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Introduction: Children are vulnerable to damage. Health problems in children, especially if necessitate hospitalization, can cause stress in their parents that may persist even long after discharge. This study aimed to investigate the effect of implementing follow-up care plans on stress in mothers of children discharged from pediatric surgical units. Methods: A quasi-experimental study was conducted on 64 mothers whose children were hospitalized in the surgical wards of two educational hospitals affiliated to Isfahan University of Medical Sciences, Iran. The participants were randomly assigned into two groups of control and experimental. The data collection tools included a demographic data questionnaire and stress response inventory (SRI). The interventions were performed using a four-stage follow-up care plan. The data were analyzed using SPSS software version 13 and descriptive statistics, independent t-test, repeated measures analysis of variance (ANOVA), and least significant difference (LSD) test. Results: The mean (SD) stress scores of the experimental group were 64.1 (28.8), 20.4 (12.4), and 11.6 (7.5) before, one week, and one month after the intervention, respectively. In the control group, these scores were 61.2 (29.2), 59.9 (25.5), and 46.7 (19.1), respectively. The results showed the mean score was significantly lower than that of the control group at one week and one month after the intervention in the experimental group. Conclusion: Our results demonstrated that a follow-up care plan can decrease the stress levels of mothers as a continuity of patient care even after discharge.

Abstract Cerebrotendinous xanthomatosis (CTX) is a lipid storage disorder that causes neurological, ophthalmic, vascular, and musculoskeletal disorders due to the deposition of cholesterol in the tissues. Hence, we report clinical and imaging of a 31‐year‐old mentally retarded man with cerebellar ataxia, bilateral swelling of the posterior aspect of Achill, and infertility.

Anastomosis leakage is a common complication in gastrointestinal surgery associated with high mortality, morbidity, and cost to health care providers. According to the significant burdens of AL, several methods have been introduced to overcome this problem. Despite the crucial complications of the AL, current approaches, including glue-based adhesives and bio-based sealants, have certain disadvantages and newly gained attractions for solving this challenge. This study focused on fabricating a sealant structure based on poly (vinyl alcohol) film patterned with gelatin particles and evaluating for prevention of AL. Here, we used a 3D printed model for dry spraying gelatin particles in a random and oriented pattern on PVA films. The mechanical and adhesion properties of both types of films were assessed further, and the efficacy of the novel sealant was evaluated in vivo. The results revealed that the film with an oriented pattern provided better adhesive and mechanical properties, expression of anti-inflammatory cytokines, and collagen deposition. In conclusion, our novel sealant enhanced mechanical features and the healing process of gastrointestinal surgical anastomosis and can be considered a novel method for the prevention of AL.

Natural and non-natural hexahydrocannabinols (HHC) were first described in 1940 by Adam and in late 2021 arose on the drug market in the United States and in some European countries. A background on the discovery, synthesis, and pharmacology studies of hydrogenated and saturated cannabinoids is described. This is harmonized with a summary and comparison of the cannabinoid receptor affinities of various classical, hybrid, and non-classical saturated cannabinoids. A discussion of structure–activity relationships with the four different pharmacophores found in the cannabinoid scaffold is added to this review. According to laboratory studies in vitro, and in several animal species in vivo, HHC is reported to have broadly similar effects to Δ9-tetrahydrocannabinol (Δ9-THC), the main psychoactive substance in cannabis, as demonstrated both in vitro and in several animal species in vivo. However, the effects of HHC treatment have not been studied in humans, and thus a biological profile has not been established.

Introduction: Guillain-Barre Syndrome (GBS) is an autoimmune acute inflammatory demyelinating polyneuropathy usually elicited by an upper respiratory tract infection. Several studies reported GBS associated with Coronavirus Disease 2019 (COVID-19) infection. In this study, we described nine GBS patients following the COVID-19 vaccine. Methods: In this study, nine patients were introduced from six referral centers for neuromuscular disorders in Iran between April 8 and June 20, 2021. Four patients received the Sputnik V, three patients received the Sinopharm, and two cases received the AstraZeneca vaccine. All patients were diagnosed with GBS evidenced by nerve conduction studies and/or cerebrospinal fluid analysis. Results: The median age of the patients was 54.22 years (ranged 26-87 years), and seven patients were male. The patients were treated with Intravenous Immunoglobulin (IVIg) or Plasma Exchange (PLEX). All patients were discharged with some improvements. Conclusion: The link between the COVID-19 vaccine and GBS is not well understood. Given the prevalence of GBS over the population, this association may be coincidental; therefore, more studies are needed to investigate a causal relationship.

Abstract ROR1 – a receptor tyrosine kinase – is overexpressed in CLL. Ibrutinib, a Bruton's tyrosine kinase inhibitor, is clinically effective in CLL but patients may develop resistance. We evaluated the effect of an ROR1 inhibitor, KAN0441571C, in CLL cells from six patients obtained before and after developing resistance to ibrutinib. The ROR1 inhibitor induced apoptosis in ibrutinib‐resistant CLL cells to the same degree as in ibrutinib‐sensitive cells and dephosphorylated ROR1. This was also noted in one patient who became resistant to both ibrutinib and the Bcl‐2 inhibitor venetoclax. The combination of ROR1 inhibitor and venetoclax had a synergistic apoptotic effect on ibrutinib‐resistant cells.

BackgroundThere are sparse and conflicting data regarding the long-term clinical course of atopic dermatitis (AD). Although often described as a childhood disease, newer population-based estimates suggest the prevalence of pediatric and adult disease may be similar.MethodsOur objective was to determine whether there is a decline in the prevalence of AD in population-based cohorts of patients followed longitudinally beyond childhood. We conducted a systematic review and meta-analysis including studies assessing AD prevalence across 3 or more points in time. The primary outcome was weighted overall risk difference (percentage decrease in AD prevalence).ResultsOf 2080 references reviewed, 7 studies with 13 515 participants were included. Participants were assessed at 3-6 time points, ranging from age 3 months to 26 years. The percentage decrease in prevalence after age 12 was 1%, which was not significantly different from zero (95% confidence interval -2%-5%). Similar results were found with other age cut-offs.ConclusionThe prevalence of AD in longitudinal birth cohort studies is similar in childhood and adolescence/early adulthood.

The ROR1 receptor tyrosine kinase is expressed in embryonic tissues but is absent in normal adult tissues. ROR1 is of importance in oncogenesis and is overexpressed in several cancers, such as NSCLC. In this study, we evaluated ROR1 expression in NSCLC patients (N = 287) and the cytotoxic effects of a small molecule ROR1 inhibitor (KAN0441571C) in NSCLC cell lines. ROR1 expression in tumor cells was more frequent in non-squamous (87%) than in squamous (57%) carcinomas patients, while 21% of neuroendocrine tumors expressed ROR1 (p = 0.0001). A significantly higher proportion of p53 negative patients in the ROR1+ group than in the p53 positive non-squamous NSCLC patients (p = 0.03) was noted. KAN0441571C dephosphorylated ROR1 and induced apoptosis (Annexin V/PI) in a time- and dose-dependent manner in five ROR1+ NSCLC cell lines and was superior compared to erlotinib (EGFR inhibitor). Apoptosis was confirmed by the downregulation of MCL-1 and BCL-2, as well as PARP and caspase 3 cleavage. The non-canonical Wnt pathway was involved. The combination of KAN0441571C and erlotinib showed a synergistic apoptotic effect. KAN0441571C also inhibited proliferative (cell cycle analyses, colony formation assay) and migratory (scratch wound healing assay) functions. Targeting NSCLC cells by a combination of ROR1 and EGFR inhibitors may represent a novel promising approach for the treatment of NSCLC patients.

This study explores the potential of halophytes, plants adapted to saline environments, as a novel source for developing herbal MRI contrast agents. Halophytes naturally accumulate various metals within their tissues. These metal ions, potentially complexed with organic molecules, are released into aqueous solutions prepared from the plants. We investigated the ability of these compounds to generate contrast enhancement in MRI using a sequential approach. First, aqueous extracts were prepared from seven selected halophytes, and their capacity to induce contrast in MR images was evaluated. Based on these initial findings, sample halophytes were chosen for further investigations. Second, chemical analysis revealed aluminum as the primary potent metal which enhances the contrast. Third, the halophyte extract was fractionated based on polarity, and the most polar fraction exhibited the strongest contrast‐generating effect. Finally, the relaxivity of this fraction, a key parameter for MRI contrast agents, was measured. We propose that aluminum, likely complexed with a polar molecule within the plant extract, is responsible for the observed contrast enhancement in MRI. [ABSTRACT FROM AUTHOR]

Considering the psychological problems of people with physical disabilities, especially in adolescence, and the importance of paying attention to them to improve their mental health, the present study aimed at investigating the effectiveness of short-term solution-focused approach training on vitality and resilience of students with physical disabilities. It was a quasi-experimental study with pretest, posttest and the control group. From among all high school students with physical disabilities in the city of Isfahan, 30 students were selected through convenience sampling method and were randomly divided into experimental and control groups. Deci Vitality Questionnaire and Conner and Davidson Resilience Scale were applied to both groups, and the experimental group received ten 45-minute sessions of solution-focused intervention once a week. Data were analyzed using multivariate analysis of covariance. The results showed that group training of solution-focused therapy had a significant influence on vitality and the negative affect tolerance of students with physical disabilities, but was not significant on overall resilience. It seems that solution-focused approach can be utilized to promote the positive psychological indicators such as vitality and negative affect tolerance in people with physical disabilities.

Abstract Epigenetic mechanisms occurring in the brain as well as alterations in the gut microbiome composition might contribute to Alzheimer’s disease (AD). Human amyloid precursor protein knock-in (KI) mice contain the Swedish and Iberian mutations (App NL-F ) or those two and also the Arctic mutation (App NL-G-F ). In this study, we assessed whether behavioral and cognitive performance in 6-month-old App NL-F , App NL-G-F , and C57BL/6J wild-type (WT) mice was associated with the gut microbiome, and whether the genotype modulates this association. The genotype effects observed in behavioral tests were test-dependent. The biodiversity and composition of the gut microbiome linked to various aspects of mouse behavioral and cognitive performance but differences in genotype modulated these relationships. These genotype-dependent associations include members of the Lachnospiraceae and Ruminococcaceae families. In a subset of female mice, we assessed DNA methylation in the hippocampus and investigated whether alterations in hippocampal DNA methylation were associated with the gut microbiome. Among other differentially methylated regions, we identified a 1 Kb region that overlapped ing 3′UTR of the Tomm40 gene and the promoter region of the Apoe gene that and was significantly more methylated in the hippocampus of App NL-G-F than WT mice. The integrated gut microbiome hippocampal DNA methylation analysis revealed a positive relationship between amplicon sequence variants (ASVs) within the Lachnospiraceae family and methylation at the Apoe gene. Hence, these microbes may elicit an impact on AD-relevant behavioral and cognitive performance via epigenetic changes in AD-susceptibility genes in neural tissue or that such changes in the epigenome can elicit alterations in intestinal physiology that affect the growth of these taxa in the gut microbiome.

One of the most important issues in the success and development of the individual and society is the discussion of talent and its recognition. There are many definitions of talent in psychology, each of which deals with different aspects, such as intrinsic or acquired. But so far no comprehensive definition has been provided, and there is much ambiguity. Since the complete aristocracy defining the subject has a special effect on the finality of the definition, this study seeks to identify and discuss the components in the definition of talent from the perspective of the Qur'an by the method of Qur'anic semantics. For this purpose, each word of the Qur'an has been studied through total induction, a semantic network of words related to the concept of talent has been formed. Then, by lexical study and semantic analysis of these words, paying attention to their Quranic usage and extracting verses containing these words, the semantic components of the concept of talent in the Holy Quran were discovered. These components are arranged in a logical order next to each other according to the context of the verses and the position of the words in them, and provide a comprehensive and different definition of the existing definitions. Among the characteristics of this definition, we can point to a holistic view of man, multi-component and process-oriented, orientation and alignment with God, the possessor of grace and social nature, and the responsibility of talent.

Abstract Carbon dioxide (CO2) sequestration through CO2 enhanced oil recovery (EOR) in oil reservoirs is one way to reduce this gas in the atmosphere. Undesirable chemical reactions that occur during these operations can affect the reservoir structure and characteristics. In this study, the effect of CO2-water-rock interaction on the rock permeability alteration and final oil recovery has been evaluated experimentally during CO2 injection into a carbonate rock. The effect of flow rate, displacement type and pressure were investigated during CO2 EOR injection. Different scenarios of miscible/immiscible displacement, secondary/tertiary recovery has been evaluated for different levels of connate water salinity and injection rate. The results show that the severity of damage is directly related to the injection rate, however change in displacement type from miscible to immiscible reduce the intensity of chemical reactions in porous medium. Moreover, in the tertiary CO2 injection, the chemical reactions become more severe due to the higher water saturations. Interestingly, this growth in the level of chemical reactions has a negligible impact on permeability reduction, since the major volume of possible reactions occurs in coarse and high permeable pores. Results reveal that damage is more intense in the case of more saline water.

Functional seizures can be challenging to properly diagnose, often leading to delays in treatment. The etiology of functional seizures is multifactorial, with psychological factors identified in many, but not all cases. Misdiagnosis may occur due to clinical features mimicking other medical conditions. Once a correct diagnosis is reached, delivery of definitive, evidence-based treatment may be challenging due to limited availability of specialized resources. Research shows psychological education and cognitive behavioral therapy (CBT) have the greatest efficacy. However, individual differences, including acceptance of the diagnosis, therapeutic alliance, duration of symptoms, comorbidities, and access to care may influence outcomes. There is a critical need for reports that can help identify barriers to effective diagnosis and treatment. We present the diagnosis and treatment of a woman who visited the emergency room after an attack of predominant left-sided paralysis, speech dysfunction and altered awareness. Following multiple daily episodes and visits to multiple medical practitioners, testing led to a diagnosis of functional seizures. While the patient was recommended to undergo a variety of therapeutic interventions, including CBT, she ultimately terminated treatment. In a subsequent interview, the patient revealed her personal experience with perceived limitations of acute management strategies. We explore the complexities of diagnosing and treating individuals with functional seizures.

There might be an association between Internet addiction (IA) and loneliness; however, inconsistent evidence suggests that the severity of this association remains unclear. This study was conducted to assess the association between IA and loneliness. A systematic literature search was conducted in four online databases, including PubMed (MESH terms), Web of Science, Scopus, and Embase. Observational studies measuring the association between IA and loneliness were screened and included in this review. A meta-analysis was conducted using the Stata software. Twenty-six articles with a total sample size of 16496 subjects were included in the analysis. A moderate positive association (r = 0.15 (95% CI: 0.13, 0.16)) was found between IA and loneliness. The individuals with IA had significantly higher scores of loneliness. According to this meta-analysis, we need more attention to the early symptoms of loneliness in individuals with IA. Longitudinal studies are needed to determine the temporality of this association considering adjustment for time varying confounders.

Objectives COVIDTrach is a UK multicentre prospective cohort study project that aims to evaluate the outcomes of tracheostomy in patients with COVID-19 receiving mechanical ventilation and record the incidence of SARS-CoV-2 infection among healthcare workers involved in the procedure.Design Data on patient demographic, clinical history and outcomes were entered prospectively and updated over time via an online database (REDCap). Clinical variables were compared with outcomes, with logistic regression used to develop a model for mortality. Participants recorded whether any operators tested positive for SARS-CoV-2 within 2 weeks of the procedure.Setting UK National Health Service departments involved in treating patients with COVID-19 receiving mechanical ventilation.Participants The cohort comprised 1605 tracheostomy cases from 126 UK hospitals collected between 6 April and 26 August 2020.Main outcome measures Mortality following tracheostomy, successful wean from mechanical ventilation and length of time from tracheostomy to wean, discharge from hospital, complications from tracheostomy, reported SARS-CoV-2 infection among operators.Results The median time from intubation to tracheostomy was 15 days (IQR 11, 21). 285 (18%) patients died following the procedure. 1229 (93%) of the survivors had been successfully weaned from mechanical ventilation at censoring and 1049 (81%) had been discharged from hospital. Age, inspired oxygen concentration, positive end-expiratory pressure setting, fever, number of days of ventilation before tracheostomy, C reactive protein and the use of anticoagulation and inotropic support independently predicted mortality. Six reports were received of operators testing positive for SARS-CoV-2 within 2 weeks of the procedure.Conclusions Tracheostomy appears to be safe in mechanically ventilated patients with COVID-19 and to operators performing the procedure and we identified clinical parameters that are predictive of mortality.Trial registration number The study is registered with ClinicalTrials.Gov (NCT04572438).

The receptor tyrosine kinase orphan receptor 1 (ROR1) is absent in most normal adult tissues but overexpressed in various malignancies and is of importance for tumor cell survival, proliferation, and metastasis. In this study, we evaluated the apoptotic effects of a novel small molecule inhibitor of ROR1 (KAN0441571C) as well as venetoclax (BCL-2 inhibitor), bendamustine, idelalisib (PI3Kδ inhibitor), everolimus (mTOR inhibitor), and ibrutinib (BTK inhibitor) alone or in combination in human MCL primary cells and cell lines. ROR1 expression was evaluated by flow cytometry and Western blot (WB). Cytotoxicity was analyzed by MTT and apoptosis by Annexin V/PI staining as well as signaling and apoptotic proteins (WB). ROR1 was expressed both in patient-derived MCL cells and human MCL cell lines. KAN0441571C alone induced significant time- and dose-dependent apoptosis of MCL cells. Apoptosis was accompanied by decreased expression of MCL-1 and BCL-2 and cleavage of PARP and caspase 3. ROR1 was dephosphorylated as well as ROR1-associated signaling pathway molecules, including the non-canonical WNT signaling pathway (PI3Kδ/AKT/mTOR). The combination of KAN0441571C and ibrutinib, venetoclax, idelalisib, everolimus, or bendamustine had a synergistic apoptotic effect and significantly prevented phosphorylation of ROR1-associated signaling molecules as compared to KAN0441571C alone. Our results suggest that targeting ROR1 by a small molecule inhibitor, KAN0441571C, should be further evaluated particularly in combination with other targeting drugs as a new therapeutic approach for MCL.

Objectives: Myasthenia gravis (MG) is an immune-mediated neuromuscular disorder responsive to immunomodulatory treatments. 10–20% of MGs are not responsive to conventional first-line therapies. Here, we sought to investigate the efficacy and safety of rituximab therapy in the treatment of patients with refractory MG.Methods: In a 48-week, multicenter, open-labeled, prospective cohort setting, 34 participants with refractory MG were assigned to receive infusions of Zytux, which is a rituximab biosimilar, according to a validated protocol. Clinical, functional, and quality of life (QoL) measurements were recorded at baseline, and seven further visits using the Myasthenia Gravis Foundation of America (MGFA), Myasthenia Gravis Composite (MGC), Myasthenia Gravis Activities of Daily Living profile (MG-ADL), and Myasthenia Gravis Quality of Life (MGQoL-15) scales. Besides, the post-infusion side effects were systematically assessed throughout the study.Results: The correlation analysis performed by generalized estimating equations analysis represented a significant reduction of MGC, MG-ADL, and MGQoL-15 scores across the trial period. The subgroup analysis based on the patients' clinical status indicated a significant effect for the interaction between time and MGFA subtypes on MG-ADL score, MGC score, and pyridostigmine prednisolone dose, reflecting that the worse clinical condition was associated with a better response to rituximab. Finally, no serious adverse event was documented.Conclusions: Rituximab therapy could improve clinical, functional, and QoL in patients with refractory MG in a safe setting. Further investigations with larger sample size and a more extended follow-up period are warranted to confirm this finding.Clinical Trial Registration: The study was registered by the Iranian Registry of Clinical Trials (IRCT) (Code No: IRCT20150303021315N18).