Sharif Digital Repository

Human infertility is a multifactorial disease that affects 8%–12% of reproductive-aged couples worldwide. However, the genetic causes of human infertility are still poorly understood. Synaptonemal complex (SC) is a conserved tripartite structure that holds homologous chromosomes together and plays an indispensable role in the meiotic progression. Here, we identified three homozygous mutations in the SC coding gene C14orf39/SIX6OS1 in infertile individuals from different ethnic populations by whole-exome sequencing (WES). These mutations include a frameshift mutation (c.204_205del [p.His68Glnfs∗2]) from a consanguineous Pakistani family with two males suffering from non-obstructive... 

Mechanical ventilation (MV) can result in long-term brain impairments that are resistant to treatment. The mechanisms underlying MV-induced brain function impairment remain unclear. Since nasal airflow modulates brain activity, here we evaluated whether reinstating airflow during MV could influence the memory performance of rats after recovery. Rats were allocated into two study groups: one group received rhythmic air-puff into the nasal cavity during MV and a control group that underwent ventilation without air-puff. During MV, air-puffs induced time-locked event potentials in OB, mPFC and vHPC and significantly increased the oscillatory activity at the air-puff frequency. Furthermore, in... 

Irregular hemodynamics affects the progression of various vascular diseases, such atherosclerosis or aneurysms. Despite the extensive hemodynamics studies on animal models, the inter-species differences between humans and animals hamper the translation of such findings. Recent advances in vascular tissue engineering and the suitability ofin vitromodels for interim analysis have increased the use ofin vitrohuman vascular tissue models. Although the effect of flow on endothelial cell (EC) pathophysiology and EC-flow interactions have been vastly studied in two-dimensional systems, they cannot be used to understand the effect of other micro- and macro-environmental parameters associated with... 

Anxiety is among the most debilitating nonmotor symptoms of Parkinson's disease (PD). This study aimed to determine how PD patients with low and high levels of anxiety (LA-PD and HA-PD, respectively) compare with age- and sex-matched controls at the level of motor control of reach-to-grasp movements during single- and dual-task conditions with varying complexity. Reach-to-grasp movement kinematics were assessed in 20 LA-PD, 20 HA-PD, and 20 sex- and age-matched healthy controls under single- as well as easy and difficult dual-task conditions. Assessment of PD patients was performed during both the on- and off-drug phases. The results obtained during dual-task conditions reveal deficits in... 

The NF-κB family includes some transcription factors which have important functions in the regulation of immune responses, therefore participating in the pathophysiology of inflammatory conditions such as peripheral neuropathies. We have quantified expression of a number of NF-κB-related transcripts in patients with Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP) versus healthy subjects. These transcripts have been previously shown to be functionally related with this family of transcription factors. Expressions of ATG5, DICER-AS1, PACER, DILC, NKILA and ADINR have been increased in both CIDP and GBS patients compared with controls. However,... 

Organ-on-a-chip technology tries to mimic the complexity of native tissues in vitro. Important progress has recently been made in using this technology to study the gut with and without microbiota. These in vitro models can serve as an alternative to animal models for studying physiology, pathology, and pharmacology. While these models have greater physiological relevance than two-dimensional (2D) cell systems in vitro, endocrine and immunological functions in gut-on-a-chip models are still poorly represented. Furthermore, the construction of complex models, in which different cell types and structures interact, remains a challenge. Generally, gut-on-a-chip models have the potential to... 

Contrast induced nephropathy (CIN) has been reported to be the third foremost cause of acute renal failure. Metabolomics is a robust technique that has been used to identify potential biomarkers for the prediction of renal damage. We aim to analyze the serum and urine metabolites changes, before and after using contrast for coronary angiography, to determine if metabolomics can predict early development of CIN. 66 patients undergoing elective coronary angiography were eligible for enrollment. Urine and serum samples were collected prior to administration of CM and 72 h post procedure and analyzed by nuclear magnetic resonance. The significant differential metabolites between patients who... 

The search for efficient chemotherapy drugs and other anti-cancer treatments would benefit from a deeper understanding of the tumor microenvironment (TME) and its role in tumor progression. Because in vivo experimental methods are unable to isolate or control individual factors of the TME and in vitro models often do not include all the contributing factors, some questions are best addressed with systems biology mathematical models. In this work, we present a new fully-coupled, agent-based, multi-scale mathematical model of tumor growth, angiogenesis and metabolism that includes important aspects of the TME spanning subcellular-, cellular- and tissue-level scales. The mathematical model is... 

Background: The purpose of this study was to propose a methodology for mechanical characterization of the ligaments in subject-specific models of the patellofemoral joint (PFJ) of living individuals. Method: PFJ laxity tests were performed on a healthy volunteer using a specially designed loading apparatus under biplane fluoroscopy. A three-dimensional (3D) parametric model of the PFJ was developed in the framework of the rigid body spring model using the geometrical data acquired from the subject's computed tomography and magnetic resonance images. The stiffness and pre-strains of the medial and lateral PFJ ligaments were characterized using a two-step optimization procedure which minimized... 

Alzheimer’s disease (AD) is an irreversible neurological disorder that progresses gradually and can cause severe cognitive and behavioral impairments. This disease is currently considered a social and economic incurable issue due to its complicated and multifactorial characteristics. Despite decades of extensive research, we still lack definitive AD diagnostic and effective therapeutic tools. Consequently, one of the most challenging subjects in modern medicine is the need for the development of new strategies for the treatment of AD. A large body of evidence indicates that amyloid-β (Aβ) peptide fibrillation plays a key role in the onset and progression of AD. Recent studies have reported... 

Background: Return to sport (RTS) criteria are widely being used to identify anterior cruciate ligament reconstructed (ACLR) athletes ready to return to sportive activity and reduce risk of ACL re-injury. However, studies show a high rate of ACL re-injury in athletes who passed RTS criteria. This indicates that the current RTS criteria might not be sufficient to determine return to sport time in ACLR athletes. Previous studies have reported a close association between altered lower limb kinematics and ACL re-injury. However, it is not clear how lower extremity kinematics differs between ACLR athletes who passed the RTS-criteria and who failed. This study compared lower extremity kinematics... 

Introduction: Some tinnitus subjects habituate to their tinnitus but some others do not and complain of its annoyance tremendously. Normal sensory memory and change detection processes are needed for detecting the tinnitus signal as a prediction error and habituation to tinnitus. The purpose of this study was to compare auditory mismatch negativity as the index of sensory memory and change detection among the studied groups to search for the factors involving in the perception of tinnitus and preventing habituation in decompensated tinnitus subjects. Methods: Electroencephalography was recorded from scalp electrodes in compensated tinnitus, decompensated tinnitus, and no tinnitus control... 

Although anxiety is one of the most prevalent psychological disorders in stroke survivors, its effect on sensory reweighting has not yet been fully studied. The aim of this work was to investigate how anticipation of collision avoidance events affects sensory reweighting in chronic stroke survivors with low and high levels of anxiety (LA-stroke and HA-stroke, respectively), as compared with healthy controls (HC), under the condition of perturbed proprioception. Eighteen LA-stroke and 18 HA-stroke survivors, as well as 18 gender- and age-matched HC, participated in this study. Postural sway variability (i.e. Root Mean Square (RMS) of the COP velocity) was measured for a duration of 180 s... 

Background: Focal segmental glomerulosclerosis (FSGS) is considered one of the most severe glomerular diseases and around 80% of cases are resistant to steroid treatment. Since a large proportion of steroid-resistant (SR) FSGS patients progress to end-stage renal disease, other therapeutic strategies may benefit this population. However, identification of non-invasive biomarkers to predict this high-risk population is needed. Objective: We aimed to identify the biomarker candidates to distinguish SR from steroid-sensitive (SS) patients using metabolomics approach and to identify the possible molecular mechanism of resistance. Methods: Urine was collected from biopsy-proven FSGS patients... 

Objectives: To investigate the effects of competitive and noncompetitive volleyball exercises on the functional performance and motor control of the upper limbs in chronic stroke survivors. Design: Randomized clinical trial. Setting: Outpatient rehabilitation center. Participants: Chronic stroke survivors (N=48). Interventions: Participants were randomly assigned to competitive (n=16) or noncompetitive (n=16) volleyball exercise groups (60min/d volleyball exercise+30min/d traditional rehabilitation, 3d/wk for 7wk) and control group (n=16). Main Outcome Measures: Reach and grasp motor control measures were evaluated through kinematic analysis. Functional outcomes were assessed via Motor... 

Using a combined musculoskeletal and finite element (FE) approach, this study aimed to evaluate stability-based muscle forces in a spine with adolescent idiopathic scoliosis (AIS) as compared to a normal spine; and subsequently, determine the effects of stress distribution on the growth plates (GPs) of the growing spine. For this purpose a nonlinear 3D FE model of one normal and one scoliotic thoracolumbar spine, consisting of GPs attached to rigid L1 to L4 vertebrae, were developed using computed tomography images coupled with a growth modulation using the Stokes’ model. Corresponding well with recent in-vivo and in-vitro studies, results of the models predicted intradiscal pressures at the... 

Background: Functional knee braces are extensively used for partially and completely torn anterior cruciate ligament (ACL) patients and those who have undergone ACL graft reconstruction, in order to support the healing ACL, improve the joint's functional stability, and restore the normal joint kinematics. Research question: Does wearing braces alter the arthrokinematics of the ACL deficient knees during lung exercise? Methods: For ten male unilateral ACL deficient subjects, 3D knee models were reconstructed from CT images, acquired in rest position. Sagittal plane fluoroscopy was then performed throughout a complete cycle of lunge in braced and non-braced conditions. The 3D kinematics of the... 

Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug... 

Background Although anxiety is a common non-motor outcome of Parkinson's disease (PD) affecting 40% of patients, little attention has been paid so far to its effects on balance impairment and postural control. Improvement of postural control through focusing on the environment (i.e. external focus) has been reported, but the role of anxiety, as a confounding variable, remains unclear. Objectives This study aimed to investigate the influence of anxiety and attentional focus instruction on the standing postural control of PD patients. Methods Thirty-four patients with PD (17 with high anxiety (HA-PD) and 17 with low anxiety (LA-PD)), as well as 17 gender- and age-matched healthy control... 

Background and Purpose: Understanding the role and significance of trunk and upper extremity muscles in paraplegic gait can help in designing more effective assistive devices for these patients and also provides valuable information for improving muscle strengthening programs. Methods: In a patient with a spinal cord injury (SCI) who could walk independently (rating scale of ambulatory capacity, 9) with the aid of bilateral ankle-foot orthosis and a walker, the kinematics, kinetics and electromyographic (EMG) activities of 16 muscles from the trunk and upper and lower extremities were recorded during gait. The onset, cessation, and duration of the EMG signal were associated with the 4 phases...