Developing systemic solutions for typhus fever eradication in resurgent Poland between 1918 and 1924

Research’s subject The research’s subject includes fundamental principles and procedures for taking preventive activities against infections. Although such a holistic solution is the domain of contemporary times, the legal solutions introduced during the current Covid pandemic were created on the basis of legislature and solutions first introduced over 100 years ago as a result of the typhus epidemic. The legislators of those times already noticed the necessity to take anti-epidemic, and preventive measures in order to neutralize the sources of infections, and cut down the spread route. The study presents solutions introduced during the typhus epidemic occurring on the Polish territories (Central Europe) in the years between 1918 and 1924. Archival epidemiological data along with taken steps and measures (including the establishment of special state institutions) are presented showing how the epidemic of those times provided the fundament for preventing epidemics on the Polish territory. Research’s aim The purpose of the research is to present, in a chronological manner, the formation of systemic solutions for combating the epidemic of typhus, which broke out in the resurgent Polish lands at the end of WWI. Material and method Presented data are based on documents and archival materials, which include registers of typhus patients from general hospitals between 1918 and1924, information from the Central Military Archives, information obtained from historical sources including medical journals of that period, as well as information from the national archives and the Central Statistical Office. These data were analyzed and presented. Results The manuscript presents data on incidence and mortality. It also consists of a step-by-step analysis of introduced preventive measures along with the problems that were caused by their enforcement, including social distrust and resistance. Conclusions Enacted institutions, including the Polish Institute of Hygiene, allowed for greater monitoring of public health. The typhus experience facilitated the development of hospital networks and provided medical care to society. What is more, because of an urgent need to educate medical staff, the training of doctors, nurses, and other medical professionals was launched in 1921 as the first in Europe, School of Hygiene. Additionally, due to the typhus epidemic, the fundaments for the State Sanitary Inspection (1954), which is functioning until this day, were laid down along with various sanitary acts

Epidemiology and the legal basis for corneal transplants in Poland

The article aims at presenting a legal basis for corneal transplantation — the most frequently conducted transplantation procedure in Poland. Applicable rules and regulations concerning transplantation can be found in the Cell, Tissue, and Organ Recovery, Storage, and Transplantation Act of July 1, 2005 and the Regulation of the Minister of Health of December 4, 2009 on detailed conditions of removal, preservation, and transplantation of cells, tissues, and organs. However, the scope and content of the above legislation does not directly refer to corneal transplantation, neither in concept nor description, which may lead to certain misinterpretations and ambiguity of information as to the adopted rules of corneal removal, transplantation and the existing formal solutions (documentation, or rules for obtaining consent). The article refers to a very important legal principle — omnia sunt interpretanda — which in practice obliges the description and proper interpretation of the legal rules pertaining in this content to such procedures. In terms of legalisation it is possible to find only norms concerning the possibility of obtaining and transplanting corneas, entities which can conduct such procedures (after obtaining the consent of the Ministry of Health), and information on the scope of the so-called presumed consent that is one of the basic legal mechanisms allowing tissue procurement from deceased donors. The summary is a synthetic and comprehensive presentation of current knowledge and the legal situation of corneal transplantation, which can prove useful in an appropriate interpretation of legal standards regarding such procedures.

Preclinical evaluation of 1,2,4-triazole-based compounds targeting voltage-gated sodium channels (VGSCs) as promising anticonvulsant drug candidates

Epilepsy is a chronic neurological disorder affecting nearly 65–70 million people worldwide. Despite the observed advances in the development of new antiepileptic drugs (AEDs), still about 30-40% of patients cannot achieve a satisfactory seizure control. In our current research, we aimed at using the combined results of radioligand binding experiments, PAMPA-BBB assay and animal experimentations in order to design a group of compounds that exhibit broad spectrum of anticonvulsant activity. The synthesized 4-alkyl-5-substituted-1,2,4-triazole-3-thione derivatives were primarily screened in the maximal electroshock-induced seizure (MES) test in mice. Next, the most promising compounds (17, 22) were investigated in 6 Hz (32 mA) psychomotor seizure model. Protective effect of compound 22 was almost similar to that of levetiracetam. Moreover, these compounds did not induce genotoxic and hemolytic changes in human cells as well as they were characterized by low cellular toxicity. Taking into account the structural requirements for good anticonvulsant activity of 4-alkyl-5-aryl-1,2,4-triazole-3-thiones, it is visible that small electron-withdrawing substituents attached to phenyl ring have beneficial effects both on affinity towards VGSCs and protective activity in the animal models of epilepsy

N-Benzyl-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) with hybrid structure as a candidate for a broad-spectrum antiepileptic drug

In our recent studies, we identified compound N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) as a broad-spectrum hybrid anticonvulsant which showed potent protection across the most important animal acute seizure models such as the maximal electroshock (MES) test, the subcutaneous pentylenetetrazole (s.c. PTZ) test, and the 6-Hz (32 mA) test in mice. Therefore, AS-1 may be recognized as a candidate for new anticonvulsant effective in different types of human epilepsy with a favorable safety margin profile determined in the rotarod test in mice. In the aim of further pharmacological evaluation of AS-1, in the current study, we examined its activity in the 6-Hz (44 mA) test, which is known as the model of drug-resistant epilepsy. Furthermore, we determined also the antiseizure activity in the kindling model of epilepsy induced by repeated injection of pentylenetetrazole (PTZ) in mice. As a result, AS-1 revealed relatively potent protection in the 6-Hz (44 mA) test, as well as delayed the progression of kindling induced by repeated injection of PTZ in mice at doses of 15 mg/kg, 30 mg/kg, and 60 mg/kg. Importantly, the isobolographic analysis showed that a combination of AS-1 and valproic acid (VPA) at the fixed ratio of 1:1 displayed a supra-additive (synergistic) interaction against PTZinduced seizures inmice. Thus, AS-1may be potentially used in an add-on therapy with VPA. Moreover, incubation of zebrafish larvae with AS-1 substantially decreased the number, cumulative but not the mean duration of epileptiform-like events in electroencephalographic assay. Finally, the in vitro ADME-Tox studies revealed that AS-1 is characterized by a very good permeability in the parallel artificial membrane permeability assay test, excellent metabolic stability on human liver microsomes (HLMs), no significant influence on CYP3A4/CYP2D6 activity, and moderate inhibition of CYP2C9 in a concentration of 10 $\mu$M, as well as no hepatotoxic properties in HepG2 cells (concentration of 10 $\mu$M)

Quality of Informed Consent in Mammography Screening—The Polish Experience

Breast cancer is one of the leading forms of cancers in women worldwide. In Poland, it accounts for approx. 20% of all cancers diagnosed, with approximately 11,000 new cases and 5000 deaths from this disease annually. To prevent unfavourable statistics, Poland introduced free breast cancer screening programmes, available to women aged 50–69. Over a million women take advantage of this programme each year. The aim of the research was to assess the quality of consent women give prior to mammography screening and address the question of whether this quality is sufficient to make an informed choice. The study was conducted on a representative group of 600 Polish women over 50 years old (475 of them had undergone mammography screening), who agreed to take part in the study. Using the computer-assisted interview technology (CATI) method, all women were asked about their perception of breast cancer and screening and those who had undergone mammography were quizzed about the consent process. They will form the focus of this research. The validated tool contained items on both the benefits and risks of screening. The results indicate that the quality of informed consent was insufficient. A discrepancy was observed in the awareness between the benefits and risks of mammography screening. The main motivations to undergo screening were: prophylactic purposes and the free-of-charge nature of this health service. Population-based screening programmes for breast cancer should be reconsidered in terms of information policy, and the quality of informed consent should be increased

Overdiagnosis in the context of access to new medical technologies

Wprowadzenie. Dynamiczny rozwój nowych technologii diagnostycznych w medycynie prowadzi do ich szerokiego wykorzystywania w praktyce medycznej i w badaniach przesiewowych, szczególnie w kierunku chorób nowotworowych. Badania te w swoich założeniach mają wykrywać stany chorobowe na wczesnym etapie rozwoju, umożliwiać podjęcie wczesnego leczenia i przyczyniać się do obniżenia śmiertelności powodowanej chorobami. Pojawiają się jednak doniesienia, wskazujące na rosnące zjawisko nadrozpoznawalności oraz zbędnego leczenia. Cel pracy. Celem niniejszej pracy jest przybliżenie zjawiska nadrozpoznawalności, wyodrębnienie omawianego problemu od podobnych zjawisk, wskazanie podstawowych obszarów jego występowania oraz konsekwencji. Skrócony opis stanu wiedzy. Nadrozpoznawalność (ang. overdiagnosis) może prowadzić do zbędnego psychicznego, fizycznego oraz finansowego obciążenia pacjenta, a także do nieuzasadnionych wydatków finansowych ze strony państwa. Zjawisko nadrozpoznawalności najczęściej wiąże się z badaniami przesiewowymi w kierunku chorób nowotworowych (np. prostaty, sutka, płuc), ale występuje również w medycynie klinicznej oraz na rynku leków wydawanych bez recepty. Pojedyncze doniesienia wskazują, że w przypadku niektórych diagnoz (np. nowotwór prostaty) nadrozpoznawalność może sięgać nawet 40–60% przypadków i niekiedy pociąga za sobą dalsze zbędne leczenie. Podsumowanie. Przy wprowadzaniu nowych technologii medycznych i planowaniu badań przesiewowych należy uwzględniać ryzyko nadrozpoznawalności oraz podjąć działania zmierzające do jej ograniczenia.Introduction. Dynamic development of new diagnostics technologies in medicine leads to their wide application in medical practice and screening tests, especially in screening for cancer. These tests in their assumptions are to detect diseases at an early stage of development, enabling early treatment and contributing to mortality reduction. However, reports indicating an increasing phenomenon of overdiagnosis and unnecessary treatment have begun to appear. Aim of the study. The aim of this study is to introduce the phenomenon of overdiagnosis, the distinction of this problem from similar phenomena, indication of the main areas of its occurrence and consequences Current state of knowledge. Overdiagnosis can be an unnecessary psychological, physical and financial burden to the patients and an unjustified financial expenditure for the country. Overdiagnosis is most frequently associated with screening for cancer (e.g. prostate, breast, lung); however, it also exists in clinical medicine and on the OTC market. Single reports indicate that in some medical diagnosis (e.g. prostate cancer), overdiagnosis can occur in even 40–60% of cases, and sometimes may lead to further unnecessary treatment. Conclusion. In introducing new medical technologies and planning screening, it is essential to take into consideration the risk of overdiagnosis, and take action in order to reduce the phenomenon

Influence of Umbelliferone on the Anticonvulsant and Neuroprotective Activity of Selected Antiepileptic Drugs: An In Vivo and In Vitro Study

Umbelliferone (7-hydroxycoumarin; UMB) is a coumarin with many biological properties, including antiepileptic activity. This study evaluated the effect of UMB on the ability of classical and novel antiepileptic drugs (e.g., lacosamide (LCM), levetiracetam (LEV), phenobarbital (PB) and valproate (VPA)) to prevent seizures evoked by the 6-Hz corneal-stimulation-induced seizure model. The study also evaluated the influence of this coumarin on the neuroprotective properties of these drugs in two in vitro models of neurodegeneration, including trophic stress and excitotoxicity. The results indicate that UMB (100 mg/kg, i.p.) significantly enhanced the anticonvulsant action of PB (p p 50 values from the 6-Hz test), UMB (100 mg/kg) did not affect motor coordination; skeletal muscular strength and long-term memory, as determined in the chimney; grip strength; or passive avoidance tests, respectively. Pharmacokinetic characterization revealed that UMB had no impact on total brain concentrations of PB or VPA in mice. The in vitro study indicated that UMB has neuroprotective properties. Administration of UMB (1 µg/mL), together with antiepileptic drugs, mitigated their negative impact on neuronal viability. Under trophic stress (serum deprivation) conditions, UMB enhanced the neurotrophic abilities of all the drugs used. Moreover, this coumarin statistically enhanced the neuroprotective effects of PB (p p < 0.001) in the excitotoxicity model of neurodegeneration. The obtained results clearly indicate a positive effect of UMB on the anticonvulsant and neuroprotective properties of the selected drugs

Influence of Umbelliferone on the Anticonvulsant and Neuroprotective Activity of Selected Antiepileptic Drugs: An In Vivo and In Vitro Study

Umbelliferone (7-hydroxycoumarin; UMB) is a coumarin with many biological properties, including antiepileptic activity. This study evaluated the effect of UMB on the ability of classical and novel antiepileptic drugs (e.g., lacosamide (LCM), levetiracetam (LEV), phenobarbital (PB) and valproate (VPA)) to prevent seizures evoked by the 6-Hz corneal-stimulation-induced seizure model. The study also evaluated the influence of this coumarin on the neuroprotective properties of these drugs in two in vitro models of neurodegeneration, including trophic stress and excitotoxicity. The results indicate that UMB (100 mg/kg, i.p.) significantly enhanced the anticonvulsant action of PB (p &lt; 0.01) and VPA (p &lt; 0.05), but not that of LCM orLEV, in the 6-Hz test. Whether alone or in combination with other anticonvulsant drugs (at their ED50 values from the 6-Hz test), UMB (100 mg/kg) did not affect motor coordination; skeletal muscular strength and long-term memory, as determined in the chimney; grip strength; or passive avoidance tests, respectively. Pharmacokinetic characterization revealed that UMB had no impact on total brain concentrations of PB or VPA in mice. The in vitro study indicated that UMB has neuroprotective properties. Administration of UMB (1 &micro;g/mL), together with antiepileptic drugs, mitigated their negative impact on neuronal viability. Under trophic stress (serum deprivation) conditions, UMB enhanced the neurotrophic abilities of all the drugs used. Moreover, this coumarin statistically enhanced the neuroprotective effects of PB (p &lt; 0.05) and VPA (p &lt; 0.001) in the excitotoxicity model of neurodegeneration. The obtained results clearly indicate a positive effect of UMB on the anticonvulsant and neuroprotective properties of the selected drugs

Prevalence and Characteristics of Orthorectic Disorders in Adolescence and Young People: Polish Preliminary Studies

The aim of this work was to assess orthorectic behaviors among young people and to evaluate their attitudes towards caring for their health. The study was conducted in 2019 on a group of 538 respondents aged 16–35. After analysis, 65 questionnaires were eliminated from further research, and the assessment of orthorectic disorders was performed using a method based on the modified ORTO-15 questionnaire on a group of 473 respondents. A large percentage of them exhibited an increased risk of orthorectic behaviors (32.8), which was higher among women than men (34.7% and 28.2%, respectively). People with higher risks of orthorectic disorders significantly more often reduced their consumption of foods high in fats and sugars. Attitudes of people with orthorectic disorders towards health care proved neutral, with a tendency to be positive. Nutritional behaviors observed in the studied group show some irregularities, which indicates the need for preventive and educational measures aimed at increasing awareness of the role of proper nutrition among young people. The obtained results may be the basis for further research on ON symptoms. One of the major areas of future research would be to create a reliable diagnostic tool which would allow for distinguishing between orthorexia and overdiagnosis