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Performance accuracy and reaction time in cognitive tasks are routinely used to evaluate the efficacy of tDCS to affect cognitive task performance. tDCS alters the excitability of targeted brain areas and thereby alters performance of cognitive tasks. The drift diffusion model (DDM) provides some additional measures to explore information processing style, such as (non)decision time, bias for decision, and speed of information processing. DDM parameters are informative for the study of cognitive impairments in children with ADHD. In the present study, we aimed to evaluate the impact of tDCS on cognitive performance via DDM measures.This study conducted DDM modeling and reanalysis of two exploratory, single-blinded, within-subject design experiments, which were published earlier. In the first experiment, twenty- four children with ADHD performed a Go/ No- Go task during anodal or sham tDCS over the right dlPFC. In the second experiment, twenty- five children with ADHD performed the 1- back working memory task during anodal or sham tDCS over the left dlPFC. We reanalyzed the data after DDM modeling.The conventional performance measures revealed no significant effect of tDCS on No- Go accuracy in the first experiment and 1-back accuracy in the second experiment. The 1-back reaction time and speed-accuracy tradeoff were however improved under the real stimulation condition. The DDM measures identified increased No-Go- bias and decision time with respect to inhibitory control, and an increased threshold and amount of information required for response in the 1- back test.In children with ADHD, anodal tDCS over the right dlPFC induces more conservative and less impulsive decisions. Furthermore, anodal tDCS over the left dlPFC enhanced efficacy of working memory performance with respect to agility and capacity. The experimental results show that drift diffusion modeling is useful for evaluation of the impact of tDCS on the style of information processing.

Ferroptosis is a regulated form of non-apoptotic cell death implicated in pathological settings. To be exploited clinically, ferroptosis requires reagents that unequivocally detect ferroptosis in human and animal tissues. Such tools may enable development of ferroptosis-based medicines for diverse diseases.

Objective: To compare the effects of Wii and conventional training on functional abilities and neurocognitive function in basketball-players with Functional Ankle Instability (FAI). Design: Single-blind matched randomized clinical trial study. Setting: Outpatients setting. Participants: Fifty-four basketball-players were randomly assigned to the Wii and control group. Interventions: All athletes in the Wii group ( n = 27) performed Wii Fit Plus games; and in the control group ( n = 27), they performed conventional training three days a week for 12 sessions. Main outcome measures: To assess functional performance and neurocognitive function, we used hop tests (8-hop, side hop, and single hop) and Deary-Liewald Reaction Time Task (DLRT), respectively. DLRT measured simple and choice reaction time and error rate. Measures were taken at baseline, four weeks, and eight weeks after baseline. Results: In all 54 athletes completed the study. The results showed no significant differences for all hop tests in between-group comparison but the neurocognitive function showed significant improvements in the Wii group compared to the control group ( P Conclusion: Based on our results, both training protocols were equal to positively affect functional abilities. Besides, Wii training improved neurocognitive function and can be applied in FAI rehabilitation protocols.

ABCA3 (ATP-binding cassette subfamily A member 3) is a lipid transporter expressed in alveolar type II cells and localized in the limiting membrane of lamellar bodies. It is crucial for pulmonary surfactant storage and homeostasis. Mutations in the ABCA3 gene are the most common genetic cause of respiratory distress syndrome in mature newborns and of interstitial lung disease in children. Apart from lung transplant, there is no cure available. To address the lack of causal therapeutic options for ABCA3 deficiency, a rapid and reliable approach is needed to investigate variant-specific molecular mechanisms and to identify pharmacologic modulators for monotherapies or combination therapies. To this end, we developed a phenotypic cell-based assay to autonomously identify ABCA3 wild-type-like or mutant-like cells by using machine learning algorithms aimed at identifying morphologic differences in wild-type and mutant cells. The assay was subsequently used to identify new drug candidates for ABCA3-specific molecular correction by using high-content screening of 1,280 Food and Drug Administration-approved small molecules. Cyclosporin A was identified as a potent corrector, specific for some but not all ABCA3 variants. Results were validated by using our previously established functional small-format assays. Hence, cyclosporin A may be selected for orphan drug evaluation in controlled repurposing trials in patients.

The aim was to investigate the effect of video game training as compared to dual-task training on gait initiation (GI) which is a sensitive indicator of balance deficiency in older adults.Sixty-six older adults were allocated to the video game-based training (intervention group) or the motor-cognitive dual-task training (active control group). The outcome measures were the mediolateral (ML)/anteroposterior (AP) displacement and velocity of COP during the phases of GI (anticipatory, weight transition, and locomotor).The results indicated in the anticipatory phase, the MLAP COP displacement were significantly increased at post-training relative to pre-training across both groups (Both treatments were effective in improving COP trajectory during the phases of anticipatory and weight transition, while the intervention group was more effective during the phase of locomotor. So, these treatments can be recommended for clinical settings.Implications for rehabilitationThe video game and dual task training were effective in improving COP trajectory during the phases of anticipatory and weight transition.The video game-based training was more effective during the phase of locomotor.The study findings could have useful implications to further introduce cognition-based rehabilitation programs such as video games for older adults.Rehabilitation professionals could use the video game to improve the postural control of older adults.

Small-molecule screening is a powerful approach to identify modulators of either specific biological targets or cellular pathways with phenotypic endpoints. A myriad of assay technologies are available to assess the activity of enzymes, monitor protein-protein interactions, measure transcription factor activity in reporter assays, or detect cellular features and activities using high-content imaging. A common challenge during small-molecule screening is, however, the presence of hit compounds generating assay interference, thereby producing false-positive hits. Thus, efforts are needed to uncover such interferences to prioritize high-quality hits for further analysis. This process encompasses (1) computational approaches to flag undesirable compounds, and (2) the use of experimental approaches like counter, orthogonal, and cellular fitness screens to identify and eliminate artifacts. In this brief guide, we provide an overview for first-time users, highlighting experimental screening strategies to prioritize high-quality bioactive hits from high-throughput screening/high-content screening (HTS/HCS) campaigns.

Objectives Ultrasound (US) imaging has been suggested to evaluate the morphology and function of trunk muscles; however, little is known about the reliability of the US measures in patients with chronic low back pain (CLBP). This study aimed to evaluate intrarater reliability of US imaging of the lateral abdominal and lumbar multifidus muscles in individuals with nonspecific CLBP. Methods In this cross-sectional study, intrarater within-day and between-day reliability of US measurements of the transversus abdominis, internal oblique, external oblique and lumbar multifidus (at the L3-L4, L4-L5, and L5-S1 levels) muscles were obtained on both sides. The resting and contracted thickness and contraction ratio of each muscle were measured in 21 individuals with nonspecific CLBP. Results All US measurements of the lateral abdominal and lumbar multifidus muscles demonstrated good to excellent within-day (Intraclass correlation coefficients (ICCs: 0.80–0.98) and between-day (ICCs: 0.80–0.97) reliability. The standard error of the measurement (SEMs) and minimal detectable change (MDCs) of the lateral abdominal muscles on both sides ranged 0.5–1.6 mm and 0.4–4.4 mm, respectively. The SEMs and MDCs of the LM muscles on both sides ranged 1.1–2.7 mm and 2.86–7.49 mm, respectively. Conclusion The findings indicate that US imaging has good to high intrarater within- and between-day reliability for assessing absolute thickness and contraction ratio of the trunk muscles on both right and left sides in patients with nonspecific CLBP. The vertical alignment of the US transducer is a reliable method for assessing the lateral abdominal muscles.

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity (“nuisance compounds”) are routinely encountered in cellular assays, including phenotypic and high-content screening assays. Much is known regarding compound-dependent assay interferences in cell-free assays. However, despite the essential role of cellular assays in chemical biology and drug discovery, there is considerably less known about nuisance compounds in more complex cell-based assays. In our view, a major obstacle to realizing the full potential of chemical biology will not just be difficult-to-drug targets or even the sheer number of targets, but rather nuisance compounds, due to their ability to waste significant resources and erode scientific trust. In this review, we summarize our collective academic, government, and industry experiences regarding cellular nuisance compounds. We describe assay design strategies to mitigate the impact of nuisance compounds and suggest best practices to efficiently address these compounds in complex biological settings. Nuisance compounds can waste significant resources by producing promising bioactivities that are attributable to undesirable mechanisms of action. Addressing nuisance compounds is particularly challenging in cellular assays. Dahlin et al. summarize academic, government, and industry experiences with assay design and hit triage to specifically address cellular nuisance compounds.

This randomized controlled study aimed to investigate the efficacy and safety of multiple treatment sessions of pulsed non-thermal atmospheric pressure nitrogen plasma compared with long-pulsed Nd:YAG laser for hand rejuvenation. To optimize the nitrogen plasma mode for rejuvenation, the relative intensity of reactive species and skin temperature was compared at different input powers and time periods. Twenty-five patients with mild-moderate photodamaged skin were recruited; one hand was randomly selected for eight weekly treatment sessions with plasma (two passes), while the other was subjected to three monthly treatments with laser (until erythema became obvious). A blinded dermatologist scored the mean wrinkle and dyschromia improvement at 1 and 2 months after the first treatment and 1 and 3 months after the last treatment. The patients’ satisfaction and the biomechanical characteristics of the skin including cutaneous resonance running time (CRRT), melanin, transepidermal water loss (TEWL), and hydration were evaluated. Clinically, both methods gave rise to a similar, significant improvement in wrinkles (49.09 ± 19.18% and 39.32 ± 18.21% after plasma and laser, respectively) and dyschromia (45.00 ± 26.32% and 30.62% ± 24.99% after plasma and laser, respectively) (P

Background: Non-communicable diseases (NCDs) are one of the greatest threats to public health, and have been related to poor quality dietary patterns. This study was conducted to determine the distribution of dietary risk factors in Iran. Methods: Cross-sectional data was gathered between April and November 2016 from 30,541 eligible adults (out of 31 050 individuals who were selected through systematic proportional to size cluster random sampling) living in urban and rural areas, using the WHO-based STEPs risk factor questionnaire. Low intakes of fruits, vegetables, dairy products, and fish, and high intakes of salty processed food (SPF), as well as daily intake of hydrogenated fat (HF) were considered as nutritional risk factors. Results: At the national level, 82.8% (95% CI: 82.4-83.2), 57.8% (95% CI: 57.2-58.4), 80.6% (95% CI: 80.1-81) and 90.3% (95% CI: 90-90.6) of participants of all age groups had sub-optimal intakes of fruits, vegetables, dairy products and fish, respectively. Furthermore, 12.8% (95% CI: 12.4-13.1), and 29.4% (95% CI: 28.9-29.9) of respondents had high SPF intakes and HF use, respectively. At the sub-national level, the highest distribution of suboptimal intake of fruits (97.2%; 95% CI:96-98.3), vegetables (79.2%; 95% CI: 76.3-82.1) and dairy products (92.9%; 95% CI: 91-94.7) was observed in Sistan and Baluchistan. Except for Boushehr and Hormozgan, the majority of the population of other provinces consumed fish less than twice a week. Similarly, the high intake of SPF was found mostly in the population of Yazd (23.7; 95% CI: 20.2-27.2). HF consumption was the highest in North Khorasan (64.2%; 95% CI: 60.3-68.1). Conclusion: These findings highlight the widespread distribution of dietary risk factors in Iran, which should be a priority for the people and the politicians in order to prevent NCDs.

Objectives To identify differences in architectural parameters (size, fiber/pennation angle, fiber length, and echogenicity) of the quadriceps muscle, as a whole or any individual part of it, using imaging techniques in individuals with patellofemoral pain (PFP) compared to contralateral, asymptomatic limb or separate control group. Background Quadriceps muscles imbalance and weakness were proposed as risk factors for developing PFP. Although the muscle architecture (size, pennation/fiber angle and fiber length) is highly associated with skeletal muscle strength, it is not clear whether atrophy or any changes in architectural parameters of the quadriceps are presented in the PFP patients. Methods Observational studies in which the total size of the quadriceps or individual parts of it were measured using imaging techniques in the PFP patients were included in this review. Electronic databases (PubMed, SCOPUS, PEDro, CINAHL, WOS, and EMBASE) were searched between January 1990 and December 2019 with no restriction of language. Study selection and data extraction and quality assessment were conducted by two independent reviewers. Results Five cross-sectional studies were eligible to include in this review. Three out of five included studies that assessed the total size of the quadriceps and reported no significant differences between the PFP and healthy control group. Two out of five of the studies assessed the total size of the quadriceps between the symptomatic and asymptomatic limb of the PFP patients and reported the statistical difference between limbs. Only one study measured the fiber angle of the VMO muscle at the patella. Controversial results were found between studies that assessed the size of individual parts of the quadriceps. Conclusion Due to the controversial results of the included studies, this systematic review failed to draw a conclusion on the role of quadriceps atrophy in PFP pathology. The limitation in PFP literature considering pennation/fiber angle, echogenicity and fiber length of individual parts of the quadriceps muscle, rises the need for research that focuses on the biomechanical properties of the quadriceps in PFP patients.

Purpose: The current study aimed to identify the prevalence of burnout and related factors in nursing faculty members through a systematic review of the literature.Methods: A comprehensive search of electronic databases, including Scopus, PubMed, Web of Science, Iranmedex, and Scientific Information Database was conducted via keywords extracted from Medical Subject Headings, including burnout and nursing faculty, for studies published from database inception to April 1, 2022. The quality of the included studies in this review was assessed using the appraisal tool for cross-sectional studies.Results: A total of 2,551 nursing faculty members were enrolled in 11 studies. The mean score of burnout in nursing faculty members based on the Maslach Burnout Inventory (MBI) was 59.28 out of 132. The burnout score in this study was presented in 3 MBI subscales: emotional exhaustion, 21.24 (standard deviation [SD]=9.70) out of 54; depersonalization, 5.88 (SD=4.20) out of 30; and personal accomplishment, 32.16 (SD=6.45) out of 48. Several factors had significant relationships with burnout in nursing faculty members, including gender, level of education, hours of work, number of classroom, students taught, full-time work, job pressure, perceived stress, subjective well-being, marital status, job satisfaction, work setting satisfaction, workplace empowerment, collegial support, management style, fulfillment of self-expectation, communication style, humor, and academic position.Conclusion: Overall, the mean burnout scores in nursing faculty members were moderate. Therefore, health policymakers and managers can reduce the likelihood of burnout in nursing faculty members by using psychosocial interventions and support.

Background Novel corona virus, named COVID-19, has spread rapidly to other countries like Italy, Iran and South Korea and affected all people, especially health-care providers. Therefore, due to the rapid spread of the disease in Iran, the aim of the present study was to explore psychological distress experienced by Iranian health-care providers in the first few weeks of the corona virus outbreak. Methods The present qualitative study was conducted on 18 Iranian health-care providers exposed to COVID − 19 using a content analysis method. Purposeful sampling was used to select the participants and continued until data saturation was reached. Data were collected using semi-structured interviews and then the qualitative data were analyzed through direct content analysis. Results By analyzing 236 primary codes, two main categories were extracted from the experiences of health-care providers during corona virus outbreak. The first category included Occupational demands with three sub-categories: nature of illness, Organizational demands and social demands. The second category was Supportive resources included personal support and social support. Conclusions The results of this study found that there were some barriers and challenges to medical personnel exposed to COVID-19 that caused psychological distress. Some of these problems related to the nature of illness, others related to social and organizational demands and some of supportive resources buffer the relationship between occupational demands and psychological distress.

While target-based drug discovery strategies rely on the precise knowledge of the identity and function of the drug targets, phenotypic drug discovery (PDD) approaches allow the identification of novel drugs based on knowledge of a distinct phenotype. Image-based high-content screening (HCS) is a potent PDD strategy that characterizes small-molecule effects through the quantification of features that depict cellular changes among or within cell populations, thereby generating valuable data sets for subsequent data analysis. However, these data can be complex, making image analysis from large HCS campaigns challenging. Technological advances in image acquisition, processing, and analysis as well as machine-learning (ML) approaches for the analysis of multidimensional data sets have rendered HCS as a viable technology for small-molecule drug discovery. Here, we discuss HCS concepts, current workflows as well as opportunities and challenges of image-based phenotypic screening and data analysis.

Chronic wounds cause a significant burden on society financially, medically, and psychologically. Unfortunately, patients with nonhealing wounds often suffer from comorbidities that further compound their disability. Given the high rate of depressive symptoms experienced by patients with chronic wounds, further studies are needed to investigate the potentially linked pathophysiological changes in wounds and depression in order to improve patient care. The English literature on wound healing, inflammatory and microbial changes in chronic wounds and depression, and antiinflammatory and probiotic therapy was reviewed on PubMed. Chronic wound conditions and depression were demonstrated to share common pathologic features of dysregulated inflammation and altered microbiome, indicating a possible relationship. Furthermore, alternative treatment strategies such as immune-targeted and probiotic therapy showed promising potential by addressing both pathophysiological pathways. However, many existing studies are limited to a small study population, a cross-sectional design that does not establish temporality, or a wide range of confounding variables in the context of a highly complex and multifactorial disease process. Therefore, additional preclinical studies in suitable wound models, as well as larger clinical cohort studies and trials are necessary to elucidate the relationship between wound microbiome, healing, and depression, and ultimately guide the most effective therapeutic and management plan for chronic wound patients.

Background The birth of premature newborns and their separation from family due to their hospitalization in the Neonatal Intensive Care Unit (NICU) cause stress in the parents, especially mothers. We conducted this study aimed to evaluate whether training the fathers to support their wives impacts premature newborn mothers’ stress and self-efficacy or not? Methods A quasi-experimental (before-after study) including one experimental and control group was used. Data were collected from Seventy-five parents with newborns hospitalized in NICU (n = 30) in the intervention and (n = 45) in usual care groups. Settings were the NICUs of the two international, educational, specialty, and subspecialty Nemazee and Hafez hospitals of the Shiraz University of Medical Science. Fathers in the intervention group learned how to support their wives and provide care for their premature newborns. The control group received the usual care. Mother’s stress and self-efficacy were measured using validated questionnaires. Results Data analysis showed that the mean scores of mothers’ stress and self-efficacy from pre-intervention to post-intervention were significantly decreased and increased respectively in the intervention group (p Conclusion When fathers are trained to support their wives and do so, it relieves the stress and improves the mothers’ self-efficacy, and has a direct effect on providing care to their premature newborns. Therefore, it is recommended that measures should be taken so that the fathers be present, participate in providing care, and support their wives and newborns in NICU. Trial registration IRCT20171130037691N1.

Backgroundpre-hospital emergency is a community-oriented system that responds to the medical needs of the injured or patients with acute and emergency illnesses outside of health care facilities until they are transferred to a medical center. This study aimed to explore pre-hospital emergency challenges in the face of the COVID-19 pandemic.Material and methodsThis study was conducted as a qualitative content analysis in Iran. Using the purposive sampling method, data were collected through in-depth individual interviews with 28 prehospital paramedic personnel from November 2020 to November 2021. Graneheim and Lundman's conventional content analysis methods were used to analyze the data and for the trustworthiness of the data, this study used Lincoln and Guba's recommendations.ResultsAfter multiple rounds of analyzing and summarizing the data and taking into consideration similarities and differences, four main categories and 10 subcategories were created based on the results of the data analysis and including (1) Culture and Community. (2) Service delivery (3) Human resources; (4) Medical supplies and equipment.ConclusionAccording to the findings of this study emergency medical system employees are suffering from a range of psychiatric problems as a result of a lack of equipment and job overload, which has a detrimental impact on the quality of pre-hospital emergency care. Therefore, emergency care senior management should develop comprehensive guidelines, provide more equipment and minimize professional challenges to improve the quality and safety of pre-hospital emergency care services.

Determining cell death mechanisms occurring in patient and animal tissues is a longstanding goal that requires suitable biomarkers and accurate quantification. However, effective methods remain elusive. To develop more powerful and unbiased analytic frameworks, we developed a machine learning approach for automated cell death classification. Image sets were collected of HT-1080 fibrosarcoma cells undergoing ferroptosis or apoptosis and stained with an anti-transferrin receptor 1 (TfR1) antibody, together with nuclear and F-actin staining. Features were extracted using high-content-analysis software, and a classifier was constructed by fitting a multinomial logistic lasso regression model to the data. The prediction accuracy of the classifier within three classes (control, ferroptosis, apoptosis) was 93%. Thus, TfR1 staining, combined with nuclear and F-actin staining, can reliably detect both apoptotic and ferroptotis cells when cell features are analyzed in an unbiased manner using machine learning, providing a method for unbiased analysis of modes of cell death.

The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort and available vaccines, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PLpro) inhibitor. NMR titrations and a co-crystal structure confirm that acriflavine blocks the PLpro catalytic pocket in an unexpected binding mode. We show that the drug inhibits viral replication at nanomolar concentration in cellular models, in vivo in mice and ex vivo in human airway epithelia, with broad range activity against SARS-CoV-2 and other betacoronaviruses. Considering that acriflavine is an inexpensive drug approved in some countries, it may be immediately tested in clinical trials and play an important role during the current pandemic and future outbreaks., Graphical abstract, Napolitano et al. discovered acriflavine (ACF), a clinically approved drug, as an effective inhibitor of SARS-CoV-2 papain-like protease (PLpro). ACF inhibits viral replication at nanomolar concentrations in vitro and ex vivo, as well as in vivo. These findings open a promising therapeutic approach against COVID-19 and other betacoronaviruses.

Trypanosomiases are life-threatening infections of humans and livestock, and novel effective therapeutic approaches are needed. Trypanosoma compartmentalize glycolysis into specialized organelles termed glycosomes. Most of the trypanosomal glycolytic enzymes harbor a peroxisomal targeting signal-1 (PTS1) which is recognized by the soluble receptor PEX5 to facilitate docking and translocation of the cargo into the glycosomal lumen. Given its pivotal role in the glycosomal protein import, the PEX5–PTS1 interaction represents a potential target to inhibit import of glycolytic enzymes and thus kill the parasite. We developed a fluorescence polarization (FP)-based assay for monitoring the PEX5–PTS1 interaction and performed a High Throughput Screening (HTS) campaign to identify small molecule inhibitors of the interaction. Six of the identified hits passed orthogonal selection criteria and were found to inhibit parasite growth in cell culture. Our results validate PEX5 as a target for small molecule inhibitors and provide scaffolds suitable for further pre-clinical development of novel trypanocidal compounds.

Background With increasing obese populations worldwide, developing interventions to modulate food-related brain processes and functions is particularly important. Evidence suggests that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may modulate the reward–control balance towards facilitation of cognitive control and possible suppression of reward-related mechanisms that drive food cue-induced craving. This protocol describes a clinical trial that investigates the neurocognitive mechanisms of action for tDCS to modulate food cue-reactivity and cravings in people with obesity. Method The NeuroStim-Obesity trial is a prospective, randomized, sham-controlled, double-blind single-session tDCS trial targeting food craving in those with obesity or overweighed. Once randomized, 64 adults with obesity or overweighed complete one session in which they receive either active or sham tDCS over the DLPFC (anode F4 and cathode F3, 2 mA intensity for 20 min). The primary outcome is change in neural response to the food cue-reactivity task in the ventral striatum after a single-session bilateral tDCS compared to sham stimulation. Secondary outcomes include changes in food craving evaluated by the Food Craving Questionnaire-State (FCQ-S). We will also explore the predictive role of brain structure and functional networks assessed by structural and functional magnetic resonance imaging (MRI) during both task performance and the resting-state that are acquired pre- and post-intervention to predict response to tDCS. Discussion The results will provide novel insight into neuroscience for the efficacy of tDCS and will advance the field towards precision medicine for obesity. Exploratory results will examine the potential predictive biomarkers for tDCS response and eventually provide personalized intervention for the treatment of obesity. Trial registration Iranian Registry of Clinical Trials (IRCT) IRCT20121020011172N4. Retrospectively registered on 4 June 2020

Background The goal of every emergency department is to provide the highest quality services in the shortest time using limited resources. However, occupational violence is so prevalent among pre-hospital paramedic personnel that some experts claim that it is impossible to find pre-hospital personnel without an experience of violence in the workplace. Therefore, it seems necessary to investigate the causes of violence among this population group and find ways to control it. Aim The present study aimed to investigate the Violence and influencing factors among paramedic pre-hospital personnel. Method This qualitative study was conducted to explore the views of a group of pre-hospital paramedic personnel (n = 45) selected through purposive sampling. The data was collected through in-depth and semi-structured interviews and analyzed using Graneheim and Lundman’s conventional content analysis methods. The trial version of MAXQDA 16 software was used to manage the coding process. Results Based on the results of the analysis of data collected from prehospital paramedic personnel, three main categories including: human factors, organizational factors, and environmental factors and 20 subcategories were detected. Conclusion If authorities neglect violence in the workplace and do not take serious actions to prevent it, violence and, more importantly, “hostility” will gradually prevail in the workplace. It also increases the stress and anxiety of staff and consequently severely deteriorates their job performance. Hence, authorities are strongly recommended not to ignore this issue and, instead, take measures, for instance hold workshops, to train personnel about the techniques of anger and violence control.

Objective The objective of this review is to identify differences in quadriceps architectural parameters between healthy individuals and those with patellofemoral pain (PFP). Introduction Patellofemoral pain is one of the most common causes of knee pain among physically active populations. Muscular imbalance may play an important role in patellar malalignment or patellar maltracking. A systematic review will clarify the possible architectural changes of quadriceps muscles in persons with PFP. Inclusion criteria Eligible observational studies will include individuals younger than 50 years who have been diagnosed with unilateral or bilateral PFP. The comparator will be the contralateral, asymptomatic limb of the individual with PFP or a healthy matched subject. Studies that include measurement of quadriceps muscle size as the primary outcome will be considered. Studies in which participants had coexisting pathology, a history of lower limb surgery or injury, or pain originating from other joints will be excluded. Methods PubMed/MEDLINE (NLM), Scopus, Embase, Physiotherapy Evidence Database, Web of Science and CINAHL databases and multiple gray literature sources will be searched. Studies published since 1 January 1990 will be considered; there will be no language restriction. Retrieval of full-text studies, assessment of methodological quality and data extraction will be performed independently by two reviewers. If possible, meta-analyses will be performed, and a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Summary of Findings presented.

The main goal of this study was to investigate the size of all portions of the quadriceps muscles in individuals with pronated foot posture compared to normal foot posture using ultrasound imaging.Twenty nine females with pronated foot posture and 29 age-, body weight-, body height-matched females with normal foot posture were recruited from university communities. The muscle thicknesses of the rectus femoris (RF), vastus medialis (VM), vastus medialis oblique (VMO), vastus lateralis (VL) and vastus intermedius (VI) were measured using ultrasound imaging.The thicknesses of the RF and VMO were significantly smaller in individuals with pronated foot posture compared to normal foot posture (p0.05). No significant differences were observed in the VM, VL, and VI muscle thicknesses in both groups.Based on the results of the present study, it seems that besides the foot and lower leg muscles, an integrated assessment of proximal knee muscles, especially quadriceps, is required in individuals with pronated foot posture.

Recently, stem-cell therapy as a promising therapeutic alternative is considered to treat retinal degenerative diseases. Here, we used small molecules and concentrated conditioned medium selectively enriched with Amicon filter units from human adipose-derived stem cells (hADSC-CM) containing various neurotrophic factors to induce hADSCs toward eye field neuroectoderm (EFN). For induction of stem cells, hADSC-CM and small molecules CKI-7, SB431542 and LDN193189 as inhibitors of Wnt, Nodal and BMP4 signaling pathways were used, respectively. We found the highest expression of β-TUB III as a neural marker in the group in which small molecules and conditioned medium were applied simultaneously. Moreover, EFN markers SIX3, PAX6 and RAX had higher expression in the presence of a conditioned medium. However, the superior expression of ENF marker OTX2 was seen in the small molecules group. Our results indicated that neurotrophic factors present in hADSCs-CM could induce hADSCs into EFN cells. Therefore, a more thorough study of these factors and their effects in hADSC-CM might pave the way for cellular and non-cellular therapy in retinal degenerative diseases.

The vast majority of drugs act through binding to their protein targets. Prediction of the interaction between small molecules and these receptors is a key element in the process of drug discovery. Advances in structural biology have enabled us to resolve the three-dimensional structure of proteins, which are the targets of the drugs. Pharmacogenetics also helped researchers to study the structural variations arise from the single nucleotide polymorphisms (SNPs) and to survey the effects these variations in drug design and development. These improvements led to the identification of structural changes caused by SNPs, which affect the drug interaction with their receptors, called drug response. In this study, the interaction between androgen receptor and bicalutamide was investigated using a computational analysis. The results of these analyses were then used for identification of nonsynonymous SNPs that are potentially involved in drug response alterations. The data show that amino acids Met895, Trp741, Arg752, Ile899, Leu707, Gly708, Gln711, Met745, Met749, Thr877, Phe764, Met742, Asn705 and Leu704 are the main residues involved in the interaction between androgen receptor and bicalutamide. The occurrence of nonsynonymous polymorphisms I843T, L708R, H690P, I870M, N757S, L713F, G744E, L678P, M788V, M781I, A722T, H875Y, I842V, and F827L in this receptor greatly affected its interaction with bicalutamide, and they were able to cause drug resistance. The results of this study could be useful in predicting the response to treatment in patients receiving bicalutamide.

By accentuating drug efficacy and impeding resistance mechanisms, combinatorial, multi‐agent therapies have emerged as key approaches in the treatment of complex diseases, most notably cancer. Using high‐throughput drug screens, we uncovered distinct metabolic vulnerabilities and thereby identified drug combinations synergistically causing a starvation‐like lethal catabolic response in tumor cells from different cancer entities. Domperidone, a dopamine receptor antagonist, as well as several tricyclic antidepressants (TCAs), including imipramine, induced cancer cell death in combination with the mitochondrial uncoupler niclosamide ethanolamine (NEN) through activation of the integrated stress response pathway and the catabolic CLEAR network. Using transcriptome and metabolome analyses, we characterized a combinatorial response, mainly driven by the transcription factors CHOP and TFE3, which resulted in cell death through enhanced pyrimidine catabolism as well as reduced pyrimidine synthesis. Remarkably, the drug combinations sensitized human organoid cultures to the standard‐of‐care chemotherapy paclitaxel. Thus, our combinatorial approach could be clinically implemented into established treatment regimen, which would be further facilitated by the advantages of drug repurposing., This study identifies novel combinatorial drug treatments to induce death of different tumor cells, and defines the mechanisms of synergism between a mitochondrial uncoupler and antidepressants or dopamine receptor antagonists.

Protein-protein interactions (PPI) are involved in a myriad of cellular processes, and their deregulation can lead to many diseases. One such process is protein ubiquitination that requires an orchestrated action of three key enzymes to add ubiquitin moieties to substrate proteins. Importantly, this process is reversible through deubiquitinating enzymes. Both ubiquitination and deubiquitination require many PPIs that once classified can be utilized to identify small molecule inhibitors counteracting these reactions. Here, we study the protein-protein interaction between the two deubiquitinating enzymes OTUB1 and OTUD6B and report for the first time that both proteins directly interact with each other. We describe the GFP-Trap immunoprecipitation as a cell-based method to analyze the OTUD6B-OTUB1 interaction in the cellular context and the AlphaScreen (amplified luminescent proximity homogeneous assay) assay as a tool to detect direct interactions and to search for PPI inhibitors.

53 p.-7 fig.-1 tab.-1 schem.-1 graph. abst., Noscapine is a natural product first isolated from the opium poppy (Papaver somniferum L.) with anticancer properties. In this work, we report the synthesis and cellular screening of a noscapine-based library. A library of novel noscapine derivatives was synthesized with modifications in the isoquinoline and phthalide scaffolds. The so generated library, consisting of fifty-seven derivatives of the natural product noscapine, was tested against MDA-MB-231 breast cancer cells in a cellular proliferation assay (with a Z' > 0.7). The screening resulted in the identification of two novel noscapine derivatives as inhibitors of MDA cell growth with IC50 values of 5 µM and 1.5 µM, respectively. Both hit molecules have a five-fold and seventeen-fold higher potency, compared with that of lead compound noscapine (IC50 26 µM). The identified active derivatives retain the tubulin-binding ability of noscapine. Further testing of both hit molecules, alongside the natural product against additional cancer cell lines (HepG2, HeLa and PC3 cells) confirmed our initial findings. Both molecules have improved anti-proliferative properties when compared to the initial natural product, noscapine., We are also grateful to the Iran National Science Foundation (INSF, grant number 98026465) for financial support of this project and Shahid Beheshti University Research Council for providing facilities of to conduct this study. This work was supported by CSIC PIE 201920E111 (MAO).

Background Contemporary mobile health (mHealth) interventions use various behavior change techniques to promote healthier lifestyles. Social comparison is one of the techniques that is consensually agreed to be effective in engaging the general population in mHealth interventions. However, it is unclear how this strategy can be best used to engage preadolescents. Nevertheless, this strategy has great potential for this target audience, as they are particularly developing their social skills. Objective This study aims to evaluate how social comparison drives preadolescents’ engagement with an mHealth app. Methods We designed a 12-week crossover experiment in which we studied 3 approaches to implementing behavior change via social comparison. This study was hosted in a school environment to leverage naturally existing social structures among preadolescents. During the experiment, students and teachers used an mHealth tool that awarded points for performing healthy activities. Participants could read their aggregated scores on a leaderboard and compare their performance with others. In particular, these leaderboards were tweaked to implement 3 approaches of the social comparison technique. The first approach focused on intragroup comparison (ie, students and teachers competing against each other to obtain the most points), whereas the other two approaches focused on intergroup comparison (ie, classes of students and their mentoring teachers collaborating to compete against other classes). Additionally, in the third approach, the performance of teachers was highlighted to further increase students’ engagement through teachers’ natural exemplary function. To obtain our results, we used linear modeling techniques to analyze the dropout rates and engagement levels for the different approaches. In such analyses, we also considered individual participant traits. Results Our sample included 313 participants—290 students (92.7%) and 23 teachers (7.3%). It was found that student engagement levels dropped over time and declined during holidays. However, students seemed to monitor the intergroup competitions more closely than the intragroup competitions, as they, on average, checked the mHealth app more often when they were engaged in team-based comparisons. Students, on average, performed the most unique activities when they were engaged in the second intergroup setting, perhaps because their teachers were most active in this setting. Moreover, teachers seemed to play an important role in engaging their students, as their relationship with their students influenced the engagement of the students. Conclusions When using social comparison to engage preadolescents with an mHealth tool, an intergroup setting, rather than an intragroup competition, motivated them to engage with the app but did not necessarily motivate them to perform more activities. It seems that the number of unique activities that preadolescents perform depends on the activeness of a role model. Moreover, this effect is amplified by preadolescents’ perceptions of closeness to that role model.

Fish as a critical food source is responsible for supplying nearly 20% of the average per capita animal protein for 3.2 billion people worldwide. However, oral exposure to potentially toxic elements (PTE) such as mercury (Hg), cadmium (Cd), lead (Pb), and arsenic (As) through marine fish consumption can cause health risks in consumers. This study aimed to collect information among databases (2000-2020), including ScienceDirect, PubMed, SCOPUS, EMBASE, and Google Scholar, regarding the concentration of PTEs in different types of fish from the Persian Gulf. In this regard, thirty articles containing 266 samples were included in the current systematic review. In addition, the non-carcinogenic risk caused by ingestion of PTEs via consumption of fish was calculated. The average PTE concentrations in fish muscles were presented in the following order: As (0.37 mg/kg ww) Pb (0.20 mg/kg ww) Cd (0.17 mg/kg ww) Hg (0.13 mg/kg ww). However, the mean concentration of PTEs was below the defined level by the World Health Organization, and the findings revealed that the calculated average daily dose (ADD) for Cd and Pb in Iranian children and adult consumers was lower than the reference dose (RfD), whereas the ADD of Hg was higher than the RfD for children consumers. The total target hazard quotient for Iranian and children consumers was1. The excess lifetime cancer risk values for Pb were safe, unlike those for Cd, which were in an unsafe range (10

BACKGROUND፡ Traditional medicine is a complete system, including diagnostic methods, etiology and treatment based on interpersonal differences. Owing to a lack of investigations in the field of Iranian traditional medicine as well as its many present challenges, certain studies in this area can prove quite practical in identifying and solving ongoing challenges. This study investigates the challenges of the health system in Iranian traditional medicine in the context of control levers.METHODS: The study was qualitative content analysis. A framework analysis, "Control Knob Approach", was considered appropriate to promote apprehension of challenges of health systems in Iranian traditional medicine. Data were collected by purposeful sampling through in-depth and semi-structured individual interviews with 35 experts of Iranian traditional medicine. Directed content analysis was used to analyze the data, which extracted the initial codes after performing the recorded interviews on paper and immersing them in the data analysis.RESULTS: Upon analysis of data by Iranian medicine experts, five main categories including financing, payment system, regulations, behavior and organization were defined alongside 13 subcategories.CONCLUSION: According to current challenges and the tendency of society to receive traditional medicine services, as well as the long history of traditional medicine in Iran, fair access to traditional medicine services should be provided. This access must be through the production of indigenous knowledge and the formulation of regulatory and educational policies and guidelines and the empowerment of relevant, healthy, effective, evidencebased and cost-effective forces.

Aim To determine the relationship of health practices with depression and maternal-fetal attachment in adolescent pregnant women. Methods This prospective study was conducted on 316 adolescent pregnant women with medical records at the health centers in Tehran, Iran. The participants were selected through the complete enumeration. Data were collected using the socio-demographic and obstetrics questionnaire, the Health Practices Questionnaire-II (HPQ-II), the Edinburgh Postnatal Depression Scale (EPDS), and the Cranley's Maternal-Fetal Attachment Scale (MFAS). The data were analyzed with the Pearson correlation test, the independent t-test, one-way ANOVA, and the general linear model. Results The mean scores of health practices, depression, and maternal-fetal attachment were 135.3 (SD 9.1, range 34–170), 10.1 (SD 5.4, range 0–30), and 91.6 (SD 8.6, range 24–120), respectively. The results of Pearson correlation test showed that health practices had a significant relationship with depression (r = −0.29) and maternal-fetal attachment (r = 0.37). Results of general linear model showed that an increase in the health practices score led to a significant decrease in depression score during pregnancy [β = −0.10; 95% CI: −0.17 to −0.04] and a significant increase in maternal-fetal attachment score [β = 0.30; 95% CI: 0.19 to 0.40]. Conclusion There is significant relationship between health practices and depression, as well as maternal-fetal attachment in adolescent pregnant women. Therefore, intervention to improve one of them may improve the other one(s).

We report a patient with new-onset ulcerated granuloma annulare with concomitant involvement of B-cell leukemia. A granuloma annulare-like eruption with concomitant B cell chronic lymphocytic leukemia involvement in the skin is extremely rare, as only three cases have been previously reported in the literature to our knowledge. Given the rarity of ulceration in conventional granuloma annulare, it is possible this finding may serve as a diagnostic clue for underlying malignancy.

The biological function and disease association of human endogenous retroviral (HERV) elements is largely elusive. HERV-K(HML-2) has been associated with neurotoxicity but there is no clear understanding of its role or mechanistic basis. We addressed the physiological functions of HERV-K(HML-2) in neuronal differentiation by using CRISPR engineering to activate or repress its expression levels in a human pluripotent stem cell-based system. We found that elevated HERV-K(HML-2) transcription is detrimental for the development and function of cortical neurons. These effects are cell type-specific, as dopaminergic neurons are unaffected. Moreover, high HERV-K(HML-2) transcription alters cortical layer formation in forebrain organoids. HERV-K(HML-2) transcriptional activation leads to hyperactivation of NTRK3 expression and other neurodegeneration-related genes. Direct activation of NTRK3 phenotypically resembles HERV-K(HML-2) induction, and reducing NTRK3 levels in context of HERV-K(HML-2) induction restores cortical neuron differentiation. Hence, these findings unravel a cell type-specific role for HERV-K(HML-2) in cortical neuron development.

Background Diabetic foot ulcers (DFUs) are the most common cause of leg amputations and their management is extremely challenging. Despite many advances and expensive therapies, there has been little success in improving outcomes of DFUs. In prior work our laboratory has examined the effects of beta-adrenergic antagonists (βAAs) on skin and skin-derived cells. We have shown that βAAs enhance the rate of keratinocyte migration, promote angiogenesis, and hasten wound healing in scratch wounds in vitro, in animal wound models, and in anecdotally reported cases of chronic wounds that healed successfully after topical application of the βAA timolol. Thus, we propose to test timolol directly on DFUs to determine if it improves healing above the current standard of care (SOC). This study will examine the efficacy and safety of topically applied beta-antagonist Timoptic-XE® (timolol maleate ophthalmic gel forming solution) in subjects with DFUs. Methods/design This is a phase two, randomized, double-blinded, controlled, and parallel-group clinical trial with two treatment arms, SOC plus topical Timoptic-XE® and SOC plus a non-biologically active gel (hydrogel, as placebo drug). Study subjects with a DFU will be selected from the Veterans Affairs Northern California Health Care System (VANCHCS). Study duration is up to 31 weeks, with three phases (screening phase for two weeks, active phase for up to 12 weeks, with an additional second consecutive confirmatory visit after 2 weeks, and follow-up phase comprising monthly visits for 4 months). Subjects will apply daily either the topical study drug or the placebo on the foot ulcer for 12 weeks or until healed, whichever comes first. Measurements of wound size and other data will be collected at baseline, followed by weekly visits for 12 weeks, and then a monthly follow-up period. Discussion This is a clinical translation study, moving the investigators’ pre-clinical laboratory research into a translational study in which we will analyze clinical outcomes to assess for safety and estimate the efficacy of a topical beta-antagonist in healing of DFUs. The results from this trial may establish new treatment paradigms and safety profile for DFU treatment. Trial registration ClinicalTrials.gov, NCT03282981. Registered on June 14th, 2018.

The aim of the study was to determine the feasibility of the Persian version of the Canadian Occupational Performance Measure (COPM) to assess self-reported occupational performance in a group of children with cancer at least one-year post-cancer diagnosis and intervention and to describe the self-reported occupational performance problems of children with cancer. Forty-three children with cancer (mean age 11.59 years; SD 4.94) participated in a cross-sectional study, using a convenience sampling approach. Performance and satisfaction were assessed through a validated Persian version of the COPM and feasibility and ease of administration were also considered. This study showed that feasibility was found to be adequate and this measurement was perceived as easy to understand; completion took from 20 to 51 minutes. Children with cancer prioritized 115 occupations within six of the nine COPM subcategories. Among the prioritized occupations, the highest number was found in self-care 61.7%, followed by productivity (26%), and leisure (12.1%). The mean ratings of performance varied from 3.7 to 8.4. The lowest mean rating was in the subgroup play/school (3.7). For satisfaction, the mean ratings were from 2.6 to 5.2, with functional mobility as the highest and play/school the lowest. The results support the use of the COPM in clinical practice for children with cancer. Based on these findings, children with cancer perceive problems with occupations related to all aspects of daily life. This underlines the need to provide rehabilitation services, especially occupational therapy services for these children.

Ferroptosis is a regulated form of cell death that occurs when phospholipids with polyunsaturated fatty acyl tails are oxidized in an iron-dependent manner. Research in recent years has uncovered complex cellular networks that induce and suppress lethal lipid peroxidation. This SnapShot provides an overview of ferroptosis-related pathways, including relevant biomolecules and small-molecule modulators regulating them.

Background: The renin-angiotensin system (RAS), which is important for controlling haemostasis in the body, can increase the development of essential hypertension (HTN). Various surveys have shown that ACE I/D polymorphism that influences ACE activity, a key component of RAS, has been known to be associated with the risk of HTN. The goal of this study was to investigate the correlation between ACE (I/D) polymorphism and HTN.Methods: Blood samples were obtained from 102 patients and 104 healthy individuals. The two groups were matched by age and sex. Informed consent was prepared for the study. The demographic data were collected using a questionnaire. White blood cells (WBCs) and then DNA were extracted from whole blood. After this, the PCR test was performed using specific primers. PCR products were examined using 1% agarose gel. Individuals with genotype II having a band of 490 bp, ID two band of 490 bp and 190 bp, and individuals with DD genotype, have a band in region 190 bp.Results: The average age of the patients was 52.7 ± 7.5 years. A significant difference was seen in the distribution of DD, II and I/D genotypes of ACE polymorphism between the essential hypertensive patients (44.1, 10.8, and 45.1%) and their ethnically matched healthy control (61.5, 3.8, and 24.6%, respectively). Our study showed an increased risk of disease in people with II genotype in comparison to ID and DD genotypes (0.46 (0.1-1.75) and 0.26 (0.05-0.94), respectively).Conclusions: The present study demonstrated that ACEI/D polymorphism is characterised with greater risk of essential HTN in the Lorestan province. II genotype increased the relative risk of essential HTN in the population. In the future, more investigations with more samples size are recommended for the better study of genetic factors in hypertensive patients.

Emerging noncommunicable diseases (NCDs) with premature mortality are one of the major concerns in health supervising organizations of the world. High intake of energy, salt, sugar, fat, and trans fatty acids are introduced as dietary risk factors of NCDs. The status of food risk factors is presented in Traffic Light (TL) food labeling through colors of red, yellow, and green as the signs of stop, wait and watch and go, respectively. This stepwise interventional study examined whether TL education can result in choosing healthier food via assessing the impact of face-to-face educational sessions on knowledge, attitudes, and practices of 673 respondents toward TL food labeling through a self-administered and structured questionnaire. Paired t test or alternatively Wilcoxon test was used to evaluate the influence of education in total scores of knowledge, attitudes, and practices in test–retest. Results indicated that before education, the average of the scores for the knowledge, attitudes, and practices was 1.003 ± 0.69, 10.97 ± 1.86, and 1.60 ± 1.84, respectively. After education, the scores were increased to 8.72 ± 3.11, 15.95 ± 2.64, and 8.42 ± 1.69. Significant differences in the scores of the respondents were observed before and after education ( p

Background This study aimed to evaluate the effect of kinesiology taping (KT) on lumbar proprioception, pain, and functional disability in individuals with nonspecific chronic low back pain (CLBP). Methods Thirty individuals with nonspecific CLBP participated in this double-blinded, randomized clinical trial from July 2017 to September 2018. The participants were randomized into two groups: KT (n = 15) and placebo group (n = 15). KT was applied with 15–25% tension for 72 h, and placebo taping was used without tension. Lumbar repositioning error was measured by a bubble inclinometer at three different angles (45° and 60° flexion, and 15° extension) in upright standing. Pain and disability were assessed by the Short-Form McGill Pain Questionnaire and Oswestry Disability Index, respectively. All measurements were recorded at baseline and 3 days after taping. Results Pain and disability scores reduced 3 days after taping in the KT group with large effect sizes (p p p > 0.05). Also, only constant error of 15° extension showed a moderate correlation with disability (r = 0.39, p = 0.02). Conclusion KT can decrease pain and disability scores after 3 days of application. Although placebo taping can reduce pain, the effect of KT is higher than placebo taping. The findings do not support the therapeutic effect of KT and placebo taping as a tool to enhance lumbar proprioception in patients with nonspecific CLBP. Trial registration The study prospectively registered on 21.05.2018 at the Iranian Registry of Clinical Trials: IRCT20090301001722N20.

Glioblastoma multiforme (GBM) possesses glioma stem cells (GSCs) that promote self-renewal, tumor propagation, and relapse. Understanding the mechanisms of GSCs self-renewal can offer targeted therapeutic interventions. However, insufficient knowledge of GSCs' fundamental biology is a significant bottleneck hindering these efforts. Here, we show that patient-derived GSCs recruit elevated levels of proteins that ensure the temporal cilium disassembly, leading to suppressed ciliogenesis. Depleting the cilia disassembly complex components is sufficient to induce ciliogenesis in a subset of GSCs via relocating platelet-derived growth factor receptor-alpha (PDGFR-α) to a newly induced cilium. Importantly, restoring ciliogenesis enabled GSCs to switch from self-renewal to differentiation. Finally, using an organoid-based glioma invasion assay and brain xenografts in mice, we establish that ciliogenesis-induced differentiation can prevent the infiltration of GSCs into the brain. Our findings illustrate a role for cilium as a molecular switch in determining GSCs' fate and suggest cilium induction as an attractive strategy to intervene in GSCs proliferation.

Estimation of growth spurt from chronological age or dental development is of clinical interest to orthodontists. Since results in this regard are highly controversial and limited, this study was conducted to investigate associations among chronological age, skeletal development (cervical vertebral maturity [CVM]), and dental calcification (Demirjian) in girls and boys, independently. Panoramic radiographs and lateral cephalographs of 112 boys and 112 girls were evaluated. Demirjian stages of dental development of the bimaxillary canines and second molars were determined. CVM stages of skeletal growth were as well estimated. Correlations among these were assessed. Differences between sexes and between maxilla/mandible arches were assessed. Cutoff points in Demirjian and chronological age reflecting skeletal growth spurt were found using receiver operator characteristic curve (α = 0.05, β = 0.9 separately for girls and boys). Sex dimorphism existed both in CVM index and in Demirjian indexes. Compared to dental development and calcification, chronological age was the best predictor of skeletal growth and maturation. In estimating chronological age by radiography means, in girls, Demirjian method was better than CVM. In boys, Demirjian was better than CVM in the case of the molars but not canines. The cutoff points estimated for chronological age and dental calcification that can reflect skeletal growth spurt (between CS-3-and-CS-4) were as follows: in boys, age of 12 years; in girls, age between 11 and 12 years; the upper and lower canines: between G and H; the maxillary and mandibular second molars: between F and G; in the case of all teeth: between F and G.

The extracellular matrix is known to modulate cell adhesion and migration during tissue regeneration. However, the molecular mechanisms that fine-tune cells to extra-cellular matrix dynamics during regeneration of the peripheral nervous system remain poorly understood. Using the RSC96 Schwann cell line, we show that Sox2 directly controls fibronectin fibrillogenesis in Schwann cells in culture, to provide a highly oriented fibronectin matrix, which supports their organization and directional migration. We demonstrate that Sox2 regulates Schwann cell behaviour through the upregulation of multiple extracellular matrix and migration genes as well as the formation of focal adhesions during cell movement. We find that mouse primary sensory neurons and human induced pluripotent stem cell-derived motoneurons require the Sox2-dependent fibronectin matrix in order to migrate along the oriented Schwann cells. Direct loss of fibronectin in Schwann cells impairs their directional migration affecting the alignment of the axons in vitro. Furthermore, we show that Sox2 and fibronectin are co-expressed in proregenerative Schwann cells in vivo in a time-dependent manner during sciatic nerve regeneration. Taken together, our results provide new insights into the mechanisms by which Schwann cells regulate their own extracellular microenvironment in a Sox2-dependent manner to ensure the proper migration of neurons.

It is hypothesized that the subtalar hyperpronation may provoke the development of a biomechanical chain of events in lower extremity alignment. Several studies have shown that pelvic alignment may alter in the presence of immediate foot hyperpronation induced by external forces. It is unknown whether these alterations are presented in chronic foot hyperpronation or not. It is also unknown if these potential postural changes could affect iliopsoas muscle size. Therefore, it appears necessary to carry out thorough research in this study. Twenty nine females with pronated foot posture and twenty seven females with normal foot posture participated in this study. The iliopsoas muscle was measured using ultrasound imaging (USI). Pelvic angle (PA) was measured using reflective markers and digital photography. Intrarater reliability of USI for the iliopsoas muscle thickness was also measured. The results indicated that the iliopsoas muscle thickness and the PA were not different in individuals with pronated foot compared to the normal foot group. However, a good intrarater reliability of USI was found for measuring the iliopsoas muscle thickness.

Elephantiasis nostras verrucosa is a progressively debilitating and disfiguring disease commonly presenting with verrucous, cobblestone-like papules, nodules, or plaques with nonpitting edema in the lower extremities. Histopathology is marked by hyperkeratosis and dermal or subcutaneous fibrosis as a result of chronic lymphedema. Risk factors include obesity, recurrent cellulitis, chronic venous insufficiency, congestive heart failure, scleroderma, radiation, trauma, and tumors. We report a 72-year-old man who presented to the dermatology clinic for an 11-year history of edematous legs, occasionally associated with ulcerations. The findings developed within a year of intrapelvic non-Hodgkin lymphoma and progressed gradually over 10 years after lymphoma remission. Physical examination revealed atypical features including compressible cysts and pitting edema extending from the lower legs to the thighs bilaterally. The patient was noncompliant for the recommended compressive devices and the condition progressively worsened over the course of 7 months of follow-up. Early interdisciplinary management using compressive devices and a lymphatic pump are recommended. Underlying causative factors should be assessed with regular follow-up to optimize treatment outcomes.

Surgical adhesions are bands of scar tissues that abnormally conjoin organ surfaces. Adhesions are a major cause of post-operative and dialysis-related complications, yet their patho-mechanism remains elusive, and prevention agents in clinical trials have thus far failed to achieve efficacy. Here, we uncover the adhesion initiation mechanism by coating beads with human mesothelial cells that normally line organ surfaces, and viewing them under adhesion stimuli. We document expansive membrane protrusions from mesothelia that tether beads with massive accompanying adherence forces. Membrane protrusions precede matrix deposition, and can transmit adhesion stimuli to healthy surfaces. We identify cytoskeletal effectors and calcium signaling as molecular triggers that initiate surgical adhesions. A single, localized dose targeting these early germinal events completely prevented adhesions in a preclinical mouse model, and in human assays. Our findings classifies the adhesion pathology as originating from mesothelial membrane bridges and offer a radically new therapeutic approach to treat adhesions., Surgical adhesions are organ-joining bands of scar tissue that remain clinically untreatable. Here, the authors show that adhesions are formed through expansive mesothelial membrane bridges, and that blocking these with small molecules prevents formation of adhesions in mice.