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OBJECTIVES: Datura stramonium , jimsonweed, is a toxic plant with hallucinogenic properties. Although there are many studies on Datura poisoning, none reported cases in Jordan. This study offers a comprehensive review on D. stramonium ingestion, covering its epidemiology, clinical presentation, and treatment. We aimed to provide better understanding of the factors for Datura ingestion, identify prevention and management strategies, and address research challenges. METHODS: This study adopted a retrospective review design to evaluate the cases of Datura poisoning in Al Karak, province of Jordan during the spring of 2022. Data collected from medical records, toxicology databases, and consultation records were analyzed using descriptive statistics. RESULTS: The common symptoms of Datura poisoning included agitation, mydriasis, and tachycardia. The management approaches comprised supportive care, administration of Diazepam for agitation, and, in some cases, neostigmine to counteract anticholinergic effects. CONCLUSIONS: Understanding the risks associated with D. stramonium poisoning and implementing effective prevention and management strategies are crucial. This study highlights the importance of recognizing Datura poisoning as a potential diagnosis in children presenting with unexplained anticholinergic symptoms or agitation to the emergency room.

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Type 2 diabetes mellitus is a multifactorial disorder whose primary manifestation usually initiates with elevated blood sugar levels. Several antidiabetic agents are used to manage type 2 diabetes mellitus, of which empagliflozin is an oral sodium-glucose co-transporter (SGLT-2) inhibitor in the kidney. This research aims to develop and validate a simple analytical method for determining empagliflozin levels in biological fluid and to further evaluate grapefruit juice's impact on empagliflozin pharmacokinetics in rats. High-Performance Liquid Chromatography (HPLC) was used to establish a simple, rapid, and accurate method for determining empagliflozin levels in rat plasma, in the presence of grapefruit juice. Four groups of rats (n = 10 rats in each) were used in the preclinical study. Group A (healthy rats) received empagliflozin alone; Group B (healthy rats) received empagliflozin with grapefruit; Group C (diabetic rats) received empagliflozin with grapefruit; and Group D (healthy, negative control) received no medication. The rats (n = 10) were given grapefruit juice instead of water for seven days before receiving the empagliflozin dose (0.16 mg/kg). Some pharmacokinetic parameters for each group were determined. The maximum plasma concentration (Cmax) and area under the curve (AUC) of empagliflozin in Group A without grapefruit intake were 730 ng/mL and 9264.6 ng × h/mL, respectively, with Tmax (2 h). In Group B, Cmax was 1907 ng/mL and AUC was 10,290.75 ng × h/mL in the presence of grapefruit, with Tmax (1 h); whereas, in Group C, the Cmax was 2936 ng/mL and AUC was 18657 ng × h/mL, with Tmax (2 h). In conclusion, our results showed that the co-administration of grapefruit with empagliflozin should be cautiously monitored and avoided, in which grapefruit elevates the plasma level of empagliflozin. This may be attributed to the inhibition of the uridine enzyme in the grapefruit by hesperidin, naringin, and flavonoid.

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BACKGROUND AND AIM: Monosodium glutamate (MSG) is used in food-additives, and the Food and Drug Administration has placed it under intense scrutiny following several reports that it causes glutamate neurotoxicity. Ashwagandha (ASH) roots are traditionally used for memory enhancement. This study aimed to evaluate the nootropic activity of ASH as well as its therapeutic anti-amnesic activity against MSG-induced hippocampal-dependent spatial memory impairment and hippocampal-NMDAR modulation. METHOD: A total of 36 rats were divided equally into six groups (n = 6 in each group); the rats in the normal and negative groups were administered daily doses of normal saline and MSG (300 mg/kg), respectively, for 21 days. Two nootropic groups were administered ASH at 300 and 500 mg/kg o.p., respectively, for 21 days. Two other treatment groups were administered daily doses of MSG 300 mg/kg o.p. as well as 300 mg/kg and 500 mg/kg o.p. of ASH for 21 days. The rats' spatial memory was assessed for five days using the MWM. Additionally, NMDAR were measured quantitatively by immunohistochemistry. RESULTS: We found that the rats in the nootropic groups showed significantly enhanced nootropic activity characterized by improved hippocampal-dependent spatial memory, as well as increases in the level of NMDAR in the Cornu Ammonis 1 region of their hippocampus. Moreover, we elucidated the therapeutic potential of ASH to protect against the depression of spatial memory caused by MSG-induced neurotoxicity. CONCLUSION: Further, we elucidated a strong correlation between NMDAR-positive cells in the hippocampus and enhancement of spatial learning induced by long-term administration of ASH as well as a strong correlation between NMDAR positive cells in the hippocampus and depression of spatial learning induced by long-term administration of ASH and MSG.

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BACKGROUND/OBJECTIVE: Alzheimer's disease (AD) is mainly characterized by amnesia that affects millions of people worldwide. This study aims to explore the effectiveness capacities of bee venom (BV) for the enhancement of the memory process in a rat model with amnesia-like AD. METHODS: The study protocol contains two successive phases, nootropic and therapeutic, in which two BV doses (D1; 0.25 and D2: 0.5 mg/kg i.p.) were used. In the nootropic phase, treatment groups were compared statistically with a normal group. Meanwhile, in the therapeutic phase, BV was administered to scopolamine (1mg/kg) to induce amnesia-like AD in a rat model in which therapeutic groups were compared with a positive group (donepezil; 1mg/kg i.p.). Behavioral analysis was performed after each phase by Working Memory (WM) and Long-Term Memory (LTM) assessments using radial arm maze (RAM) and passive avoidance tests (PAT). Neurogenic factors; Brain-derived neurotrophic factor (BDNF), and Doublecortin (DCX) were measured in plasma using ELISA and Immunohistochemistry analysis of hippocampal tissues, respectively. RESULTS: During the nootropic phase, treatment groups demonstrated a significant (P < 0.05) reduction in RAM latency times, spatial WM errors, and spatial reference errors compared with the normal group. In addition, the PA test revealed a significant (P < 0.05) enhancement of LTM after 72 hours in both treatment groups; D1 and D2. In the therapeutic phase, treatment groups reflected a significant (P < 0.05) potent enhancement in the memory process compared with the positive group; less spatial WM errors, spatial reference errors, and latency time during the RAM test, and more latency time after 72 hours in the light room. Moreover, results presented a marked increase in the plasma level of BDNF, as well as increased hippocampal DCX-positive data in the sub-granular zone within the D1 and D2 groups compared with the negative group (P < 0.05) in a dose-dependent manner. CONCLUSION: This study revealed that injecting BV enhances and increases the performance of both WM and LTM. Conclusively, BV has a potential nootropic and therapeutic activity that enhances hippocampal growth and plasticity, which in turn improves WM and LTM. Given that this research was conducted using scopolamine-induced amnesia-like AD in rats, it suggests that BV has a potential therapeutic activity for the enhancement of memory in AD patients in a dose-dependent manner but further investigations are needed.

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Alzheimer's disease is regarded as a common neurodegenerative disease that may lead to dementia and the loss of memory. We report here the nootropic and anti-amnesic effects of both peppermint and rosemary oils using a rat model of scopolamine-induced amnesia-like AD. Rats were administered orally with two doses (50 and 100 mg/kg) of each single oil and combined oils. The positive group used donepezil (1 mg/kg). In the therapeutic phase, rats were administered scopolamine (1 mg/kg) through the oral administration of oils. During the nootropic phase, both oils showed a significant (p < 0.05) decrease in radial arm maze latency times, working memory, and reference memory errors compared with the normal group, along with significant (p < 0.05) enhancements of long-term memory during the passive avoidance test. Therapeutic phase results revealed significant enhancements of memory processing compared with the positive groups. In the hippocampus, oils exhibited an elevation of BDNF levels in a dose-dependent manner. Immunohistochemistry findings showed increased hippocampal neurogenesis suppressed by scopolamine in the sub-granular zone, and the anti-amnesic activity of single oil was enhanced when the two oils combined. Gas chromatography-mass spectrometry (GCMS) of the two oils revealed sufficient compounds (1,8-Cineole, α-Pinene, menthol and menthone) with potential efficacy in the memory process and cognitive defects. Our work suggests that both oils could enhance the performance of working and spatial memory, and when combined, more anti-amnesic activity was produced. A potential enhancement of hippocampal growth and neural plasticity was apparent with possible therapeutic activity to boost memory in AD patients.

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Overexpression of c-Myc plays an essential role in leukemogenesis and drug resistance, making c-Myc an attractive target for cancer therapy. However, targeting c-Myc directly is impossible, and c-Myc upstream regulator pathways could be targeted instead. This study investigated the effects of thymoquinone (TQ), a bioactive constituent in Nigella sativa, on the activation of upstream regulators of c-Myc: the JAK/STAT and PI3K/AKT/mTOR pathways in HL60 leukemia cells. Next-generation sequencing (NGS) was performed for gene expression profiling after TQ treatment. The expression of c-Myc and genes involved in JAK/STAT and PI3K/AKT/mTOR were validated by quantitative reverse transcription PCR (RT-qPCR). In addition, Jess assay analysis was performed to determine TQ's effects on JAK/STAT and PI3K/AKT signaling and c-Myc protein expression. The results showed 114 significant differentially expressed genes after TQ treatment (p < 0.002). DAVID analysis revealed that most of these genes' effect was on apoptosis and proliferation. There was downregulation of c-Myc, PI3K, AKT, mTOR, JAK2, STAT3, STAT5a, and STAT5b. Protein analysis showed that TQ also inhibited JAK/STAT and PI3K/AKT signaling, resulting in inhibition of c-Myc protein expression. In conclusion, the findings suggest that TQ potentially inhibits proliferation and induces apoptosis in HL60 leukemia cells by downregulation of c-Myc expression through inhibition of the JAK/STAT and PI3K/AKT signaling pathways.

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BACKGROUND: This study sought to determine whether (1) evidence is available of interactions between anodal tDCS and oscillated tDCS stimulation patterns to increase the power of endogenous brain oscillations and (2) the frequency matching the applied anodal otDCS's frequency and the brain's dominant intrinsic frequency influence power shifting during stimulation pattern sessions by both anodal DCS and anodal oscillated DCS. METHOD: Rats received different anodal tDCS and otDCS stimulation patterns using 8.5 Hz and 13 Hz state-related dominant intrinsic frequencies of anodal otDCS. The rats were divided into groups with specific stimulation patterns: group A: tDCS-otDCS (8.5 Hz)-otDCS (13 Hz); group B: otDCS (8.5 Hz)-tDCS-otDCS (13 Hz); group C: otDCS (13 Hz)-tDCS-otDCS (8.5 Hz). Acute relative power changes (i.e., following 10 min stimulation sessions) in six frequency bands-delta (1.5-4 Hz), theta (4-7 Hz), alpha-1 (7-10 Hz), alpha-2 (10-12 Hz), beta-1 (12-15 Hz) and beta-2 (15-20 Hz)-were compared using three factors and repeated ANOVA measurement. RESULTS: For each stimulation, tDCS increased theta power band and, above bands alpha and beta, a drop in delta power was observed. Anodal otDCS had a mild increasing power effect in both matched intrinsic and delta bands. In group pattern stimulations, increased power of endogenous frequencies matched exogenous otDCS frequencies-8.5 Hz or 13 Hz-with more potent effects in upper bands. The power was markedly more potent with the otDCS-tDCS stimulation pattern than the tDCS-otDCS pattern. SIGNIFICANCE: The findings suggest that the otDCS-tDCS pattern stimulation increased the power in matched intrinsic oscillations and, significantly, in the above bands in an ascending order. We provide evidence for the successful corporation between otDCS (as frequency-matched guidance) and tDCS (as a power generator) rather than tDCS alone when stimulating a desired brain intrinsic band (herein, tES specificity).

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There is a paucity of data about the at home monitoring and the outpatient setting and care of patients with non-invasive ventilation. We here show, in a prospective study, that both standardized outpatient care visits as well as quality of life monitoring at home are safe and feasible. Monitoring and managing the quality of care at home did not lead to an increase of non-elective hospitalisations or deterioration of respiratory disease burden.

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This study was conducted to determine the prevalence rate of VTEC in slaughtered sheep and goats and to evaluate the contamination rate of VTEC in slaughterhouses and butchers' shops in southern Jordan. 201 E. coli isolates from animals' faecal samples and 33 E. coli isolates from slaughterhouse/butcher shop samples were characterized by multiplex PCR (mPCR) reaction for detection of stx1, stx2, eae A and E-hly A virulent genes. Twenty-six virulent E. coli isolates were characterized by mPCR to seven different virulent patterns: stx1, stx1+stx2, stx1+eae A, stx1+E-hly A, stx1+eae A+E-hly A, eae A and E-hly A. It was found that VTEC comprised 6.4% and 21% of the total E. coli isolates from slaughtered small ruminants and slaughterhouses/ butchers' shops, respectively. The VTEC comprised 76.2% of the virulent isolates. The proportion of stx1:stx1+stx2 patterns was 19:1. It was found that the characterized complex VTEC (containing eae A and/or E-hly A) possessed three virulence patterns, including (VTEC) stx1 +eae A, (VTEC/EHEC) stx1 +E-hly A and (VTEC/EHEC) stx1 +eae A +E-hly A in percentages of 30%, 25% and 10%, respectively, in relation to the total VTEC isolates. Only two VTEC isolates were characterized as E. coli O157 and O26 serotypes, as highly pathogenic strains. Each of the O157 and O26 VTEC isolates was in a percentage of 0.4% in relation to the total E. coli isolates with virulent patterns stx1, eae A and E-hly A. The rest of the VTEC isolates were non-O157 VTEC. The antibiotic sensitivity test showed that the isolated VTEC was highly sensitive to gentamicin and co-trimoxazole and highly resistant to tetracycline and ampicillin.

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In a prospective study carried out on 78 patients with chronic constipation (31, with slow transit, 47 with obstructive defecation disorders) the evacuation function of the rectum during defecation was assessed by defecoflowmetry. These patients were compared to a control group of normal volunteers (n = 32). The following parameters were evaluated: defecation and retention volume, defecation fraction, defecation time, maximum flow, mean flow rate and time to maximum flow. As expected, there was no difference in evacuation function between the group of patients with slow transit and the control group. Significant differences, however, existed between the two types of constipation, as well as between obstructive defecation disease and controls, regarding all parameters mentioned above. Evacuation function depends neither on rectal neck pressure nor on intrarectal pressure. In patients with obstructive defecation disorders, three subgroups were discernable: one with prolonged time of defecation and satisfactory evacuation, one with prolonged time of defecation and poor evacuation, and one small group of patients who were not able to defecate. Each group is based on a different underlying pathomechanism. We conclude that changes in evacuation function of the rectum refer either to volume or to time of defecation, or to both. Changes are found only in obstructive type constipation, not in slow transit constipation. Therefore, defeconflowmetry as a dynamic procedure can be used in screening for the classification of chronic constipation.

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UNLABELLED: Our aim was to review the results and to investigate the prognosis in a prospective study of aggressive surgical treatment in 186 patients (59% women, 41% men, age 18 to 65 years) treated during the past 9 1/2 years by conventional laying open of the fistula (n = 71), endorectal advancement flap repair (n = 89) and by fistulectomy without internal sphincterotomy (n = 37). 54 (29%) patients had intersphincteric, 57 (30.5%) transsphincteric, 10 (5.5%) suprasphincteric, 37 (20%) low rectovaginal and 28 (15%) had complex fistulas without internal opening. Four sphincter saving techniques were performed by the high and fistulas (n = 89) with primary occlusion of the intraanal ostium and endorectal mucosal flap (n = 29), endorectal advancement flap (n = 41), anodermal flap (n = 8) and transperineal repair with levator interposition (n = 11). Postoperatively 18 cases (20.2%) of suture leakage occurred, 27% in the mucosal flap group, 17.6% in the advancement flap group, 12.5% in the anodermal group, and 27% in the transperineal group. A complete primary healing of perianal wounds was noted in 73% of the patients within 6 months. The presence of rectal disease (n = 77) did not adversely influence the rate and duration of healing. Persistent or recurrent fistula occurs in 29 patients (15.6%), 22% in the sphincter saving group, 4% in the intersphincteric group and 32% in the complex type of fistulas. Disturbance of continence was observed in 9 patients (4.8%). Postoperatively, there was no significant change in resting anal pressure and maximum voluntary conctraction pressure in any fistula group (n = 104). CONCLUSION: The presented clinical and functional long term results of patients with Crohn's fistulas underline the importance of experience in the treatment of perianal fistula disease. A successful treatment depends primarily on an aggressive therapeutic strategy and the appropriate method of operation.

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A prospective study was carried out on 55 patients with complicated anal fistulas (41 transsphincteric, 5 suprasphincteric and 9 rectovaginal) to evaluate the value of two sphincter-conserving techniques with primary occlusion of the internal ostium and endorectal advancement flap (group A, n = 34) or mucosal flap (group B, n = 21). Ten of the patients had Crohn's disease. Both techniques consist in one-stage fistulectomy without drainage of the intersphincteric space. The inflamed proctodeal and granulation tissue was carefully cleared. The site of the former primary orifice of the fistula was adapted by means of two or three peranally performed single stitches. The peranally applied suture included the layers of the internal anal sphincter muscle only. A mobilized flap of rectal wall (group A) and rectal mucosa and submucosa (group B) about 4 cm x 3 cm in size was stitched below the muscular sphincter. The perianal part of the wound was left to heal by second intention. Postoperatively there were 16 cases of suture leakage (23.5% in group A, and 38% in group B), and 19 patients (26% or 47% in both groups) had to have revision surgery because of recurrent fistula or sutur leakage; 2 patients (3.6%) developed incontinence with intermittent fecal soiling. Complete incontinence was not observed in any patient. No significant difference in clinical and functional results was determined between the two groups.

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Retroileal colorectal anastomosis following a complete resection of left-sided colon was performed in 28 patients with differing diseases of the colon. Concerning the rate of leakage of anastomosis dextraposition appeared to be as safe as conventional techniques. Turnbull originally created this technique to perform a tension-free anastomosis after resection of the left sided colon. In doing so the retained colon reduces the risk of incontinence especially seen with elderly patients.

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In a prospective study on 224 patients with so-called high-fistula in ano (189 transsphincteric, 35 suprasphincteric) the long-term results of a sphincter-saving operation technique were assessed. The follow-up period was 1 to 7.5 years. This technique consists of one-stage fistulectomy as well as of drainage of the intersphincteric space by internal sphincterotomy. The site of the former primary orifice of the fistula is adapted by multiple peranally performed single stitches, including mucosal advancement flap distal to the original fistulous opening. Postoperatively, 24 cases of suture leakage occurred (9% with the transsphincteric and 20% with the suprasphincteric fistula). 27 patients developed late complications like fistula recurrences or combinations of fistula and anal abscess (10.7% with the transsphincteric and 19.9% with the suprasphincteric fistula). Anal manometry was carried out preoperatively as well as postoperatively. A significant decrease in the postoperative resting pressure compared to the preoperative value was determined. The two fistula groups differed statistically both with regard to the resting pressure and the contraction pressure. Significant impairment of continence developed in 21% of patients with transsphincteric fistula but in 43% of patients with suprasphincteric fistula (intermittent fecal spoiling/use of perineal pads). The total percentage of complications rose with the number of previous fistula operations.

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A prospective clinical manometric and radiological study has been performed, before and after anterior levatorplasty and sphincter plication on 18 patients (mean age 61.6 years) with neurogenic faecal incontinence. Continence was improved on 15 (83%) patients, 13 (72%) patients were continent to solid and liquid stool, 3 (17%) of whom regained normal continence only, at a minimum of 6 months follow-up (phi 21.5 months). Postoperatively there was a significant increase in the resting anal pressure (p = 0.05) an maximum voluntary contraction pressure (p = 0.001). No significant change in sphincter length, duration of the action potentials, pudendal nerve terminal motor latency (PNTML), pelvic descent or anorectal angle was seen postoperatively. The incontinence and defaecation-score showed postoperatively a significant difference concerning soiling, time from urgency to defaecation, and discrimination between flatus and stool.

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On 182 patients undergoing closure of a stoma 149 colostoma and 33 ileostoma closures were performed. The complication rate with 5-8% leakages in site of the anastomosis comes out very high. Furthermore the surgeon has to count with a high quote of wound infections. The complication rate of the ileostoma closures with 18% appears distinctly higher than those of the colostoma closures with 6.7%. One patient belonging to the group of colostoma closures died. The extraperitoneal closure with Turnbull's procedure was conspicuous by reason of the high rate of enterocutaneous fistulas and the high rate of incisional herniations, so that this method should only be used in special cases. We routinely enforce an intraperitoneal closure of the stoma. The resection with an end-to-end anastomosis in comparison to the suture of the anterior wall implies in our opinion neither advantages nor disadvantages.

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