FIM: A fatigued-injured muscle model based on the sliding filament theory.

Skeletal muscle modeling has a vital role in movement studies and the development of therapeutic approaches. In the current study, a Huxley-based model for skeletal muscle is proposed, which demonstrates the impact of impairments in muscle characteristics. This model focuses on three identified ions: H+, inorganic phosphate Pi, and Ca2+. Modifications are made to actin-myosin attachment and detachment rates to study the effects of H+ and Pi. Additionally, an activation coefficient is included to represent the role of calcium ions interacting with troponin, highlighting the importance of Ca2+. It is found that maximum isometric muscle force decreases by 9.5% due to a reduction in pH from 7.4 to 6.5 and by 47.5% in case of the combination of a reduction in pH and an increase of Pi concentration up to 30 mM, respectively. Then the force decline caused by a fall in the active calcium ions is studied. When only 15% of the total calcium in the myofibrillar space is able to interact with troponin, up to 80% force drop is anticipated by the model. The proposed fatigued-injured muscle model is useful to study the effect of various shortening velocities and initial muscle-tendon lengths on muscle force; in addition, the benefits of the model go beyond predicting the force in different conditions as it can also predict muscle stiffness and power. The power and stiffness decrease by 40% and 6.5%, respectively, due to the pH reduction, and the simultaneous accumulation of H+ and Pi leads to a 50% and 18% drop in power and stiffness.

Clinical and laboratory features of SARS-CoV-2 variants across multiple rounds of pandemic waves in hospitalized children in an Iranian referral hospital.

BACKGROUND: Since the onset of the COVID-19 pandemic, SARS-CoV-2 has evolved into independent new forms, variants of concern (VOCs). While epidemiological data showed increased transmissibility of VOCs, their impact on clinical outcomes is less clear. This study aimed to investigate the differences between the clinical and laboratory features of children infected with VOCs. METHODS: This study included all cases with SARS-CoV-2-positive nasopharyngeal swabs obtained from patients referred to Children's Medical Center (CMC), an Iranian referral hospital, between July 2021 and March 2022. The inclusion criteria for this study included all patients, regardless of age, who had a positive test anywhere in the hospital setting. Exclusion criteria for the study included those whose data was obtained from non-hospital outpatient settings, or referred from another hospital. The SARS-CoV-2 genome area encoding the S1 domain was amplified and sequenced. The type of variant in each sample was identified based on the mutations in the S1 gene. Demographic characteristics, clinical data, and laboratory findings were collected from the patient's medical records. RESULTS: This study included 87 pediatric cases with confirmed COVID-19, with a median age of 3.5 years (IQR: 1-8.12). Data from sequencing reveals the type of variants as 5 (5.7%) alpha, 53 (60.9%) Delta, and 29 (33.3%) Omicron. The incidence of seizure was higher in patients with Alpha and Omicron infection compared to the Delta group. A higher incidence of diarrhea was reported in Alpha-infected patients, and a higher risk of disease severity, distress, and myalgia was associated with Delta infection. CONCLUSION: Laboratory parameters did not mostly differ among the patients infected with Alpha, Delta, and Omicron. However, these variants may manifest different clinical features. Further studies with larger sample sizes are required to fully understand the clinical manifestations of each variant.

Ferroptosis Inhibitors as New Therapeutic Insights into Radiation-Induced Heart Disease.

Radiation-induced heart disease (RIHD) is a significant cause of morbidity in breast and other mediastinal cancers. The many molecular and cellular patho-mechanisms that have a role in RIHD are not completely understood. Endothelial injury, oxidative stress, and inflammation, as well as endoplasmic reticulum and mitochondrial damage, are considered the primary causes of RIHD. Ferroptosis is a newly discovered type of cell death that results from irondependent lipid peroxide accumulation. As ferroptosis plays an important role in the pathogenesis of cardiovascular diseases, it seems that it has a significant effect on RIHD. It was recently shown that ionizing radiation (IR) generates severe ferroptosis, which is a critical component of Radiotherapy-mediated normal cell toxicity. These findings support the use of a ferroptosis inhibitor to reduce RIHD. In this perspective review, we summarize the role of ferroptosis in pathogens of cardiovascular disease and radiation toxicity, and we will introduce ferroptosis inhibitors as a new strategy to prevent or reduce RIHD.

Evaluation of the Effect of Chelating Arms and Carrier Agents on t he Radiotoxicity of TAT Agents.

Targeted Alpha Therapy (TAT) is considered an evolving therapeutic option for cancer cells, in which a carrier molecule labeling with an α-emitter radionuclide make the bond with a specific functional or molecular target. α-particles with high Linear Energy Transfer (LET) own an increased Relative Biological Effectiveness (RBE) over common ß-emitting radionuclides. Normal tissue toxicity due to non-specific uptake of mother and daughter α-emitter radionuclides seems to be the main conflict in clinical applications. The present survey reviews the available preclinical and clinical studies investigating healthy tissue toxicity of the applicable α -emitters and particular strategies proposed for optimizing targeted alpha therapy success in cancer patients.

The Neurotoxic Mechanisms of Graphene Family Nanomaterials at the Cellular Level: A Solution-based Approach Review.

The graphene family nanomaterials (GFNs) have been recognized to have potential applications in biomedicine, especially in the rag nostic, drug delivery and neuroimaging. Multiple studies have examined the neurotoxicity of GFNs to assay their toxic effects on organisms and ecosystems. In this article, we reviewed the different neurotoxicity effects of GFNs at intracellular levels, including nucleus-related effects and cytosolic mechanisms, as well as extracellular levels, including effects on enzyme activity, oxidative stress, behavior, neurotransmitters, and central nervous system (CNS). Furthermore, for the sake of the solution, we discussed the reducing ways of graphene toxicity. A schematic description is shown in Fig. (1).

Multisystem inflammatory syndrome associated with SARS-CoV-2 infection in children: update and new insights from the second report of an Iranian referral hospital.

INTRODUCTION: Here, we are sharing our second report about children affected by Multisystem Inflammatory Syndrome in Children (MIS-C). The aim of the present study was to update our knowledge about children with MIS-C. Furthermore, we tried to compare clinical manifestations, laboratory features and final outcome of patients based on disease severity, in order to better understanding of the nature of this novel syndrome. METHODS: This retrospective study was conducted at Children's Medical Center Hospital, the hub of excellence in paediatrics in Iran, located in Tehran, Iran. We reviewed medical records of children admitted to the hospital with the diagnosis of MIS-C from July 2020 to October 2021. RESULTS: One hundred and twenty-two patients enrolled the study. Ninety-seven (79.5%) patients had mild to moderate MIS-C (MIS-C without overlap with KD (n = 80); MIS-C overlapping with KD (n = 17)) and 25 (20.5%) patients showed severe MIS-C. The mean age of all patients was 6.4 ± 4.0 years. Nausea and vomiting (53.3%), skin rash (49.6%), abdominal pain (46.7%) and conjunctivitis (41.8%) were also frequently seen Headache, chest pain, tachypnea and respiratory distress were significantly more common in patients with severe MIS-C (P < 0.0001, P = 0.021, P < 0.0001 and P < 0.0001, respectively). Positive anti-N severe acute respiratory syndrome coronavirus 2 IgM and IgG were detected in 14 (33.3%) and 23 (46.9%) tested patients, respectively. Albumin, and vitamin D levels in children with severe MISC were significantly lower than children with mild to moderate MIS-C (P < 0.0001, P = 0.05). Unfortunately, 2 (1.6%) of 122 patients died and both had severe MIS-C. CONCLUSION: Patients with MIS-C in our region suffer from wide range of signs and symptoms. Among laboratory parameters, hypoalbuminemia and low vitamin D levels may predict a more severe course of the disease. Coronary artery dilation is frequently seen among all patients, regardless of disease severity.

Novel NAD-independent Avibacterium paragallinarum: Isolation, characterization and molecular identification in Iran.

BACKGROUND: Infectious coryza (IC) is an invasive upper respiratory disease caused by Avibacterium paragallinarum that affects birds, particularly chickens. The objective of this study is to isolate, characterize and molecularly identify the bacterium A. paragallinarum in poultry birds, as well as to determine its antibiotic sensitivity and resistance. METHODS: A total of 10 chickens from four different Iranian farms with typical IC symptoms were used in this study. The nasal swabs were streaked onto chocolate agar plates and blood agar plates and incubated at 37°C in 5% CO2 for 24 to 48 h. As part of the identification of bacteria, bacteriological observations and polymerase chain reaction (PCR) testing are conducted. The antibiotic sensitivity tests were also performed using the disk diffusion method against A. paragallinarum and the prevalence in different farms was determined. RESULTS: By using biochemical assays and PCR analyses, seven strains of A. paragallinarum were isolated from samples of four chicken farms with typical IC clinical signs. Most isolates (4/7) showed the typical requirement for nicotinamide adenine dinucleotide (NAD) and an enriched CO2 atmosphere for growth. Three of the seven strains of A. paragallinarum were found to be novel NAD-independent under anaerobic conditions. There was one biochemical biovar identified in terms of carbohydrate fermentation patterns, although changes in maltose carbohydrate fermentation patterns were detected in the No. 5 strain. All isolates were sensitive to gentamicin and spectinomycin. Three novel NAD-independent strains (Nos.1, 5 and 7) were found to be multidrug-resistant (MDR) and resistant to at least three classes of antibiotics. There was greater antibiotic resistance in the three NAD-independent isolates than in normal NAD-dependent bacteria. CONCLUSION: By discovering NAD-independent forms of A. paragallinarum, these species have a greater range than previously believed. A clear, cautious approach should be taken in diagnosing and possibly controlling IC.

Maternal opioid use is reflected on leukocyte telomere length of male newborns.

Opioid use accelerates normal aging in adults that raises a question on whether it may trans-generationally affect aging and aging biomarkers in the offspring of users as well? In the present research, we investigated the relative telomere length in umbilical cord blood of newborns born to opioid consuming mothers compared to normal controls. Telomere length shortening is a known biomarker of aging and aging related diseases. Its measure at birth or early in life is considered as a predictor of individual health in adulthood. Here, we performed a case-control study to investigate whether maternal opioid use affects newborns relative telomere length (RTL). 57 mother-newborn dyads were included in this study, 30 neonates with opioid using mothers (OM), and 27 with not-opioid using mothers (NOM)). RTL was measured in leukocyte cells genomic DNA using real-time PCR. The correlation of maternal opioid use with neonates telomer length was assessed using logistic regression analysis. The results displayed a significant association between odds ratio of long RTL and maternal opioid use when sensitivity analysis was performed by neonate sex; where the data indicates significantly increased odds ratio of long leukocyte RTL in association with maternal opioid use in male neonates only. Further work is necessary to assess this association in larger samples and test the potential underlying mechanisms for this observation.

Awareness and Knowledge About Kidney Transplantation: A Reflection on the Current State Among Iranian Patients with End-stage Renal Disease (ESRD) Treated by Dialysis.

INTRODUCTION: Kidney transplantation is the treatment of choice in the majority of end-stage renal disease (ESRD) patients. However, most of the incident ESRD patients are not given the necessary information regarding kidney transplantation. The aim of this study was to evaluate awareness and knowledge about kidney transplantation in ESRD patients who were on dialysis. METHODS: In this cross-sectional study, a total of 300 ESRD patients who underwent hemodialysis or peritoneal dialysis and could be eligible for kidney transplant, were included. A questionnaire with 15 multiple choice questions (MCQs) was designed to collect the data. SPSS version 16 was used for data analysis and a P value less than .05 was considered statistically significant. RESULTS: Two hundred thirty- four patients participated in the study (response rate of 78%). Among them 58.1% were male with the mean age (SD) of 52.5 (12.1) years. The majority of the patients (94.0%) were on hemodialysis. About 87.6% wanted to receive kidney transplant; but despite the desire of the patients, this method was initially offered to about 11.5 % of the patients as a possible method of renal replacement therapy. Patients who had desire to receive kidney transplantation were significantly younger, male, married, employed, and had high level of education (P < .05). CONCLUSION: Although most of the patients wanted to receive a kidney transplant, it was initially offered to a small population. Age, gender, marital status, employment condition, and level of education were significant factors for the patient's tendency to receive a kidney transplant. DOI: 10.52547/ijkd.6512.

Nursing strikes among infants and its affecting factors in Rafsanjan city.

The infant's refusal to breastfeed can be a stressful and concerning matter for a mother. This study aimed to investigate the frequency and factors leading to nursing strikes in Rafsanjan city. This descriptive study was performed on infants who had been referred to the pediatrician's office with a complaint of a nursing strike. The research sample included 70 infants, and all the required data, including the causes of the nursing strike and the demographic information of the mother and the infant, were collected using a checklist. The Statistical Package for the Social Sciences (SPSS) software version 20 was used to analyze the data. The percentage was used to express qualitative indices, and the mean and standard deviation were used to express quantitative indices. The results showed that the most common factors contributing to the infants' breast refusal were playfulness and distraction (50%) and recent vaccinations in the last 12 days (48.6%). Besides, the most common maternal factors affecting breast refusal were level of education (67.1%), recent acute stress (41.4%), and inadequate milk production (35.7%). The results of the present study showed that playfulness and distraction of the baby, recent vaccination, use of a pacifier, level of education and recent stress of the mother, breastfeeding program, and insufficient milk production are the most common reasons for nursing strikes.

No man's land: Species-specific formation of exclusion zones bordering Actinomyces graevenitzii microcolonies in nanoliter cultures.

To survive within complex environmental niches, including the human host, bacteria have evolved intricate interspecies communities driven by competition for limited nutrients, cooperation via complementary metabolic proficiencies, and establishment of homeostatic relationships with the host immune system. The study of such complex, interdependent relationships is often hampered by the challenges of culturing many bacterial strains in research settings and the limited set of tools available for studying the dynamic behavior of multiple bacterial species at the microscale. Here, we utilize a microfluidic-based co-culture system and time-lapse imaging to characterize dynamic interactions between Streptococcus species, Staphylococcus aureus, and Actinomyces species. Co-culture of Streptococcus cristatus or S. salivarius in nanoliter compartments with Actinomyces graevenitzii revealed localized exclusion of Streptococcus and Staphylococcus from media immediately surrounding A. graevenitzii microcolonies. This community structure did not occur with S. mitis or S. oralis strains or in co-cultures containing other Actinomycetaceae species such as S. odontolyticus or A. naeslundii. Moreover, fewer neutrophils were attracted to compartments containing both A. graevenitzii and Staphylococcus aureus than to an equal number of either species alone, suggesting a possible survival benefit together during immune responses.

Enhanced osteogenesis properties of titanium implant materials by highly uniform mesoporous thin films of hydroxyapatite and titania intermediate layer.

Titanium (Ti) has been widely used for medical and dental applications; however, bare Ti cannot be properly connected to a living bone, and hence some modifications are needed for this purpose. The present study describes the synthesis of mesoporous hydroxyapatite thin films (MHF) on titanium implant materials for speeding up and shortening the processes of osteointegration. The uniform MHF was coated on a Ti substrate following the insertion of intermediate titania (TiO2) film via the sol-gel dip-coating method. The intermediate titania layer improved the bonding strength between the MHF and Ti substrate. MHFs were synthesized using a precursor solution containing phosphoric acid, calcium nitrate tetrahydrate, and a nonionic surfactant (C12E10) as the phosphate source, calcium source, and structure-directing agent, respectively. The effect of calcination temperature on phase composition, morphology, microstructure, roughness, and wettability of the MHFs was investigated using XRD, FE-SEM, COM, AFM, and contact angle measurement. The XRD results revealed the crystalline hydroxyapatite phase, which was improved with an increase in the calcination temperature. Moreover, the FE-SEM images showed the crack-free MHFs, uniform thickness of the layer, and mesoporous surface morphology. In addition, it was found that the roughness and wettability of the samples change upon the alteration of calcination temperature. The biological studies demonstrated that MHFs support the adhesion and proliferation of the mesenchymal stem cells (MSCs) and guid them toward osteogenic differentiation. Therefore, the MHFs prepared in this study may be useful in a wide range of applications, particularly in bone regeneration medicine.

A microscale, full-thickness, human skin on a chip assay simulating neutrophil responses to skin infection and antibiotic treatments.

Human skin models are essential for understanding dermatological diseases and testing new treatment strategies. The use of skin biopsies ex vivo is the most accurate model. However, their use is expensive and exposes the donor to pain and scarring. While bioengineered skin samples provide a cheaper alternative, they have limitations due to their simple structure and functionality compared to human skin. Here, we present a skin-on-a-chip device designed to study neutrophil responses to Staphylococcus aureus skin infections. We integrate human skin microcolumns, which have a cross-section that is ∼100 times smaller than traditional skin biopsies, are full-thickness, and are collected using minimally invasive skin sampling techniques. We use human neutrophils directly from one drop of blood, without the need for blood separation. Using the skin-on-a-chip device with skin and blood samples from healthy donors, we show that the neutrophil responses correlate with the bacteria-load in the skin. A pre-incubation step increases the number of migrating neutrophils in response to a low concentration of bacteria. Antibiotic treatment of S. aureus-infected skin samples reduces the number of neutrophils migrating towards the skin. Overall, we validate a skin on a chip model that enables the study of neutrophil migration to the skin in the presence of microbes and following the administration of antibiotics, two situations relevant to clinical cases of human skin and soft tissue infections.

Microfluidic arenas for war games between neutrophils and microbes.

Measurements of neutrophil activities such as cell migration and phagocytosis are generally performed using low-content bulk assays, which provide little detail activity at the single cell level, or flow cytometry methods, which have the single cell resolution but lack perspective on the kinetics of the process. Here, we present a microfluidic assay for measuring the essential functions that contribute to the antimicrobial activity of neutrophils: migration towards the target, and killing of microbes. The assay interrogates the interactions between isolated human neutrophils and populations of live, proliferating microbes. The outcome is measured in a binary mode that is reflective of in vivo infections, which are either cleared or endure the host response. The outcome of the interactions is also characterized at single cell resolution for both the neutrophils and the microbes. We applied the assay to test the response of neutrophils from intensive care patients to live Staphylococcus aureus, and observed alterations of antimicrobial neutrophil activity in patients, including those with sepsis. By directly measuring neutrophil activity against live targets at high spatial and temporal resolution, this assay provides unique insights into the life-or-death contest shaping the outcome of interactions between populations of neutrophils and microbes.

Large-scale patterning of living colloids for dynamic studies of neutrophil-microbe interactions.

Neutrophils are the first white blood cells to respond to microbes and to limit their invasion of the body. However, the growth of the microbes into colonies often challenges the neutrophils ability to contain them. To study the interactions between neutrophils and microbial colonies, we designed an assay for arranging microbes in clusters of controlled size (i.e. living colloids). The patterned microbes in the living colloid are mechanically trapped inside the wells and fully accessible to neutrophils. Using the assay, we studied the interactions between human neutrophils and Candida albicans and Staphylococcus aureus, two common human pathogens. We also probed the susceptibility of C. albicans colloids to caspofungin, a common antifungal drug.

Chilling causes perivitelline granule formation in activated zebrafish oocytes.

Chilling sensitivity in oocytes of the zebrafish represents a potential obstacle to their successful cryopreservation. Here, we report the first cryomicroscopic observations of the response of zebrafish oocytes to chilling conditions. In activated stage V oocytes that had been exposed to hypothermic temperatures, we observed a latent effect of chilling, manifesting as a granular precipitate that appeared in the perivitelline fluid upon return to 28.5 °C. The granules were visible in unstained oocytes under transmitted light microscopy, and the resulting perivitelline turbidity increased in a dose-dependent manner with decreasing chilling temperature (p < 0.001), as well as with increasing time of hypothermic exposure (p < 0.0001). The change in appearance of the perivitelline space in oocytes that had been chilled and rewarmed became statistically significant after a 7-min exposure to 10 °C and after only 30 s at 1 °C (p < 0.05). Thus, even moderate chilling exposures can lead to detectable changes in activated zebrafish oocytes.

Microscale arrays for the profiling of start and stop signals coordinating human-neutrophil swarming.

Neutrophil swarms protect healthy tissues by sealing off sites of infection. In the absence of swarming, microbial invasion of surrounding tissues can result in severe infections. Recent observations in animal models have shown that swarming requires rapid neutrophil responses and well-choreographed neutrophil migration patterns. However, in animal models physical access to the molecular signals coordinating neutrophil activities during swarming is limited. Here, we report the development and validation of large microscale arrays of zymosan-particle clusters for the study of human neutrophils during swarming ex vivo. We characterized the synchronized swarming of human neutrophils under the guidance of neutrophil-released chemokines, and measured the mediators released at different phases of human-neutrophil swarming against targets simulating infections. We found that the network of mediators coordinating human-neutrophil swarming includes start and stop signals, proteolytic enzymes and enzyme inhibitors, as well as modulators of activation of other immune and non-immune cells. We also show that the swarming behavior of neutrophils from patients following major trauma is deficient and gives rise to smaller swarms than those of neutrophils from healthy individuals.

Relationship between Dyspnea Descriptors and Underlying Causes of the Symptom; a Cross-sectional Study.

INTRODUCTION: History taking and physical examination help clinicians identify the patient's problem and effectively treat it. This study aimed to evaluate the descriptors of dyspnea in patients presenting to emergency department (ED) with asthma, congestive heart failure (CHF), and chronic obstructive pulmonary disease (COPD). METHOD: This cross-sectional study was conducted on all patients presenting to ED with chief complaint of dyspnea, during 2 years. The patients were asked to describe their dyspnea by choosing three items from the valid and reliable questionnaire or articulating their sensation. The relationship between dyspnea descriptors and underlying cause of symptom was evaluated using SPSS version 16. RESULTS: 312 patients with the mean age of 60.96±17.01 years were evaluated (53.2% male). Most of the patients were > 65 years old (48.7%) and had basic level of education (76.9%). "My breath doesn't go out all the way" with 83.1%, "My chest feels tight " with 45.8%, and "I feel that my airway is obstructed" with 40.7%, were the most frequent dyspnea descriptors in asthma patients. "My breathing requires work" with 46.3%, "I feel that I am suffocating" with 31.5%, and "My breath doesn't go out all the way" with 29.6%, were the most frequent dyspnea descriptors in COPD patients. "My breathing is heavy" with 74.4%, "A hunger for more air" with 24.4%, and "I cannot get enough air" with 23.2%, were the most frequent dyspnea descriptors in CHF patients. Except for "My breath does not go in all the way", there was significant correlation between studied dyspnea descriptors and underlying disease (p = 0.001 for all analyses). CONCLUSION: It seems that dyspnea descriptors along with other findings from history and physical examination could be helpful in differentiating the causes of the symptom in patients presenting to ED suffering from dyspnea.

Rapid antibiotic sensitivity testing in microwell arrays.

The widespread bacterial resistance to a broad range of antibiotics necessitates rapid antibiotic susceptibility testing before effective treatment could start in the clinic. Among resistant bacteria, Staphylococcus aureus is one of the most important, and Methicillin-resistant (MRSA) strains are a common cause of life threatening infections. However, standard susceptibility testing for S. aureus is time consuming and thus the start of effective antibiotic treatment is often delayed. To circumvent the limitations of current susceptibility testing systems, we designed an assay that enables measurements of bacterial growth with higher spatial and temporal resolution than standard techniques. The assay consists of arrays of microwells that confine small number of bacteria in small spaces, where their growth is monitored with high precision. These devices enabled us to investigate the effect of different antibiotics on S. aureus growth. We measured the Minimal Inhibitory Concentration (MIC) in less than 3 hours. In addition to being significantly faster than the 48 hours needed for traditional microbiological methods, the assay is also capable of differentiating the specific effects of different antibiotic classes on S. aureus growth. Overall, this assay has the potential to become a rapid, sensitive, and robust tool for use in hospitals and laboratories to assess antibiotic sensitivity.