Physicochemical and biological evaluation of a cinnamamide derivative R,S‐(2E)‐1‐(3‐hydroxypiperidin‐1‐yl)‐3‐phenylprop‐2‐en‐1‐one (KM‐608) for nervous system disorders

A cinnamamide scaffold has been successfully incorporated in several compounds possessing desirable pharmacological activities in central and peripheral nervous system such as anticonvulsant, antidepressant, neuroprotective, analgesic, anti‐inflammatory, muscle relaxant, and sedative/hypnotic properties. R,S‐(2E)‐1‐(3‐hydroxypiperidin‐1‐yl)‐3‐phenylprop‐2‐en‐1‐one (KM‐608), a cinnamamide derivative, was synthesized, its chemical structure was confirmed by means of spectroscopy and crystallography, and additionally, thermal analysis showed that it exists in one crystalline form. The compound was evaluated in vivo in rodents as anticonvulsant, antiepileptogenic, analgesic, and neuroprotective agent. The beneficial properties of the compound were found in animal models of seizures evoked electrically (maximal electroshock test, 6‐Hz) and chemically (subcutaneous pentylenetetrazole seizure test) as well as in three animal models of epileptogenesis: corneal‐kindled mice, hippocampal‐kindled rats, and lamotrigine‐resistant amygdala‐kindled rats. Quantitative pharmacological parameters calculated for the tested compound were comparable to those of currently used antiepileptic drugs. In vivo pharmacological profile of KM‐608 corresponds with the activity of valproic acid.     

Levels of agreement between clinical examination and transabdominal ultrasound evaluation of fetal head position in the second stage of labor

Aim: To compare transvaginal digital examination performed by residents and attending physicians to transabdominal suprapubic ultrasound in the evaluation of fetal head position in the second stage of labor.

Methods: A prospective study was conducted at a tertiary center and included pregnant women at term, with normal singleton cephalic presentation fetuses. All patients had ruptured membranes and were evaluated during the second stage of labor. Fetal head position was assessed consecutively by two clinicians (one resident and one attending physician). Afterwards, transabdominal suprapubic ultrasound was performed by another observer. Examiners were blinded to each other’s findings. Cohen’s kappa test was used to assess the degree of agreement between the evaluation methods.

Results: One-hundred sixty-one women were included. Transvaginal examination was consistent with the ultrasound in 45.0% of cases (95% CI: 37–53%) when the examination was performed by residents (k?=?0.349) and in 67% (95% CI: 60–74%) if the attending physician carried out the evaluation (k?=?0.604). When considering only the anterior positions, the Cohen’s kappa test was 0.426 and 0.709, respectively.

Conclusion: Transabdominal suprapubic ultrasound improved the accuracy of the evaluation of fetal head position, namely when transvaginal digital examination was performed by residents. This may be important especially when instrumental deliveries are considered.     

Procalcitonin kinetics – prognostic and diagnostic significance in septic patients

Introduction

Severe sepsis and septic shock are advanced clinical conditions representing the patient''s response to infection and having a variable but high mortality rate. Early evaluation of sepsis stage and choice of adequate treatment are key factors for survival. Some study results suggest the necessity of daily procalcitonin (PCT) monitoring because of its prognostic and discriminative value.

Material and methods

An observational and prospective study was conducted to evaluate the prognostic and discriminative value of PCT kinetics in comparison to PCT absolute value measurements. In a group of 50 intensive care unit patients with diagnosis of severe sepsis or septic shock, serum PCT measurements were performed on admission, and on the 2^nd, 3^rd and 5^th day of therapy. The level of PCT was determined with a commercially available test according to the manufacturer''s protocol.

Results

The kinetics of PCT assessed by ΔPCT was statistically significant in the survivors vs. the non-survivors subgroup (ΔPCT_3/1, p = 0.022; ΔPCT_5/1, p = 0.021). ΔPCT has no statistical significance in the severe sepsis and septic shock subgroups for all analyzed days. Only the 5^th day PCT level was significantly higher in the non-survivors vs. survivors group (p = 0.008). The 1^st day PCT level in the severe sepsis vs. septic shock group has a discriminative impact (p = 0.009).

Conclusions

According to the results, single serum PCT measurement, regardless of absolute value, has a discriminative impact but no prognostic significance, during the first 2 days of therapy. The PCT kinetics is of prognostic value from the 3^rd day and is of earlier prognostic significance in comparison to changes in the patient''s clinical condition evaluated by SOFA score kinetics.     

Antichlamydial antibodies and citric acid in patients with chronic prostatitis

Introduction The aim of the study was to evaluate the correlation between the presence of anti-C. trachomatis (C.t.) antibodies in serum and expressed prostatic secretions (EPS) and the concentration of citric acid in patients with chronic prostatitis. Materials and Methods The study involved 34 men with chronic prostatitis. The leukocyte count, presence of anti-C.t. antibodies (IgA, IgG), and citric acid concentration were determined in the EPS. The serum was examined for IgM, IgA, and IgG anti-C.t. antibodies. Specific antibodies were determined using the EIA method. The concentration of citric acid was measured using the ultraviolet method. Results Inflammation of the prostate ( ≥ 10 PMN) was found in 61.8% of the patients. A reduction in citric acid concentration in the EPS was detected in 58.8% of the men. Specific serum antibodies were detected in 58.8% of the patients, including 23.5% with IgM, 32.4% with IgA, and 44.1% with IgG. In all patients, serum IgM and IgA antibody titers were low, while those of IgG antibodies were strongly positive in 46.7% of the patients. Anti-C.t. antibodies in the EPS were detected in 44.1% of the patients, including 32.4% with IgA and 35.3% with IgG. In contrast to serum, the titers of IgG antibodies in the EPS were low in all the patients, while those of IgA were strongly positive in 54.5% of cases. In patients with positive serological outcomes, 85% had reduced concentrations of citric acid. Conclusions The occurrence of anti-C.t. antibodies is usually accompanied by a decrease in the concentration of citric acid in the prostatic secretion.     

A predictive model of anxiety and depression symptoms after a lower limb amputation

Background

Patients with Diabetic Foot Ulcer (DFU) show high levels of depression and anxiety symptoms. The loss of a limb is undoubtedly a devastating experience and several studies have shown that anxiety and depression symptoms are a common reaction after a lower limb amputation (LLA). However, no study has focused on the immediate emotional reactions to LLA as a personal factor based on the ICF Model.

Effect of poplar-type propolis on oxidative stability and rheological properties of O/W emulsions

Propolis is known to possess antioxidant activity. However, there is no information on this activity in emulsions O/W. The protective effect of propolis on the oxidation and rheological properties of emulsions O/W containing wheat germ and almond oils was evaluated. Emulsions O/W were prepared with different concentration of propolis extract, almond oil and wheat germ oil. All emulsions physically stable without phase separation were stored at 37?°C for 9?weeks. Chemical composition of propolis was established by Gas chromatography coupled to mass spectrometry. Rheological characterization of different emulsions was performed evaluating consistency index and flow behavior index. The oxidation was monitored by measuring the lipid hydroperoxides and thiobarbituric acid-reactive substances (TBARS) methods. Flavonoids, phenolic acid esters, and aromatic acids were the main groups of compounds found in propolis. The results showed that popolis was good antioxidant in the concentration of 0.02 and 0.04% when lipid phase was constituted by almond oil. The rheological behavior is typical of a non-Newtonian fluid, being almond oil more adequate for having a higher stable O/W emulsion.     

How should hospital reimbursement be refined to support concentration of complex care services?

The English National Health Service is promoting concentration of the treatment of patients with relatively rare and complex conditions into a limited number of specialist centres. If these patients are more costly to treat, the prospective payment system based on Healthcare Resource Groups (HRGs) may need refinement because these centres will be financially disadvantaged. To assess the funding implications of this concentration policy, we estimate the cost differentials associated with caring for patients that receive complex care and examine the extent to which complex care services are concentrated across hospitals and HRGs. We estimate random effects models using patient‐level activity and cost data for all patients admitted to English hospitals during the 2013/14 financial year and construct measures of the concentration of complex services. Payments for complex care services need to be adjusted if they have large cost differentials and if provision is concentrated within a few hospitals. Payments can be adjusted either by refining HRGs or making top‐up payments to HRG prices. HRG refinement is preferred to top‐payments the greater the concentration of services among HRGs.     

Therapeutic drug monitoring of digoxin–20 years of experience

Background

Digoxin is the oldest drug used in the pharmacotherapy of heart failure (HF). However, digoxin remains an important therapeutic option for patients with persistent symptoms of HF occurring despite the implementation of standard pharmacotherapy. Digoxin concentration serum (SCD) should equal 1–2 ng/ml. The aim of our study was to measure of SCD among the hospitalized patients as well as to determine the selected factors influencing the concentration of the digoxin in the blood.

Mining Knowledge of Respiratory Rate Quantification and Abnormal Pattern Prediction

The described application of granular computing is motivated because cardiovascular disease (CVD) remains a major killer globally. There is increasing evidence that abnormal respiratory patterns might contribute to the development and progression of CVD. Consequently, a method that would support a physician in respiratory pattern evaluation should be developed. Group decision-making, tri-way reasoning, and rough set–based analysis were applied to granular computing. Signal attributes and anthropomorphic parameters were explored to develop prediction models to determine the percentage contribution of periodic-like, intermediate, and normal breathing patterns in the analyzed signals. The proposed methodology was validated employing k-nearest neighbor (k-NN) and UMAP (uniform manifold approximation and projection). The presented approach applied to respiratory pattern evaluation shows that median accuracies in a considerable number of cases exceeded 0.75. Overall, parameters related to signal analysis are indicated as more important than anthropomorphic features. It was also found that obesity characterized by a high WHR (waist-to-hip ratio) and male sex were predisposing factors for the occurrence of periodic-like or intermediate patterns of respiration. It may be among the essential findings derived from this study. Based on classification measures, it may be observed that a physician may use such a methodology as a respiratory pattern evaluation-aided method.