Hierarchical Macro-Mesoporous Silica Monolithic Tablets as a Novel Dose-Structure-Dependent Delivery System for the Release of Confined Dexketoprofen.

This study reports the application of hierarchical porous monoliths as carriers for controlled and dose-adjustable release of model pharmaceutical (dexketoprofen, DEX). The synthesis and detailed characterization of the hierarchical porous scaffolds are provided before and after the adsorption of three doses of DEX─a widely used nonsteroidal anti-inflammatory drug. The drug incorporated in the mesopores of silica was stabilized in an amorphous state, while the presence of macropores provided sufficient space for drug crystallization as we demonstrated via a combination of powder X-ray diffraction, differential scanning calorimetry, and imaging techniques (scanning electron microscopy and EDX analysis). Drug release from silica matrices was tested, and a mechanistic model of this release based on the Fick diffusion equation was proposed. The hierarchical structure of the carrier, due to the presence of micrometric macropores and nanometric mesopores, turned out to be critical for the control of the drug phase and drug release from the monoliths. It was found that at low drug content, the presence of an amorphous component in the pores promoted the rapid release of the drug, while at higher drug contents, the presence of macropores favored the crystallization of DEX, which naturally slowed down its release. Both the hierarchical porous structure and the control of the drug phase (amorphous and/or crystalline) were proven important for adjustable (fast or prolonged) release kinetics, desirable for effective pharmacotherapy and patient compliance. Therefore, the developed materials may serve as a versatile formulation platform for the smart manipulation of drug release kinetics.

Comparative Evaluation of the Essential Oil of the New Ukrainian Lavandula angustifolia and Lavandula x intermedia Cultivars Grown on the Same Plots.

New cultivars of lavender adapted to arid steppe conditions were developed by the Institute of Rice of Ukrainian National Academy of Agrarian Sciences (NAAS). This work is a part of the characterization process of the new cultivars. The chemical composition of the essential oil of the seven new Lavandula angustifolia and eight new Lavandula x intermedia cultivars was investigated and compared. In total, 71 different compounds were identified. Linalool and linalool acetate were the main components in both species in ranges of 26.14-57.07% and 9.08-24.45%, respectively. They were followed by terpinen-4-ol (2.16-22.44%), lavandulyl acetate (2.12-10.23%), and lavandulol (1.30-3.14) in the case of L. angustifolia and camphor (10.11-12.55%), borneol (5.49-8.71%), and eucalyptol (0.47-7.41%) in the case of L. x intermedia. The oils had a valuable terpene profile-a high linalool content and the substantial presence of lavandulol and its ester. Nevertheless, they did not comply with the industry standards, mostly due to high levels of terpinene-4-ol. Evidently, a high content of terpinen-4-ol is a characteristic feature of L. angustifolia oils bred in Ukraine. Additionally, the LA3 cultivar yielded an oil with some of the highest linalool contents reported in the literature. Statistical analysis and literature data allowed for the comparative analysis of the gathered data. MANOVA, PCA, and HCA marked caryophyllene oxide as another potential differentiating compound between studied species.

The role of anthranilic acid in the increase of depressive symptoms and major depressive disorder during treatment for hepatitis C with pegylated interferon-α2a and oral ribavirin.

Background: Tryptophan metabolism via the kynurenine pathway is considered the link between the immune and endocrine systems. Dysregulation of serotonergic transmission can stem from the direct influence of interferon-α on the activity of serotonergic receptors 5-HT1A and 5-HT2A, and from its indirect effect on tryptophan metabolism. Induction of the kynurenine pathway increases the concentration of neurotoxic kynurenine metabolites, and the activity of kynurenine derivatives is linked to the onset of depression. The aim of our study was to evaluate the relationships between depressive symptoms and kynurenine, tryptophan, anthranilic acid and kynurenic acid concentrations, indolamine 2,3-dioxygenase (IDO) activity and tryptophan availability to the brain. Methods: The study followed a prospective longitudinal cohort design. We evaluated 101 patients with chronic hepatitis C who were treated with pegylated interferon-α2a, and 40 controls who were awaiting treatment. We evaluated the relationships between total score on the Montgomery-Åsberg Depression Rating Scale and kynurenine, tryptophan, anthranilic acid and kynurenic acid concentrations, IDO activity and tryptophan availability to the brain. A logistic regression model was adapted for the diagnosis of major depressive disorder at each time point, taking into account changes in parameters of the kynurenine pathway between a given time point and the baseline measurement. Results: Of the treated patients, 44% fulfilled the criteria for major depressive disorder at least once during the 24 weeks of treatment. Anthranilic acid concentrations were significantly increased compared to baseline for all time points except week 2. Tryptophan availability showed a significant decrease (ß = -0.09, p = 0.01) only in week 12 of treatment. Over time, kynurenine, tryptophan and anthranilic acid concentrations, as well as IDO activity and tryptophan availability to the brain, were significantly associated with total score on the Montgomery-Åsberg Depression Rating Scale. A logistic regression model revealed that participants with decreased tryptophan availability to the brain at 12 weeks of treatment and participants with increased anthranilic acid concentrations at week 24 of treatment were at increased risk for diagnosis of major depressive disorder (odds ratios 2.92 and 3.59, respectively). Limitations: This study had an open-label design in a population receiving naturalistic treatment. Conclusion: The present study provides the first direct evidence of the role of anthranilic acid in the pathogenesis of inflammation-induced major depressive disorder during treatment for hepatitis C with pegylated interferon-α2a.

Relationships between Circulating Matrix Metalloproteinases, Tissue Inhibitor TIMP-2, and Renal Function in Patients with Myocarditis.

INTRODUCTION: Under physiological conditions, the myocardial extracellular matrix (ECM) is maintained by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). However, changes in the balance between MMPs and TIMPs can lead to pathological remodeling of the ECM, which contributes to cardiovascular and kidney diseases. The aim of our study was to assess levels of MMPs and TIMP-2 in patients with myocarditis and their relationship to renal function. MATERIALS AND METHODS: Forty five patients with myocarditis who underwent CMR were included, comprising 11 with concurrent chronic kidney disease (CKD). Blood samples were obtained to assess serum levels of MMP-2, MMP-3, MMP-9, and TIMP-2. RESULTS: Serum MMP-2, MMP-3, and TIMP-2 levels negatively correlated with the ejection fraction in patients with myocarditis, while MMP-3 levels correlated with longitudinal deformation (p < 0.05). Serum MMP-2, MMP-3, and TIMP-2 levels also negatively correlated with renal function, as assessed by the estimated glomerular filtration rate (eGFR) (p < 0.05). Patients with myocarditis and concurrent CKD had higher levels of MMP-2 and TIMP-2 than those without kidney damage. CONCLUSIONS: (1) We demonstrated that MMP-2, MMP-3, and TIMP-2 concentrations were related to left-ventricular ejection fraction, and MMP-3 levels correlated with longitudinal deformation, indicating MMPs play an important role in the post-inflammatory remodeling of the myocardium. (2) A negative correlation between the eGFR and MMP-2, MMP-3, and TIMP-2 and a positive correlation between creatinine and MMP-3 levels indicate the role of MMPs and TIMP-2 in renal dysfunction.

Factors affecting rehabilitation of infants with Central Coordination Disorders during a three-month-long observation.

BACKGROUND: Central coordination disorders (CCD) encompass various abnormalities observed in infants but early therapy may have an impact on their condition. The aim was to seek factors that may affect the early results of therapy of infants with CCD. METHODS: We analyzed the outcomes of a three-month period of rehabilitation of infants living with CCD. Children were treated at Non-public Specialist Healthcare Institution Medi-Reh in Kalisz in the period from 1 Jan 2014 to 31 Nov 2019. In our retrospective study results of three-month therapy of infants, aged 1 to 6 months, with CCD were analysed regards to the effectiveness and the potential impact of different factors. Therapy and assessment of children were conducted with the use of the Vojta method, which was performed during the first visit (WW) and the follow-up visit (after 3 months- 1WK). The analysis of the influence of various factors on the effect of therapy included: mother's age at the time of delivery, duration of breastfeeding, child APGAR, gestational age in which the child was born, sex of the child, birth weight, age of the child at WW, type of delivery, craniosacral therapy as an additive treatment. RESULTS: Based on the examination results from 66 medical records it was demonstrated that after active period of the therapy, improvement was observed in 54 (81.81%) (p=0.48) children (condition during WW versus 1WK among the group). The sole factor impacting improvement after 3 months was the age of the child at WW, when the child started therapy. This factor significantly (p=0.002) increased the chance of achieving improvement - by 3.2 times (OR= 3,2; CI= 95). No statistically significant differences were shown for the other studied factors. CONCLUSIONS: Prompt implementation of rehabilitation in children with CCD provides a better chance of improving their motor function. The rehabilitation should be started as soon as possible after the diagnosis is constituted.

Public Perception of the Risks Associated with Infectious Diseases in Poland: Ebola and Influenza and Their Impact on the Attitude to Vaccination.

While the Ebola outbreak in 2014 was strongly highlighted in mainstream media and perceived as a threat to public health in Poland, influenza was regarded as a triviality and the vaccination coverage was low. In the present study, by analyzing feedback from an on-line questionnaire (from November 2014 to January 2015) we assessed the knowledge concerning Ebola and influenza together with attitudes to immunization of 544 respondents (45% medical staff). The findings were that 92.6% of respondents declared readiness to vaccination before traveling to endemic regions if a vaccine against Ebola would have existed, but adverse reactions, high costs, and low effectiveness would adversely affect that decision. While 84.2% of respondents declared awareness of influenza attributing significantly to the cause of death, only 65.4% considered influenza as an actual danger for people in Poland and 46.7% thought that Poland was not an endemic region for influenza. Nearly 23% declared that they were already vaccinated against influenza. The majority of respondents (67.5%) were not going to be vaccinated. We conclude that awareness of risk related to infectious diseases is an important determinant when deciding whether to vaccinate. However, negative information about the vaccine has some bearing on the decision to get vaccinated.

FORMULATION AND EVALUATION OF MICROSPHERES CONTAINING LOSARTAN POTASSIUM BY SPRAY-DRYING TECHNIQUE.

Despite numerous applications of microspheres, few works devoted to the preparation of microspheres containing cardiac medications have been published. This study presents the potential of receiving microspheres containing losartan potassium, based on a matrix containing Eudragit L30D55. The study focuses on the possibilities of controlled release of losartan potassium from microspheres in order to reduce the dosage frequency, and also provides information on the effect of the addition of excipients to the quality of the microspheres. Microspheres are monolithic, porous or smooth microparticles ranging from 1 to 500 microns in size. For the preparation of microspheres containing losartan potassium, the spray-drying method was used. The performed study confirmed that the spray-drying technology used to obtain microspheres meets the criteria of size and morphology of the microparticles. The assessment of the kinetics of losartan potassium release from the examined microspheres demonstrated that the release profile followed the first- and/or zero-order kinetics. The use of spray-drying techniques as well as Eudragit L30D55 polymer matrix to obtain the microspheres containing losartan potassium makes it possible to obtain a product with the required particle morphology and particle size ensuring the release of the active substance up to 12 h.

Stability evaluation of thermosensitive drug carrier systems based on Pluronic F-127 polymer.

The aim of this study was to evaluate the stability of thermosensitive systems based on Pluronic F-127 polymer, in aspects of their possible application in novel drug technology. A formulation was prepared without any active ingredient, consisting of 16% (w/w) of polymer dissolved in aqueous medium. Such preparation was autoclaved and then subjected to 3-month conditioning at elevated (40 degrees) and reduced (5 degrees C) temperature. Rheological parameters: viscosity, consistency and sol-gel transition characteristics were studied in 1-month interval. The significance of measured changes was evaluated by proper statistical analyses. Significant changes exceeding the established criteria (+/- 10% of every initial value) were observed during the study. Furthermore, total involution of sol-gel transition phenomenon was observed in samples stored at 40 degrees C. Results indicate the lack of stability in tested formulation at both of storage conditions. However, some regularity indicates that the stability at reduced temperature could be confirmed, if only the concentration of polymer and the measurements schedule were slightly modified.

Influence of spray drying manufacturing parameters on quality of losartan potassium microspheres.

A general aim of the research was to develop a technology of manufacturing microspheres with losartan potassium as an active substance, and Eudragit L30D55 as a matrix with the use of spray drying technique. During the first step of the study, optimal values of parameters in spray drying process were established (i.e., operating temperature, peristaltic pump performance, aspiration value). Those values have a crucial effect on morphological parameters, and the size and homogeneity of received particles. In the obtained microspheres, the activity of excipients, which modify morphological properties of microspheres, were tested. Additionally, we studied the impact of the type and amount of plasticizer, as well as the amount of an adopted polymer in proportion to dry matter of losartan potassium, on quality of final product. Triethyl citrate and citric acid, plasticizers tested in reported studies, were also verified. A detailed study of the influence of both plasticizers on the qualities of microspheres containing losartan potassium on Eudragit L30D55 matrix indicated a positive influence of triethyl citrate and a negative influence of citric acid on morphological properties, shape and size of particles. The application of optimal parameters of spray drying and triethyl citrate as a plasticizer in the amount of 10 to 15% allows to obtain microspheres from 1.27 to 7.24 µm.

Level and limitations of physical activity in patients with excess body weight or diabetes.

Physical activity (PA) is recommended to prevent or treat many diseases, but various factors may limit it. We analyse the level of PA and the barriers to undertaking it. Patients aged 18-64 with diabetes or at least overweight completed the following questionnaires: International Physical Activity Questionnaire (IPAQ) and Accompanying Survey (AS). For statistical analysis, non-parametric Mann-Whitney U, χ2-Pearson, correspondence analysis and meta-analysis (OR with ±95% CI) were used, and α=0.05 was assumed. Of 191 sets of questionnaires were analysed (67% from women). The median (MD) age for the group was 50.5 years, MD for metabolic equivalents (METs): 2079 (MET-min/week); 16.23% of subjects scored insufficient, 46.07% sufficient and 37.7% high PA according to the IPAQ scale. A relationship between the IPAQ and PA level results from the AS was confirmed (χ2; p=0.00047). The most common reasons indicated for not taking up PA were lack of time due to professional work (49%) and additional duties (32%) as well as fatigue from daily duties (44%). Participants <45 years were more likely to indicate additional duties (p=0.013), participants >45 years illnesses (p=0.04) and people with BMI (body mass index) ≥30 kg/m2, 'fatigue from daily duties' (p=0.019) as an obstacle to undertaking PA. 'Lack of suitable conditions to undertake PA' was indicated more often by patients with primary education (p<0.01), diabetes (p=0.037), after myocardial infarction (p=0.039) and those under psychiatric treatment (p=0.039). Women more often declared a lack of motivation (p=0.018). Residents of big cities and those with BMI ≥30 were more likely to assess their PA as 'insufficient' (p=0.0260 and p=0.0081, respectively). The overwhelming number of respondents who were in the age of professional activity had a sufficient level of PA. The most common barriers to undertaking PA were lack of time and fatigue, related to both work and non-work activities, but specific barriers were also found for women and patients with various diseases.

Spot urine sodium as a marker of urine dilution and decongestive abilities in acute heart failure.

The decongestion ability in response to diuretic treatment plays a crucial role in the treatment of acute heart failure. This effectiveness is evaluated through the assessment of sodium concentration and urine volume, which are also treatment goals themselves. However, the bidirectional interconnection between these factors remains not fully understood. The objective of this study is to provide mechanistic insights into the correlation between spot urine sodium concentrations (UNa+) and urine dilution. This aims to better understand of the decongestive abilities in acute heart failure (AHF). The study was single-center, prospective, conducted on a group of 50 AHF patients. Each participant received a standardized furosemide dose of 1 mg per kg of body weight. Hourly diuresis was measured in the first 6 h of the study, and urine composition was assessed at predefined timepoints. The study group presented the exponential (rather than linear) pattern of relationship between UNa+ and 6-h urine volume, whereas relationship between eGFR and 6-h urine volume was linear (r = 0.61, p < 0.001). The relationship between UNa+ and all other analyzed indices of urine dilution, including the change from baseline in urine creatinine concentration, urine osmolarity, and urine osmolarity corrected for urine sodium, also exhibited an exponential relationship. Patients who were chronically exposed to furosemide demonstrated a significantly lower urine dilution (1.78 [1.18-3.54] vs 11.58 [3.9-17.88]; p < 0.001) in comparison to naïve individuals. In conclusion, it should be noted that in AHF higher UNa+ is associated with disproportionally higher urine dilution, and patients naïve to furosemide have significantly greater ability to dilute urine when compare to chronic furosemide users.

Pluronic F-127 Enhances the Antifungal Activity of Fluconazole against Resistant Candida Strains.

Candida strains as the most frequent causes of infections, along with their increased drug resistance, pose significant clinical and financial challenges to the healthcare system. Some polymeric excipients were reported to interfere with the multidrug resistance mechanism. Bearing in mind that there are a limited number of marketed products with fluconazole (FLU) for the topical route of administration, Pluronic F-127 (PLX)/FLU formulations were investigated in this work. The aims of this study were to investigate (i) whether PLX-based formulations can increase the susceptibility of resistant Candida strains to FLU, (ii) whether there is a correlation between block polymer concentration and the antifungal efficacy of the FLU-loaded PLX formulations, and (iii) what the potential mode of action of PLX assisting FLU is. The yeast growth inhibition upon incubation with PLX formulations loaded with FLU was statistically significant. The highest efficacy of the azole agent was observed in the presence of 5.0 and 10.0% w/v of PLX. The upregulation of the CDR1/CDR2 genes was detected in the investigated Candida strains, indicating that the efflux of the drug from the fungal cell was the main mechanism of the resistance.

Assessment of the Prescribing Pharmacist's Role in Supporting Access to Prescription-Only Medicines-Metadata Analysis in Poland.

In 2020, pharmacists in Poland received additional authority to prescribe drugs. In this study, we analyzed prescribing after the implementation of this new responsibility. We assessed how the new regulation works in practice and what it means for the healthcare system in the area of access to prescription-only medicines. Data analysis included information on the prescriptions written, the type of substance according to the ATC classification, and data on the prescribing pharmacists. The study used over 2.994 million e-prescriptions written by pharmacists in Poland, which were made available by the e-Health Center. The largest group of drugs prescribed were drugs used in the treatment of cardiovascular diseases, accounting for 25% of all prescribed medications during the time of the analysis. The next prescription groups were for drugs used in gastrointestinal diseases and metabolic disorders, and those acting on the central nervous system, the respiratory system, and the musculoskeletal system. Among pharmaceutical prescriptions, 73% were pharmaceutical prescriptions issued in pharmacies at full price to the patient. The results indicate that pharmacists are eager to use their permission to prescribe drugs in authority situations. Almost three million records showed improved patient access to medicines in the healthcare system (approximately 5% of repeat prescriptions for all patients during the study period). These data confirm the possibility of cooperation between physicians and pharmacists in strengthening the efficiency of the patient healthcare system. An important conclusion from this work is the need to create the possibility for the pharmacist to access the information resources of the implemented Internet Patient Account system, including therapeutic indications for the drugs used.

Risk Factors for Calcium-Phosphate Disorders after Thyroid Surgery.

INTRODUCTION: Iatrogenic hypoparathyroidism following thyroidectomy is one of the most common complications significantly reducing patients' quality of life. OBJECTIVES: This study aimed to analyze the risk factors for calcium-phosphate disorders following thyroidectomy. PATIENTS AND METHODS: The study group consisted of 211 patients who underwent thyroidectomy for different conditions in 2018-2020. Demographic, clinical and surgical risk factors were analyzed against hypoparathyroidism and hypocalcemia. RESULTS: Hypoparathyroidism occurred in 15.63% of patients, and hypocalcemia occurred in 45% of those operated on. There was statistical significance between hypoparathyroidism and the extent of thyroid surgery: thyroidectomy vs. lobectomy (p = 0.02, OR = 4.5) and surgeon experience (p = 0.016, OR = 6.9). Low preoperative PTH levels were associated with a higher incidence of hypoparathyroidism (p = 0.055, OR = 0.9). There was a statistically significant correlation between the occurrence of hypocalcemia and preoperative vitamin D deficiency (p = 0.04, OR = 3.5). Low calcium levels before surgery were associated with a higher incidence of hypocalcemia (p = 0.051, OR = 0.5). Meta-analyses of selected risk factors confirmed that the most significant factor in the incidence of hypocalcemia was a decrease in PTH levels (p < 0.001). CONCLUSIONS: The extent of thyroid surgery and the experience of the surgeon are the most significant risk factors for hypoparathyroidism. Hypocalcemia is much more common than hypoparathyroidism. Among the risk factors for hypocalcemia, in addition to the decrease in parathormone levels due to iatrogenic parathyroid damage, we should mention vitamin D deficiency in the preoperative period.

Analysis of Methylglyoxal Concentration in a Group of Patients with Newly Diagnosed Prediabetes.

BACKGROUND: The abnormal serum concentration of methylglyoxal (MGO) has been presented as an indicator of chronic complications in diabetes (DM). Because such complications are also found in pre-DM, we decided to assess the concentration of this compound in individuals with pre-DM, without cardio-vascular diseases. METHODS: Frozen samples from individuals newly diagnosed with pre-DM (N = 31) and healthy subjects (N = 11) were prepared and MGO concentration was determined using UHPLC-ESI-QqTOF-MS. RESULTS: Statistical significance was established when the groups were compared for body weight, BMI, fasting glucose level, fatty liver and use of statins but not for the other descriptive parameters. The positive linear correlation showed that the higher HbA1c, the higher MGO concentration (p = 0.01). The values of MGO were within the normal range in both groups (mean value for pre-DM: 135.44 nM (±SD = 32.67) and for the control group: 143.25 nM (±SD = 17.93); p = 0.46 (±95% CI)), with no statistical significance between the groups. CONCLUSIONS: We did not confirm the elevated MGO levels in the group of patients with pre-DM. The available data suggests a possible effect of statin intake on MGO levels. This thesis requires confirmation on a larger number of patients with an assessment of MGO levels before and after the introduction of statins.

Proving the Superiority of Intraoperative Recurrent Laryngeal Nerve Monitoring over Visualization Alone during Thyroidectomy.

Vocal fold paralysis after thyroid surgery is still a dangerous complication that significantly reduces patients' quality of life. Since the intraoperative neuromonitoring (IONM) technique has been introduced and standardized, the most frequently asked question is whether its use has significantly reduced the rate of RLN injury during thyroid surgery compared to visual identification alone (VA). The aim of this study was to attempt to prove the superiority of IONM over VA of the RLN during thyroid surgery in the prevention of vocal fold paralysis, taking into account risk factors for complications. The medical records of 711 patients (1265 recurrent laryngeal nerves at risk of injury) were analyzed retrospectively: in 257 patients/469 RLNs at risk, thyroid surgery was performed with IONM; in 454 patients/796 RLNs at risk, surgery was performed with VA. The statistical analysis showed that in the group of patients with IONM only one risk factor-the surgeon's experience-proved statistically significant (OR = 3.27; p = 0.0478) regarding the overall risk of vocal fold palsy. In the group of patients where only visualization was used, 5 of the 12 factors analyzed were statistically significant: retrosternal goiter (OR = 2.23; p = 0.041); total thyroid volume (OR = 2.30; p = 0.0284); clinical diagnosis (OR = 2.5; p = 0.0669); gender (OR = 3.08; p = 0.0054) and risk stratification (OR = 3.30; p = 0.0041). In addition, the cumulative risk, taking into account the simultaneous influence of all 12 factors, was slightly higher in the group of patients in whom only VA was used during the procedure: OR = 1.78. This value was also considerably more statistically significant (p < 0.0001) than that obtained in the group of patients in whom IONM was used: OR = 1.73; p = 0.004. Conclusions: Risk factors for complications in thyroid surgery are not significant for any increase in the rate of vocal fold paralysis as long as surgery is performed with IONM, in contrast to thyroid surgery performed only with VA, thus proving the superiority of IONM over VA for safety.

Validity and reliability of the Polish version of the Michigan Neuropathy Screening Instrument.

BACKGROUND: Diabetic sensorimotor polyneuropathy is an important risk factor for foot ulceration and amputation. Thus, patients with diabetes should be screened for this disorder according to local guidelines. An obstacle to the diagnosis of this disease may be the lack of unified diagnostic criteria due to the lack of properly validated scales used for assessment. AIM: To validate both sections (A and B) of the Michigan Neuropathy Screening Instrument (MNSI) in Polish (PL) patients with diabetes. METHODS: A cross-sectional study using a test (A1, B1) and re-test (A2, B2) formula was performed in 80 patients with diabetes. The gold standard used for neuropathy detection was a nerve conduction study (NCS) which was performed in all participants. Reliability of the MNSI-PL was assessed using the Cronbach's alpha, Kuder-Richardson formula 20 (KR-20), split-half reliability, the Gottman split-half tests, and correlation between first and second half was accessed. Stability was assessed using an intraclass correlation coefficient (ICC). For external validation, we used simple linear correlation, binomial regression, and agreement between two different tools using a Bland-Altman plot analysis. RESULTS: The scale was internally consistent (Cronbach's alpha for the full scale: 0.81 for A and 0.87 for B). MNSI-PL scores in test/retest showed high stability (ICC = 0.73 for A and ICC = 0.97 for B). The statistically important correlations between MNSI-PL and NCS were found for B1, B2, and A1 (P < 0.005). The cut-off points of ≥ 3 for section A (sensitivity of 90%-100%; specificity of 33%-40%) and ≥ 2 for section B (sensitivity of 81%-84%; specificity of 60%-70%) were obtained during neuropathy detection. CONCLUSION: The MNSI-PL is a reliable and valid instrument in screening for diabetic neuropathy.

Physical Activity Modifies the Severity of COVID-19 in Hospitalized Patients-Observational Study.

BACKGROUND AND AIM: Physical activity (PA) can modulate the immune response, but its impact on infectious disease severity is unknown. We assess if the PA level impacts the severity of COVID-19. METHODS: Prospective, cohort study for adults hospitalized due to COVID-19, who filled out the International Physical Activity Questionnaire (IPAQ). Disease severity was expressed as death, transfer to intensive care unit (ICU), oxygen therapy (OxTh), hospitalization length, complications, C-reactive protein, and procalcitonin level. RESULTS: Out of 326 individuals, 131 (57; 43.51% women) were analyzed: age: median-70; range: 20-95; BMI: mean-27.18 kg/m²; and SD: ±4.77. During hospitalization: 117 (83.31%) individuals recovered, nine (6.87%) were transferred to ICU, five (3.82%) died, and 83 (63.36%) needed OxTh. The median for the hospital stay was 11 (range: 3-49) for discharged patients, and mean hospitalization length was 14 (SD: ±5.8312) for deaths and 14.22 days (SD: ±6.92) for ICU-transferred patients. The median for MET-min/week was 660 (range: 0-19,200). Sufficient or high PA was found in recovered patients but insufficient PA was observed in dead or ICU-transferred patients (p = 0.03). The individuals with poor PA had a higher risk of death (HR = 2.63; ±95%CI 0.58-11.93; p = 0.037). OxTh was used more often in the less active individuals (p = 0.03). The principal component analysis confirmed a relationship between insufficient PA and an unfavorable course of the disease. CONCLUSION: A higher level of PA is associated with a milder course of COVID-19.

The blunted loop diuretic response in acute heart failure is driven by reduced tubular responsiveness rather than insufficient tubular delivery. The role of furosemide urine excretion on diuretic and natriuretic response in acute heart failure.

AIMS: Diuretic response in heart failure is blunted when compared to healthy individuals, but the pathophysiology underlying this phenomenon is unclear. We aimed to investigate whether the diuretic resistance mechanism is related to insufficient furosemide tubular delivery or low tubular responsiveness. METHODS AND RESULTS: We conducted a prospective, observational study of 50 patients with acute heart failure patients divided into two groups based on previous furosemide use (furosemide naïve: n = 28 [56%] and chronic furosemide users: n = 22 [44%]). Each patient received a protocol-derived, standardized furosemide dose based on body weight. We measured diuretic response and urine furosemide concentrations. The furosemide naïve group had significantly higher urine volumes and natriuresis when compared to chronic users at all timepoints (all p < 0.05). Urine furosemide delivery was similar in furosemide naïve versus chronic users after accounting for differences in estimated glomerular filtration rate (28.02 [21.03-35.89] vs. 29.70 [18.19-34.71] mg, p = 0.87). However, the tubular response to delivered diuretic was dramatically higher in naïve versus chronic users, that is the urine volume per 1 µg/ml of urine furosemide at 2 h was 148.6 ± 136.1 versus 50.6 ± 56.1 ml (p = 0.005). CONCLUSIONS: Patients naïve to furosemide have significantly better diuresis and natriuresis when compared to chronic furosemide users. The blunted diuretic response in patients with chronic loop diuretic exposure is driven by decreased tubular responsiveness rather than insufficient furosemide tubular delivery.

The clinical complexity of patients with acromegaly.

OBJECTIVES: The main aim of the study was to investigate the factors related to the biopsychosocial complexity in the group of patients with acromegaly with different disease activity. METHODS: A cross-sectional observational study was performed. First, a linguistic adaptation of the INTERMED - self-assessment questionnaire (IMSA) and after that the assessment of the biopsychosocial complexity among patients with acromegaly and the factors which relate to the complexity was made. The following tools were used to assess: biopsychosocial complexity: The INTERMED -self-assessment (IMSA); quality of life: The World Health Organization Quality of Life - BREF (WHOQoL) and Acromegaly Quality of Life questionnaire (AcroQol); mental state: The General Health Questionnaire - 28 (GHQ-28). RESULTS: The final analysis included 71 patients. According to the principal component analysis the mental state (GHQ-28) and the quality of life (AcroQol) are the most important factors related to the clinical complexity among patients with acromegaly. In the model created by a stepwise regression analysis for the total IMSA score higher growth hormone (GH) concentration, longer illness duration, and better general quality of life were included as the protective factors of the clinical complexity. By contrast, a high score in the severe depression subscale of GHQ-28 was a factor of higher clinical complexity. CONCLUSION: The mental state and quality of life are the most important determinants of the clinical complexity in the group of patients with acromegaly whereas the biochemical normalization is of lesser importance.