Alzheimer’s disease (AD), the primary cause of dementia accounting for 60% to 70% of cases globally, results in a gradual decline in cognitive abilities, affecting memory, executive function, and daily activities. Recent research highlights the essential involvement of the microbiota-gut-brain axis in AD pathogenesis, characterized by complex bidirectional signaling that modulates neuroinflammation, neurogenesis, neurotransmission, and immune functions. This manuscript extends the discussion beyond the gut alone by emphasizing the significance of the oral-gut microbiota axis as a dynamic and relatively under-investigated factor in AD progression. Microbial populations in both the oral cavity and gastrointestinal tract produce key neurotransmitters, such as gamma-aminobutyric acid, noradrenaline, and dopamine, as well as neuroactive metabolites like short-chain fatty acids, which together impact brain physiology. Disturbances in gut and oral microbial balance can compromise barrier integrity, promoting systemic inflammation and neuroinflammation, and facilitating amyloid-β plaque formation and tau-related changes typical of AD. This review introduces a novel probiotic, prebiotics, synbiotics, and postbiotics (PPSP) therapeutic model designed to modulate both oral and gut microbiota, aiming to restore homeostasis, regulate neuroimmune interactions, and counteract cognitive impairment.We comprehensively assess emerging clinical and translational findings supporting the effectiveness of microbiota-targeted therapies in the scope of this dual-axis framework, addressing both their potential to alter disease course and recognized limitations.By underscoring the importance of the integrated oral-gut microbiota axis alongside targeted PPSP interventions, this manuscript puts forth a paradigm-shifting conceptual strategy that may redefine approaches to AD management and improve cognitive outcomes.

Translating progress in neuroscience into clinical benefits for patients with psychiatric disorders is challenging because it involves the brain as the most complex organ and its interaction with a complex environment and condition. Dealing with such complexity requires powerful techniques. Computational neuroscience approach to psychiatry integrates multiple levels and types of simulation, analysis and computation according to the different types of computational models to enhance comprehending, prediction and treatment of psychiatric disorder. This approach comprises two approaches: theory-driven and data-driven. In this review, we focus on recent advances in theory-driven approaches that mathematically and mechanistically examine the relationships between disorder-related changes and behavior at different level of brain organization. We discuss recent progresses in computational neuroscience models that relate to psychiatry and show how principles of neural computational modeling can be employed to explain psychopathology.

OBJECTIVE: To determine the effectiveness and safety of essential oil from Citrus aurantium on anxiety in patients undergoing coronary angiography. METHODS: A single-blind, randomized controlled trial was conducted in 80 patients experiencing coronary angiography in Imam Ali Hospital in Kermanshah, Iran from April to November in 2016. All patients were randomly divided into intervention and control groups by a random number table, 40 cases in each group. The patients in the intervention group inhaled Citrus aurantium essential oil for 15-20 min about 60 min before angiography. Following the same procedure, distilled water was used instead of Citrus aurantium in the control group. Spielbergers State-Trait Anxiety Inventory (STAI) was filled in and vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory and pulse rate were recorded before and 20 min after the intervention. Adverse reactions after intervention were observed. RESULTS: In the intervention group, the mean scores of STAI, SBP, DBP, respiratory and pulse rate were 53.30 ± 10.13, 134.82 ± 11.75 mm Hg, 84.49 ± 6.99 mm Hg, 17.87 ± 1.73 times/min, and 76.48 ± 12.55 beats/min at baseline and significantly decreased to 42.37 ± 10.15, 124.49 ± 10.48 mm Hg, 79.23 ± 6.62 mm Hg, 14.54 ± 1.43 times/min, and 70.03 ± 13.66 beats/min respectively 20 min after intervention (all P<0.05); however, in the control group, neither anxiety scores nor vital signs changed significantly (P>0.05). All subjects reported no adverse reactions. CONCLUSION: Inhalation of the essential oil from Citrus aurantium was effective in reducing anxiety and stress levels in patients undergoing coronary angiography. TRIAL REGISTRATION IRCT2016040816797N2 (retrospectively registered on 21 April 2016, https://en.irct.ir/trial/15600 ).

Background: Nummular eczema (NE) is an inflammatory skin disease characterized by pruritic coin-shaped lesions and a long-lasting and easy-relapsing course, which severely decreases patients' qual-ity of life. This case was designed to observe the effects of specific acupuncture techniques on pruritic NE management.Case presentation: A 22-year-old female was first diagnosed with pruritic NE three years earlier. No al-lergies were found in the patch test;while emotional stress would trigger and aggravate the NE. External application of 0.1％tacrolimus failed to reverse this condition over a long period of treatment. Treatment&outcomes: An individualized acupuncture treatment protocol was identified. Half needling and encircling needling were applied at local eczematous lesions, with routine needling at meridian points, once per week, for 12 treatment sessions. All outcome measures, including the Eczema Area and Severity Index, Visual Analogue Scale score for pruritus, Self-Rating Anxiety Score, and Dermatology Quality Life Index, substantially improved over 6 months from pre-treatment to 3 months post-treatment. Conclusion: Acupuncture might be a promising non-pharmacological treatment method for patients with NE, especially for those with emotional stress. A randomized controlled trial with an adequate sample size and rigorous study design is required to verify the results of the study.

Objective: To explore the analgesic effects and uterine hemodynamics of perpendicular needling (PN) and transverse needling (TN) at SP 6 in patients with primary dysmenorrhea (PD). Methods: In this randomized controlled trial, patients with PD diagnosed with cold-dampness con-gealing pattern were randomly assigned in a ratio of 1:1 to receive PN or TN at bilateral SP 6 for 10 min. Acupuncture was performed when the menstrual pain score was over 40 mm on the first day of menstruation, as measured using the visual analog scale for pain (VAS-P). The primary outcome was average menstrual pain (VAS-P). Secondary outcomes included the pulsatility index (PI), resistance index (RI), and systolic-diastolic peaks ratio (S/D) in uterine arteries as measured using color Doppler ultra-sonography;anxiety as assessed using the Hamilton Anxiety Rating Scale (HAMA), blood pressure (BP), and heart rate (HR). Results: Forty-eight patients completed the study. The TN group exhibited a significant reduction in VAS-P scores (-5.71 mm, 95％ confidence interval (CI): -8.78, -2.63, P = .001), RI values (-0.05, 95％ CI:-0.09,-0.01, P=.015), and HAMA values (-2.50, 95％CI:-4.78,-0.22, P=.032) when compared with the PN group. No significant differences in PI, S/D, BP, or HR values were observed between the two groups (P>.05). Conclusion: TN at SP 6 was superior to PN in alleviating menstrual pain and anxiety in patients with PD. This analgesic effect of TN may be due to its better ability to improve uterine arterial blood flow via decreases in RI values.

Background and aim Cholestasis-associated renal injury or cholemic nephropathy (CN) is a serious clinical problem. Previous studies mentioned that oxidative stress and mitochondrial impairment play a role in CN. There is no specific pharmacological intervention for CN. Metformin is an anti-diabetic drug administered for decades. On the other hand, novel pharmacological properties have emerged for this drug. The effect of metformin on oxidative stress parameters has been well-recognized in different experimental models. It has also been found that metformin positively affected mitochondrial function. The current study aimed to evaluate the effects of metformin in an animal model of CN. Methods Rats underwent bile duct ligation (BDL) and were treated with metformin (250 and 500 mg/kg) for 14 consecutive days. Two weeks after the BDL operations, urine, serum, and kidney samples were collected and analyzed. Results Markers of oxidative stress, including reactive oxygen species (ROS) formation, lipid peroxidation, protein carbonylation, depleted antioxidant capacity, and decreased glutathione (GSH) levels were detected in BDL animals. Moreover, mitochondrial indices, including adenosine triphosphate (ATP) level, dehydrogenase activity, mitochondrial membrane potential, and mitochondrial permeability, were impaired in the kidney of cholestatic rats. Renal histopathological alterations in cholestatic animals included tubular degeneration and interstitial inflammation, cast formation, and fibrosis. It was found that metformin significantly alleviated oxidative stress and improved mitochondrial indices in the kidney of cholestatic rats. Tissue histopathological alterations were also mitigated in metformin-treated groups. Conclusions Metformin could be a candidate for managing CN. The nephroprotective role of metformin is primarily associated with its effects on oxidative stress parameters and mitochondrial function.

Purpose: Colorectal cancer is becoming an increasing concern in the middle-aged population of Iran. This study aimed to compare the preliminary results of short-course and long-course neoadjuvant chemoradiotherapy treatment for rectal cancer patients. Materials and Methods: Patients in group I received three-dimensional conformational radiotherapy with a dose of 25 Gy/5 fractions in 1 week plus concurrent XELOX regimen (capecitabine 625 mg/m2 from day 1–5 twice daily and oxaliplatin 50 mg/m2 on day 1 once daily). Patients in group II received a total dose of 50–50.4 Gy/25–28 fractions for 5 to 5.5 weeks plus capecitabine 825 mg/m2 twice daily. Both groups underwent delayed surgery at least 8 weeks after radiotherapy completion. The pathological response was assessed with tumor regression grade. Results: In this preliminary report on complications and pathological response, 66 patients were randomized into study groups. Mean duration of radiotherapy in the two groups was 5 ± 1 days (range, 5 to 8 days) and 38 ± 6 days (range, 30 to 58 days). The median follow-up was 18 months. Pathological complete response was achieved in 32.3% and 23.1% of patients in the short-course and long-course groups, respectively (p = 0.558). Overall, acute grade 3 or higher treatment-related toxicities occurred in 24.2% and 22.2% of patients in group I and II, respectively (p = 0.551). No acute grade 4 or 5 adverse events were observed in either group. Within one month of surgery, no significant difference was seen regarding grade ≥3 postoperative complications (p = 0.333). Conclusion For patients with rectal cancer located 5 cm above the anal verge, short-course radiotherapy with concurrent and consolidation chemotherapy and delayed surgery is not different in terms of acute toxicity, postoperative morbidity, complete resection, and pathological response compared to long-course chemoradiotherapy.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by major impairments in social communication, stereotyped and ritualistic behaviors and deficits in sensory reactivity. Recently, noninvasive brain stimulation (NIBS) methods, namely transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), have been examined as possible new therapeutic options for modifying the pathological neuroplasticity involved in neuropsychiatric disorders including ASD. Therefore, we conducted a systematic review on the therapeutic uses of tDCS and repetitive TMS (rTMS) in ASD patients. A systematic search was performed on Scopus, Web of Science, PubMed, Cochrane and Embase. Original articles reporting the use of tDCS or rTMS to treat ASD were screened and studied by two researchers independently based on PRISMA guidelines. We found 32 eligible studies including 8 tDCS reports, 23 rTMS reports and one report with both tDCS and rTMS. These studies comprised 6 case-reports, 9 non-controlled trials and 17 controlled trials which assessed NIBS effects on the three cognitive, behavioral and biological dimensions in ASD. Existing evidence demonstrates that NIBS methods could be helpful for treating some dimensions of ASD such as repetitive behavior, sociability or some aspects of executive and cognitive functions. However, such evidence should be regarded with care because of the quality of original researches and serious publication bias as well as the heterogeneity of data. Further randomized, double-blind, sham-controlled trials with appropriate follow-up periods should be designed to assess the efficacy of NIBS methods for ASD treatment.

OBJECTIVES: Genetic determinants conferring resistance to macrolide, lincosamide, and streptogramin B (MLSB) via ribosomal modification such as, erm, msrA/B and ereA/B genes are distributed in bacteria. The main goals of this work were to evaluate the dissemination of MLSB resistance phenotypes and genotypes in methicillin-resistant Staphylococcus aureus (MRSA) isolates collected from clinical samples. METHODS: A total of 106 MRSA isolates were studied. Isolates were recovered from 3 hospitals in Tehran between May 2016 to July 2017. The prevalence of MLSB-resistant strains were determined by D-test, and then M-PCR was performed to identify genes encoding resistance to macrolides, lincosamides, and streptogramins in the tested isolates. RESULTS: The frequency of constitutive resistance MLSB, inducible resistance MLSB and MSB resistance were 56.2%, 22.9%, and 16.6%, respectively. Of 11 isolates with the inducible resistance MLSB phenotype, ermC, ermB, ermA and ereA were positive in 81.8%, 63.6%, 54.5% and 18.2% of these isolates, respectively. In isolates with the constitutive resistance MLSB phenotype, the prevalence of ermA, ermB, ermC, msrA, msrB, ereA and ereB were 25.9%, 18.5%, 44.4%, 0.0%, 0.0%, 11.1% and 0.0%, respectively. CONCLUSION: Clindamycin is commonly administered in severe MRSA infections depending upon the antimicrobial susceptibility findings. This study showed that the D-test should be used as an obligatory method in routine disk diffusion assay to detect inducible clindamycin resistance in MRSA so that effective antibiotic treatment can be provided.
Bacteria ; Clindamycin ; Diffusion ; Drug Resistance ; Genotype ; Lincosamides ; Macrolides ; Methicillin-Resistant Staphylococcus aureus ; Methods ; Phenotype ; Prevalence ; Staphylococcus aureus ; Staphylococcus ; Streptogramin B ; Streptogramins

Preliminary studies have claimed that short term fasting would negatively affect school performance and cognition. In contrast some other studies have reported not important decline in cognition and executive function as a result of fasting. Also limited attention was generally devoted to dietetic regimens, nutritional status and body weight. Yet neuroscience and neuro-cognitive aspects of acute hunger on the electroencephalogram and differences between obese and non-obese cases is not well understood. Hence, we decided to design and perform a case study in a more controlled situation similar to reality. Therefore, we performed several examinations including subjective tests (for eating status) and objective tests (cognitive tests such as Stroop effect and Sternberg search and electroencephalogram measures such as steady-state visual evoked potential and auditory steady-state responses) for an obese and a non-obese academic case before and after a simple breakfast. The results showed that the breakfast effects on the neuro-cognitive functions depend on either obesity status, nutritional status of the case or the type of cognitive task (visual or auditory). This paper would open a new insight to answer some important questions about the neuro-cognitive implications of fasting and feeding in obese and non-obese human cases.
Body Weight ; Breakfast ; Cognition ; Eating ; Electroencephalography ; Evoked Potentials, Visual ; Executive Function ; Fasting* ; Humans ; Hunger ; Neurosciences ; Nutritional Status ; Obesity ; Stroop Test