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GFRAL-expressing neurons actuate aversion and nausea, are targets for obesity treatment, and may mediate metformin effects by long-term GDF15-GFRAL agonism. Whether GFRAL + neurons acutely regulate glucose and energy homeostasis is, however, underexplored. Here, we report that cell-specific activation of GFRAL + neurons using a variety of techniques causes a torpor-like state, including hypothermia, the release of stress hormones, a shift from glucose to lipid oxidation, and impaired insulin sensitivity, glucose tolerance, and skeletal muscle glucose uptake but augmented glucose uptake in visceral fat. Metabolomic analysis of blood and transcriptomics of muscle and fat indicate alterations in ketogenesis, insulin signaling, adipose tissue differentiation and mitogenesis, and energy fluxes. Our findings indicate that acute GFRAL + neuron activation induces endocrine and gluco- and thermoregulatory responses associated with nausea and torpor. While chronic activation of GFRAL signaling promotes weight loss in obesity, these results show that acute activation of GFRAL + neurons causes hypothermia and hyperglycemia., Competing Interests: Declaration of interests F.B. is a co-founder and shareholder of Roxbiosens, Inc., and Implexion Pharma AB, receives research funding from Biogaia AB, and is a member of the scientific advisory board of Bactolife A/S., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Calcitonin gene related peptide (CGRP) expressing neurons in the parabrachial nucleus have been shown to encode danger. Through projections to the amygdala and other forebrain structures, they regulate food intake and trigger adaptive behaviors in response to threats like inflammation, intoxication, tumors and pain. Despite the fact that this danger-encoding neuronal population has been defined based on its CGRP expression, it is not clear if CGRP is critical for its function. It is also not clear if CGRP in other neuronal structures is involved in danger-encoding. To examine the role of CGRP in danger-related motivational responses, we used male and female mice lacking αCGRP, which is the main form of CGRP in the brain. These mice had no, or only very weak, CGRP expression. Despite this, they did not behave differently compared to wildtype mice when they were tested for a battery of danger-related responses known to be mediated by CGRP neurons in the parabrachial nucleus. Mice lacking αCGRP and wildtype mice showed similar inflammation-induced anorexia, conditioned taste aversion, aversion to thermal pain and pain-induced escape behavior, although it should be pointed out that the study was not powered to detect any possible differences that were minor or sex-specific. Collectively, our findings suggest that αCGRP is not necessary for many threat-related responses, including some that are known to be mediated by CGRP neurons in the parabrachial nucleus., (© 2021. The Author(s).)

Opioid signaling controls the activity of the brain's reward system. It is involved in signaling the hedonic effects of rewards and has essential roles in reinforcement and motivational processes. Here, we focused on opioid signaling through mu and delta receptors on dopaminoceptive neurons and evaluated the role these receptors play in reward-driven behaviors. We generated a genetically modified mouse with selective double knockdown of mu and delta opioid receptors in neurons expressing dopamine receptor D1. Selective expression of the transgene was confirmed using immunostaining. Knockdown was validated by measuring the effects of selective opioid receptor agonists on neuronal membrane currents using whole-cell patch clamp recordings. We found that in the nucleus accumbens of control mice, the majority of dopamine receptor D1-expressing neurons were sensitive to a mu or delta opioid agonist. In mutant mice, the response to the delta receptor agonist was blocked, while the effects of the mu agonist were strongly attenuated. Behaviorally, the mice had no obvious impairments. The mutation did not affect the sensitivity to the rewarding effects of morphine injections or social contact and had no effect on preference for sweet taste. Knockdown had a moderate effect on motor activity in some of the tests performed, but this effect did not reach statistical significance. Thus, we found that knocking down mu and delta receptors on dopamine receptor D1-expressing cells does not appreciably affect some of the reward-driven behaviors previously attributed to opioid signaling., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Multiple paternity is relatively common across diverse taxa; however, the drivers and implications related to paternal and maternal fitness are not well understood. Several hypotheses have been offered to explain the occurrence and frequency of multiple paternity. One set of hypotheses seeks to explain multiple paternity through direct and indirect benefits including increased genetic diversity or enhanced offspring fitness, whereas another set of hypotheses explains multiple paternity as a by-product of sexual conflict and population-specific parameters such as density. Here, we investigate mating system dynamics in a historically studied population of the American alligator ( Alligator mississippiensis ) in coastal South Carolina. We examine parentage in 151 nests across 6 years and find that 43% of nests were sired by multiple males and that male reproductive success is strongly influenced by male size. Whereas clutch size and hatchling size did not differ between singly sired and multiply sired nests, fertility rates were observed to be lower in multiply sired clutches. Our findings suggest that multiple paternity may exert cost in regard to female fitness, and raise the possibility that sexual conflict might influence the frequency of multiple paternity in wild alligator populations., Competing Interests: None declared., (© 2019 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Maternal care is crucial for infants and profoundly affects their responses to different kinds of stressors. Here, we examined how maternal separation affects inflammatory gene expression and the corticosterone response to an acute immune challenge induced by lipopolysaccharide (LPS; 40 µg/kg ip) in mouse pups, 8-9 days old. Maternal separation initially attenuated LPS-induced hypothalamic pro-inflammatory gene expression, but later, at 3 h after immune challenge, robustly augmented such gene expression and increased serum corticosterone levels. Providing the pups with a warm and soft object prevented the separation-induced augmented hypothalamic-pituitary-adrenal (HPA)-axis response. It also prevented the potentiated induction of some, but not all, inflammatory genes to a similar extent as did the dam. Our results show that maternal separation potentiates the inflammatory response and the resulting HPA-axis activation, which may have detrimental effects if separation is prolonged or repeated., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Hot flushes are common and troublesome symptoms of menopause. The neuropeptide calcitonin gene-related peptide (CGRP) is increased in plasma during hot flushes but it has not been clear if CGRP is causally involved in the mechanism underpinning the flushes. Here, we examined the effect of interventions with CGRP in a mouse model of hot flushes based on flush-like temperature increases triggered by forced physical activity in ovariectomized mice. Compared to normal mice, ovariectomized mice reacted with an exaggerated, flush-like, temperature increase after physical exercise. This increase was completely blocked by the non-peptide CGRP-antagonist MK-8825 (-0.41 degrees Celsius, 95% CI: -0,83 to 0,012, p < 0.0001) at a dose that had no obvious effects on locomotor activity (50 mg/kg). Further, the flush-like temperature increases were strongly attenuated in ovariectomized mice lacking αCGRP due to a genetic modification. Collectively, our findings suggest that CGRP is an important mediator of experimentally induced hot flushes and they identify CGRP antagonists as promising treatment candidates for women and possibly also men with hot flushes.

The risk factors for developing alcohol addiction include impulsivity, high sensitivity to the rewarding action of ethanol, and low sensitivity to its sedative and intoxicating effects. Genetic variation in GABA A receptor subunits, including the ɣ2 subunit (Gabrg2), affects the risk for developing alcoholism. Alcohol directly potentiates GABA A receptors and activates the mesolimbic dopamine system. Here, we deleted Gabrg2 selectively in dopamine cells of adult mice. The deletion resulted in elevated firing of dopamine neurons and made them less sensitive to drugs acting at GABA A receptors. At the behavioral level, the deletion increased exploratory behavior and augmented both correct and incorrect responding in the go/no-go task, a test often used to assay the response inhibition component of impulsivity. In addition, conditioned place preference to alcohol, but not to cocaine or morphine, was increased. Ethanol-induced locomotor activation was enhanced in the mice lacking Gabrg2 on dopaminergic cells, whereas the sedative effect of alcohol was reduced. Finally, the alcohol drinking, but not the alcohol preference, at a high concentration was increased in the mutant mice. In summary, deletion of Gabrg2 on dopamine cells induced several behavioral traits associated with high risk of developing alcoholism. The findings suggest that mice lacking Gabrg2 on dopaminergic cells could be used as models for individuals at high risk for developing alcoholism and that GABA A receptors on dopamine cells are protective against the development of excessive alcohol drinking.

Objectives: Biologics are medications widely applied in the management of inflammatory rheumatic diseases. The drugs were found to be effective but their application is associated with some disadvantages. Medication with biologics is relatively expensive, and in Poland, it is carried out in specialized centers. The study was designed to evaluate various aspects of satisfaction and dissatisfaction of Polish patients treated with biologics., Material and Methods: An anonymous questionnaire was distributed in 23 Polish rheumatological centers involved in the treatment; 1212 returned questionnaires were used for analysis. Responses were received from 606 patients with rheumatoid arthritis, 427 with ankylosing spondylitis, 117 psoriatic arthritis, and 62 adult patients with juvenile idiopathic arthritis (in whom administration of the drugs had been introduced before they were 18 years old). The investigated group constituted about one-fifth of all rheumatic patients on biologics in Poland., Results: A beneficial or very beneficial influence of the medication on the state of physical health was found mostly in patients with rheumatoid arthritis (51.3 and 30.5%) and ankylosing spondylitis (51.0 and 36.8%). Family life was improved by the treatment especially in patients with ankylosing spondylitis (40.7 and 35.6% beneficial and very beneficial, respectively), sleep quality and sexual life mostly in those with ankylosing spondylitis (beneficial/very beneficial influence 41.5/38.4, and 38.7/23.9, respectively). There was a rather small influence of biological treatment on the financial situation of the patients. In general, satisfaction with the treatment was evaluated as positive or very positive in 88% of all investigated patients.In a significant part of the patients, transportation to the medical center was considered as a disadvantage of the treatment. About one-third of the patients considered laboratory and imaging tests to be done before initiation of the medication as a difficulty, and for about 40% waiting time for qualification for the medication was a significant disadvantage. The route of drug administration was without importance for 4/5 of the patients., Conclusions: Summing up, the results were similar in the patients suffering from various diseases although those with psoriatic arthritis felt the highest satisfaction (possibly due to the positive aesthetic effect), and those with ankylosing spondylitis had significant improvement in sexual life (probably due to younger age). Relatively low satisfaction was found in patients with juvenile idiopathic arthritis. There was a small influence of medication on financial status of the patients. Application of biologics has few disadvantages and most of them are associated with the organization of health services (waiting time for the tests, transportation to the medical centers)., Competing Interests: The authors declare no conflict of interest.

For several years, we have observed the dynamic development of technologies that allow patients to access medical care from the comfort of their homes, without direct contact with the doctor. Innovative solutions based on telemedicine improve care coordination and communication among clinicians, patients, and their families, as well as increases patients' security and gives them greater independence, thus eliminating health care inequalities. The rapidly growth of telemedicine and the adoption of new technologies in clinical practice is also observed in Poland. Crucial moment for the telemedicine facilitation process in our country was Baltic Declaration approved by Minister of Health in 2015, as well as the Medical Profession Amendment Act and remote medical care admission. Since then, as part of the work of the Information Technology and Telemedicine Committee of the Polish Cardiac Society and the Telemedical Working Group, important steps have been taken to implement a telemedicine solutions in the Polish healthcare system, resulting in improved quality and efficiency of this system. The presented document reflects the above actions and encompasses following issues: available telemedicine solutions in the world, analysis of their effectiveness based on clinical trials, funding opportunities, legal status and development prospects telecardiology in Poland.

Introduction: The development of patient rights and increasing number of lawsuits based on medical malpractice make medical doctors constantly improve knowledge regarding the acceptability of changing the scope of operation. This is particularly important when patients have expressed their refusal to changing the scope and type of procedure (ESTP) or no informed consent (IC) has been obtained from the patient prior to the procedure., Material and Methods: The method of study comprised content analysis of existing legislation. The current jurisprudence and doctrine were confronted with existing regulations. An algorithm of correct formal procedures was elaborated., Results: The doctor has right to realize ESTP when the patient has not given the consent to it or the refusal expressed by him was not fully conscious. Healthcare providers are absolutely prohibited from realizing ESTP when patient objected to any changes being thoroughly informed by the physician prior to the operation. When patient refuses possible ESTP, the doctor has the right to withdraw from performing surgery but should inform the patient about other places, where a similar procedure can be provided.

Fever occurs upon binding of prostaglandin E 2 (PGE 2 ) to EP 3 receptors in the median preoptic nucleus of the hypothalamus, but the origin of the pyrogenic PGE 2 has not been clearly determined. Here, using mice of both sexes, we examined the role of local versus generalized PGE 2 production in the brain for the febrile response. In wild-type mice and in mice with genetic deletion of the prostaglandin synthesizing enzyme cyclooxygenase-2 in the brain endothelium, generated with an inducible CreER T2 under the Slco1c1 promoter, PGE 2 levels in the CSF were only weakly related to the magnitude of the febrile response, whereas the PGE 2 synthesizing capacity in the hypothalamus, as reflected in the levels of cyclooxygenase-2 mRNA, showed strong correlation with the immune-induced fever. Histological analysis showed that the deletion of cyclooxygenase-2 in brain endothelial cells occurred preferentially in small- and medium-sized vessels deep in the brain parenchyma, such as in the hypothalamus, whereas larger vessels, and particularly those close to the neocortical surface and in the meninges, were left unaffected, hence leaving PGE 2 synthesis largely intact in major parts of the brain while significantly reducing it in the region critical for the febrile response. Furthermore, injection of a virus vector expressing microsomal prostaglandin E synthase-1 (mPGES-1) into the median preoptic nucleus of fever-refractive mPGES-1 knock-out mice, resulted in a temperature elevation in response to LPS. We conclude that the febrile response is dependent on local release of PGE 2 onto its target neurons and not on the overall PGE 2 production in the brain. SIGNIFICANCE STATEMENT By using mice with selective deletion of prostaglandin synthesis in brain endothelial cells, we demonstrate that local prostaglandin E 2 (PGE 2 ) production in deep brain areas, such as the hypothalamus, which is the site of thermoregulatory neurons, is critical for the febrile response to peripheral inflammation. In contrast, PGE 2 production in other brain areas and the overall PGE 2 level in the brain do not influence the febrile response. Furthermore, partly restoring the PGE 2 synthesizing capacity in the anterior hypothalamus of mice lacking such capacity with a lentiviral vector resulted in a temperature elevation in response to LPS. These data imply that the febrile response is dependent on the local release of PGE 2 onto its target neurons, possibly by a paracrine mechanism., (Copyright © 2017 the authors 0270-6474/17/375035-10$15.00/0.)

Pain is fundamentally unpleasant and induces a negative affective state. The affective component of pain is mediated by circuits that are distinct from those mediating the sensory-discriminative component. Here, we have investigated the role of prostaglandins in the affective dimension of pain using a rodent pain assay based on conditioned place aversion to formalin injection, an inflammatory noxious stimulus. We found that place aversion induced by inflammatory pain depends on prostaglandin E2 that is synthesized by cyclooxygenase 2 in neural cells. Further, mice lacking the prostaglandin E2 receptor EP3 selectively on serotonergic cells or selectively in the area of the dorsal raphe nucleus failed to form an aversion to formalin-induced pain, as did mice lacking the serotonin transporter. Chemogenetic manipulations revealed that EP3 receptor activation elicited conditioned place aversion to pain via inhibition of serotonergic neurons. In contrast to their role in inflammatory pain aversion, EP3 receptors on serotonergic cells were dispensable for acute nociceptive behaviors and for aversion induced by thermal pain or a κ opioid receptor agonist. Collectively, our findings show that prostaglandin-mediated modulation of serotonergic transmission controls the affective component of inflammatory pain.

Cyclooxygenase-2 (COX-2) is the main source of inducible prostaglandin E2 production and mediates inflammatory symptoms including fever, loss of appetite and hyperalgesia. COX-1 is dispensable for fever, anorexia and hyperalgesia but is important for several other functions both under basal conditions and during inflammation. The differential functionality of the COX isoforms could be due to differences in the regulatory regions of the genes, leading to different expression patterns, or to differences in the coding sequence, resulting in distinct functional properties of the proteins. To study the molecular underpinnings of the functional differences between the two isoforms in the context of inflammatory symptoms, we used mice in which the coding sequence of COX-2 was replaced by the corresponding sequence of COX-1. In these mice, COX-1 mRNA was induced by inflammation but COX-1 protein expression did not fully mimic inflammation-induced COX-2 expression. Just like mice globally lacking COX-2, these mice showed a complete lack of fever and inflammation-induced anorexia as well as an impaired response to inflammatory pain. However, as previously reported, they displayed close to normal survival rates, which contrasts to the high fetal mortality in COX-2 knockout mice. This shows that the COX activity generated from the hybrid gene was strong enough to allow survival but not strong enough to mediate the inflammatory symptoms studied, making the line an interesting alternative to COX-2 knockouts for the study of inflammation. Our results also show that the functional differences between COX-1 and COX-2 in the context of inflammatory symptoms are not only dependent on the features of the promoter regions. Instead they indicate that there are fundamental differences between the isoforms at translational or posttranslational levels., Competing Interests: The authors have declared that no competing interests exist.

Plasticity of the brain's dopamine system plays a crucial role in adaptive behavior by regulating appetitive motivation and the control of reinforcement learning. In this study, we investigated drug- and natural-reward conditioned behaviors in a mouse model in which the NMDA receptor-dependent plasticity of dopaminoceptive neurons was disrupted. We generated a transgenic mouse line with inducible selective inactivation of the NR1 subunit in neurons expressing dopamine D1 receptors (the NR1(D1CreERT2) mice). Whole-cell recordings of spontaneous EPSCs on neurons in the nucleus accumbens confirmed that a population of neurons lacked the NMDA receptor-dependent component of the current. This effect was accompanied by impaired long-term potentiation in the nucleus accumbens and in the CA1 area of the ventral, but not the dorsal, hippocampus. Mutant mice did not differ from control animals when tested for pavlovian or instrumental conditioning. However, NR1(D1CreERT2) mice acquired no preference for a context associated with administration of drugs of abuse. In the conditioned place preference paradigm, mutant mice did not spend more time in the context paired with cocaine, morphine, or ethanol, although these mice acquired a preference for sucrose jelly and an aversion to naloxone injections, as normal. Thus, we observed that the selective inducible ablation of the NMDA receptors specifically blocks drug-associated context memory with no effect on positive reinforcement in general.

Systemic inflammation causes malaise and general feelings of discomfort. This fundamental aspect of the sickness response reduces the quality of life for people suffering from chronic inflammatory diseases and is a nuisance during mild infections like common colds or the flu. To investigate how inflammation is perceived as unpleasant and causes negative affect, we used a behavioral test in which mice avoid an environment that they have learned to associate with inflammation-induced discomfort. Using a combination of cell-type–specific gene deletions, pharmacology, and chemogenetics, we found that systemic inflammation triggered aversion through MyD88-dependent activation of the brain endothelium followed by COX1-mediated cerebral prostaglandin E2 (PGE2) synthesis. Further, we showed that inflammation-induced PGE2 targeted EP1 receptors on striatal dopamine D1 receptor–expressing neurons and that this signaling sequence induced aversion through GABA-mediated inhibition of dopaminergic cells. Finally, we demonstrated that inflammation-induced aversion was not an indirect consequence of fever or anorexia but that it constituted an independent inflammatory symptom triggered by a unique molecular mechanism. Collectively, these findings demonstrate that PGE2-mediated modulation of the dopaminergic motivational circuitry is a key mechanism underlying the negative affect induced by inflammation.

For several decades we have observed the development of data transmission technology on an unprecedented scale. With the development of such technology there has also appeared concepts on the use of these solutions in health care systems. Over the last decade telemedicine has been joined by the concept of mHealth, which is based on mobile devices mainly to monitor selected biomedical parameters. On 10 October 2014, during the conference Baltic Electrocardiology Autumn - Telemedicine and Arrhythmia (BEATA), a debate was held with the participation of physicians, politicians, businessmen, and representatives of the Government (Ministry of Health, National Health Fund, Social Insurance Institution) concerning the use of telecardiology services in daily practice. During the meeting issues were discussed such as: telemedicine solutions available throughout the world, analysis of their effectiveness based on clinical trials, funding opportunities, their legal status, and the development perspectives of telecardiology in Poland. The result of the meeting was a document called the "Baltic Declaration". The declaration is a call for proven and profitable technologies to be introduced into clinical practice. The declaration also indicates that the variety of available technological solutions are merely tools, and the utility of such tools stems not only from their modernity, but also primarily from matching their functionality to the features of the health interventions that are to be improved.

Here, we describe a new model of voluntary alcohol drinking by group-housed mice. The model employs sensor-equipped cages that track the behaviors of the individual animals via implanted radio chips. After the animals were allowed intermittent access to alcohol (three 24 h intervals every week) for 4 weeks, the proportions of licks directed toward bottles containing alcohol were 50.9% and 39.6% for the male and female mice, respectively. We used three approaches (i.e., quinine adulteration, a progressive ratio schedule and a schedule involving a risk of punishment) to test for symptoms of compulsive alcohol drinking. The addition of 0.01% quinine to the alcohol solution did not significantly affect intake, but 0.03% quinine induced a greater than 5-fold reduction in the number of licks on the alcohol bottles. When the animals were required to perform increasing numbers of instrumental responses to obtain access to the bottle with alcohol (i.e., a progressive ratio schedule), they frequently reached a maximum of 21 responses irrespective of the available reward. Although the mice rarely achieved higher response criteria, the number of attempts was ∼ 10 times greater in case of alcohol than water. We have developed an approach for mapping social interactions among animals that is based on analysis of the sequences of entries into the cage corners. This approach allowed us to identify the mice that followed other animals in non-random fashions. Approximately half of the mice displayed at least one interaction of this type. We have not yet found a clear correlation between imitative behavior and relative alcohol preference. In conclusion, the model we describe avoids the limitations associated with testing isolated animals and reliably leads to stable alcohol drinking. Therefore, this model may be well suited to screening for the effects of genetic mutations or pharmacological treatments on alcohol-induced behaviors.

Introduction: The doctor's decision whether to save the life of a minor who has attempted to commit suicide depends on the decision of the person who, under legal regulations, is responsible for the minor. In everyday medical practice doctors are often placed in difficult situations and often cannot make any decision. Such doubts arise when it is impossible to contact the person(s) responsible for the minor. The doctor encounters similar issues when the parents of a minor under 16 years of age express different opinions on the recommended procedures, and are against the doctor's decision and do not want their child to be hospitalized., Materials and Methods: The current legislation and doctrine was analyzed and an attempt was made to determine the way of conduct with regard to suicidal minors, and algorithmize the way of conduct towards such suicidal minors. The conduct was discussed on the two examples, based on real clinical cases., Results: With regard to minors in a clinical state demanding urgent procedures, who have of the decision made by the guardian, and regardless of the fact there is no contact with the guardian. If the status is stable, the physician's modus operandi depends on various accompanying circumstances. However, he is still obliged to provide medical help., Discussion: A practical algorithm is presented and all the possible legal variations discussed and clarified.

Objectives: In Poland, 95% of medical personnel had not received legal education before they completed their studies. Having been given these facts, we have started questioning legal awareness of people providing medical services., Aim of the Study: The study aimed at evaluating the knowledge of allergists and pulmonologists., Material and Methods: The group consisting of 328 allergists and/or pulmonologist completed the questionnaire., Results: The participants possess the best knowledge in providing information to patients about their health status (CV1). Sixty nine % of responders replied correctly, and the difference was significant (p < 0.001) in comparison with next aspect referring to the principles of providing medical services following guidelines created by think-tanks and also possibilities to take autonomous decisions by physicians (CV2). The correct answers in relation to CV2 were given by 57% of responders. The third compared aspect was physicians' awareness of patients' right to giving a consent or refusal before undertaking the medical procedure CV3. Only 55% of physicians gave correct answers and the difference was significant compared to CV1 (p < 0.001) as well as CV2 (p < 0.05). Younger doctors showed to have better knowledge than their older colleagues (p < 0.05). Working in urban workplaces proved to be more associated with better knowledge than in rural ones (p < 0.05)., Discussion: Insufficient knowledge results in a low quality of provided services and puts the doctors at risk of being liable. The rates indicate that doctors are not aware of the fact that only legal regulations are binding, while standards not published by the Minister of Health are not legally valid. Half of the respondents have the wrong belief that the opinions expressed by experts make the doctor feel exempt from liability. Probably there are specialities, like occupational medicine which are specially linked with awareness of valid legal rules.

Introduction: Legislation systems of most countries prohibited using the handheld mobile phone while driving due to the fact that it disturbs concentration and causes hand involvement. Every phone owner is accustomed to the ringtone of his phone and almost involuntarily endeavors to pick it up or check who calls. This engages one's psychomotor skills, which in our opinion contributes to the attenuation of reaction time needed for performing other crucial functions., Objectives: The aim of the study was: (1) to evaluate the influence of the sound of a ringing mobile phone on the complex reaction time (RT) score in healthy subjects (owners), and (2) to check if there are any differences in RT when a landline phone and mobile phone ring., Methods: To assess RT we used our system and protocol of examination, previously validated. The examination conditions were standardized. All tests were performed in the same room with the same light and general acoustic conditions. The test group consisted of 23 women and 24 men, aged 19-24 years. The examination comprised 4 sessions: Training Session (TS) during which the subjects were accustomed with the application and sample stimuli, Control Session (CS) with no telephone ringing, Landline Session (LS) with landline phone ringing, Mobile Session (MS) with mobile phone ringing., Results: The median RT in the study population was significantly elongated (p < 0.001) in MS. In women and in men RTs were significantly longer in MS than in CS and non-significantly longer than in LS. Reaction times in CS, LS and MS were longer in women, however the differences were not significant (p > 0.05)., Conclusions: We think that the specific 'bond' between a person and their private phone can significantly disrupt their attention and thus affect the attention-demanding activities.

Due diligence in the process of provision of healthcare services refers, among other elements, to the application of pharmacological therapy at a time which offers the greatest chance for a successful outcome of treatment, i.e. for achieving the optimum expected effect understood as an improvement in the patient's health, reduction of health risks or elimination of the disease. However, due diligence may also refer to actions aimed at ensuring that neither the patient nor the healthcare payer is required to incur unreasonable costs in the process of treatment. The validity of that statement stems not only from normative acts but also from ethical standards laid down in the Medical Code of Ethics (Article 57 section 2). It often happens that the provision of optimal treatment calls for deviations from the formal provisions included in Summary Product Characteristics (SPCs), and the application of drugs that are bioequivalent to reference drugs, which translates into a significant reduction of costs. The present study addresses the problem of acceptability of a specific form of drug substitution consisting in the replacement of a reference drug with a generic drug. Also explored are legal aspects associated with the possibility of therapy based on "off-label use". The study reviews normative acts existing in the Polish and EU legislation. It also provides a clear definition of orphan drug, which has made it possible to make a distinction and investigate mutual relations between the concepts of brand-name (reference) drug, orphan drug and generic drug.

Introduction: According to the general idea a doctor can start the medical management process in an adult and not legally incapacitated patient after the patient has given consent to initiate such a process. The patient's refusal makes rendering medical services impossible, irrespective of their scope and kind. It should be emphasized that such a refusal is respected if it is expressed fully, clearly and consciously. Cases in which such a refusal is expressed by an intoxicated suicidal patient, remaining under the influence of narcotics, drugs or medicaments which characterize with a similar activity should be particularly analysed. Although such a person is able to verbally declare his objection, his ability to process the information given by the doctor before initiating medical procedures is limited, or even non-existant. The refusal therefore cannot be regarded as reliable, which results in rendering medical services to the patient., Materials and Methods: An analysis was made of Acts of Law and the opinions of the judiciar by comparing and excluding contradictory and incoherent elements., Results: Despite the lack of clear regulations of a patient rejecting procedures aimed at saving the patient's life, or the prevention of serious health impairment or sustaining injury, it should be assumed that the objection expressed by the patient who does not demonstrate the ability to process the information provided by the doctor is not reliable, and the doctor is therefore still obliged to render medical services. External factors, such as consumption of alcohol, narcotics and drugs, which characterize with a similar activity impair perception and make the taking of a conscious decision impossible. Not providing medical help and introducing direct compulsion would mean neglecting provision of due diligence in the process of treatment and, as a consequence, placing the patient's health at risk, and suffering from negative implications for the patient's life and/or health in the future., Conclusions: Current provisions should directly regulate the negligence of respecting a refusal expressed 'unconsciously' by a patient who remains under the influence of alcohol, narcotics, drugs or medicaments which characterize with a similar activity. Moreover, apart from legal provisions, the law providers should consider introducing a direct compulsion in patients who are unable to make a conscious decision in the treatment process.

Introduction: Mobile phone conversation decreases the ability to concentrate and impairs the attention necessary to perform complex activities, such as driving a car. Does the ringing sound of a mobile phone affect the driver's ability to perform complex sensory-motor activities? We compared a subject's reaction time while performing a test either with a mobile phone ringing or without., Material and Methods: The examination was performed on a PC-based reaction time self-constructed system Reactor. The study group consisted of 42 healthy students. The protocol included instruction, control without phone and a proper session with subject's mobile phone ringing. The terms of the study were standardised., Results: There were significant differences (p < 0.001) in reaction time in control (597 ms), mobile (633 ms) and instruction session (673 ms). The differences in female subpopulation were also significant (p < 0.01). Women revealed the longest reaction time in instruction session (707 ms), were significantly quicker in mobile (657 ms, p < 0.01) and in control session (612 ms, p < 0.001). In men, the significant difference was recorded only between instruction (622 ms) and control session (573 ms, p < 0.01). The other differences were not significant (p > 0.08). Men proofed to complete significantly quicker than women in instruction (p < 0.01) and in mobile session (p < 0.05). Differences amongst the genders in control session was not significant (p > 0.05)., Conclusions: The results obtained proofed the ringing of a phone exerts a significant influence on complex reaction time and quality of performed task.

Current legal regulations do not explicitly state whether the doctor should or should not ignore the patient's refusal to be provided with medical services when such refusal is given by the patients who is temporarily unable to take conscious decisions. The fact that there is no clear jurisdiction over the issue makes the relation between doctor and patient legally complicated. The doctor has no doubts whether he/she should or should not initiate the medical procedure when the patient clearly expresses the declaration of will, in which either refusal or consent is given to be provided with medical care. However, the patient remaining under the influence of alcohol, i.e. a substance which to some or great extent impairs cognitive functions, rational thinking, and the ability to evaluate incoming information. Alcohol makes the patient unable to interpret the information given by the doctor. Thus, the patient's consent or refusal to be provided with medical care is lacking in the needed elements of "informing" and "conscious declaration of will", which are considered by doctors and lawyers to be absolutely necessary to make such will valid. There are no clear, unambiguous regulations explaining how the doctor should behave in such cases. The authors of the presented study state that it is highly important to determine whether the intoxicated patient is able to understand the incoming information, evaluate it, make a conscious decision and finally, express an explicit (and therefore binding) refusal to accept recommended medical services. In the opinion of the authors, while dealing with such patients, the doctor should bear in mind the patient's right to make autonomous decisions, but that it is also the doctor's duty to provide the patient with medical services.

Any medicinal product marketed in the country has its registration, under which are strictly defined indications and the extent to which a product can be used. It is of significance that the use of the product which is registered in the given range produces an effect similar to or identical to that effect, which is obtained after applying the product having a registration in a given indication. Relied on to justify the use of a medicinal product or medical product "off-label use" in Poland, there is also the fact that the same product has a registration in a particular indication in another EU member state or outside the Community. It is worth noting that the medicinal product may be used in therapeutic management of omitting or reducing the principles resulting from the SPC. However, this applies only to cases where the use of the medicinal product "off-label use" dictated by the necessity of saving life or health of the patient, and the previous ways and methods of treatment with the use of registered medicines have proved ineffective or insufficient to achieve the desired therapeutic effect.

Background: This paper is composed of two parts, the first one addresses the issue of legal grounds for teleconsultation and telemedicine in Poland, the other tries to answer the questions whether the provision of health services with use of telemedical tools does not breach medical professional secrecy or personal data protection., Material and Methods: The material comprised a whole set of Polish and European legal acts that could have any impact on the legal basis of telemedicine in Poland. The method applied was of interpretative nature, and the texts of above-mentioned acts were thoroughly analyzed, providing the first comprehensive study on this subject., Results: The medical professional secrecy is not violated if the range of transmitted data is limited to those, which are absolutely necessary in the diagnostic and therapeutic process. This rule involves the transmission of indispensable personal and medical data, however, sharing the patient's appearance should be preceded by his/her informed consent., Conclusions: The achievements of information technology greatly contribute to the quality of diagnostic and therapeutic processes. Due to the rapid development of modern means of telemedicine we face the need to establish legal regulations, specifying the principles of distant exchange of medical data.

Background: The aim of the study was to analyze the doctor-patient communication on the basis of selected clinical and demographic factors., Material and Methods: The author assessed the level of patients' knowledge about their rights, availability, scope and reliability of the information conveyed by doctors, completeness and influence of information given by doctors on the validity of consent given by patients. The mentioned variables were analyzed on the basis of selected clinical and demographic factors including age, gender, education, place of residence, employment, form of employment, marital status, income, number of hospitalizations (NoH) and ICD10. The data were collected by questionnaires completed by 500 patients., Results: Performing the doctor's duty of giving information to the patient and the patients' knowledge about their rights depends on their education, monthly income, place of residence, cause of hospitalization and NoH. The scope, way and perception of the conveyed information depends on patients' education, place of residence, income, cause and NoH. The influence of the information given by the doctor on the validity of consent given by the patient depends on his/her education, place of residence, income and cause and NoH. Patients have limited knowledge about their right to have a contact person established., Conclusions: The importance of obtaining adequate information before the patient gives informed consent, insufficient patients' knowledge concerning their rights and lack of similar analyses carried out in the past indicate the need to continue the relevant research in the future.

Background: The issue concerning the duty of physicians to inform about health problems, which could be a contraindication to driving a motor vehicle, give in practice rise to many questions. Existing regulations do not apply to this issue directly, and the available literature lacks a definite stand on this matter. Information collected by the competent authorities about health problems, which may be a contraindication to driving a motor vehicle could contribute enormously to reducing or eliminating health risks among drivers and other potential road users., Material and Methods: Current legislation that could in any way refer to the discussed problem were subjected to a thorough analysis and interpretation. with reference to the existing case law., Results: Despite the lack of clear regulations, physicians are obliged to provide the authorized agencies with the information about health problems, which could be a contraindication to driving a motor vehicle. The transfer of this kind of information is a legitimate exemption from doctor-patient confidentiality, therefore, physicians who transfer it do not expose themselves to bearing the responsibility. In the absence of clear standards governing the scope of information that physicians should make available for relevant authorities, the information does not need, but may include a specific medical diagnosis., Conclusions: This article presents first comprehensive approach to the exchange of information between physicians and the body entitled to obtain information on medical unfit to drive motor vehicle, which is a helpful guide in daily practice.

Background: Employers are, among their numerous responsibilities, obliged to refer their employees or the person applying for the job to prophylactic examinations. Initial, seasonal and check-up examinations should be carried out in the primary occupational health care institution the employer is obliged to sign the contract for this kind of services, according to the binding regulations. However, due to the fact that these regulations do not contain an imperative that prophylactic examinations must be performed in the institution with which the employer is under contract, it is theoretically possible that the examinations are carried out in an outpatient department chosen by an individual who is to be examined., Material and Methods: The critical analysis of existing rules, judgments and writs was performed., Results: In practice, such a possibility exists only in case of those who apply for the job. This results from the fact that job candidates unlike employees, are not obliged to follow the employer's official order concerning initial examinations. Employees and those employed on the basis of the civil-law contract have to obey the employer's official orders concerning the type and place of performing prophylactic examinations. The employee's disobedience in this matter may have serious consequences arising from the contravention of order and work organization rules., Conclusions: Employees employed on the basis of the civil-law contract are obliged to undergo prophylactic examinations. However, the time and the type of institution in which the examination is performed depends on the legal basis of employment. Persons applying for the job do not have to obey the employer's official orders and thus cannot be forced to perform the examination in a given time or institution. If the conditional contract is signed, the employee can start his or her work without presenting the certificate of working ability at a given post.

Background: A special relationship occurring between the doctor and the patient, besides many stipulations of the ethical nature, is controlled by numerous legal regulations. In the Polish legislative system, there are no clear and unequivocal regulations that would precisely define the diagnostic-therapeutic process. Communication, namely the exchange of information between the doctor and the patient plays a particular role in this process in which the doctor bears much greater responsibility than the patient, and thus is obliged to provide the patient with the comprehensible information presented in such a way that he or she would be able to interpret it properly., Material and Methods: The analysis comprised the binding legislation concerning prophylactic examination as well as drivers examination. The problem was discussed taking into account the current court judgments., Results: The doctor should pay particular attention to adjusting the quality, quantity and way of conveying the information to the patient's ability to acquire and interpret it properly. This ability is associated with the patient's personal traits. There are no algorithms for the doctor-patient communication. The occupational medicine doctors are in a better situation as legislative regulations pertaining to specificity of their health services may indicate proper communication between the doctor and the patient., Conclusions: The importance of this communication has been notified in the legislative doctrine, where the idea of informative mistake has been formed. Such a mistake may have significant consequences especially for the occupational medicine doctors due to the specificity of performed functions. The article discusses legislative aspects concerning the exchange of information at the doctor-patient level, and presents some examples of judgments of Polish courts as well as numerous indications useful in everyday practice.

57-years old woman with spotted bones was reported, with concomitant rheumatoid arthritis. It was great concern because of low incidence of osteopoikilia and diagnosis obstacles concerning coexistence of this two pathologies.

Ability to produce bacteriocin (lactostrepcin) is demonstrated in Streptococcus cremoris. However, lactostrepcin was found to be produced by only one strain (strain 202) out of the 17 S. cremoris strains tested. This bacteriocin is preliminarily characterized, it differs from other lactic streptococci bacteriocins. The strain 202 bacteriocin acts on many strains of lactic streptococci, strains of Bacillus cereus, and some strains of Leuconostoc and Lactobacillus. It was shown that strain 202 contains some plasmids, but we were not able by preliminary observations to prove the plasmid localization of the determinant(s) for lactostrepcin production by this strain. In persistent lactostrepcin-negative variants of strain 202, in comparison with the parental strain, the plasmid pattern may be changed or unchanged.

Eighty-seven strains of lactic streptococci (46 of Streptococcus lactis, 24 of S. diacetilactis, and 17 of S. cremoris) were tested for lysogeny; 12 S. lactis strains produced nisin. Lysogeny was found in five S. lactis strains (two of them were nisin producers) and in two S. diacetilactis strains. Four S. lactis and two S. diacetilactis lysogens liberated phages both spontaneously and after ultraviolet treatment, and one S. lactis strain liberated phages spontaneously only. No lysogens were found among the S. cremoris strains tested. An initial characterization of the lysogens and their phages was made. The lytic spectrum of some of the examined phages was very narrow (homospecific), whereas that of others was wide, including strains of the three investigated species.