Clinical utility of adjunctive retigabine in partial onset seizures in adults

In ~30% of epileptic patients, full seizure control is not possible, which is why the search for novel antiepileptic drugs continues. Retigabine exhibits a mechanism of action that is not shared by the available antiepileptic drugs. This antiepileptic enhances potassium currents via Kv7.2–7.3 channels, which very likely results from destabilization of a closed conformation or stabilization of the open conformation of the channels. Generally, the pharmacokinetics of retigabine are linear and the drug undergoes glucuronidation and acetylation. Results from clinical trials indicate that, in the form of an add-on therapy, retigabine proves an effective drug in refractory epileptic patients. The major adverse effects of the add-on treatment are dizziness, somnolence, and fatigue. This epileptic drug is also considered for other conditions – neuropathic pain, affective disorders, stroke, or even Alzheimer’s disease

Occupational exposure to biological agents in Polish paramedics: a narrative review

INTRODUCTION: Research into occupational exposure to biological pathogens during medical personnel workis to a small degree concerned with paramedics. Coming in contact with biological pathogens, like HIV, HCVand HBV viruses, tubercle bacilli, or recently the SARS-CoV-2 virus in the workplace is a contamination risk.This study aims to analyze the occupational exposure of paramedics to biological pathogens at work, thepossibilities of paramedics developing contagious diseases as occupational illnesses, and the prophylaxisthis involves.MATERIAL AND METHODS: The publication was prepared on the basis of a literature review of works availablein the PubMed, SCOPUS, and Google Scholar databases, and on websites of institutions functioning in thearea of public health.BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: In Poland, in 2020, there were 1 255 625 cases of SARSCoV-2 registered, 3020 of which are cases found in paramedics, and 12 524 cases of Lyme borreliosis,990 HBV cases, 942 HCV cases, 934 HIV cases. In 2020, there were 1861 occupational diseases, 504 of whichwere contagious or parasitic. Approximately 37 000 needlesticks are estimated to happen every year in medicalfacilities. 40% to 80% of the people who got injuries or cut in the workplace did not report the incident.CONCLUSIONS: There is a need to implement prophylactic and preventative measures to prevent occupationalneedlestick injuries and blood-borne infections amongst paramedics. Paramedics show insufficientknowledge of their ability to apply for an occupational disease diagnosis caused by exposure to biologicalpathogens present in the work environment

Spinal pain syndrome incidence among paramedics in Emergency Response Teams

INTRODUCTION: Spinal pain syndrome is a condition people of different ages suffer from. Its incidence is determined by many factors: age, gender, genetic disposition, lifestyle, the type and characteristics of one’s occupation, years of work experience. Paramedics are particularly vulnerable to musculoskeletal ailments, due to the professional activities carried out at work: lifting, moving, and carrying patients or medical equipment, crossing architectural barriers, forced posture during work, standing, walking, and sitting for long periods. The study aimed to indicate the effect of professional work on the incidence of spinal pain syndrome in paramedics working in mobile Emergency Response Teams. MATERIAL AND METHODS: The research took place between May and September 2019, using diagnostic survey methodology on 238 (223 male, 15 female) paramedics in mobile Emergency Response Teams (ERT) operating in the Masovian voivodship. The mean age was 39.03 ± 9.27 years for males, 31.93 ± 7.76 years for females. The research tool was a self-developed questionnaire. RESULTS: All participants (100%) suffered from spinal pain syndrome. A majority of the participants (98; 41.18%) reported pain being located in the lumbar area and being related to lifting, moving and carrying patients in teams (149; 62.60%). CONCLUSIONS: Spinal pain syndrome is a widespread phenomenon among ERT paramedics. The incidence and nature of lumbar area pain are strictly related to the type of work paramedics do. Applying rules of work ergonomics and using aid affects incidence and decreases the frequency of SPS

Occupational hazards in the consciousness of the paramedic in emergency medical service

INTRODUCTION: Due to their occupational responsibilities and volatile work environment, paramedics are in constant contact with harmful, dangerous factors, making them vulnerable to a number of occupational health risks. These include harmful biological, chemical, physical, as well as psychophysical factors (musculoskeletal system strain, stress, patient aggression, occupational burnout). The present study aims to evaluate occupational hazard prevalence among emergency medical service (EMS) paramedics, the possibility of occupational illness incidence, and related prophylaxis.MATERIAL AND METHODS: The participant sample consisted of paramedics employed in five mobile EMS operational areas in the Masovian voivodship. The study involved 238 people, including 223 men and 15 women. The mean age was 39.03 ± 9.27 years for males, and 31.93 ± 7.76 years for females. The study took place between May and September 2019 using diagnostic survey methodology.RESULTS: Participants ordered the following factors based on a scale of threat: biological factors (47%), psychophysical factors (41%), chemical factors (7%), and physical factors (5%). Health issues included musculoskeletal system discomfort (39%) and mental overload (33%). Participants indicated harmful biological factors to cause illnesses such as influenza (85%), tuberculosis (79%), and hepatitis B or C (70%). The study showed that 73% of the participants are occupationally exposed to patient aggression, while 15% experienced occupational burnout.CONCLUSIONS: Paramedics are exposed to a number of occupational hazards daily. The ones most significant in terms of serious disease development are harmful biological factors, musculoskeletal risk factors, fatigue, mental overload related to occupational responsibilities

Prevalence of sleep disturbances among emergency response team paramedics working in shift systems

INTRODUCTION: Due to the nature and specifics of their work, paramedics carry out work activities in an organized shift system. Working in shifts is related to various health complications, disturbing the natural biological rhythm and adversely affecting the quality of sleep. The purpose of the study was the evaluation the effect of shift work on the quality of sleep of the paramedics who are members of Emergency Response Teams.MATERIAL AND METHODS: The research took place between May and September 2019, using diagnostic survey methodology on 238 (223 male, 15 female) paramedics in mobile Emergency Response Teams (ERT) employed in five operational areas of the Masovian voivodeship. The mean age was 39.03 ± 9.27 years for males, and 31.93 ± 7.76 years for females. To examine the differences between the groups, the χ2 test was employed, with an established statistical significance value of p < 0.05.RESULTS: Insomnia was most often reported by paramedics aged between 45 and 54 (29; 12.18%) and above the age of 55 (23; 9.66%). The participating paramedics are most often in the above-norm bounds of the Athens Insomnia Scale norms (112; 47.05%) or in the group classified as suffering from insomnia (77; 32.35%).CONCLUSIONS: In order to minimize the possible health consequences resulting from the nature of shift work, it is suitable to implement elements of sleep hygiene theory into the health education of paramedics, as well as to continuously monitor their health condition as part of occupational medicine practice

Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

Histone deacetylase inhibitors (HDIs) are promising anti-cancer agents that inhibit proliferation of many types of cancer cells including breast carcinoma (BC) cells. In the present study, we investigated the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two HDIs, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), in luminal-like BC cells. The type of drug-drug interaction between CDDP and HDIs was determined by isobolographic analysis. MCF7 cells were genetically modified to express differential levels of Notch1 activity. The cytotoxic effect of SAHA or VPA was higher on cells with decreased Notch1 activity and lower for cells with increased Notch1 activity than native BC cells. The isobolographic analysis demonstrated that combinations of CDDP with SAHA or VPA at a fixed ratio of 1:1 exerted additive or additive with tendency toward synergism interactions. Therefore, treatment of CDDP with HDIs could be used to optimize a combined therapy based on CDDP against Notch1-altered luminal BC. In conclusion, the combined therapy of HDIs and CDDP may be a promising therapeutic tool in the treatment of luminal-type BC with altered Notch1 activity

Identification of compounds with anti-convulsant properties in a zebrafish model of epileptic seizures

The availability of animal models of epileptic seizures provides opportunities to identify novel anticonvulsants for the treatment of people with epilepsy. We found that exposure of 2-day-old zebrafish embryos to the convulsant agent pentylenetetrazole (PTZ) rapidly induces the expression of synaptic-activity-regulated genes in the CNS, and elicited vigorous episodes of calcium (Ca2+) flux in muscle cells as well as intense locomotor activity. We then screened a library of ∼2000 known bioactive small molecules and identified 46 compounds that suppressed PTZ-inducedtranscription of the synaptic-activity-regulated gene fos in 2-day-old (2 dpf) zebrafish embryos. Further analysis of a subset of these compounds, which included compounds with known and newly identified anticonvulsant properties, revealed that they exhibited concentration-dependent inhibition of both locomotor activity and PTZ-induced fos transcription, confirming their anticonvulsant characteristics. We conclude that this in situ hybridisation assay for fos transcription in the zebrafish embryonic CNS is a robust, high-throughput in vivo indicator of the neural response to convulsant treatment and lends itself well to chemical screening applications. Moreover, our results demonstrate that suppression of PTZ-induced fos expression provides a sensitive means of identifying compounds with anticonvulsant activities

In Vivo and Ex Vivo Evaluation of L-Type Calcium Channel Blockers on Acid β-Glucosidase in Gaucher Disease Mouse Models

Gaucher disease is a lysosomal storage disease caused by mutations in acid β-glucosidase (GCase) leading to defective hydrolysis and accumulation of its substrates. Two L-type calcium channel (LTCC) blockers—verapamil and diltiazem—have been reported to modulate endoplasmic reticulum (ER) folding, trafficking, and activity of GCase in human Gaucher disease fibroblasts. Similarly, these LTCC blockers were tested with cultured skin fibroblasts from homozygous point-mutated GCase mice (V394L, D409H, D409V, and N370S) with the effect of enhancing of GCase activity. Correspondingly, diltiazem increased GCase protein and facilitated GCase trafficking to the lysosomes of these cells. The in vivo effects of diltiazem on GCase were evaluated in mice homozygous wild-type (WT), V394L and D409H. In D409H homozygotes diltiazem (10 mg/kg/d via drinking water or 50–200 mg/kg/d intraperitoneally) had minor effects on increasing GCase activity in brain and liver (1.2-fold). Diltiazem treatment (10 mg/kg/d) had essentially no effect on WT and V394L GCase protein or activity levels (<1.2-fold) in liver. These results show that LTCC blockers had the ex vivo effects of increasing GCase activity and protein in the mouse fibroblasts, but these effects did not translate into similar changes in vivo even at very high drug doses