Pharmacologically Induced Accommodation Palsy and the Bioelectrical Activity of the Muscular System: A Preliminary Investigation.

The aim of this study was to pharmacologically induce accommodative paralysis and evaluate its effects on the bioelectrical activity of the muscular system. The study included two participant groups: those with myopia and those with normal vision (emmetropes). Electromyographic assessments were performed using the Noraxon Ultium DTS 8-K MR 3 myo Muscle Master Edition system. The muscles analyzed in this study were the temporalis, masseter, sternocleidomastoid, trapezius, abdominal muscles, biceps brachii, and the external oblique muscles of the abdomen. It is important to acknowledge that, based on the current findings, it cannot be definitively stated that the observed effects have clinical significance, and additional studies are encouraged.

Lymphocytic hypophysitis - various course of the disease and individualized therapeutic approach. An algorithm of the follow-up.

INTRODUCTION: Lymphocytic hypophysitis (LH) is a rare inflammatory disorder of the pituitary or/and hypothalamus with variable disease course: from spontaneous remission to pituitary atrophy. The diagnosis, treatment and follow-up remain challenging. The aim of the study is to present long-term data and an individualized therapeutic approach and propose an algorithm for the follow-up of patients with probable LH. MATERIAL AND METHODS: A retrospective analysis of 18 consecutive adult patients (13 W/5 M, mean age 45.2 years) with LH diagnosed and treated in a tertiary referral center. RESULTS: The first manifestations were headaches (50.0%), polyuria/polydipsia (33.3%) and symptoms of hypopituitarism (16.7%). Somatotropic, adrenal, gonadal and thyroid axis insufficiencies were found in 44.4%, 33.3%, 33.3%, and 27.8% of patients, respectively. Arginine vasopressin deficiency was diagnosed in 8 patients (44.4%). Some of the dysfunctions were transient. Magnetic resonance imaging (MRI) revealed thickened pituitary stalk in all but 2 cases. In 2 patients an anterior pituitary lesion, most likely inflammatory was described. Four patients were given steroids (severe headaches) with clinical recovery and stable/improved MRI. One woman was operated on due to the progressive mass-related symptoms - histopathological examination confirmed LH. In the remaining 13/18 patients watchful waiting approach allowed to obtain hormonal and radiological stabilization/improvement. CONCLUSIONS: LH is a disease with a complex clinical picture and challenging diagnosis. Treatment requires an individual approach: vigilant observation is the cornerstone of therapy, with steroid/surgical treatment reserved for cases with mass-related symptoms. Further multicenter research might help in better understanding of the LH and creating standards of care in this rare disease.

Surface Electromyography in Dentistry-Past, Present and Future.

Surface electromyography (sEMG) is a technique for measuring and analyzing the electrical signals of muscle activity using electrodes placed on the skin's surface. The aim of this paper was to outline the history of the development and use of surface electromyography in dentistry, to show where research and technical solutions relating to surface electromyography currently lie, and to make recommendations for further research. sEMG is a diagnostic technique that has found significant application in dentistry. The historical section discusses the evolution of sEMG methods and equipment, highlighting how technological advances have influenced the accuracy and applicability of this method in dentistry. The need for standardization of musculoskeletal testing methodology is highlighted and the needed increased technical capabilities of sEMG equipment and the ability to specify parameters (e.g., sampling rates, bandwidth). A higher sampling rate (the recommended may be 2000 Hz or higher in masticatory muscles) allows more accurate recording of changes in the signal, which is essential for accurate analysis of muscle function. Bandwidth is one of the key parameters in sEMG research. Bandwidth determines the range of frequencies effectively recorded by the sEMG system (the recommended frequency limits are usually between 20 Hz and 500 Hz in masticatory muscles). In addition, the increased technical capabilities of sEMG equipment and the ability to specify electromyographic parameters demonstrate the need for a detailed description of selected parameters in the methodological section. This is necessary to maintain the reproducibility of sEMG testing. More high-quality clinical trials are needed in the future.

A Meta-Analysis of the Global Prevalence of Temporomandibular Disorders.

Background: This meta-analysis aims to evaluate the proportion of people with TMDs in different studies, considering factors such as geographical region, patient age, and sample size. Methods: The search yielded 6984 articles on the incidence of TMDs. Finally, 74 studies with 172,239 subjects and 35,259 with TMDs were selected for final analysis. Analyses were performed using the R statistical language. Results: The incidence of TMDs in the world population was 34%. The age group 18-60 years is the most exposed to TMDs. From the data presented, we observed that for each continent, the female group was 9% to 56% larger than the male group. The highest female-to-male ratio (F:M) was reported in South America (1.56), whereas the lowest F:M ratio was reported in Europe (1.09), suggesting an almost equal distribution of males and females. Conclusions: This suggests that geographical location may play a role in the results of the studies. The prevalence of TMDs was significantly higher in South America (47%) compared to Asia (33%) and Europe (29%). Larger epidemiological studies of TMDs in African and Australian populations are recommended. In conclusion, both visual and statistical assessments suggest that the results of our meta-analysis are robust and unlikely to be significantly affected by publication bias. This suggests that geographical location may play a role in the prevalence of TMDs.

Obesity-Related Hemodynamic Alterations in Patients with Cushing's Disease.

Background: Cushing's disease (CD) is associated with a specific form of metabolic syndrome that includes visceral obesity, which may affect cardiovascular hemodynamics by stimulating hypercortisolism-related metabolic activity. The purpose of this study was to evaluate the relationship between obesity and the hemodynamic profile of patients with CD. Methods: This prospective clinical study involved a hemodynamic status assessment of 54 patients newly diagnosed with CD with no significant comorbidities (mean age of 41 years). The assessments included impedance cardiography (ICG) to assess such parameters as stroke index (SI), cardiac index (CI), velocity index (VI), acceleration index (ACI), Heather index (HI), systemic vascular resistance index (SVRI), and total arterial compliance index (TACI) as well as applanation tonometry to assess such parameters as central pulse pressure (CPP) and augmentation index (AI). These assessments were complemented by echocardiography to assess cardiac structure and function. Results: Compared with CD patients without obesity, individuals with CD and obesity (defined as a body mass index ≥ 30 kg/m2) exhibited significantly lower values of ICG parameters characterizing the pumping function of the heart (VI: 37.0 ± 9.5 vs. 47.2 ± 14.3 × 1*1000-1*s-1, p = 0.006; ACI: 58.7 ± 23.5 vs. 76.0 ± 23.5 × 1/100/s2, p = 0.005; HI: 11.1 ± 3.5 vs. 14.6 ± 5.5 × Ohm/s2, p = 0.01), whereas echocardiography in obese patients showed larger heart chamber sizes and a higher left ventricular mass index. No significant intergroup differences in blood pressure, heart rate, LVEF, GLS, TACI, CPP, or AI were noted. Conclusions: Hemodynamic changes associated with obesity already occur at an early stage of CD and manifest via significantly lower values of the ICG parameters illustrating the heart's function as a pump, despite the normal function of the left ventricle in echocardiography.

Relevance of mutations in protein deubiquitinases genes and TP53 in corticotroph pituitary tumors.

Introduction: Corticotroph pituitary neuroendocrine tumors (PitNETs) develop from ACTH-producing cells. They commonly cause Cushing's disease (CD), however, some remain clinically silent. Recurrent USP8, USP48, BRAF and TP53 mutations occur in corticotroph PitNETs. The aim of our study was to determine frequency and relevance of these mutations in a possibly large series of corticotroph PitNETs. Methods: Study included 147 patients (100 CD and 47 silent tumors) that were screened for hot-spot mutations in USP8, USP48 and BRAF with Sanger sequencing, while 128 of these patients were screened for TP53 mutations with next generation sequencing and immunohistochemistry. Results: USP8 mutations were found in 41% CD and 8,5% silent tumors, while USP48 mutations were found in 6% CD patients only. Both were more prevalent in women. They were related to higher rate of biochemical remission, non-invasive tumor growth, its smaller size and densely granulated histology, suggesting that these mutation may be favorable clinical features. Multivariate survival analyses did not confirm possible prognostic value of mutation in protein deubiquitinases. No BRAF mutations were found. Four TP53 mutations were identified (2 in CD, 2 in silent tumors) in tumors with size >10mm including 3 invasive ones. They were found in Crooke's cell and sparsely granulated tumors. Tumors with missense TP53 mutations had higher TP53 immunoreactivity score than wild-type tumors. Tumor with frameshift TP53 variant had low protein expression. TP53 mutation was a poor prognostic factor in CD according to uni- and multivariate survival analyses in spite of low mutations frequency. Conclusions: We confirmed high prevalence of USP8 mutations and low incidence of USP48 and TP53 mutations. Changes in protein deubiquitinases genes appear to be favorable prognostic factors in CD. TP53 mutations are rare, occur in both functioning and silent tumors and are related to poor clinical outcome in CD.

The Heart's Function as a Pump Assessed via Impedance Cardiography and the Autonomic System Balance in Patients with Early-Stage Acromegaly.

BACKGROUND: Acromegaly is a rare, chronic disease that involves structural and functional abnormalities of the cardiovascular system. Acromegaly likely affects interactions between the cardiovascular system and the autonomic nervous system (ANS). Therefore, assessing the relationship between sympathetic-parasympathetic balance by analyzing heart rate variability (HRV) and the hemodynamic profile via impedance cardiography (ICG) may be useful in learning the exact nature of interactions between the ANS and the cardiovascular system. The purpose of this study was to assess a possible association between HRV and ICG-based parameters of cardiac function in patients newly diagnosed with acromegaly. METHODS: This observational cohort study was conducted on 33 patients (18 men, mean age of 47 years) newly diagnosed with acromegaly and no significant comorbidities. A correlation analysis (Spearman's rank coefficient R) of the parameters assessed via ICG and the HRV assessed via 24 h ambulatory electrocardiography was performed. ICG assessments included the following parameters: stroke volume index (SI), cardiac index (CI), acceleration index (ACI), velocity index (VI), and Heather index (HI). The analysis of HRV included both time-domain parameters (pNN50, SDNN, SDSD, rMSSD) and frequency-domain parameters (total power (TP) and its individual frequency bands: low-frequency (LF day/night), high-frequency (HF day/night), and the LF/HF ratio (day/night)). RESULTS: Frequency-domain HRV analysis showed the following correlations: (1) lower nighttime LF values with higher ACI (R = -0.38; p = 0.027) and HI (R = -0.46; p = 0.007) values; (2) higher nighttime HF values with higher ACI (R = 0.39; p = 0.027) and HI (R = 0.43; p = 0.014) values; (3) lower nighttime LF/HF values with higher ACI (R = -0.36; p = 0.037) and HI (R = -0.42; p = 0.014) values; (4) higher nighttime TP values with higher SI values (R = 0.35; p = 0.049). Time-domain parameters of HRV showed a significant correlation only between the nighttime values of SDSD and SI (R = 0.35; p = 0.049) and between the daytime and nighttime values of SDNN and HR (R = -0.50; p = 0.003 and R = -0.35; p = 0.046). In multivariate regression, only ACI was revealed to be independently related to HRV. CONCLUSIONS: In patients newly diagnosed with acromegaly, the relationship between the sympathetic-parasympathetic balance assessed via HRV and the hemodynamic profile assessed via ICG was revealed. Better function of the left ventricle was associated with a parasympathetic shift in the autonomic balance.

DNA Methylation Pattern in Somatotroph Pituitary Neuroendocrine Tumors.

INTRODUCTION: Growth hormone secretion by sporadic somatotroph neuroendocrine pituitary tumors (PitNETs) is a major cause of acromegaly. These tumors are relatively heterogenous in terms of histopathological and molecular features. Our previous transcriptomic profiling of somatotroph tumors revealed three distinct molecular subtypes. This study aimed to investigate the difference in DNA methylation patterns in subtypes of somatotroph PitNETs and its role in distinctive gene expression. METHODS: Genome-wide DNA methylation was investigated in 48 somatotroph PitNETs with EPIC microarrays. Gene expression was assessed with RNAseq. Bisulfite pyrosequencing and qRT-PCR were used for verifying the results of DNA methylation and gene expression. RESULTS: Clustering tumor samples based on methylation data reflected the transcriptome-related classification. Subtype 1 tumors are densely granulated without GNAS mutation, characterized by high expression of NR5A1 (SF-1) and GIPR. The expression of both genes is correlated with specific methylation of the gene body and promoter. This subtype has a lower methylation level of 5' gene regions and CpG islands than the remaining tumors. Subtype 2 PitNETs are densely granulated and frequently GNAS-mutated, while those in subtype 3 are mainly sparsely granulated. Methylation/expression analysis indicates that ∼50% genes located in differentially methylated regions are those differentially expressed between tumor subtypes. Correlation analysis revealed DNA methylation-controlled genes, including CDKN1B, CCND2, EBF3, CDH4, CDH12, MGMT, STAT5A, PLXND1, PTPRE, and MMP16, and genes encoding ion channels and semaphorins. CONCLUSION: DNA methylation profiling confirmed the existence of three molecular subtypes of somatotroph PitNETs. High expression of NR5A1 and GIPR in subtype 1 tumors is correlated with specific methylation of both genes.

Pathologic Characteristics of Somatotroph Pituitary Tumors-An Observational Single-Center Study.

The pathologic evaluation of a tumor tissue is an essential part of an acromegaly patient's assessment. This study aimed to analyze the pathologic characteristics of pituitary tumors in patients with acromegaly. The demographic data, in addition to the hormonal, imaging, and pathologic results of 120 patients with acromegaly after pituitary surgery, were extracted from the Polish Acromegaly Registry. We compared sparsely and densely granulated tumors, GH(+), mixed GH(+)/PRL(+) and plurihormonal tumors, α-subunit-positive and α-subunit-negative tumors, and tumors of various Ki-67 indices in terms of the abovementioned features. Sparsely granulated tumors were more frequent in women than in men (p = 0.001) and in younger patients (p = 0.011), and they were larger (p < 0.001) compared to densely granulated tumors. Tumors with positive α-subunit were smaller (p = 0.013), showed extrasellar extension less often (p = 0.039), and were more often densely granulated (p < 0.001) compared to α-subunit-negative tumors. Patients with a higher Ki-67 index were younger (p < 0.001) and more often diagnosed with genetic syndromes (p = 0.02); they had higher GH concentrations (p = 0.007), larger tumors (p = 0.006), and cavernous sinus invasions more frequently (p = 0.022). Conclusions: The pathologic characteristics of somatotroph pituitary tumors are associated with patient's age, sex, hormonal results, tumor size, and the degree of extrasellar expansion.

Myopia & painful muscle form of temporomandibular disorders: connections between vision, masticatory and cervical muscles activity and sensitivity and sleep quality.

The main aim of this study is to evaluate the effects of painful muscle form of temporomandibular disorders and myopia on the connections between the visual organ, the bioelectrical activity and sensitivity of the masticatory and cervical muscles, and sleep quality. Subjects were divided into 4 groups (Myopia & TMDs, Myopia (Without TMDs), Emmetropic & TMDs and Emmetropic (Without TMDs)). The study was conducted in the following order of assessment: examination for temporomandibular disorders, assessment of the muscle activity by electromyograph, pressure pain thresholds examination, ophthalmic examination and completion of the Pittsburgh Sleep Quality Index. It was observed that the Myopia & TMDs group had higher muscle tenderness, higher resting and lower functional muscle bioelectrical activity. The visual organ is clinical related to the masticatory and cervical muscles. TMDs and myopia alter masticatory and cervical muscle activity. The thickness of the choroid in people with myopia is related to muscle tenderness. TMDs and myopia impair sleep quality. It is recommended to determine the number of people with refractive error and its magnitude in the sEMG study in order to be able to replicate the research methodology.

The Relationship between the Burden of Acromegaly, Associated Comorbidities, Complications and Disease Status.

Uncontrolled acromegaly causes increased morbidity and mortality. The analysis of acromegaly comorbidities and complications is important when establishing a standard of care for the entire population of acromegaly patients. The aim of this study was to determine the frequency of comorbidities and complications of acromegaly and their dependence on the activity of the disease. A retrospective analysis of medical records from 124 patients with acromegaly was carried out, including 39 who were cured, 73 treated with somatostatin analogs and 12 newly diagnosed patients. The incidence of comorbidities and complications was very high, and those most frequently observed were arterial hypertension, multinodular goiter, lipid disorders, hypopituitarism and degenerative changes. At least one complication of acromegaly was observed in 92% of patients undergoing successful neurosurgery and in all pharmacologically treated patients. By contrast, two or more complications were observed in 77% of cured patients and in pharmacologically controlled and uncontrolled patients, 82% and 91%, respectively. Conclusions: Acromegaly is associated with a high prevalence of complications. Active acromegaly is associated with a higher incidence of complications than in treated groups. Untreated patients have more complications than treated patients. Successfully cured patients have significantly fewer complications than pharmacologically controlled patients and patients with active acromegaly.

The patient's sex determines the hemodynamic profile in patients with Cushing disease.

Background: Cushing disease (CD) may lead to accelerated cardiovascular remodeling and increased mortality. There are suspected differences in the mechanism of cardiovascular dysfunction between males and females with CD. The purpose of this study was to assess the effect of patient sex on the hemodynamic profile assessed via impedance cardiography and echocardiography in patients newly diagnosed with CD. Material and methods: The 54 patients newly diagnosed with CD (mean age 41 years; 77.8% of females) who were included in this prospective clinical study underwent impedance cardiography to assess specific parameters (including systemic vascular resistance index [SVRI], total arterial compliance index [TACI], Heather index [HI], stroke index [SI], cardiac index [CI], velocity index [VI], and acceleration index [ACI]) and transthoracic echocardiography to assess heart chamber diameters and left ventricular systolic and diastolic function. Results: Males with CD exhibited higher afterload, with higher SVRI (3,169.3 ± 731.8 vs. 2,339.3 ± 640.8 dyn*s*cm-5*m² in males and females, respectively; p=0.002), lower TACI (0.80 ± 0.30 vs. 1.09 ± 0.30 mL/mmHg*m2; p=0.008), and lower hemodynamic parameters of left ventricular function, with lower HI (9.46 ± 2.86 vs. 14.1 ± 5.06 Ohm/s2; p=0.0007), lower VI (35.1 ± 11.9 vs. 44.9 ± 13.1 1*1000-1*s-1; p=0.009), lower SI (36.5 ± 11.7 vs. 43.6 ± 9.57 mL/m2; p=0.04), lower CI (2.36 ± 0.46 vs. 3.17 ± 0.76 mL*m-2*min-1; p=0.0009), and lower ACI (50.4 ± 19.8 vs. 73.6 ± 25.0 1/100/s2; p=0.006). There were no significant differences between the sexes in left ventricular systolic or diastolic function assessed by echocardiography. Conclusion: In comparison with females with CD, males with CD have a less favorable hemodynamic profile, with higher afterload and worse left ventricular function. Sex differences in cardiovascular system function should be taken into consideration in designing personalized diagnostic and therapeutic management of patients with CD.

Progression of a corticotroph tumour during durable medical therapy with osilodrostat in a patient with persistent Cushing's disease.

Not required for Clinical Vignette.

Osteoporosis as the First Sign of Cushing's Disease in a Thin 16-Year-Old Boy-A Case Report.

Cushing's disease (CD) is an extremely rare diagnosis in children. In this report, we present the case of an almost 16-year-old, short and thin boy with CD, the first symptoms of which were spinal pain and vertebral fractures as a result of osteoporosis. In light of his growth retardation and short stature, the boy underwent diagnostics, which excluded growth hormone (GH) deficiency, hypothyroidism and celiac disease. Finally, based on cortisol profile results, dexamethasone suppression tests and bilateral sampling during catheterization of the inferior petrosal sinuses, CD was diagnosed.

GH-secreting pituitary adenoma in the course of McCune­Albright syndrome in a 21-year-old patient complicated by hepatocellular carcinoma.

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Study protocol: Accommodative effects on the musculoskeletal system.

Accommodation is a phenomenon of the eyeball, which consists of adapting to view objects at different distances. The main aim of this study is to evaluate the effect of accommodations on the musculoskeletal system in myopic and emmetropic subjects. To date, the effect of accommodative paralysis on the musculoskeletal system has not been studied. The research hypothesis based on the current research reports is that accommodation affects the musculoskeletal system in myopic and emmetropic subjects. A smaller aim of the study is to evaluate the effect of unilateral accommodative palsy on the musculoskeletal system in myopic and emmetropic subjects. According to the authors of the previous reports, unilateral accommodative palsy will affect increased musculoskeletal asymmetry in myopic and emmetropic subjects. The surface electromyography (sEMG) of the musculoskeletal system will be performed by using the Noraxon Ultium DTS 8-K MR 3 myo Muscle Master Edition. Cycloftyal (10 mg/ml, eye drops, solution) will be used to paralyze accommodation. After the paralysis of unilateral accommodation, the test will be repeated. Both-sided accommodation will be paralyzed next, and the test will be repeated. The study may provide insight into the effects of accommodation on the musculoskeletal system, and it may also help in understanding the connections between these systems.

Targeted sequencing of cancer-related genes reveals a recurrent TOP2A variant which affects DNA binding and coincides with global transcriptional changes in glioblastoma.

High-grade gliomas are aggressive, deadly primary brain tumors. Median survival of patients with glioblastoma (GBM, WHO grade 4) is 14 months and <10% of patients survive 2 years. Despite improved surgical strategies and forceful radiotherapy and chemotherapy, the prognosis of GBM patients is poor and did not improve over decades. We performed targeted next-generation sequencing with a custom panel of 664 cancer- and epigenetics-related genes, and searched for somatic and germline variants in 180 gliomas of different WHO grades. Herein, we focus on 135 GBM IDH-wild type samples. In parallel, mRNA sequencing was accomplished to detect transcriptomic abnormalities. We present the genomic alterations in high-grade gliomas and the associated transcriptomic patterns. Computational analyses and biochemical assays showed the influence of TOP2A variants on enzyme activities. In 4/135 IDH-wild type GBMs we found a novel, recurrent mutation in the TOP2A gene encoding topoisomerase 2A (allele frequency [AF] = 0.03, 4/135 samples). Biochemical assays with recombinant, wild type (WT) and variant proteins demonstrated stronger DNA binding and relaxation activity of the variant protein. GBM patients carrying the altered TOP2A had shorter overall survival (median OS 150 vs 500 days, P = .0018). In the GBMs with the TOP2A variant we found transcriptomic alterations consistent with splicing dysregulation. luA novel, recurrent TOP2A mutation, which was found exclusively in four GBMs, results in the TOP2A E948Q variant with altered DNA binding and relaxation activities. The deleterious TOP2A mutation resulting in transcription deregulation in GBMs may contribute to disease pathology.

High Myopia and Thickness of Extraocular and Masticatory Muscles-7T MRI, Preliminary Study.

(1) Background: Myopia is one of the most common refractive errors in the world. The aim of this study was to evaluate the transverse dimensions of selected masticatory muscles (temporalis muscle and masseter muscle) versus the transverse dimensions of selected extraocular muscles (superior rectus, inferior rectus, medial rectus and lateral rectus) in emmetropic and high myopic subjects. (2) Methods: Twenty-seven individuals were included in the analysis, resulting in 24 eyeballs of patients with high myopia and 30 eyeballs of emmetropic subjects. A 7 Tesla resonance was used to analyze the described muscles. (3) Results: Statistical analysis showed differences in all analyzed extraocular muscles and all analyzed masticatory muscles between emmetropic subjects and high myopic subjects. In the high myopic subject group, statistical analysis showed four correlations. The three negative correlations were between the lateral rectus muscle and an axial length eyeball, refractive error and an axial length eyeball, and the inferior rectus muscle and visual acuity. The positive correlation was between the lateral rectus muscle and the medial rectus muscle. (4) Conclusions: The high myopic subjects are characterized by a larger cross-sectional area of extraocular muscles and masticatory muscles compared to the emmetropic subjects. Correlations were observed between the thickness of the extraocular muscles and the masticatory muscles. The lateral rectus muscle was related to the length of the eyeball. The phenomenon requires further study.