones (ACTH, corticosterone, melatonin, and oxytocin), oxidative stress biomarkers (glutathione, glutathione-S-transferase, and ascorbic acid), and cytokines (IL-6, IL-1α, IL-10, and IFNγ) were measured in the brain tissue of all the animals. The results showed a sex dimorphic social response to PPA treatment, where males were more susceptible to the PPA treatment and exhibited a significant reduction in social behavior with no effects observed in females. Also, sex differences were observed in the levels of hormones, antioxidants, and cytokines. Female rats showed significantly higher corticosterone and lower oxytocin, antioxidants, and cytokine levels than males. The PPA treatment later modulated these baseline differences. Our study indicates that the behavioral manifestation of autism in PPA-treated males and not females could be linked to neural biochemical differences between the sexes at baseline, which might play a protective role in females. Our results can contribute to early intervention strategies and treatments used to control autism, an increasingly prevalent disorder.