Functional neuroimaging in patients with catatonia: A systematic review.

BACKGROUND: Catatonia is a challenging and heterogeneous neuropsychiatric syndrome of motor, affective and behavioral dysregulation which has been associated with multiple disorders such as structural brain lesions, systemic diseases, and psychiatric disorders. This systematic review summarized and compared functional neuroimaging abnormalities in catatonia associated with psychiatric and medical conditions. METHODS: Using PRISMA methods, we completed a systematic review of 6 databases from inception to February 7th, 2024 of patients with catatonia that had functional neuroimaging performed. RESULTS: A total of 309 studies were identified through the systematic search and 62 met the criteria for full-text review. A total of 15 studies reported patients with catatonia associated with a psychiatric disorder (n = 241) and one study reported catatonia associated with another medical condition, involving patients with N-methyl-d-aspartate receptor antibody encephalitis (n = 23). Findings varied across disorders, with hyperactivity observed in areas like the prefrontal cortex (PFC), the supplementary motor area (SMA) and the ventral pre-motor cortex in acute catatonia associated to a psychiatric disorder, hypoactivity in PFC, the parietal cortex, and the SMA in catatonia associated to a medical condition, and mixed metabolic activity in the study on catatonia linked to a medical condition. CONCLUSION: Findings support the theory of dysfunction in cortico-striatal-thalamic, cortico-cerebellar, anterior cingulate-medial orbitofrontal, and lateral orbitofrontal networks in catatonia. However, the majority of the literature focuses on schizophrenia spectrum disorders, leaving the pathophysiologic characteristics of catatonia in other disorders less understood. This review highlights the need for further research to elucidate the pathophysiology of catatonia across various disorders.

Normative values of functional reach test, single-leg stance test, and timed "UP and GO" with and without dual-task in healthy Iranian adults: A cross-sectional study.

Background: Balance impairment is a common problem in all age groups. There are several tools to assess balance. Functional reach test (FRT), single-leg stance (SLS) test, timed up and go (TUG) test, and TUG with the cognitive dual-task (TUGcog) are commonly employed balance tests. The current study aimed to determine the normative values of FRT, SLST, TUG, and TUGcog across age groups and genders in healthy Iranian adults. Methods: We designed a cross-sectional study, and 240 healthy adults (120 males and 120 females) in six age groups (18-29, 30-39, 40-49, 50-59, 60-69, ≥70 years) completed FRT, SLST, TUG, and TUGcog based on the Persian version of BESTest instructions. Results: There were significant age-specific declines in balance performances. Gender had effects on 18-29 years and older adults (≥60 years), and males performed better than females. Male and females had similar performance on the TUG and TUGcog tests in 60-69 years (p > 0.05). Conclusions: The normative values of FRT, SLS, TUG, and TUGcog provided for healthy Iranian adults increase the clinical utility of tests, and serve as a reference to estimating the individuals' balance performance across age and gender groups.

Prevalence and predictors of low back pain among the Iranian population: Results from the Persian cohort study.

BACKGROUND AND OBJECTIVES: Low back pain (LBP) is a common health condition in populations. Limited large-scale population-based studies evaluated the prevalence and predictors of LBP in developing countries. This study aimed to evaluate the prevalence and factors associated with LBP among the Iranian population. METHODS: We used baseline information from the Prospective Epidemiological Research Studies in Iran (PERSIAN), including individuals from 16 provinces of Iran. LBP was defined as the history of back pain interfering with daily activities for more than one week during an individual's lifetime. Various factors hypothesized to affect LBP, such as age, sex, marital status, educational status, ethnicity, living area, employment status, history of smoking, body mass index (BMI), physical activity, sleep duration, wealth score, history of joint pain, and history of morning stiffness in the joints were evaluated. RESULTS: In total, 163770 Iranians with a mean age of 49.37 (SD = 9.15) were included in this study, 44.8% of whom were male. The prevalence of LBP was 25.2% among participants. After adjusting for confounders, the female gender [OR:1.244(1.02-1.50)], middle and older ages [OR:1.23(1.10-1.33) and OR:1.13(1.07-1.42), respectively], being overweight or obese [OR:1.13(1.07-1.19) and OR:1.21(1.16-1.27), respectively], former and current smokers (OR:1.25(1.16-1.36) and OR:1.28(1.17-1.39), respectively], low physical activity [OR:1.07(1.01-1.14)], and short sleep duration [OR: 1.09(1.02-1.17)] were significantly associated with LBP. CONCLUSION: In this large-scale study, we found the lifetime prevalence of LBP to be lower among the Iranian population in comparison to the global prevalence of LBP; further studies are warranted to evaluate the causality of risk factors on LBP.

Protective effects of hydroalcoholic extracts from an ancient apple variety 'Mela Rosa dei Monti Sibillini' against renal ischemia/reperfusion injury in rats.

The purpose of this work was to investigate the effect of hydroalcoholic extracts from the peel (APE) and pulp (APP) of a traditional apple variety of central Italy, the 'Mela Rosa dei Monti Sibillini', on the damage caused by renal ischemia/reperfusion injury (IRI) in rats. Thirty mg per kg b.w. of the extracts were administered intraperitoneally to male adult Wistar rats 3 days before the induction of IRI by pedicle clamping. A significant decrease in the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNFα), interleukin 1 beta (IL-1ß) and nuclear factor-κB (NF-κB) was observed in the groups pre-treated with APE when compared with IRI rats. The chemical composition of APE was determined by HPLC-DAD-MSn highlighting a significant amount of proanthocyanidins (52.9 mg g-1), flavonols (42.27 mg g-1) and dihydrochalcones (11.75 mg g-1). These findings indicated that this ancient apple variety is a promising source of nutraceuticals and functional foods helpful to manage complications of renal disorders.

Role of p53 in neurodegenerative diseases.

BACKGROUND: p53 plays an important role in many areas of cellular physiology and biology, ranging from cellular development and differentiation to cell cycle arrest and apoptosis. Many of its functions are attributed to its role in assuring proper cellular division. However, since the establishment of its role in cell cycle arrest, damage repair, and apoptosis (thus also establishing its importance in cancer development), numerous reports have demonstrated additional functions of p53 in various cells. In particular, p53 appears to have important functions as it relates to neurodegeneration and synaptic plasticity. OBJECTIVE: In this review, we will address p53 functions as it relates to various neurodegenerative diseases, mainly its implications in the development of HIV-associated neurocognitive disorders. CONCLUSION: p53 plays a pivotal role in the development of neurodegenerative diseases through its interaction with cellular factors, viral factors, and/or small RNAs that have the ability to promote the development of these diseases. Hence, inhibition of p53 may present an ideal target to restore neuronal functions.

C/EBPbeta regulates human immunodeficiency virus 1 gene expression through its association with cdk9.

Transcriptional regulation of the human immunodeficiency virus type 1 (HIV-1) is a complex event that requires the cooperative action of both viral (e.g. Tat) and cellular (e.g. C/EBPbeta, NF-kappaB) factors. The HIV-1 Tat protein recruits the human positive transcription elongation factor P-TEFb, consisting of cdk9 and cyclin T1, to the HIV-1 transactivation response (TAR) region. In the absence of TAR, Tat activates the HIV-1 long terminal repeat (LTR) through its association with several cellular factors including C/EBPbeta. C/EBPbeta is a member of the CCAAT/enhancer-binding protein family of transcription factors and has been shown to be a critical transcriptional regulator of HIV-1 LTR. We examined whether Tat-C/EBPbeta association requires the presence of the P-TEFb complex. Using immunoprecipitation followed by Western blot, we demonstrated that C/EBPbeta-cyclin T1 association requires the presence of cdk9. Further, due to its instability, cdk9 was unable to physically interact with C/EBPbeta in the absence of cyclin T1 or Tat. Using kinase assays, we demonstrated that cdk9, but not a cdk9 dominant-negative mutant (cdk9-dn), phosphorylates C/EBPbeta. Our functional data show that co-transfection of C/EBPbeta and cdk9 leads to an increase in HIV-1 gene expression when compared to C/EBPbeta alone. Addition of C/EBP homologous protein (CHOP) inhibits C/EBPbeta transcriptional activity in the presence and absence of cdk9 and causes a delay in HIV-1 replication in T-cells. Together, our data suggest that Tat-C/EBPbeta association is mediated through cdk9, and that phosphorylated C/EBPbeta may influence AIDS progression by increasing expression of HIV-1 genes.

The role of Vpr in the regulation of HIV-1 gene expression.

Expression of the viral protein R, Vpr, of HIV-1 affects many biological events in host cells including cell cycle progression, and modulates HIV-1 gene transcription. Earlier studies implicating the cellular protein p21(WAF1) (p21) in regulation of HIV-1 transcription, led us to investigate the functional and physical interaction of Vpr and p21. Our results show that Vpr modestly activated HIV-LTR in cells lacking p21 gene. Here, we describe the mechanisms by which p21 and Vpr leading to stimulation of HIV-1 transcription. Data from the protein-protein interaction experiments revealed the ability of Vpr, p21 and p300 to form a complex. Further, we show that, Vpr interacts with the N- and the C-terminal domains of p21. Furthermore, in cells expressing Vpr, p21 localizes to both the cytoplasm and the nucleus. Interestingly, expression of Vpr alleviates p21-mediated inhibition of cell departure from G1 phase. Expression of a mutant Vpr, with arginine 73 altered to serine, did not affect the ability of p21 to cause cells arrest or its sub-cellular localization. These observations reveal a new cellular partner for Vpr, and provide a new therapeutic avenue for controlling HIV-1 expression.

Cdk9 phosphorylates p53 on serine 392 independently of CKII.

The tumor suppressor p53 is an important cellular protein, which controls cell cycle progression. Phosphorylation is one of the mechanisms by which p53 is regulated. Here we report the interaction of p53 with another key regulator, cdk9, which together with cyclin T1 forms the positive transcription elongation complex, p-TEFb. This complex cooperates with the HIV-1 Tat protein to cause the phosphorylation of the carboxyl terminal domain (CTD) of RNA polymerase II and this facilitates the elongation of HIV-1 transcription. We demonstrate that cdk9 phosphorylates p53 on serine 392 through their direct physical interaction. Results from protein-protein interaction assays revealed that cdk9 interacts with the C-terminal domain (aa 361-393) of p53, while p53 interacts with the N-terminal domain of cdk9. Transfection and protein binding assays (EMSA and ChIP) demonstrated the ability of p53 to bind and activate the cdk9 promoter. Interestingly, cdk9 phosphorylates serine 392 of p53, which could be also phosphorylated by casein kinase II. Kinase assays demonstrated that cdk9 phosphorylates p53 independently of CKII. These studies demonstrate the existence of a feedback-loop between p53 and cdk9, pinpointing a novel mechanism by which p53 regulates the basal transcriptional machinery.