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الأدب الفارسي القديم
يتناول هذا الكتاب الأدب الفارسي القديم حيث إن الأدب البهلوى موفور الماده إلى حد فيه الكفايه إذا ما قصدنا منه جانبه الأخلاقى فإنه يتضمن تعاليم خاصه بتوجيه السلوك والدعوه للتي هي أقوم والنصح بما تصلح به الحال والحض على ما تستقيم به الحياه وذلك برمته مقرون بما أمر به الدين ونهى عنه وهو صوره جليه لحضاره الساسانيين التي بلغت قمه ازدهارها وأصبحت من أعظم حضارات الشرق القديم.
Book
الأدب الفارسي القديم
إن الأدب البهلوى موفور الماده إلى حد فيه الكفايه، إذا ما قصدنا منه جانبه الأخلاقى، فإنه يتضمن تعاليم خاصه بتوجيه السلوك، والدعـوه للتى هى أقوم، والنصح بما تصلح به الحال، والحض على ما تستقيم به الحياه، وذلك برمته مقرون بما أمر به الدين ونهى عنه، وهو صوره جليه لحضاره الساسانيين التى بلغت قمه ازدهارها وأصبحت من أعظم حضارات الشرق القديم.
Book
Key takeaways from the updated multidisciplinary European MASLD guidelines
The new European clinical practice guidelines from three scientific societies (European Association for the Study of the Liver, European Association for the Study of Diabetes and European Association for the Study of Obesity) on the management of metabolic dysfunction-associated steatotic liver disease (MASLD) provide detailed recommendations on diagnosis, risk stratification, monitoring strategies, treatment and prevention. Lifestyle interventions (eg, weight reduction, Mediterranean diet, exercise, alcohol abstinence) and the treatment of cardiometabolic risk factors continue to be the mainstay of treatment and prevention of the disease. Incretin mimetics that are approved to treat obesity and/or type 2 diabetes such as semaglutide and tirzepatide have benefits for ameliorating metabolic dysfunction-associated steatohepatitis (MASH). Novel developments include adapted strategies for screening (case finding) using non-invasive tests (NITs) with a focus on detecting fibrosis or cirrhosis, risk-adjusted monitoring of MASLD by NITs as well as the recommendation to use, if locally approved, the thyroid hormone receptor β-agonist resmetirom in patients with non-cirrhotic MASH fibrosis (≥F2 stage).
Journal Article
Frontal cortex hyperactivation and gamma desynchrony in Fragile X syndrome: Correlates of auditory hypersensitivity
Fragile X syndrome (FXS) is an X-linked disorder that often leads to intellectual disability, anxiety, and sensory hypersensitivity. While sound sensitivity (hyperacusis) is a distressing symptom in FXS, its neural basis is not well understood. It is postulated that hyperacusis may stem from temporal lobe hyperexcitability or dysregulation in top-down modulation. Studying the neural mechanisms underlying sound sensitivity in FXS using scalp electroencephalography (EEG) is challenging because the temporal and frontal regions have overlapping neural projections that are difficult to differentiate. To overcome this challenge, we conducted EEG source analysis on a group of 36 individuals with FXS and 39 matched healthy controls. Our goal was to characterize the spatial and temporal properties of the response to an auditory chirp stimulus. Our results showed that males with FXS exhibit excessive activation in the frontal cortex in response to the stimulus onset, which may reflect changes in top-down modulation of auditory processing. Additionally, during the chirp stimulus, individuals with FXS demonstrated a reduction in typical gamma phase synchrony, along with an increase in asynchronous gamma power, across multiple regions, most strongly in the temporal cortex. Consistent with these findings, we observed a decrease in the signal-to-noise ratio, estimated by the ratio of synchronous to asynchronous gamma activity, in individuals with FXS. Furthermore, this ratio was highly correlated with performance in an auditory attention task. Compared to controls, males with FXS demonstrated elevated bidirectional frontotemporal information flow at chirp onset. The evidence indicates that both temporal lobe hyperexcitability and disruptions in top-down regulation play a role in auditory sensitivity disturbances in FXS. These findings have the potential to guide the development of therapeutic targets and back-translation strategies.
Journal Article
Results of a phase Ib study of SB-121, an investigational probiotic formulation, a randomized controlled trial in participants with autism spectrum disorder
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by core impairments in social communication as well as restricted, repetitive patterns of behavior and/or interests. Individuals with ASD, which includes about 2% of the US population, have challenges with activities of daily living and suffer from comorbid medical and mental health concerns. There are no drugs indicated for the core impairments of ASD. As such, there is a significant need for the development of new medication strategies for individuals with ASD. This first-in-human placebo-controlled, double-blind, crossover study investigated the safety (primary objective) and efficacy of oral SB-121, a combination of L. reuteri, Sephadex® (dextran microparticles), and maltose administered once daily for 28 days in 15 autistic participants. SB-121 was safe and well tolerated. SB-121-associated directional improvements in adaptive behavior measured by Vineland-3 and social preference as measured with eye tracking were noted. These results provide support for further clinical evaluation of SB-121 as a treatment in autistic patients. To evaluate the safety and tolerability of multiple doses of SB-121 in subjects with autism spectrum disorder. Single-center, randomized, placebo-controlled, double-blind, crossover trial. 15 patients with autism spectrum disorder were randomized and analyzed. Daily dosing of SB-121 or placebo for 28 days, followed by approximately a 14 day washout, then 28 days of dosing with other treatment. Incidence and severity of adverse events, presence of
Limosilactobacillus reuteri
and Sephadex® in stool, and incidence of bacteremia with positive
L. reuteri
identification. Additional outcomes include changes from baseline on cognitive and behavior tests as well as biomarker levels. Adverse event rates were similar between SB-121 and placebo, with most reported as mild. There were no severe or serious adverse events. No participants had features of suspected bacteremia or notable changes in vital signs, safety laboratory, or ECG parameters from baseline. There was a statistically significant increase from baseline in the Vineland-3 Adaptive Behavior Composite score (p = 0.03) during SB-121 treatment. There was a trend for increased social/geometric viewing ratio following SB-121 treatment compared to placebo. SB-121 was safe and well tolerated. SB-121-associated directional improvements in adaptive behavior measured by Vineland-3 and social preference as measured with eye tracking were noted.
Trial registration:
clinicaltrials.gov Identifier: NCT04944901.
Journal Article
CCR5 receptor antagonism inhibits hepatitis C virus (HCV) replication in vitro
The hepatitis C virus (HCV) is a single-strand RNA virus that infects millions of people worldwide. Recent advances in therapy have led to viral cure using two- and three- drug combinations of direct acting inhibitors of viral replication. CCR5 is a chemokine receptor that is expressed on hepatocytes and represents a key co-receptor for HIV. We evaluated the effect of CCR5 blockade or knockdown on HCV replication in Huh7.5JFH1 cells.
Cells were exposed to varying concentrations of maraviroc (CCR5 inhibitor), cenicriviroc (CCR2/CCR5 inhibitor), sofosbuvir (nucleotide polymerase inhibitor), or raltegravir (HIV integrase inhibitor).
HCV RNA was detected utilizing two qualitative strand-specific RT-PCR assays. HCV core antigen and NS3 protein was quantified in the supernatant and cell lysate, respectively. siRNA was utilized to knockdown CCR5 gene expression in hepatocytes. Alternatively, anti-CCR5 antibodies were employed to block the receptor. Supernatant levels of HCV RNA (expressed as fold change) were not reduced in the presence of raltegravir but were reduced 8.55-fold and 12.42-fold with cenicriviroc and maraviroc, respectively. Sofosbuvir resulted in a 16.20-fold change in HCV RNA levels. HCV core and NS3 protein production was also reduced in a dose-dependent manner. Two distinct anti-CCR5 antibodies also resulted in a significant reduction in HCV protein expression, as did siRNA knockdown of CCR5 gene expression.
These data provide evidence that CCR5 modulation could have a significant effect on HCV replication in an in vitro system. Further evaluation of the role of CCR5 inhibition in clinical settings may be warranted.
Journal Article
Examining the feasibility and utility of heart rate variability on intervention outcomes targeting emotion regulation in autism: a brief report
Autistic youth experience several behavioral and emotional characteristics that can predispose them to emotion dysregulation (ED). Current literature examining ED in autism spectrum disorder (ASD) is limited to parent- and self-reported measures, indicating a need for biological or physiological methods to better assess emotion regulation in ASD. Utilizing the autonomic nervous system, specifically heart rate variability (HRV), may be a promising method to objectively measure ED in ASD, given it is one of the body’s primary means of regulating physiological arousal. Our pilot study is one of the first to examine the feasibility, utility, and construct validity of HRV along with clinical measures within an intervention targeting ED-specific symptoms in ASD. Participants included 30 autistic youth ages 8–17 years who participated in the pilot study of
Regulating Together
, a group-based intervention targeting emotion regulation. We demonstrate HRV is feasible, demonstrates adequate test–retest reliability, and is complimentary to clinician- and parent-reported measures. Our preliminary findings also point to certain HRV profiles being indicative of long-term outcomes after receiving treatment. HRV may be a useful, objective tool in determining differential needs of long-term follow-up care for treatment maintenance at screening or baseline stages.
Journal Article