Increasing evidence points towards mitochondria as crucial players in the initiation and progression of auto-immune and degenerative disorders, to which impaired cell metabolism is but a facet of the subjacent etiopathogenesis. This review aims to introduce the reader to essential concepts of mitochondrial abnormalities in idiopathic inflammatory myopathy (IIM), underscoring inclusion-body myositis and dermatomyositis. Far surpassing the initial simplistic view of being responsible for energy generation, mitochondria have gathered attention regarding their role in inflammatory processes, being able to fuel autoimmunity, as shown by the presence of anti-mitochondrial antibodies (AMAs) in up to 10% of IIM patients. As cellular respiration takes place, mitochondrial metabolites might help to shape the pro-inflammatory milieu in affected muscle, beyond generating reactive oxygen species, which are well-recognized inducers of damage-associated molecular patterns. A series of mitochondrial components might facilitate the sterile activation of pro-inflammatory cells and the production of several cytokines responsible for enhancing auto-immune responses. Marked variation in the mitochondrial genome has also been reported in IIM patients. As such, we summarize key historical and recent advances linking aberrations and instabilities of mitochondrial DNA to impaired muscle function. Besides discussing mitochondrial dysfunction as an essential part of IIM development, we also highlight possible associations between presence of AMAs and a particular phenotype of IIM, with its own characteristic clinical and radiological pattern. Finally, we present promising treatment approaches targeting mitochondria, while briefly discussing experimental models for gaining deeper insight into the disease process, and ultimately leading to novel drug development.
Systemic sclerosis (SSc) is a chronic immune-mediated disease characterized by microangiopathy, immune dysregulation, and progressive fibrosis of the skin and internal organs. Though not fully understood, the pathogenesis of SSc is dominated by microvascular injury, endothelial dysregulation, and immune response that are thought to be associated with fibroblast activation and related fibrogenesis. Among the main clinical subsets, diffuse SSc (dSSc) is a progressive form with rapid and disseminated skin thickening accompanied by internal organ fibrosis and dysfunction. Despite recent advances and multiple randomized clinical trials in early dSSc patients, an effective disease-modifying treatment for progressive skin fibrosis is still missing, and there is a crucial need to identify new targets for therapeutic intervention. Eotaxin-2 (CCL24) is a chemokine secreted by immune cells and epithelial cells, which promotes trafficking of immune cells and activation of pro-fibrotic cells through CCR3 receptor binding. Higher levels of CCL24 and CCR3 were found in the skin and sera of patients with SSc compared with healthy controls; elevated levels of CCL24 and CCR3 were associated with fibrosis and predictive of greater lung function deterioration. Growing evidence supports the potency of a CCL24-blocking antibody as an anti-inflammatory and anti-fibrotic modulating agent in multiple preclinical models that involve liver, skin, and lung inflammation and fibrosis. This review highlights the role of CCL24 in orchestrating immune, vascular, and fibrotic pathways, and the potential of CCL24 inhibition as a novel treatment for SSc.
Objectives: This review aimed to critically appraise the evidence for biomarkers in blood serum, gingival crevicular fluid (GCF), saliva, and urine in comparison with standard radiographic indices for skeletal maturation assessment.
Materials and Methods: A thorough literature search in multiple databases was conducted for biomarkers in body fluids for skeletal maturation assessed with cervical vertebrae in lateral cephalograms or on hand-wrist radiographs. Different combinations including free text, MeSH terms, and Boolean operators were used. Two researchers used strict inclusion and exclusion criteria to screen title, abstract, and full text, and used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 instrument for risk of bias assessment of individual studies. Meta-analysis was performed on eligible studies using RevMan 5 software.
Results: A total of 344 articles were screened, of which 33 met the inclusion criteria and quality assessment. The skeletal maturity indicators included insulin-like growth factors (IGF-1), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), dehydroepiandrosterone sulfate (DHEAS), vitamin D binding protein (DBP), parathormone-related protein (PTHrP), osteocalcin, metalloproteins, and serotransferrin (TF) along with different metabolites. At puberty, a significant rise was seen in IGF-1, DBP, ALP, osteocalcin, TF, and BALP. However, the serum DHEAS and PTHrP increased from pre-pubertal to post-pubertal stages. Due to the data heterogeneity, a meta-analysis could be performed on seven studies in total on IGF-1 in serum and blood. Of these, five were included for data in males and six in females, and four studies on IGF-1 in serum and blood. A significant difference in IGF-1 levels was seen between stages of peak pubertal growth spurt (CS3 and CS4) and decelerating pubertal growth (CS5) compared with growth initiation stage (CS2).
Conclusions: Pubertal growth spurts were correlated with peak serum IGF-1 and BALP in both sexes individually. Peak ALP levels in GCF were correlated with the pubertal spurt in a combined sample of males and females. Standard biofluid collection protocols and homogeneity in sampling and methodology are strongly recommended for future research.
The appointment of a new chancellor in 1933 marked the beginning of the Third Reich in Germany. The ideology of the Nazi Party focused on establishing a pure Aryan state characterized by nationalism and racial superiority. Their goals would be achieved through a totalitarian form of government that enforced the subjugation, exclusion, and elimination of those they defined as inferior minorities, particularly Jews, who were depicted as non-human. Implementation of the Nazi ideology required the exclusion of Jewish people and other dissenters, particularly Jewish physicians, from their professions. The exclusion of Jewish physicians, referred to herein as a “Medical Professional Elimination Program,” was gradually imposed on other Jewish professions in nations absorbed by the Third Reich, and particularly enforced by incorporated Austria. Why did German and Austrian doctors support the Nazi racial ideology, the removal of Jewish physicians from every possible sphere of influence, and subsequently participate in criminal medical research and experimentation, as well as euthanasia of perceived non-contributors to society, and become involved in refining the effectiveness of the death camps? Was the Medical Professional Elimination Program an opportunistic political concept, or was it part of an entrenched ideology? With these questions in mind, the lives of four key Nazi physicians and two institutions are examined.
Introduction: Antisemitism and antisemitic incidents have been increasing in United States medical institutions since the Hamas attack of October 7, 2023. Such incidents include anecdotal reports of antisemitic displays at medical school commencements. This study examined unprofessional behavior observed at the commencement ceremonies of the 25 US medical schools top-ranked for research excellence. This issue is significant since these graduates are expected to become future leaders in the field of medicine.
Materials and Methods: Based on publicly available videotaped commencements, we assessed the number of students in the graduating classes wearing non-school-provided regalia, carrying signs, wearing protest buttons, or engaging in verbal protests related to the Israel–terror groups conflict that were either openly antisemitic or potentially offensive or insensitive.
Results: Symbols representing antisemitic themes (keffiyehs and three-part graduation stoles conveying antisemitic messages) were worn by students at just under half (12) of the medical schools. The mean number of students in each school wearing keffiyehs or non-official school stoles was 4.0 (95% confidence interval [CI] 2.2–5.8), ranging from 0%–13% of the classes, or 2.5% of the overall graduating cohort. The wearing of buttons, carrying of banners or signs, verbal protests interrupting the ceremony, or students deviating from script ranged from 0% to 22.5% of graduating students, with a mean of 2.7 per school (95% CI -0.8–6.2), or 1.7% of the medical schools graduating cohort.
Conclusions: We identified unprofessional behavior at commencements of top-ranked medical schools consisting of antisemitism and displaying offensive and insensitive symbols and messaging. There is an urgent need for medical schools in the US to educate medical trainees about the dangers of antisemitism and all forms of hate and insensitivity.
Background: The dental needs of cerebral palsy children are an area of study much in need of attention. The neglect of this aspect should be rectified, and simpler diagnostic methodologies should be established and used to serve this purpose.
Aim: This study aimed to determine oral health status and salivary biomarkers (salivary flow rate, pH, buffering capacity) among children with cerebral palsy (CP), to compare their data with that of their healthy siblings, and to evaluate the relationship between salivary biomarkers and dental caries.
Methods: A total of 30 CP children (study group) and 30 normal healthy siblings (controls) were selected between the ages of 5 and 12 years. Salivary biomarkers were assessed, and oral health status was examined.
Statistical Analysis: Chi-square test was used for comparison of oral health status. “Unpaired t test was used to compare caries indexes (decay/filled teeth–primary dentition [dft] and decay/missing/filled teeth–permanent dentition [DMFT]) and salivary biomarkers between the groups. Pearson correlation was used to find the correlation between salivary biomarkers and caries.
Results: The dft scores were significantly higher in the study group (P<0.05). The pH values and salivary flow rates were significantly lower in the study group (P<0.05 and P<0.001, respectively). There was a significant correlation between DMFT scores and salivary flow rate in the study group (P<0.05).
Conclusion: Low pH and low salivary flow rate might be risk factors for dental caries in CP populations; moreover, the significant correlation between DMFT score and salivary flow rate suggests that salivary flow rate could be used as a screening tool for assessing at-risk subjects in such populations.
Objectives: Our study aimed to determine the relationship between serum periostin levels, and the neutrophil–lymphocyte ratio (NLR) with ischemic stroke subtypes, clinical stroke scales, and acute prognosis in patients with acute ischemic stroke.
Materials and Methods: Forty-two ischemic stroke patients and 39 age- and sex-matched healthy volunteers were included in our study. Demographic characteristics including age and gender were recorded. Blood serum periostin and NLR values were evaluated in the first 24 hours after admission. Serum periostin levels were compared with healthy controls of similar age and sex. Lesion localization was determined by cranial CT or diffusion MRI of the patients. Stroke scales were recorded on days 1 and 7 of hospitalization in the study group.
Results: The mean serum periostin levels were higher than in the control group, but no statistically significant difference was found. There was no correlation between serum periostin levels and prognosis of stroke. First admission NLRs were statistically higher than in the control group. The first admission NLRs were positively correlated with the first admission National Institute of Health Stroke Scale score and the day 7 modified Rankin score.
Conclusion: Our study is the first study to evaluate both NLR and serum periostin levels in all types of acute ischemic stroke. While our study did not show that first admission serum periostin levels can be used as a biomarker in ischemic stroke, it did indicate that the first admission NLR can be used for acute prognosis of ischemic stroke.
Aim: The aim of this study was to assess the density of the segmental branches of the middle cerebral artery (MCA) quantitatively as a predictor of acute ischemic stroke in patients without definitive infarct findings at cerebral parenchyma by non-contrast computed tomography (CT).
Clinical rationale for the study: The clinical rationale for the study is to evaluate if the measurement of Sylvian fissure dot sign (SDS) would help early management of patients with stroke at the emergency department.
Methods: Computed tomography scans of 101 patients admitted to the emergency department with stroke symptoms and/or signs were included in the study, retrospectively. In the patient group, the quantitative density of the segmental branches of the MCA in the Sylvian fissure was measured on the affected side and the contralateral side.
Results: Quantitative density of SDS was significantly higher on the ischemic side of the brain. Receiver operating characteristic (ROC) analysis showed a cut-off value of 38.5 Hounsfield units (HU) as a predictor for acute ischemic stroke, with a sensitivity and specificity of 79% and 92%, respectively.
Conclusion: Quantitative density of SDS on the affected side in patients without definitive cerebral infarct findings of parenchyma can be used in the emergency room as an objective predictor sign for the diagnosis of acute ischemic stroke. Considering this finding in the differential diagnosis of acute stroke patients in the emergency room has the potential to improve their clinical management, particularly for the patients without early parenchymal and vascular signs of stroke.
Aim: The aim of this study was to assess the density of the segmental branches of the middle cerebral artery (MCA) quantitatively as a predictor of acute ischemic stroke in patients without definitive infarct findings at cerebral parenchyma by non-contrast computed tomography (CT).
Clinical rationale for the study: The clinical rationale for the study is to evaluate if the measurement of Sylvian fissure dot sign (SDS) would help early management of patients with stroke at the emergency department.
Methods: Computed tomography scans of 101 patients admitted to the emergency department with stroke symptoms and/or signs were included in the study, retrospectively. In the patient group, the quantitative density of the segmental branches of the MCA in the Sylvian fissure was measured on the affected side and the contralateral side.
Results: Quantitative density of SDS was significantly higher on the ischemic side of the brain. Receiver operating characteristic (ROC) analysis showed a cut-off value of 38.5 Hounsfield units (HU) as a predictor for acute ischemic stroke, with a sensitivity and specificity of 79% and 92%, respectively.
Conclusion: Quantitative density of SDS on the affected side in patients without definitive cerebral infarct findings of parenchyma can be used in the emergency room as an objective predictor sign for the diagnosis of acute ischemic stroke. Considering this finding in the differential diagnosis of acute stroke patients in the emergency room has the potential to improve their clinical management, particularly for the patients without early parenchymal and vascular signs of stroke.
Aim: The aim of this study was to assess the density of the segmental branches of the middle cerebral artery (MCA) quantitatively as a predictor of acute ischemic stroke in patients without definitive infarct findings at cerebral parenchyma by non-contrast computed tomography (CT).
Clinical rationale for the study: The clinical rationale for the study is to evaluate if the measurement of Sylvian fissure dot sign (SDS) would help early management of patients with stroke at the emergency department.
Methods: Computed tomography scans of 101 patients admitted to the emergency department with stroke symptoms and/or signs were included in the study, retrospectively. In the patient group, the quantitative density of the segmental branches of the MCA in the Sylvian fissure was measured on the affected side and the contralateral side.
Results: Quantitative density of SDS was significantly higher on the ischemic side of the brain. Receiver operating characteristic (ROC) analysis showed a cut-off value of 38.5 Hounsfield units (HU) as a predictor for acute ischemic stroke, with a sensitivity and specificity of 79% and 92%, respectively.
Conclusion: Quantitative density of SDS on the affected side in patients without definitive cerebral infarct findings of parenchyma can be used in the emergency room as an objective predictor sign for the diagnosis of acute ischemic stroke. Considering this finding in the differential diagnosis of acute stroke patients in the emergency room has the potential to improve their clinical management, particularly for the patients without early parenchymal and vascular signs of stroke.
