Background and Objectives: Muscle fatigue is characterised by (1) loss of force, (2) decreased maximal shortening velocity and (3) a greater resistance to stretch that could be due to reduced intracellular Ca²⁺ and increased Pi, which alter cross bridge kinetics. Materials and Methods: To investigate this, we used (1) 2,3-butanedione monoxime (BDM), believed to increase the proportion of attached but non-force-generating cross bridges; (2) Pi that increases the proportion of attached cross bridges, but with Pi still attached; and (3) reduced activating Ca²⁺. We used permeabilised rat soleus fibres, activated with pCa 4.5 at 15 °C. Results: The addition of 1 mM BDM or 15 mM Pi, or the lowering of the Ca²⁺ to pCa 5.5, all reduced the isometric force by around 50%. Stiffness decreased in proportion to isometric force when the fibres were activated at pCa 5.5, but was well maintained in the presence of Pi and BDM. Force enhancement after a stretch increased with the length of stretch and Pi, suggesting a role for titin. Maximum shortening velocity was reduced by about 50% in the presence of BDM and pCa 5.5, but was slightly increased by Pi. Neither decreasing Ca²⁺ nor increasing Pi alone mimicked the effects of fatigue on muscle contractile characteristics entirely. Only BDM elicited a decrease of force and slowing with maintained stiffness, similar to the situation in fatigued muscle. Conclusions: This suggests that in fatigue, there is an accumulation of attached but low-force cross bridges that cannot be the result of the combined action of reduced Ca²⁺ or increased Pi alone, but is probably due to a combination of factors that change during fatigue. Full article

Ceruminous pleomorphic adenoma is a very rare, mostly benign tumor originating from the ceruminal glands in the external auditory canal. Histologically, it is a mixed tumor with epithelial and stromal parts of different proportions, and is recognized today by the World Health Organization (WHO) as a ceruminous adenoma. Similar to the pleomorphic adenoma of salivary glands, recurrence or malignant degeneration with cellular atypia and metastasis can occur on rare occasions. Here, we describe an 87-year old female patient with a growing spherical mass in the right external auditory canal. After exclusive endoscopic tumor resection, a ceruminous pleomorphic adenoma was histologically diagnosed. Due to the absence of nuclear pleomorphism, no increased mitotic rate, no perineural invasion and no fusion transcripts of the MYB or MYBL1 gene loci, an adenoid cystic carcinoma could be excluded. The postoperative course was without any evidence of complications. A literature review identified 44 articles with 49 patients that were considered. Hearing loss and ear sensations were the most commonly reported symptoms. Most cases underwent an excision via an endaural or retroauricular approach. Recurrences were described in four patients, three of which had a malignant transformation. Full article

Background and objectives: Health is partly determined by the state of one’s nutrition; it stimulates the body’s functional and metabolic adaptations to physical strain and helps one prevent sports injuries and get in shape in terms of body composition. This study aims to investigate the actual nutrition and dietary supplements taken by elite Lithuanian athletes and to identify the relationship between the dietary intake, dietary supplementation and body composition of elite athletes. Materials and Methods: The research subjects were 76.7% of Lithuanian elite athletes (N = 247). The actual diet was investigated using the 24 h recall dietary survey method. Dietary supplementation was studied applying the questionnaire method. Measurements of body composition were performed using the BIA (bioelectrical impedance analysis) tetra-polar electrodes and measuring resistivity with 8–12 tangent electrodes at different frequencies of signal: 5, 50 and 250 kHz. Results: Results indicate that among the athletes, 62% use too few carbohydrates and 77% use too much fat. Although the 3.5% increase in lean body mass (95% CI: −0.107, 7.070) helps gain an increased protein intake with food (p = 0.057), 38% of athletes consume too little protein with food. The athletes mostly use carbohydrates (86%), vitamins (81%), protein supplements (70%), and multivitamins (62%). We did not determine the impact (p > 0.05) of individual or complex supplement use on the lean body mass (%) or fat mass (%) values of athletes. Conclusions: Athletes consume insufficient carbohydrates, vitamin D, calcium, polyunsaturated fatty acids, omega-3 and omega-6 fatty acids and too much fat, saturated fatty acids, cholesterol, and they use proteins irrationally. Sport nutritionists should also focus on the risk of malnutrition for female athletes. Nutritional supplements partially offset macronutrient and micronutrient deficiency. Nevertheless, the effect of food supplements on the body composition of athletes is too small compared to the normal diet. Athletes ought to prioritize the formation of eating habits and only then use supplements. Full article

Background and objectives: Opinions differ regarding the optimal diagnostic methods for patients with suspected choledocholithiasis. The aim of this study was to assess the diagnostic accuracy of laparoscopic ultrasonography (LUS) and compare it to pre-operative magnetic resonance cholangio-pancreatography (MRCP); Materials and Methods: In all patients with suspected choledocholithiasis LUS was performed during laparoscopic cholecystectomy to evaluate biliary stones. According to availability, part of the patients had pre-operative MRCP. Data for diagnostic accuracy and main outcomes were collected prospectively and analyzed retrospectively; Results: Choledocholithiasis was detected in 178 of 297 patients by LUS (59.93%) and in 39 of 87 patients by MRCP (44.8%), p = 0.041. LUS yielded a sensitivity of 99.4%, a specificity of 94.3%, a positive predictive value of 96.1% and a negative predictive value of 99.1%. However, pre-operative MRCP had a sensitivity of 61.7%, a specificity of 92.3%, a positive predictive value of 94.9% and a negative predictive value of 51.1%. Moreover, of the 47 patients with no choledocholithiasis by MRCP, in 23 cases it was later detected by LUS (a false negative MRCP finding—38.3%), p < 0.001. Median duration of hospitalization was significantly shorter in patients evaluated without pre-operative MRCP—8 days (interquartile range – IQR 11–6) vs. 11 days (IQR 14–9), p = 0.001; Conclusions: LUS may reduce the role of pre-operative MRCP and can become a rational alternative to MRCP as a primary imaging technique for the detection of choledocholithiasis. Full article

Recently, connections have been made between feeding and eating problems and autism spectrum disorder (ASD) and between autism pathophysiology and diet issues. These could explain some of the mechanisms which have not yet been discovered or are not sufficiently characterized. Moreover, there is an increased awareness for micronutrients in ASD due to the presence of gastrointestinal (GI) problems that can be related to feeding issues. For example, levels of vitamins B₁, B₆, B₁₂, A and D are often reported to be low in ASD children. Thus, in the present mini review we focused on describing the impact of some vitamins deficiencies and their relevance in ASD patients. Full article

Background and objectives: Tick-borne encephalitis virus (TBEV) infections have been the cause of threatening outbreaks for many years. Apart from several physical and chemical methods to prevent tick bites, active vaccination of people highly exposed to infection is still the most important strategy of prevention. However, in some subjects, the lack of or low response to TBEV antigens is observed. The aim of the current study was to assess the prevalence of seronegative rate for anti-TBEV antibodies and the risk factors for waning immunity. Materials and Methods: 2315 at least primary vaccinated subjects from the high risk group for TBEV infections participated in this study. A commercial enzyme-linked immunosorbent assay (ELISA) test was used for the assessment of anti-TBEV IgG serum level. Results: Data showed that 86.2% of subjects who underwent vaccination were positive for anti-TBEV antibodies within 5 years. As much as 13.8% of subjects that underwent primary or primary and booster vaccination were barely protected after vaccination. Women and subjects under 60 years underwent more effective protection but sex and older age was not a risk factor for being a subject of waning immunity. A logistic regression showed that both a longer time since the vaccination and a lower number of booster doses constantly increased the chance of lost anti-TBEV antibodies. Conclusions: This study demonstrates that the vaccination schedule should be reevaluated. The extension of the interval of booster immunization is risky and all subjects should be surrounded by care consisting of more frequent monitoring of serum antibodies by personalized schedule to adjust the frequency of subsequent doses of booster vaccination. Full article

This study purposed to validate the accuracy of an artificial neural network (ANN) model for predicting the mortality after hip fracture surgery during the study period, and to compare performance indices between the ANN model and a Cox regression model. A total of 10,534 hip fracture surgery patients during 1996–2010 were recruited in the study. Three datasets were used: a training dataset (n = 7374) was used for model development, a testing dataset (n = 1580) was used for internal validation, and a validation dataset (1580) was used for external validation. Global sensitivity analysis also was performed to evaluate the relative importances of input predictors in the ANN model. Mortality after hip fracture surgery was significantly associated with referral system, age, gender, urbanization of residence area, socioeconomic status, Charlson comorbidity index (CCI) score, intracapsular fracture, hospital volume, and surgeon volume (p < 0.05). For predicting mortality after hip fracture surgery, the ANN model had higher prediction accuracy and overall performance indices compared to the Cox model. Global sensitivity analysis of the ANN model showed that the referral to lower-level medical institutions was the most important variable affecting mortality, followed by surgeon volume, hospital volume, and CCI score. Compared with the Cox regression model, the ANN model was more accurate in predicting postoperative mortality after a hip fracture. The forecasting predictors associated with postoperative mortality identified in this study can also bae used to educate candidates for hip fracture surgery with respect to the course of recovery and health outcomes. Full article

Background and objectives. Venous thromboembolic events (VTEs) are among the most important complications of nephrotic syndrome (NS). We conducted a study that aimed to determine the prevalence of inherited risk factors for VTE in NS and to identify which factors are independent predictors of VTE. Materials and Methods. Thirty-six consecutive patients with primary NS that underwent percutaneous kidney biopsy between January 2017 and December 2017 were enrolled in this retrospective, observational study. VTEs were the primary outcome. Baseline demographic and biochemical data were collected from medical records, and genetic testing was done for polymorphisms of Factor V, PAI, MTHFR, and prothrombin genes. Results. The incidence of VTE was 28%, and the median time to event was 3 months (IQR: 2–9). The prevalence of inherited risk factors was 14% for Factor V Leiden mutation, 5.6% for prothrombin G20210A, 44.5% for PAI, and 27.8% for each of the two polymorphisms of the MTHFR gene. On multivariate analysis, the presence of at least two mutations was independently associated with the risk of VTE (HR, 8.92; 95% confidence interval, CI: 1.001 to 79.58, p = 0,05). Conclusions. These findings suggest that genetic testing for inherited thrombophilia in NS could play an important role in detecting high-risk patients that warrant prophylactic anticoagulation. Full article

Background and Objectives: The aim of this study was to assess and compare the drag and energy cost of three cyclists assessed by computational fluid dynamics (CFD) and analytical procedures. Materials and methods: A transradial (Tr) and transtibial (Tt) were compared to a full-body cyclist at different speeds. An elite male cyclist with 65 kg of mass and 1.72 m of height volunteered for this research with his competition cloths, helmet and bicycle with 5 kg of mass. A 3D model of the bicycle and cyclist in the upright position was obtained for numerical simulations. Upon that, two more models were created, simulating elbow and knee-disarticulated athletes. Numerical simulations by computational fluid dynamics and analytical procedures were computed to assess drag and energy cost, respectively. Results: One-Way ANOVA presented no significant differences between cyclists for drag (F = 0.041; p = 0.960; η² = 0.002) and energy cost (F = 0.42; p = 0.908; η² = 0.002). Linear regression presented a very high adjustment for absolute drag values between able-bodied and Tr (R² = 1.000; Ra² = 1.000; SEE = 0.200) and Tt (R² = 1.00; Ra² = 1.000; SEE = 0.160). The linear regression for energy cost presented a very high adjustment for absolute values between able-bodied and Tr (R² = 1.000; Ra² = 1.000; SEE = 0.570) and Tt (R² = 1.00; Ra² = 1.00; SEE = 0.778). Conclusions: This study suggests that drag and energy cost was lower in the able-bodied, followed by the Tr and Tt cyclists. Full article

Sepsis is a potentially life-threatening condition caused by a systemic dysregulated host response to infection. The brain is particularly susceptible to the effects of sepsis with clinical manifestations ranging from mild confusion to a deep comatose state. Sepsis-associated delirium (SAD) is a cerebral manifestation commonly occurring in patients with sepsis and is thought to occur due to a combination of neuroinflammation and disturbances in cerebral perfusion, the blood brain barrier (BBB) and neurotransmission. The neurological impairment associated with SAD can persist for months or even longer, after the initial septic episode has subsided which may impair the rehabilitation potential of sepsis survivors. Early identification and treatment of the underlying sepsis is key in the management of SAD as once present it can be difficult to control. Through the regular use of validated screening tools for delirium, cases of SAD can be identified early; this allows potentially aggravating factors to be addressed promptly. The usefulness of biomarkers, neuroimaging and electroencephalopathy (EEG) in the diagnosis of SAD remains controversial. The Society of Critical Care Medicine (SCCM) guidelines advise against the use of medications to treat delirium unless distressing symptoms are present or it is hindering the patient’s ability to wean from organ support. Full article

Background and objectives: Alterations in mitochondrial DNA (mtDNA) have been observed and studied in various diseases. However, the clinical value of the mtDNA copy number (mtDNA-CN) alterations in osteonecrosis of the femoral head (ONFH) is poorly understood. In the present study, we investigated whether alterations in mtDNA-CNs are associated with clinicopathological parameters in ONFH. Materials and methods: MtDNA-CNs in the synovial tissue of 34 patients with ONFH and 123 control tissues (femoral neck fracture) were measured using quantitative real-time PCR. The present study then analyzed the correlation between the mtDNA-CN and the clinicopathological characteristics of ONFH and fracture patients. Results: The average mtDNA-CN (mean ± standard deviation) was 23.82 ± 22.37 and 25.04 ± 24.27 in ONFH and control tissues, respectively, and was not significantly different between the groups (p = 0.792). The mtDNA-CN was positively associated with age (27.7% vs. 45.9%, p = 0.018) and negatively associated with the erythrocyte sedimentation rate (ESR) (11.8% vs. 39.7%, p = 0.024) in all of the samples. The study also found further associations with age (22.2% vs. 68.8%, p = 0.014), gender (30.0% vs. 64.3%, p = 0.048), and ESR (0% vs. 57.7%, p = 0.043) in ONFH. Conclusions: in this study, we demonstrated that mtDNA-CN might be a significant marker for predicting clinical characteristics in ONFH. Full article

Background and Objectives: Despite the growing number of new research publications, normative references for children’s optical coherence tomography (OCT) parameters are still not completed. We chose to explore this topic because of the lack of normative parameters that is due to an improvement in different technologies and instruments. Our aim was to determine referential rates of retinal nerve fiber layer (RNFL) thickness and flow deficits (FD%) in the macular choriocapillaris (CC) in normal eyes of ophthalmologically healthy children. Materials and Methods: Ophthalmologically healthy 8- to 14-year-old individuals participated (n = 75) in this study. OCT images were taken using an swept-source-OCT (SS-OCT) instrument (DRI-OCT Triton, Topcon, Tokyo, Japan). The early treatment diabetic retinopathy study (EDTRS) grid (6 × 6 mm) divided the RNFL into the thickness maps. The FD% values of the CC were calculated on the 3 × 3-mm scans in a 1-mm circle (C₁), 1.5-mm rim (R_1.5), and the entire 2.5-mm circle (C_2.5), and on the 6 x 6-mm scans in a 1-mm circle (C₁), 1.5-mm rim (R_1.5), the entire 2.5-mm circle (C_2.5), 2.5-mm rim (R_2.5), and 5-mm circle (C₅). Results: Both scan quantifications of FD% in the C₁, C_2.5, and R_1.5 sectors were similar, but the 6 × 6-mm scan measurements were statistically significantly smaller than the 3 × 3-mm ones. Significant moderate correlations were found between axial length (AxL) and FD% in the 6 × 6-mm scans, namely C₁ (r = −0.347, p = 0.002), C_2.5 (r = −0.337, p = 0.003), R_1.5 (r = −0.328, p = 0.004), R_2.5 (r = −0.306, p = 0.008), and C₅ (r = −0.314, p = 0.006). Conclusions: The thinnest RNFL layers were on the temporal and nasal sides. FD% values in the C₁, C_2.5, and R_1.5 sectors were similar between the 3 × 3-mm and 6 × 6-mm scans. The negative moderate correlations between AxL and FD% were found in all C₁, C_2.5, C_5, R_1.5, and R_2.5 sectors of the 6 × 6-mm scans. Further prospective studies are needed to determine more accurate normative references for children’s OCT parameters. Full article

Cannabis has been used for centuries for therapeutic purposes. In the last century, the plant was demonized due to its high abuse liability and supposedly insufficient health benefits. However, recent decriminalization policies and new scientific evidence have increased the interest in cannabis therapeutic potential of cannabis and paved the way for the release of marketing authorizations for cannabis-based products. Although several synthetic and standardized products are currently available on the market, patients’ preferences lean towards herbal preparations, because they are easy to handle and self-administer. A literature search was conducted on multidisciplinary research databases and international agencies or institutional websites. Despite the growing popularity of medical cannabis, little data is available on the chemical composition and preparation methods of medical cannabis extracts. The authors hereby report the most common cannabis preparations, presenting their medical indications, routes of administration and recommended dosages. A practical and helpful guide for prescribing doctors is provided, including suggested posology, titration strategies and cannabinoid amounts in herbal preparations obtained from different sources of medical cannabis. Full article

Background and Objectives: The optimal range of serum potassium at hospital discharge is unclear. The aim of this study was to assess the relationship between discharge serum potassium levels and one-year mortality in hospitalized patients. Materials and Methods: All adult hospital survivors between 2011 and 2013 at a tertiary referral hospital, who had available admission and discharge serum potassium data, were enrolled. End-stage kidney disease patients were excluded. Discharge serum potassium was defined as the last serum potassium level measured within 48 h prior to hospital discharge and categorized into ≤2.9, 3.0–3.4, 3.5–3.9, 4.0–4.4, 4.5–4.9, 5.0–5.4 and ≥5.5 mEq/L. A Cox proportional hazards analysis was performed to assess the independent association between discharge serum potassium and one-year mortality after hospital discharge, using the discharge potassium range of 4.0–4.4 mEq/L as the reference group. Results: Of 57,874 eligible patients, with a mean discharge serum potassium of 4.1 ± 0.4 mEq/L, the estimated one-year mortality rate after discharge was 13.2%. A U-shaped association was observed between discharge serum potassium and one-year mortality, with the nadir mortality in the discharge serum potassium range of 4.0–4.4 mEq/L. After adjusting for clinical characteristics, including admission serum potassium, both discharge serum potassium ≤3.9 mEq/L and ≥4.5 mEq/L were significantly associated with increased one-year mortality, compared with the discharge serum potassium of 4.0–4.4 mEq/L. Stratified analysis based on admission serum potassium showed similar results, except that there was no increased risk of one-year mortality when discharge serum potassium was ≤3.9 mEq/L in patients with an admission serum potassium of ≥5.0 mEq/L. Conclusion: The association between discharge serum potassium and one-year mortality after hospital discharge had a U-shaped distribution and was independent of admission serum potassium. Favorable survival outcomes occurred when discharge serum potassium was strictly within the range of 4.0–4.4 mEq/L. Full article

Background and Objectives: The evolution of allergic rhinitis to asthma is a part of “atopic march”. The aim of this study was to analyze possible predictive markers for asthma occurrence in patients with allergic rhinitis to house dust mites (HDM). Materials and Methods: Fifty-eight patients with persistent allergic rhinitis (PAR) were included. The clinical, biological evaluation and fractionated exhaled nitric oxide (FeNO) measurement were performed at enrolment. The patients were clinically evaluated after one year to determine asthma occurrence. Results: The severity of rhinitis symptoms, levels of total immunoglobulin E (IgE), ICAM-1, VCAM-1, E-selectin and IL-6, but not IL-8 and TNF-α were higher in patients with allergic rhinitis who developed asthma compared to non-asthmatics, but the differences were not significant to considered them as predictive factors for asthma occurrence. The risk of asthma was independently influenced by patients aged over 30 years ((OR-3.74; CI95% 0.86–16.31; p = 0.07), a duration of allergic rhinitis over 12 months ((OR-4.20; CI95% 0.88–20; p = 0.07) and a basal FeNO over 28 parts per billion (pbb) ((OR-18.68; CI95% 3.79–92.05; p < 0.001). Conclusion: Clinical and biological parameters may predict asthma occurrence in patients with persistent allergic rhinitis to HDM. Adult patients with a longer duration of rhinitis symptoms and a high level of FeNO have a greater risk to develop asthma. Full article

Background and Objectives: Khat chewing is considered as a daily habit that is practiced by more than five million people globally. The effect of khat chewing on the surface roughness and the color stability of natural teeth and the material used in the fabrication of dental prosthesis remains unknown. This study was conducted to explore and compare the effect of khat homogenate (KH) on the surface roughness (Ra) and the average color changes (ΔE*) amongst natural teeth and selected shades from different porcelain types, namely, feldspathic metal ceramic (MC) VM13, computer-aided design/computer assisted manufacture (CAD/CAM) feldspathic (Vitablocs Mark II), and multilayer zirconia (Ceramill Zolid PS) porcelains. Materials and Methods: Seventy samples were prepared from natural teeth, feldspathic MC, CAD/CAM Vitablocs Mark II, and zirconia porcelain. The Ra values were measured using a profilometer and expressed in micrometers, whereas the ΔE* values were measured using VITA Easyshade^® V spectrophotometer for all samples before and after frequent immersion and thermocycling in KH for 30 days. The surface topography was used to assess the materials surfaces (glazed or polished) after KH immersion by using a white light interferometry machine. Results: Results revealed that the Ra and the ΔE* values of the different types of tested porcelain were influenced by KH. The order of surface roughness values was glazed or polished MC > polished Zircon > polished Vitablocs Mark II > natural teeth. The lowest ΔE* values were recorded for glazed Vitablocs Mark II and MC, and the values could be arranged as polished zircon > natural teeth > glazed zircon > polished MC > polished Vitablocs Mark II. P values were significantly varied (<0.001) among all the tested groups, except the zircon group (>0.05) for both Ra and ΔE*. Conclusions: KH significantly affected both surface parameter and color of glazed or polished porcelain materials and natural teeth. Full article

In a special issue that focuses on complex presentations related to Autism, we ask the question in this editorial whether an Autism Spectrum Condition without complexity is a disorder, or whether it represents human diversity? Much research into Autism Spectrum Conditions (ASCs) over the years has focused on comparisons between neuro-typical people and people with Autism Spectrum Conditions. These comparisons have tended to draw attention to ‘deficits’ in cognitive abilities and descriptions of behaviours that are characterised as unwanted. Not surprisingly, this is reflected in the classification systems from the World Health Organisation and the American Psychiatric Association. Public opinion about ASC may be influenced by presentations in the media of those with ASC who also have intellectual disability. Given that diagnostic systems are intended to help us better understand conditions in order to seek improved outcomes, we propose a more constructive approach to descriptions that uses more positive language, and balances descriptions of deficits with research finding of strengths and differences. We propose that this will be more helpful to individuals on the Autism Spectrum, both in terms of individual self-view, but also in terms of how society views Autism Spectrum Conditions more positively. Commentary has also been made on guidance that has been adjusted for people with ASC in relation to the current COVID-19 pandemic. Full article

Biologic drugs are widely used in pediatric medicine. Monoclonal antibodies (mAbs) in particular are a therapeutic option for rheumatic, autoinflammatory and oncologic diseases. Adverse drug reactions and hypersensitivity reactions (HSR) to mAbs may occur in children. Clinical presentation of HSRs to mAbs can be classified according to phenotypes in infusion-related reactions, cytokine release syndrome, both alpha type reactions and type I (IgE/non-IgE), type III, and type IV reactions, all beta-type reactions. The aim of this review is to focus on HSRs associated with the most frequent mAbs in childhood, with particular attention to beta-type reactions. When a reaction to mAbs is suspected a diagnostic work-up including in-vivo and in-vitro testing should be performed. A drug provocation test is recommended only when no alternative drugs are available. In selected patients with immediate IgE-mediated drug allergy a desensitization protocol is indicated. Despite the heavy use of mAbs in childhood, studies evaluating the reliability of diagnostic test are lacking. Although desensitization may be effective in reducing the risk of reactions in children, standardized pediatric protocols are still not available. Full article