Cedrol supplementation ameliorates memory deficits by regulating neuro-inflammation and cholinergic function in lipopolysaccharide-induced cognitive impairment in rats.

Background: Cedrol, a sesquiterpene alcohol, is found in a high amount in several conifers. It possess several beneficial health effects, including antioxidant and anti-inflammatory properties. Objective: This study evaluates the neuroprotective role of cedrol against lipopolysaccharide (LPS)-induced neuroinflammation and memory loss in rats. Methods: Wistar rats were treated with cedrol (7.5, 15, and 30 mg/kg, oral, two weeks). During the last week, the rats (except for the control group) were treated with LPS (intraperitoneal injection, 1 mg/kg) to induce memory impairment. After that, the animals were subjected to behavioral studies (Morris water maze and passive avoidance) and biochemical assessments. Results: Our results showed a significant decrease in learning and memory function-in LPS-induced rats which were reversed by cedrol. Also, there was a significant increase in the cerebral levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and malondialdehyde (MDA) as well as acetylcholinesterase (AChE) activity in LPS-treated rats. Besides, a significant reduction in total thiol and superoxide dismutase levels was observed in LPS-treated rats. However, cedrol significantly decreased the brain level of AChE, TNF-α, and IL-1ß. Administration of cedrol also restored the oxidative stress markers. Conclusion: the beneficial effects of cedrol against LPS-induced memory impairment could be due to antioxidant activities and modulation of neuro-inflammatory mediators.

Chronic meningitis in adults: a comparison between neurotuberculosis and neurobrucellosis.

BACKGROUND: In regions endemic for tuberculosis and brucellosis, distinguishing between tuberculous meningitis (TBM) and brucella meningitis (BM) poses a substantial challenge. This study investigates the clinical and paraclinical characteristics of patients with TBM and BM. METHODS: Adult patients diagnosed with either TBM or BM who were admitted to two referral hospitals between March 2015 and October 2022, were included, and the characteristics of the patients were analyzed. RESULTS: Seventy patients formed the study group, 28 with TBM and 42 with BM, were included. TBM patients had a 2.06-fold (95% CI: 1.26 to 3.37, P-value: 0.003) higher risk of altered consciousness and a 4.80-fold (95% CI: 1.98 to 11.61, P-value: < 0.001) higher risk of extra-neural involvement as compared to BM patients. Cerebrospinal fluid (CSF) analysis revealed a significantly higher percentage of polymorphonuclear leukocytes (PMN) in TBM compared to BM (Standardized mean difference: 0.69, 95% CI: 0.18 to 1.20, P-value: 0.008). Neuroimaging findings indicated higher risks of hydrocephalus (P-value: 0.002), infarction (P-value: 0.029), and meningeal enhancement (P-value: 0.012) in TBM compared to BM. Moreover, TBM patients had a 67% (95% CI: 21% to 131%, P-value:0.002) longer median length of hospital stay and a significantly higher risk of unfavorable outcomes (Risk ratio: 6.96, 95% CI: 2.65 to 18.26, p < 0.001). CONCLUSIONS: Our study emphasizes that TBM patients displayed increased frequencies of altered consciousness, PMN dominance in CSF, extra-neural involvement, hydrocephalus, meningeal enhancement, and brain infarction. The findings emphasize the diagnostic difficulties and underscore the importance of cautious differentiation between these two conditions to guide appropriate treatment strategies.

Neuro-protective Effect of Acetyl-11-keto-ß-boswellic Acid in a Rat Model of Scopolamine-induced Cholinergic Dysfunction.

BACKGROUND: Acetyl-11-keto-ß-boswellic acid (AKBA) is a major component of the oleo-gum resin of B. serrata with multiple pharmacological activities. The objective of this study was to explore the underlying mechanisms of neuroprotective potential of AKBA against scopolamine-mediated cholinergic dysfunction and memory deficits in rats. METHODS: The rats received AKBA (2.5, 5, and 10 mg/kg, oral) for 21 days. In the third week, scopolamine was administered 30 min before the Morris water maze and passive avoidance tests. In order to perform biochemical assessments, the hippocampus and prefrontal cortex were extracted from the rats euthanized under deep anesthesia. RESULTS: In the MWM test, treatment with AKBA (5 and 10 mg/kg) decreased the latency and distance to find the platform. Moreover, in the PA test, AKBA remarkably increased latency to darkness and stayed time in lightness while decreasing the frequency of entry and time in the darkness. According to the biochemical assessments, AKBA decreased acetylcholinesterase activity and malondialdehyde levels while increasing antioxidant enzymes and total thiol content. Furthermore, AKBA administration restored the hippocampal mRNA and protein levels of brain-derived neurotrophic factor (BDNF) and mRNA expression of B-cell lymphoma (Bcl)- 2 and Bcl-2- associated X genes in brain tissue of scopolamine-injured rats. CONCLUSION: The results suggested the effectiveness of AKBA in preventing learning and memory dysfunction induced by scopolamine. Accordingly, these protective effects might be produced by modulating BDNF, cholinergic system function, oxidative stress, and apoptotic markers.

Evaluation of epidemiological and microbiological characteristics, clinical features, and outcomes of adult patients with infective endocarditis in Mashhad, Iran.

INTRODUCTION: Infective endocarditis (IE) is a serious problem with high morbidity and mortality. However, there is a paucity of data regarding its epidemiology in non-high-income settings. Here, we described the characteristics of patients with IE. METHODOLOGY: Between March 2012 to March 2020, all adults (≥ 16 years) with a diagnosis of IE who were admitted to a university hospital in Mashhad, Iran, were included in the study. RESULTS: We evaluated 46 cases of IE with a median age of 42 years (interquartile range 31 to 58.3 years), of whom 21 (46%) had a definite diagnosis. The presence of a prosthetic valve or intracardiac device was the leading predisposing factor (N = 14, 30%). The etiology of IE in 22 subjects (48%) remained unknown. Staphylococcus aureus (N = 12, 26%) was the most common causative pathogen. Echocardiography revealed the mitral valve as the most affected valve (N = 18, 39%). Intravenous drug users (IVDU) had a higher chance of right-sided IE, as compared to no IVDU patients (odds ratio: 35, 95% CI: 3.7 to 425.0). The most prevalent complications were lung infarction, acute heart failure, and neurologic involvement (N = 5, 11% for each), and 15 patients (33%) died because of IE. CONCLUSIONS: In our study, the median age of IE onset was relatively low. The most frequent predisposing factor was a prosthetic valve or intracardiac device. The proportion of negative blood cultures was unacceptably high. Thus, our findings emphasize promoting laboratory infrastructure, developing a national protocol for early initiation of appropriate treatment, and eliminating predisposing factors.

Does the postoperative quality of reduction, regardless of the surgical method used in treating a calcaneal fracture, influence patients' functional outcomes?

BACKGROUND: The extensile lateral approach (ELA) and sinus tarsi approach (STA) are commonly utilized for surgically treating calcaneal fractures. This study compared the outcomes of ELA and STA in the management of calcaneal fractures and assessed the influence of postoperative quality of reduction on functional and pain scores. METHODS: The study included 68 adults with Sanders type-II and type-III calcaneal fractures who underwent either ELA or STA surgery. Pre- and postoperative radiographs and computed tomography scans were analyzed, and functional and pain scores were evaluated using the Manchester Oxford Foot Questionnaire (MOXFQ), American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and Visual Analogue Score (VAS) during follow-up visits. RESULTS: Out of the total patients, 50 underwent ELA surgery while 18 underwent STA surgery. The anatomic (excellent) reduction was achieved in 33 (48.5%) patients. There were no significant differences between the ELA and STA groups concerning functional scores, pain scores, the proportion of excellent reduction, and complications. Additionally, anatomic reduction, compared to near or non-anatomic (good, fair, or poor) reduction, demonstrated a decrease in MOXFQ (unstandardized ß coefficient: -13.83, 95% CI: -25.47 to -2.19, p = 0.021), an increase in AOFAS (unstandardized ß coefficient: 8.35, 95% CI: 0.31 to 16.38, p = 0.042), and a reduction in VAS pain (unstandardized ß coefficient: -0.89, 95% CI: -1.93 to -0.16, p = 0.095) scores. CONCLUSION: In conclusion, we found no significant differences regarding complications, excellent reduction, and functional scores between STA and ELA surgeries. Therefore, STA may be an effective alternative for the treatment of calcaneal fractures in Sanders type II and type III calcaneal fractures. Furthermore, the anatomic reduction of the posterior facet correlated with improved functional scores, emphasizing the importance of achieving it for restoring foot function regardless of surgery type or time between injury and surgery.

Medicinal plants for the treatment of neuropathic pain: A review of randomized controlled trials.

Neuropathic pain is a disabling condition caused by various diseases and can profoundly impact the quality of life. Unfortunately, current treatments often do not produce complete amelioration and can be associated with potential side effects. Recently, herbal drugs have garnered more attention as an alternative or a complementary treatment. In this article, we summarized the results of randomized clinical trials to evaluate the effects of various phytomedicines on neuropathic pain. In addition, we discussed their main bioactive components and potential mechanisms of action to provide a better view of the application of herbal drugs for treating neuropathic pain.

The effect of topical olive oil application on the symptoms of infantile colic: A randomized, double-blind, placebo-controlled clinical trial.

Background and Aims: Infantile colic is one of the most common disorders in the first months of infants' lives. This condition hurts parents' moods. This study was carried out to investigate the effect of the topical use of olive oil on infantile colic symptoms. Methods: The study was carried out on 80 infants 1-3 months old, randomly allocated into two groups, receiving abdominal massage with olive oil thrice a day in the intervention group (n = 40) and the same procedure with liquid paraffin in the placebo group (n = 40), for 14 successive days. During this period, the parents recorded the episodes of colic, duration of colic, crying intensity, and episodes of defecation. These variables were assessed and compared at the beginning and on the 7th and 14th days. Results: The mean crying duration changed from 4.05 ± 2.44 to 1.41 ± 1.03 h/day (65% decrease) in the olive oil group and from 3.85 ± 1.37 to 1.60 ± 1.32 h/day (58% decrease) in the paraffin group (p = 0.38). The episodes of crying were reduced from 5.79 ± 4.56 to 2.51 ± 4.93 episodes/day (↓57%) in the olive group and from 6.01 ± 3.40 to 3.01 ± 2.40 episodes/day (↓50%) in the paraffin oil group (p = 0.14). Furthermore, the intensity of crying was decreased from 9.04 ± 1.54 to 4.48 ± 2.17 (p < 0.001) in the olive oil group and from 9.0 ± 1.20 to 4.77 ± 1.68 (p < 0.001) in the paraffin oil group. On the 14th day, the crying intensity showed no significant difference between the two groups. Conclusion: Abdominal massage with olive oil has the same effect as massage with paraffin oil in reducing the symptoms of infantile colic.

Diagnostic Accuracy of Ultrasonography for Detection of Intussusception in Children; a Systematic Review and Meta-Analysis.

Introduction: The diagnosis of intussusception can be challenging in children due to the fact that the findings of clinical evaluations are nonspecific and most of the patients present with unclear history. Therefore, in this systematic review and meta-analysis, we aimed to investigate the diagnostic accuracy of ultrasonography for detection of intussusception and also compare the efficacy of point-of-care ultrasound (POCUS) with radiologist-performed ultrasound (RADUS). Methods: Two independent reviewers systematically searched different online electronic databases including MEDLINE, Scopus, Web of Science, Google Scholar, Embase, and Cochrane from inception to December 1, 2022 to identify published papers reporting accuracy of ultrasonography for diagnosis of intussusception. The quality assessment of the included studies was investigated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. Results: A total of 1446 records were retrieved in the initial search of databases. After screening the titles, a total of 344 studies were retrieved for the detailed assessment of full-text. Finally, 37 studies were included in qualitative and quantitative analysis. The pooled sensitivity and specificity of ultrasonography for diagnosis of intussusception were 0.96 (95% CI: 0.95-0.97) and 0.97 (95% CI: 0.97-0.98), respectively. The pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 24.57 (95% CI: 8.26-73.03) and 0.05 (95% CI: 0.04-0.08), respectively. The area under the hierarchical summary receiver operating characteristic (HSROC) curve was 0.989. Mete-regression showed that there is no significant difference between diagnostic performance of POCUS and RADUS (p = 0.06 and rDOR (diagnostic odds ratio) = 4.38 (95% CI: 0.92-20.89)). Conclusion: This meta-analysis shows that ultrasonography has excellent sensitivity, specificity, and accuracy for diagnosis of intussusception in pediatric patients. Moreover, we found that diagnostic performance of POCUS is similar to that of RADUS for diagnosis of intussusception.

Platinum Nanoparticles in Biomedicine: Preparation, Anti-Cancer Activity, and Drug Delivery Vehicles.

Cancer is the main cause of morbidity and mortality worldwide, excluding infectious disease. Because of their lack of specificity in chemotherapy agents are used for cancer treatment, these agents have severe systemic side effects, and gradually lose their therapeutic effects because most cancers become multidrug resistant. Platinum nanoparticles (PtNPs) are relatively new agents that are being tested in cancer therapy. This review covers the various methods for the preparation and physicochemical characterization of PtNPs. PtNPs have been shown to possess some intrinsic anticancer activity, probably due to their antioxidant action, which slows tumor growth. Targeting ligands can be attached to functionalized metal PtNPs to improve their tumor targeting ability. PtNPs-based therapeutic systems can enable the controlled release of drugs, to improve the efficiency and reduce the side effects of cancer therapy. Pt-based materials play a key role in clinical research. Thus, the diagnostic and medical industries are exploring the possibility of using PtNPs as a next-generation anticancer therapeutic agent. Although, biologically prepared nanomaterials exhibit high efficacy with low concentrations, several factors still need to be considered for clinical use of PtNPs such as the source of raw materials, stability, solubility, the method of production, biodistribution, accumulation, controlled release, cell-specific targeting, and toxicological issues to human beings. The development of PtNPs as an anticancer agent is one of the most valuable approaches for cancer treatment. The future of PtNPs in biomedical applications holds great promise, especially in the area of disease diagnosis, early detection, cellular and deep tissue imaging, drug/gene delivery, as well as multifunctional therapeutics.

Antimicrobial Resistance among Community-Acquired Uropathogens in Mashhad, Iran.

Background: Antimicrobial resistance among community-acquired uropathogens is an emerging concern over the past decades that warrants a continuing reevaluation of the appropriateness of recommended empiric antimicrobial regimens for treatment of urinary tract infections (UTIs). Aims: To describe the microbial spectrum and resistance profile of community-acquired uropathogens and predictors of isolation of resistant strains. Methods: Between October 2017 and June 2019, individuals who visited the outpatient clinics for diagnosis of UTIs or screening of asymptomatic bacteriuria were included in the study if they were tested for urine culture in one of the three main medical diagnostic laboratories of Mashhad, Iran. The standard disk diffusion antimicrobial susceptibility testing was used, with the Clinical and Laboratory Standards Institute (CLSI) threshold cutoffs for susceptibility of isolated uropathogens. Results: Three hundred thirty cases were included with a median age of 47 years. Two hundred seventy-six (83.6%) were female. The most common isolated uropathogens were Escherichia coli in 201 (60.9%) cases and Klebsiella species in 46 (13.9%) cases. E. coli isolates showed the highest rates of susceptibility to nitrofurantoin (89.3%), cefixime (75%), and gentamicin (72.4%). Exposure to antibiotics in the past 3 months was a predictor of resistance to ciprofloxacin (OR: 2.8, 95% CI: 1.33-6.28), and older age was a predictor of resistance to TMP-SMX (OR: 2.1, 95% CI: 1.07-3.97) among E. coli isolates. Conclusion. E. coli and Klebsiella species accounted for about two-thirds of community-acquired uropathogens. In regard to the high susceptibility rates, nitrofurantoin was identified as the first-choice agent for empiric treatment of community-acquired cystitis, while cefixime and gentamicin might be the second-choice alternatives. Ciprofloxacin and TMP-SMX, on the other hand, cannot be considered appropriate agents for empiric therapy of community-acquired UTIs, particularly in those who had exposure to antibiotics in the past 3 months and the elderly.

Association between smoking and non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND/AIMS: Non-alcoholic fatty liver disease is one of the most common chronic liver diseases. Some risk factors are known to influence the development of non-alcoholic fatty liver disease, but the effect of tobacco smoking on the progression of non-alcoholic fatty liver disease is controversial. The main goal of this systematic review and meta-analysis is to investigate the association between smoking and non-alcoholic fatty liver disease. METHOD: Electronic databases (PubMed, Scopus, and ISI Web of Science) were searched to find published articles on non-alcoholic fatty liver disease and smoking until December 2016. All relevant studies were screened by inclusion and exclusion criteria and compatible studies were chosen. The Newcastle-Ottawa Scale was used to assess the methodological quality of eligible articles. Subsequently, information was gathered based on the following: author, publication year, keywords, country, inclusion and exclusion criteria, main results, study design, conclusion, and confounder variables (age, body mass index, gender, ethnicity, and diabetes). Finally, analyses were performed using Comprehensive Meta-Analysis Software. RESULTS: Data were extracted from 20 observational studies (9 cross-sectional, 6 case-control, 4 cohort studies, and 1 retrospective cohort study). A significant association was observed between smoking and non-alcoholic fatty liver disease with a pooled odds ratio of 1.110 (95% confidence interval, 1.028-1.199), p-value = 0.008. The statistical heterogeneity was medium with an I2 of 40.012%, p-heterogeneity = 0.074. Also there was a significant relation between non-alcoholic fatty liver disease and passive smoking with a pooled odds ratio of 1.380 (95% confidence interval, 1.199-1.588; p-value = 0.001; I2 = 59.41; p-heterogeneity = 0.117). CONCLUSION: Our meta-analysis demonstrated that smoking is significantly associated with non-alcoholic fatty liver disease. Further prospective studies exploring the underlying mechanisms of this association should be pursued. Also passive smoking increases the risk of non-alcoholic fatty liver disease about 1.38-fold. The effects of smoking cigarettes on active smokers (current smoker, former smoker, and total smoker) are less than passive smokers. Further studies are needed to compare the of effects of passive and active smoking on non-alcoholic fatty liver disease.