Altered brain connectivity in mild cognitive impairment is linked to elevated tau and phosphorylated tau, but not to GAP-43 and Amyloid-ß measurements: a resting-state fMRI study.

Mild Cognitive Impairment (MCI) is a neurological condition characterized by a noticeable decline in cognitive abilities that falls between normal aging and dementia. Along with some biomarkers like GAP-43, Aß, tau, and P-tau, brain activity and connectivity are ascribed to MCI; however, the link between brain connectivity changes and such biomarkers in MCI is still being investigated. This study explores the relationship between biomarkers like GAP-43, Aß, tau, and P-tau, and brain connectivity. We enrolled 25 Participants with normal cognitive function and 23 patients with MCI. Levels of GAP-43, Aß1-42, t-tau, and p-tau181p in the CSF were measured, and functional connectivity measures including ROI-to-voxel (RV) correlations and the DMN RV-ratio were extracted from the resting-state fMRI data. P-values below 0.05 were considered significant. The results showed that in CN individuals, higher connectivity within the both anterior default mode network (aDMN) and posterior DMN (pDMN) was associated with higher levels of the biomarker GAP-43. In contrast, MCI individuals showed significant negative correlations between DMN connectivity and levels of tau and P-tau. Notably, no significant correlations were found between Aß levels and connectivity measures in either group. These findings suggest that elevated levels of GAP-43 indicate increased functional connectivity in aDMN and pDMN. Conversely, elevated levels of tau and p-tau can disrupt connectivity through various mechanisms. Thus, the accumulation of tau and p-tau can lead to impaired neuronal connectivity, contributing to cognitive decline.

NEXUS: A 28nm 3.3pJ/SOP 16-Core Spiking Neural Network with a Diamond Topology for Real-Time Data Processing.

The realization of brain-scale spiking neural networks (SNNs) is impeded by power constraints and low integration density. To address these challenges, multi-core SNNs are utilized to emulate numerous neurons with high energy efficiency, where spike packets are routed through a network-on-chip (NoC). However, the information can be lost in the NoC under high spike traffic conditions, leading to performance degradation. This work presents NEXUS, a 16-core SNN with a diamond-shaped NoC topology fabricated in 28-nm CMOS technology. It integrates 4096 leaky integrate-and-fire (LIF) neurons with 1M 4-bit synaptic weights, occupying an area of 2.16 mm2. The proposed NoC architecture is scalable to any network size, ensuring no data loss due to contending packets with a maximum routing latency of 5.1µs for 16 cores. The proposed congestion management method eliminates the need for FIFO in routers, resulting in a compact router footprint of 0.001 mm2. The proposed neurosynaptic core allows for increasing the processing speed by up to 8.5× depending on input sparsity. The SNN achieves a peak throughput of 4.7 GSOP/s at 0.9 V, consuming a minimum energy per synaptic operation (SOP) of 3.3 pJ at 0.55 V. A 4-layer feed-forward network is mapped onto the chip, classifying MNIST digits with 92.3% accuracy at 8.4Kclassification/ s and consuming 2.7-µJ/classification. Additionally, an audio recognition task mapped onto the chip achieves 87.4% accuracy at 215-µJ/classification.

Tale of Two Polymorphs: Investigating the Structural Differences and Dynamic Relationship between Nirmatrelvir Solid Forms (Paxlovid).

Two anhydrous polymorphs of the novel antiviral medicine nirmatrelvir were discovered during the development of Paxlovid, Pfizer's oral Covid-19 treatment. A comprehensive experimental and computational approach was necessary to distinguish the two closely related polymorphs, herein identified as Forms 1 and 4. This approach paired experimental methods, including powder X-ray diffraction and single-crystal X-ray diffraction, solid-state experimental methods, thermal analysis, solid-state nuclear magnetic resonance and Raman spectroscopy with computational investigations comprising crystal structure prediction, Gibbs free energy calculations, and molecular dynamics simulations of the polymorphic transition. Forms 1 and 4 were ultimately determined to be enantiotropically related polymorphs with Form 1 being the stable form above the transition temperature of ∼17 °C and designated as the nominated form for drug development. The work described in this paper shows the importance of using highly specialized orthogonal approaches to elucidate the subtle differences in structure and properties of similar solid-state forms. This synergistic approach allowed for unprecedented speed in bringing Paxlovid to patients in record time amidst the pandemic.

DFT study of Ti3C2 MXene nanosheets as a drug delivery system for 5-fluorouracil.

In this study, we modeled a drug delivery system consisting of Ti3C2 MXene nanosheets as a carrier and 5-fluorouracil (FU) as a selected drug molecule using density functional theory (DFT) computations. During the adsorption procedure, electronic, magnetic and structural properties were calculated. Our results showed that the adsorption of FU drugs on the Ti3C2 surface is thermodynamically favorable. Our spin-polarized calculations also determined that the magnetization of Ti3C2 after FU adsorption does not change significantly, which is an important factor for magnetic hyperthermia and drug delivery. In addition, our calculations indicate that in the slightly acidic environment of tumor tissue, FU could start to be released (by increasing distance from the MXene surface and then instability of the complex) from the Ti3C2 surface without any substantial change in the structural properties. This study could provide a deep understanding of the interaction mechanism of 2-dimensional (2D) MXene materials with drugs at the atomistic scale and have an important contribution to the discovery and application of novel 2D materials as drug delivery systems.

The Effect of Sensory Reweighting on Postural Control and Cortical Activity in Parkinson's Disease.

Aims: Balance requires the cortical control of visual, somatosensory, and vestibular inputs. The aim of this cross-sectional study was to compare the contributions of each of these systems on postural control and cortical activity using a sensory reweighting approach between participants with Parkinson's disease (PD) and controls. Methods: Ten participants with PD (age: 72 ± 9; 3 women; Hoehn & Yahr: 2 [1.5 - 2.50]) and 11 controls (age: 70 ± 3; 4 women) completed a sensory organization test in virtual reality (VR-SOT) while cortical activity was being recorded using electroencephalography (EEG). Conditions 1 to 3 were completed on a stable platform; conditions 4 to 6 on a foam. Conditions 1 and 4 were done with eyes open; conditions 2 and 5 in a darkened VR environment; and conditions 3 and 6 in a moving VR environment. Linear mixed models were used to evaluate changes in center of pressure (COP) displacement and EEG alpha and theta/beta ratio power between the two groups across the postural control conditions. Condition 1 was used as reference in all analyses. Results: Participants with PD showed greater COP displacement than controls in the anteroposterior (AP) direction when relying on vestibular input (condition 5; p<0.0001). The mediolateral (ML) COP sway was greater in PD than in controls when relying on the somatosensory (condition 2; p = 0.03), visual (condition 4; p = 0.002), and vestibular (condition 5; p < 0.0001) systems. Participants with PD exhibited greater alpha power compared to controls when relying on visual input (condition 2; p = 0.003) and greater theta/beta ratio power when relying on somatosensory input (condition 4; p = 0.001). Conclusions: PD affects reweighting of postural control, exemplified by greater COP displacement and increased cortical activity. Further research is needed to establish the temporal dynamics between cortical activity and COP displacement.

Rickettsia conorii subsp. israelensis infection in a pediatric patient presenting skin rash and abdominal pain: a case report from Southeast Iran.

BACKGROUND: The healthcare system in Iran appears to overlook Mediterranean spotted fever (MSF) as an endemic disease, particularly in pediatric cases, indicating the need for greater attention and awareness. CASE PRESENTATION: A six-year-old patient with fever, abdominal pain, headache, skin rashes, diarrhea, vomiting, and black eschar (tache noire) from southeast Iran was identified as a rickettsiosis caused by Rickettsia conorii subsp. israelensis through clinical and laboratory assessments, including IFA and real-time PCR. The patient was successfully treated with doxycycline. CONCLUSIONS: Symptoms like rash, edema, eschar, and abdominal pain may indicate the possibility of MSF during the assessment of acute febrile illness, IFA and real-time PCR are the primary diagnostic methods for this disease.

Digital Hardware Implementation of ReSuMe Learning Algorithm for Spiking Neural Networks.

Within this paper, we demonstrate the feasibility of the FPGA implementation as well as the 180nm CMOS circuit design of a particular biologically plausible supervised learning algorithm (ReSuMe). Based on the Spike-Timing-Dependent Plasticity (STDP) learning phenomenon, this design proposes a fully configurable implementation of STDP learning window function to adjust the learning process for different applications, optimizing results for each use case. The CMOS implementation in 180nm technology node supplied with 1.8V shows a core area of 0.78mm2 and verifies the suitability of an on-chip ReSuMe learning algorithm implementation and its capability of integration with a multitude of external and already designed structures of Spiking Neural Networks (SNNs).

Effect of gamma-irradiated honey bee venom on blood parameter and histopathological observations of liver and kidney in a mice animal model.

Honey bee venom is a valuable product with a wide range of biological effects, whose use is rapidly increasing in apitherapy. In this study, the effect of gamma-irradiated honey bee venom (doses of 0, 2, 4, 6, and 8 kGy, volume of 0.1 ml, and concentration of 0.2 mg/ml) was evaluated on median lethal dose (LD50) determinations, liver and kidney histology, biochemical marker level, and serum protein analyses. Hence, the LD50 induced by the honey bee venom irradiated at 4, 6, and 8 kGy was increased, compared with the one at 0 and 2 kGy. Normal histology was observed in the liver and kidney of the mice receiving the honey bee venom irradiated at 4, 6, and 8 kGy. The serum levels of alanine aminotransferase (ALT) and all serum proteins were reduced at 4, 6, and 8 kGy compared with 0 and 2 kGy. Therefore, gamma irradiation at 4, 6, and 8 kGy had no negative effect on LD50, liver and kidney tissues, ALT, and serum protein levels by decreasing the allergen compounds of the honey bee venom.

Localization and Registration of 2D Histological Mouse Brain Images in 3D Atlas Space.

To accurately explore the anatomical organization of neural circuits in the brain, it is crucial to map the experimental brain data onto a standardized system of coordinates. Studying 2D histological mouse brain slices remains the standard procedure in many laboratories. Mapping these 2D brain slices is challenging; due to deformations, artifacts, and tilted angles introduced during the standard preparation and slicing process. In addition, analysis of experimental mouse brain slices can be highly dependent on the level of expertise of the human operator. Here we propose a computational tool for Accurate Mouse Brain Image Analysis (AMBIA), to map 2D mouse brain slices on the 3D brain model with minimal human intervention. AMBIA has a modular design that comprises a localization module and a registration module. The localization module is a deep learning-based pipeline that localizes a single 2D slice in the 3D Allen Brain Atlas and generates a corresponding atlas plane. The registration module is built upon the Ardent python package that performs deformable 2D registration between the brain slice to its corresponding atlas. By comparing AMBIA's performance in localization and registration to human ratings, we demonstrate that it performs at a human expert level. AMBIA provides an intuitive and highly efficient way for accurate registration of experimental 2D mouse brain images to 3D digital mouse brain atlas. Our tool provides a graphical user interface and it is designed to be used by researchers with minimal programming knowledge.

High cancer selectivity and improving drug release from mesoporous silica nanoparticles in the presence of human serum albumin in cisplatin, carboplatin, oxaliplatin, and oxalipalladium treatment.

In this project, drug release was examined based on the adsorption of cisplatin, carboplatin, oxaliplatin, and oxalipalladium on aminated mesoporous silica nanoparticles (N-HMSNs) and human serum albumin (HSA). These compounds were characterized by different techniques where three clinical Pt-drugs, cisplatin, carboplatin, oxaliplatin, plus oxalipalladium were loaded and investigated for release. Based on loading analysis, the loading ability of the mentioned metallodrug on N-HMSNs was dependent on the nature of the drug structure as well as hydrophobic or hydrophilic interactions. Different adsorption and release profiles were observed for all mentioned compounds via dialysis and ICP method analysis. Although the maximum to minimum loading occurred for oxalipalladium, cisplatin, and oxaliplatin to carboplatin, respectively, release from a surface with greater control belonged to carboplatin to cisplatin systems in the absence and presence of HSA to 48 h due to weak interaction for carboplatin drug. The quick release of all mentioned compounds from the protein level at high doses of the drug during chemotherapy occurred very fast within the first 6 h. In addition, the cytotoxic activity of both free drugs and drug-loaded@N-HMSNs samples on cancerous MCF-7, HCT116, A549, and normal HFF cell lines was evaluated by MTT assay. It was found that free metallodrugs exhibited more active cytotoxic behavior on both cancerous and normal cell lines than drug-loaded@N-HMSNs. Data demonstrated that the Cisplatin@N-HMSNs with SI=6.0 and 6.6 for MCF7 and HCT116 cell lines, respectively, and Oxaliplatin@N-HMSNs with SI=7.4 for HCT116 cell line can be good candidates as an anticancer drug with minimal side effects by protecting cytotoxic drugs as well as controlled release and high selectivity.

Predictors of sexual and reproductive health self-care based on demographic factors in adolescent girls.

OBJECTIVES: Global access to sexual and reproductive health is an essential human right, especially to adolescent girls. For improvement sexual and reproductive self-care needs to determine the related factors on utilization and acceptance by adolescents. Therefore, the aim of this study was to examine the SRH self-care and its predictors among adolescent girls in Neyshabur city at Northeast of Iran. METHODS: The present study was a cross-sectional correlational study performed on 265 girl students from 15 girls' high schools in Neyshabour, in Razavi Khorasan province, Northeastern Iran. The sampling method was multistage probability sampling. Data were collected using demographic information and female adolescents' sexual reproductive self-care scale. Data were analyzed using descriptive, frequency, percentage, mean, standard deviation, and ANOVA, Pearson correlation coefficient, and multiple linear regression model. The significant level was p<0.05 using SPSS16. RESULTS: The results of the present study showed that the mean score of the sexual reproductive health self-care was 61.23 of 100 ± 10.5, it had a significantly relationship with fathers education high school [B=-7.241 CI: (-11.088 to -3.393)], diploma [B=-7.221 CI: -10.707 to -3.735] than academic. The rank of children birth in the family first [B=6.012 CI: (0.931-11.092)] second [B=4.436 CI: (1.437-8.309)] than third and above. Economic status of household Excellent [B=3.159 CI: (2.193-8.511)], Favorable [B=5.866 CI: (1.355-10.378)], relatively favorable [B=2.705 CI: (1.802-7.213)] than poor level economic. CONCLUSIONS: sexual and reproductive health is associated to father's education, the rank of children birth in the family, and economic status. So these variables will help to strategies and progress educational programs.

Effect of gamma-irradiated honey bee venom on gene expression of inflammatory and anti-inflammatory cytokines in mice.

In this study, the effect of gamma-irradiated honey bee venom (doses of 0, 2, 4, 6, and 8 kGy, volume of 0.1 ml and concentration of 0.2 mg/ml) was evaluated on the reduction of allergen compounds and the gene expression of inflammatory and anti-inflammatory cytokines in mice. Hence, edema activity induced by the bee venom irradiated at 4, 6, and 8 kGy was reduced, compared with the control group and that irradiated at 2 kGy. In contrast, the paw edema induced by the bee venom irradiated at 8 kGy increased, compared with 4 and 6 kGy. At all the time periods, there was a significant decrease in the gene expression of interferon gamma (IFN-γ), interleukin 6 (IL-6), and interleukin 10 (IL-10) in the bee venoms irradiated at 4, 6, and 8 kGy, compared with the control group and that irradiated at 2 kGy. In contrast, there was an increase in the gene expression of IFN-γ and IL-6 in the bee venom irradiated at 8 kGy, compared with those irradiated at 4 and 6 kGy. Therefore, gamma irradiation at 4 and 6 kGy reduced the gene expression of cytokines at each time period by decreasing the allergen compounds of honey bee venom.

A cycle-consistent adversarial network for brain PET partial volume correction without prior anatomical information.

PURPOSE: Partial volume effect (PVE) is a consequence of the limited spatial resolution of PET scanners. PVE can cause the intensity values of a particular voxel to be underestimated or overestimated due to the effect of surrounding tracer uptake. We propose a novel partial volume correction (PVC) technique to overcome the adverse effects of PVE on PET images. METHODS: Two hundred and twelve clinical brain PET scans, including 50 18F-Fluorodeoxyglucose (18F-FDG), 50 18F-Flortaucipir, 36 18F-Flutemetamol, and 76 18F-FluoroDOPA, and their corresponding T1-weighted MR images were enrolled in this study. The Iterative Yang technique was used for PVC as a reference or surrogate of the ground truth for evaluation. A cycle-consistent adversarial network (CycleGAN) was trained to directly map non-PVC PET images to PVC PET images. Quantitative analysis using various metrics, including structural similarity index (SSIM), root mean squared error (RMSE), and peak signal-to-noise ratio (PSNR), was performed. Furthermore, voxel-wise and region-wise-based correlations of activity concentration between the predicted and reference images were evaluated through joint histogram and Bland and Altman analysis. In addition, radiomic analysis was performed by calculating 20 radiomic features within 83 brain regions. Finally, a voxel-wise two-sample t-test was used to compare the predicted PVC PET images with reference PVC images for each radiotracer. RESULTS: The Bland and Altman analysis showed the largest and smallest variance for 18F-FDG (95% CI: - 0.29, + 0.33 SUV, mean = 0.02 SUV) and 18F-Flutemetamol (95% CI: - 0.26, + 0.24 SUV, mean = - 0.01 SUV), respectively. The PSNR was lowest (29.64 ± 1.13 dB) for 18F-FDG and highest (36.01 ± 3.26 dB) for 18F-Flutemetamol. The smallest and largest SSIM were achieved for 18F-FDG (0.93 ± 0.01) and 18F-Flutemetamol (0.97 ± 0.01), respectively. The average relative error for the kurtosis radiomic feature was 3.32%, 9.39%, 4.17%, and 4.55%, while it was 4.74%, 8.80%, 7.27%, and 6.81% for NGLDM_contrast feature for 18F-Flutemetamol, 18F-FluoroDOPA, 18F-FDG, and 18F-Flortaucipir, respectively. CONCLUSION: An end-to-end CycleGAN PVC method was developed and evaluated. Our model generates PVC images from the original non-PVC PET images without requiring additional anatomical information, such as MRI or CT. Our model eliminates the need for accurate registration or segmentation or PET scanner system response characterization. In addition, no assumptions regarding anatomical structure size, homogeneity, boundary, or background level are required.

Toxoplasmosis and symptoms severity in patients with COVID-19 in referral centers in Northern Iran.

Toxoplasmosis has been categorized as one of the long-lasting protozoan parasitic infections. It affects almost one-third of the world's population. In recent years, several documented studies have elucidated that infected individuals have a remarkably higher incidence of distinct health problems and show various adverse effects. In the PCR-positive COVID-19 patients in Gonbad-e-Kavus, Kalaleh, and Minoodasht counties in the northern part of Iran from June 2021 to December 2021, we sought to investigate any potential relationships between the severity of COVID-19 symptoms and acute and latent toxoplasmosis caused by Toxoplasma gondii (T. gondii). Whole blood samples of 161 COVID-19 patients with positive PCR. The samples were centrifuged to separate serum and screened for two important antibodies against T. gondii (IgM and IgG) by using ELISA kits for human anti-T. gondii IgM and IgG. Anti-T. gondii IgM and IgG antibodies were detected in 8/161 (5.0%) and 42/161 (26.1%) COVID-19 patients, respectively. No significant relationships were found between Toxoplasma IgM and IgG results with clinical signs, age, sex, contact with animals, comorbidities, and also the mortality rate of people with COVID-19. These findings showed that acute and latent toxoplasmosis infections are common among patients with COVID-19; however, no significant associations were found between toxoplasma infections and the symptoms of COVID-19. Therefore, toxoplasmosis is not considered a risk factor for COVID-19.

Long-Distance Protonation-Conformation Coupling in Phytochrome Species.

Phytochromes are biological red/far-red light sensors found in many organisms. The connection between photoconversion and the cellular output signal involves light-mediated global structural changes in the interaction between the photosensory module (PAS-GAF-PHY, PGP) and the C-terminal transmitter (output) module. We recently showed a direct correlation of chromophore deprotonation with pH-dependent conformational changes in the various domains of the prototypical phytochrome Cph1 PGP. These results suggested that the transient phycocyanobilin (PCB) chromophore deprotonation is closely associated with a higher protein mobility both in proximal and distal protein sites, implying a causal relationship that might be important for the global large-scale protein rearrangements. Here, we investigate the prototypical biliverdin (BV)-binding phytochrome Agp1. The structural changes at various positions in Agp1 PGP were investigated as a function of pH using picosecond time-resolved fluorescence anisotropy and site-directed fluorescence labeling of cysteine variants of Agp1 PGP. We show that the direct correlation of chromophore deprotonation with pH-dependent conformational changes does not occur in Agp1. Together with the absence of long-range effects between the PHY domain and chromophore pKa, in contrast to the findings in Cph1, our results imply phytochrome species-specific correlations between transient chromophore deprotonation and intramolecular signal transduction.

Evaluation of multiple linear regression function and generalized linear model types in estimating natural menopausal age: A cross-sectional study.

Background: Since women spend about one-third of their lifespan in menopause, accurate prediction of the age of natural menopause and its effective parameters are crucial to increase women's life expectancy. Objective: This study aimed to compare the performance of generalized linear models (GLM) and the ordinary least squares (OLS) method in predicting the age of natural menopause in a large population of Iranian women. Materials and Methods: This cross-sectional study was conducted using data from the recruitment phase of the Shahedieh Cohort Study, Yazd, Iran. In total, 1251 women who had the experience of natural menopause were included. For modeling natural menopause, the multiple linear regression model was employed using the ordinary least squares method and GLMs. With the help of the Akaike information criterion, root-mean-square error (RMSE), and mean absolute error, the performance of regression models was measured. Results: The mean age of menopausal women was 49.1 ± 4.7 yr (95% CI: 48.8-49.3) with a median of 50 yr. The analysis showed similar Akaike criterion values for the multiple linear models with the OLS technique and the GLM with the Gaussian family. However, the RMSE and mean absolute error values were much lower in GLM. In all the models, education, history of salpingectomy, diabetes, cardiac ischemic, and depression were significantly associated with menopausal age. Conclusion: To predict the age of natural menopause in this study, the GLM with the Gaussian family and the log link function with reduced RMSE and mean absolute error can be a good alternative for modeling menopausal age.

VIP-expressing interneurons in the anterior insular cortex contribute to sensory processing to regulate adaptive behavior.

Adaptive behavior critically depends on the detection of behaviorally relevant stimuli. The anterior insular cortex (aIC) has long been proposed as a key player in the representation and integration of sensory stimuli, and implicated in a wide variety of cognitive and emotional functions. However, to date, little is known about the contribution of aIC interneurons to sensory processing. By using a combination of whole-brain connectivity tracing, imaging of neural calcium dynamics, and optogenetic modulation in freely moving mice across different experimental paradigms, such as fear conditioning and social preference, we describe here a role for aIC vasoactive intestinal polypeptide-expressing (VIP+) interneurons in mediating adaptive behaviors. Our findings enlighten the contribution of aIC VIP+ interneurons to sensory processing, showing that they are anatomically connected to a wide range of sensory-related brain areas and critically respond to behaviorally relevant stimuli independent of task and modality.

Improved fluorescent phytochromes for in situ imaging.

Modern biology investigations on phytochromes as near-infrared fluorescent pigments pave the way for the development of new biosensors, as well as for optogenetics and in vivo imaging tools. Recently, near-infrared fluorescent proteins (NIR-FPs) engineered from biliverdin-binding bacteriophytochromes and cyanobacteriochromes, and from phycocyanobilin-binding cyanobacterial phytochromes have become promising probes for fluorescence microscopy and in vivo imaging. However, current NIR-FPs typically suffer from low fluorescence quantum yields and short fluorescence lifetimes. Here, we applied the rational approach of combining mutations known to enhance fluorescence in the cyanobacterial phytochrome Cph1 to derive a series of highly fluorescent variants with fluorescence quantum yield exceeding 15%. These variants were characterised by biochemical and spectroscopic methods, including time-resolved fluorescence spectroscopy. We show that these new NIR-FPs exhibit high fluorescence quantum yields and long fluorescence lifetimes, contributing to their bright fluorescence, and provide fluorescence lifetime imaging measurements in E.coli cells.

Concurrent omphalomesenteric duct cyst and ileal diverticulum causing small bowel obstruction; a case report.

INTRODUCTION AND IMPORTANCE: The omphalomesenteric duct (OMD) usually involutes by the ninth gestational week. If this obliteration fails, OMD remnant will result in different pathologies mostly in the pediatrics and infrequently in adults. The most well-known OMD remnant disease is Meckel's diverticulum. Omphalomesenteric cyst is rather rare, and their combination is even more exceptional with few cases in literature. CASE PRESENTATION: We present an adolescent patient with nausea and vomiting and occasional periumbilical abdominal pain who was diagnosed with concurrent omphalomesenteric cyst and ileal diverticulum, causing internal hernia and bowel obstruction that underwent surgery. CLINICAL DISCUSSION: OMD remnants mostly present in childhood with symptoms of intestinal obstruction, and rarely internal hernias for which conservative management is usually not curative, warranting surgery. Imaging presence of cystic lesion in mid abdomen in young patient with bowel obstruction should raise the suspicion for OMD remnants. Presence of OMD cyst together with Meckel's diverticulum necessitates more extensive resection, rare concurrence which is better to be prepared for in advance. CONCLUSION: Preoperative radiologic workup is helpful to diagnose the obstruction and its probable cause. Presence of periumbilical cyst should raise the suspicion of OMD remnant specially in young adults with previous episodes of crampy abdominal pain and obstruction without history of abdominal surgery. Being familiar with possible concurrence of OMD cyst and Meckel's diverticulum will increase preparedness at the time of surgery.

Disease-modifying therapies and T1 hypointense lesions in patients with multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Previous research has shown that cerebral T1 hypointense lesions are positively correlated with the disability of multiple sclerosis (MS) patients. Hence, they could be used as an objective marker for evaluating the progression of the disease. Up to this date, there has not been a systematic evaluation of the effects of disease-modifying therapies (DMTs) on this prognostic marker. OBJECTIVES: To evaluate the effects of FDA-approved DMTs on the numbers and volume of T1 hypointense lesions in adult patients with MS. METHODS: We included studies with the mentioned desired outcomes. In March 2021, we searched MEDLINE (Ovid), Embase, and CENTRAL to find relevant studies. All included studies were assessed for the risk of bias using the RoB-2 tool. Extracted data were analyzed using a random-effects model. Certainty of evidence was assessed using GRADE. RESULTS: Thirteen studies with 7484 participants were included. Meta-analysis revealed the mean difference between the intervention and comparator groups for the number of lesions was -1.3 (95% CI: -2.1, -0.5) and for the mean volume of lesions was -363.1 (95% CI: -611.6, -114.6). Certainty of evidence was judged to be moderate. Heterogeneity was considerable. DISCUSSION: DMTs reduce the number and volume of T1 hypointense lesions. Although, these findings must be interpreted cautiously due to the high values of heterogeneity.