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Recent studies have established a concept of tumour necrosis factor-α (TNF-α)/Fas signalling crosstalk, highlighting TNF-α as a critical cytokine in sensitizing hepatocytes to death induced by Fas activation. However, in the exact inflammatory response, besides TNF-α, many other mediators, that might modulate apoptotic response differentially, are released. To resolve the issue, we studied the effects of lipopolysaccharide (LPS), one of the crucial inductors of inflammation in the liver, on apoptotic outcome. We show that LPS-induced inflammation diminishes the sensitivity of hepatocytes to Fas stimulus in vivo at caspase-8 level. Analysis of molecular mechanisms revealed an increased expression of various pro-inflammatory cytokines in non-parenchymal liver cells and hepatocyte-specific increase in Bcl-xL, associated with signal transducer and activator of transcription 3 (Stat3) phosphorylation. Pre-treatment with ruxolitinib, a selective Janus kinase (JAK) 1/2 inhibitor, prevented the LPS-induced Stat3 phosphorylation and restored the sensitivity of hepatocytes to Fas-mediated apoptosis. Furthermore, ruxolitinib pre-treatment diminished the LPS-induced Bcl-xL up-regulation without an inhibitory effect on LPS-induced expression of pro-inflammatory cytokines. In summary, although the reports are showing that the effects of isolated pro-inflammatory mediators, such as TNF-α or neutrophils, are pro-apoptotic, the overall effect of inflammatory milieu on hepatocytes in vivo is Stat3-dependent desensitization to Fas-mediated apoptosis.
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Inflamación/tratamiento farmacológico , Pirazoles/farmacología , Factor de Transcripción STAT3/genética , Factor de Necrosis Tumoral alfa/genética , Receptor fas/genética , Animales , Apoptosis/efectos de los fármacos , Caspasa 8/genética , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Humanos , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/patología , Lipopolisacáridos/toxicidad , Hígado/efectos de los fármacos , Hígado/patología , Ratones , Nitrilos , Pirimidinas , Factor de Transcripción STAT3/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Proteína bcl-X/genéticaRESUMEN
BACKGROUND: All-trans retinoic acid (ATRA)-based treatment of acute promyelocytic leukemia (APL) is the most successful pharmacological treatment of acute myeloid leukemia (AML). Recent development of inhibitors of mutated isocitrate dehydrogenase and dihydroorotate dehydrogenase (DHODH) has revived interest in differentiation therapy of non-APL AML. Our previous studies demonstrated that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAr) induced differentiation of monocytic cell lines by activating the ATR/Chk1 via pyrimidine depletion. In the present study, the effects of AICAr on the viability and differentiation of primary AML blasts isolated from bone marrow of patients with non-APL AML were tested and compared with the effects of DHODH inhibitor brequinar and ATRA. METHODS: Bone marrow samples were obtained from 35 patients and leukemia blasts were cultured ex vivo. The cell viability was assessed by MTT assay and AML cell differentiation was determined by flow cytometry and morphological analyses. RNA sequencing and partial data analysis were conducted using ClusterProfiler package. Statistical analysis was performed using GraphPad Prism 6.0. RESULTS: AICAr is capable of triggering differentiation in samples of bone marrow blasts cultured ex vivo that were resistant to ATRA. AICAr-induced differentiation correlates with proliferation and sensitivity to DHODH inhibition. RNA-seq data obtained in primary AML blasts confirmed that AICAr treatment induced downregulation of pyrimidine metabolism pathways together with an upregulation of gene set involved in hematopoietic cell lineage. CONCLUSION: AICAr induces differentiation in a subset of primary non-APL AML blasts, and these effects correlate with sensitivity to a well-known, potent DHODH inhibitor.
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Aminoimidazol Carboxamida/análogos & derivados , Biomarcadores de Tumor/metabolismo , Crisis Blástica/tratamiento farmacológico , Médula Ósea/efectos de los fármacos , Diferenciación Celular , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Leucemia Mieloide Aguda/tratamiento farmacológico , Ribonucleósidos/farmacología , Aminoimidazol Carboxamida/farmacología , Biomarcadores de Tumor/genética , Crisis Blástica/genética , Crisis Blástica/metabolismo , Crisis Blástica/patología , Médula Ósea/metabolismo , Médula Ósea/patología , Estudios de Casos y Controles , Proliferación Celular , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , RNA-Seq , Células Tumorales CultivadasRESUMEN
Liver transplantation has become standard practice for treating end-stage liver disease. The success of the procedure relies on effective immunosuppressive medications to control the host's immune response. Despite the liver's inherent capacity to foster tolerance, the early post-transplant period is marked by significant immune reactivity. To ensure favorable outcomes, it is imperative to identify and manage various rejection types, encompassing T-cell-mediated, antibody-mediated, and chronic rejection. However, the approach to prescribing immunosuppressants relies heavily on clinical judgment rather than evidence-based criteria. Given that the majority of patients will require lifelong immuno suppression as the mechanisms underlying operational tolerance are still being investigated, healthcare providers must possess an understanding of immune responses, rejection mechanisms, and the pathways targeted by immunosuppressive drugs. This knowledge enables customization of treatments and improved patient care, even though a consensus on an optimal immunosuppressive regimen remains elusive.
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Low-dose cytarabine (LDAC) is a standard therapy for elderly acute myeloid leukemia (AML) patients unfit for intensive chemotherapy. While high doses of cytarabine induce cytotoxicity, the precise mechanism of action of LDAC in AML remains elusive. In vitro studies have demonstrated LDAC-induced differentiation; however, such differentiation is seldom observed in vivo. We hypothesize that this discrepancy may be attributed to the influence of bone marrow (BM) stromal cells on AML cells. Thus, this study aimed to investigate the impact of BM stromal cells on LDAC-induced differentiation of AML cell lines and primary samples. Our results demonstrate that the presence of MS-5 stromal cells prevented LDAC-induced cell cycle arrest, DNA damage signaling and differentiation of U937 and MOLM-13 cell lines. Although transcriptomic analysis revealed that the stroma reduces the expression of genes involved in cytokine signaling and oxidative stress, data obtained with pharmacological inhibitors and neutralizing antibodies did not support the role for CXCL12, TGF-ß1 or reactive oxygen species. The presence of stromal cells reduces LDAC-induced differentiation in primary samples from AML-M4 and myelodysplastic syndrome/AML patients. In conclusion, our study demonstrates that BM stroma reduces differentiation of AML induced by LDAC. These findings provide insights into the limited occurrence of terminal differentiation observed in AML patients, and suggest a potential explanation for this observation.
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The research objectives were to find out the extent of presenteeism and absenteeism in manual workers and whether it differs in clerks that perform sedentary jobs. For that purpose 121 manual workers of "3.maj" were polled, of whom 61 are employed by the shipyard in state ownership and 60 are sub-contracted workers. Also 120 clerks were interviewed, 60 postal employees of "Telecom" Zadar and 60 of the police administration. The Stanford Presenteeism Scale (SPS-6), the internationally recognized questionnaire for assessing presenteeism was used as well as the Rijeka Presenteeism Scale (RPS-6), the new questionnaire compiled for this research, and also the Rijeka Absenteeism Scale (RAS-6). The results have shown that in our country the RPS-6 test is adequate for assessment of presenteeism with high reliability for this type of testing, Crombach's alpha = 0.757. The RAS-6 test has shown a low level of reliability and so have our questions on absenteeism which therefore cannot be considered an official scale. All four groups of employees have shown high positive presenteeism with no considerable differences, p = 0.3610, p > 0.05. Only when the question referred to one's performing efficient work with maximum care there were considerable differences p = 0.023, p < 0.05. The research has shown that the use of SPS-6 is not suitable in our parts probably because of cross-cultural differences, reasoning and speech differences. The research has also shown that the notion presenteeism as a positive presenteeism has to be distinguished from the "sickness-presenteeism" for which the SPS-6 scale could conditionally be suitable, which showed medium presenteeism in our workers, but that cannot be considered reliable due to low correlations. To conclude, although the workers show good, positive presenteeism the working conditions are to be further enhanced as well as the contact with the company management, to maintain such presenteeism and not to exhaust the worker's positive energy.
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Absentismo , Empleo/estadística & datos numéricos , Agencias Gubernamentales/estadística & datos numéricos , Salud Laboral/estadística & datos numéricos , Sector Privado/estadística & datos numéricos , Ausencia por Enfermedad/estadística & datos numéricos , Adulto , Croacia/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conducta Sedentaria , Adulto JovenRESUMEN
Bendamustine is an alkylating agent classified into the group of nitrogen mustard analogues, synthesized almost sixty years ago. It was registered in former East Germany in 1971 and approved by the US Food and Drug Administration in 2008 for treatment of chronic lymphocytic leukemia and indolent Bcell nonHodgkin lymphoma. Considering its beneficial properties in the therapy of relapsed or refractory hematological malignancies, synergistic effects with other antineoplastic agents and increasing recent reports on its immunomodulatory effects, bendamustine has once again gained its justified attention. The uniqueness of bendamustinemediated effects should be observed keeping in mind its distinctive structure with structural similarities to both alkylating agents and purine analogs. In the present review, the current knowledge on the use of bendamustine in oncology, its pharmacokinetics, mechanism of action and toxicity was summarized. In addition, its immunemodulating effects that have not been fully elucidated so far are emphasized, hoping to encourage further investigations of this unique drug.
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Antineoplásicos , Leucemia Linfocítica Crónica de Células B , Linfoma de Células B , Compuestos de Mostaza Nitrogenada , Antineoplásicos/farmacología , Clorhidrato de Bendamustina/farmacología , Clorhidrato de Bendamustina/uso terapéutico , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Linfoma de Células B/tratamiento farmacológico , Compuestos de Mostaza Nitrogenada/química , Compuestos de Mostaza Nitrogenada/farmacología , Compuestos de Mostaza Nitrogenada/uso terapéuticoRESUMEN
Acute myeloid leukemia (AML) is characterized by arrested differentiation making differentiation therapy a promising treatment strategy. Recent success of inhibitors of mutated isocitrate dehydrogenase (IDH) invigorated interest in differentiation therapy of AML so that several new drugs have been proposed, including inhibitors of dihydroorotate dehydrogenase (DHODH), an enzyme in pyrimidine synthesis. Cytarabine, a backbone of standard AML therapy, is known to induce differentiation at low doses, but the mechanism is not completely elucidated. We have previously reported that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAr) and brequinar, a DHODH inhibitor, induced differentiation of myeloid leukemia by activating the ataxia telangiectasia and Rad3-related (ATR)/checkpoint kinase 1 (Chk1) via pyrimidine depletion. In this study, using immunoblotting, flow cytometry analyses, pharmacologic inhibitors and genetic inactivation of Chk1 in myeloid leukemia cell lines, we show that low dose cytarabine induces differentiation by activating Chk1. In addition, cytarabine induces differentiation ex vivo in a subset of primary AML samples that are sensitive to AICAr and DHODH inhibitor. The results of our study suggest that leukemic cell differentiation stimulated by low doses of cytarabine depends on the activation of Chk1 and thus shares the same pathway as pyrimidine synthesis inhibitors.
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Citarabina , Leucemia Mieloide Aguda , Diferenciación Celular , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/metabolismo , Citarabina/farmacología , Citarabina/uso terapéutico , Dihidroorotato Deshidrogenasa , Inhibidores Enzimáticos/farmacología , Humanos , Leucemia Mieloide Aguda/genética , Pirimidinas/uso terapéuticoRESUMEN
All-trans retinoic acid (ATRA)-based therapy for acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML), is the most successful example of differentiation therapy. Although ATRA can induce differentiation in some non-APL AML cell lines and primary blasts, clinical results of adding ATRA to standard therapy in non-APL AML patients have been inconsistent, probably due to use of different regimens and lack of diagnostic tools for identifying which patients may be sensitive to ATRA. In this study, we exposed primary blasts obtained from non-APL AML patients to ATRA to test for differentiation potential in vitro. We observed increased expression of differentiation markers, indicating a response to ATRA, in four out of fifteen primary AML samples. Three samples in which CD11b increased in response to ATRA had an inversion of chromosome 16 as well as the CBFB-MYH11 fusion gene, and the fourth sample was from a patient with KMT2A-rearranged, therapy-related AML. In conclusion, we identified a subgroup of non-APL AML patients with inv(16) and CBFB-MYH11 as the most sensitive to ATRA-mediated differentiation in vitro, and our results can help identify patients who may benefit from ATRA treatment.
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Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Crisis Blástica/genética , Crisis Blástica/patología , Inversión Cromosómica/genética , Cromosomas Humanos Par 16/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Tretinoina/farmacología , Tretinoina/uso terapéutico , Antígeno CD11b/metabolismo , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Subunidad beta del Factor de Unión al Sitio Principal/genética , Fusión Génica/efectos de los fármacos , Reordenamiento Génico/genética , N-Metiltransferasa de Histona-Lisina/genética , Humanos , Proteína de la Leucemia Mieloide-Linfoide/genética , Cadenas Pesadas de Miosina/genéticaRESUMEN
The coronavirus disease 19 (COVID-19) pandemic has had a tremendous impact on every facet of private life and work organisation in virtually all social and economic sectors worldwide. People who stand on the first line of defence are healthcare workers (HCWs) risking exposure to infected patients. However, even though they are often affected by COVID-19 and associated somatic and mental health problems, COVID-19 as a new illness was not immediately acknowledged as occupational disease. This is why several groups of HCWs contacted their occupational medicine physicians in 2020 with a request to register the infection with SARS-CoV-2 as occupational disease. In an attempt to support their appeals and show that hospital workers have a high occupational risk of COVID-19, this study presents COVID-19 incidence and symptoms in 100 employees working at 11 clinics of the Clinical Hospital Centre (CHC) Rijeka, Croatia from 1 June to end December 2020. All of them were infected with SARS-CoV-2 and took sick leave, which lasted 13.6±2.6 days in average. This study also looks into the role of occupational medicine physicians in prospective monitoring of acute and long-acting consequences of COVID-19 that might occur in HCWs.
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COVID-19 , Enfermedades Profesionales , Croacia/epidemiología , Personal de Salud , Hospitales , Humanos , Enfermedades Profesionales/epidemiología , Estudios Prospectivos , SARS-CoV-2RESUMEN
5-Aminoimidazole-4-carboxamide ribonucleoside (AICAr) has been one of the most commonly used pharmacological modulators of AMPK activity. The majority of early studies on the role of AMPK, both in the physiological regulation of metabolism and in cancer pathogenesis, were based solely on the use of AICAr as an AMPK-activator. Even with more complex models of AMPK downregulation and knockout being introduced, AICAr remained a regular starting point for many studies focusing on AMPK biology. However, there is an increasing number of studies showing that numerous AICAr effects, previously attributed to AMPK activation, are in fact AMPK-independent. This review aims to give an overview of the present knowledge on AMPK-dependent and AMPK-independent effects of AICAr on metabolism, hypoxia, exercise, nucleotide synthesis, and cancer, calling for caution in the interpretation of AICAr-based studies in the context of understanding AMPK signaling pathway.
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Aminoimidazol Carboxamida/análogos & derivados , Hipoglucemiantes/farmacología , Proteínas Quinasas/metabolismo , Ribonucleótidos/farmacología , Quinasas de la Proteína-Quinasa Activada por el AMP , Aminoimidazol Carboxamida/farmacología , Animales , Carcinogénesis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Humanos , Miocitos Cardíacos/efectos de los fármacosRESUMEN
OBJECTIVE: To evaluate clinical and laboratory effects of delaying ocrelizumab infusions during the COVID-19 pandemics in people with multiple sclerosis (pwMS). METHODS: We have retrospectively searched our electronic database and identified 33 pwMS who had a delay in treatment due to COVID-19 pandemics. The following data were extracted: age, sex, multiple sclerosis (MS) phenotype: relapsing-remitting (RRMS) or primary progressive multiple sclerosis (PPMS), disease duration, Expanded Disability Status scale (EDSS), previous disease modifying therapy (DMT), number of ocrelizumab cycles prior to the lockdown, dates of first ocrelizumab infusion, last ocrelizumab infusion prior to the lockdown and delayed ocrelizumab infusion after the lockdown. Flow cytometry results, relapses and EDSS progression prior to the delayed ocrelizumab infusion after the lockdown were extracted. RESULTS: The mean time between two ocrelizumab infusion during the lockdown was 7.72±0.64 (range 6.07 to 8.92) months. The mean time between last ocrelizumab infusion and the lymphocyte sampling prior to post COVID infusion was 6.59±0.95 (range 5.18 to 8.49) months. In this period, none of the studied patients had a relapse. In a multivariable linear regression analysis, time from last ocrelizumab infusion to lymphocyte sampling prior to the next infusion was the only significant predictor for CD19+ B cells count, when corrected for the number of previous ocrelizumab cycles and MS phenotype (RRMS or PPMS) (B=7.981, 95% C.I. 3.277-12.686, p=0.002). CONCLUSIONS: We have not shown clinical consequences of delaying ocrelizumab due to COVID-19 pandemics. However, the delay in dosing of ocrelizumab was an independent predictor of repopulation of B cells.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , COVID-19 , Factores Inmunológicos/administración & dosificación , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/sangre , Esclerosis Múltiple Crónica Progresiva/inmunología , Esclerosis Múltiple Recurrente-Remitente/sangre , Esclerosis Múltiple Recurrente-Remitente/inmunología , Estudios Retrospectivos , Factores de Tiempo , Tiempo de TratamientoRESUMEN
Occupational medicine has taken over from Family practice the treatment of work injuries and occupational diseases in the Republic of Croatia since January 1, 2008. The reason was too many long-lasting sick leaves which general practitioners were unable to curb adequately. The research objective was to show the results of the one-year follow-up of the carried out reform, i.e. the efficiency of Occupational medicine in the new function. The methods of data comparison and McNemar statistics were used of one-year follow-up in an Occupational medicine surgery that cares for 5800 employees in Littoral-Mountainous County. From 32 patients in February 2008, 30 work injuries and 2 occupational diseases, the overall number diminished in February 2009 to 13 patients with work injuries and no diagnosed occupational disease, p < 0.001 for work injuries. Also the number of patients on sick leave over three months fell from 14 to 4. Occupational medicine has proved to be more efficient than Family practice in assessing sick leave. This does not mean that family practice, due to a number of reasons mentioned in the research, is of less importance. For the patient can always return to his general practitioner for further treatment, and sick leave if necessary, but not on the grounds of work injury and occupational disease.
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Medicina Familiar y Comunitaria , Enfermedades Profesionales/terapia , Medicina del Trabajo , Heridas y Lesiones/terapia , Adulto , Croacia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Ausencia por Enfermedad/estadística & datos numéricosRESUMEN
In December 2003 in Rijeka, Croatia, a work accident happened when in the meat industry 'Vir" a forklift damaged the ammonia pipe. Two butchers were acutely poisoned. The objective is to warn of the danger of ammonia and of the need to improve preventive programs of occupational medicine. The method of comparing the two injured workers, i.e. their spirometric values, was used. The results showed progressive diminishing of patients' respiratory abilities, in the patient with lungs transplanted VC 32%, FVC 33%, FEV1 16% and FEF75% = 6% in 2006, the year when he died. In the patient that survived, the values in 2008 were VC 43.5%, FVC 27.2%, FEV1% 56.7% and FEF75% = 6%. The patients' CT showed diffused fibrosing and bronchiectasiae. Obliterating bronchiolitis developed in both patients. The second patient is the lung transplantation candidate. The first patient developed post transplantation cytomegalovirus pneumonia so he fought CMV antigenemia and infection till the end.
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Amoníaco/envenenamiento , Enfermedades Profesionales/terapia , Adulto , Humanos , Pulmón/fisiopatología , Masculino , Carne , Persona de Mediana Edad , Enfermedades Profesionales/diagnóstico , Enfermedades Profesionales/fisiopatología , Lugar de TrabajoRESUMEN
The purpose is to find out whether the diagnostics and registration of patients with mesothelioma in the Littoral Mountainous County of Croatia corresponds to the world trends. Further, the intention was to show the incidence of the disease and suggest the measures of prevention in the county of 400,000 inhabitants and its center Rijeka with 140,000 people. To that purpose 43 patients with mesothelioma were monitored in two groups: 25 shipyard workers, mean age 66, and 18 workers in other occupations, mean age 62. Statistically the group did not differ significantly in the incidence of placks, left or right side effusion. The pleural puncture showed the significance (p < 0.05) for incidence of rouse cells. In 20 patients out of 43 mesothelioma was confirmed by taking the material for pathohistology by means of VATS (video assisted thoracoscopy) and in 14 patients by TTB (transthoracic biopsy) with CT control. Spirometric values showed moderate restrictive difficulties. Although a considerable improvement in diagnosing mesothelioma has been achieved in the last five years an improved prevention activity by occupational medicine is required not only by periodic checkups of the exposed persons and examinations for retired workers with respiratory difficulties, but also by stimulating work case histories.
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Mesotelioma/prevención & control , Enfermedades Profesionales/prevención & control , Neoplasias Pleurales/prevención & control , Anciano , Biopsia con Aguja/métodos , Croacia/epidemiología , Femenino , Humanos , Incidencia , Masculino , Mesotelioma/epidemiología , Mesotelioma/patología , Persona de Mediana Edad , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/patología , Neoplasias Pleurales/epidemiología , Neoplasias Pleurales/patología , Cirugía Torácica Asistida por VideoRESUMEN
The aim of the study was to find out whether firefighters' professional exposure to the noise of sirens, motor water pumps and transportation by heavy vehicles causes biauricular hearing impairment. Furthermore, on the basis of the results the aim was to find out whether it is necessary to launch a hearing preservation program and additional health protection measures for this specific working population. The method of physical examination and audiometry was used. Thirty-four professional firefighters from Opatija and 30 workers of Rijeka Promet employed at the town parking lots underwent audiometry on a Sibelmed AC 50 device and then analyzed. The results of biauricular audiometry showed significant differences in hearing damage between the firefighters and Rijeka Promet employees at higher frequencies where hearing damage begins, i.e. at 4 kHz and 8 kHz (P < 0.05). The firefighters' maximal hearing loss of 30.58 +/- 24.66 dB for the right ear at 4 kHz and of 28.52 +/- 24.66 dB for the right ear at 8 kHz were higher than the hearing loss of the parking lot employees with maximal hearing loss of 17.00 +/- 13.10 dB at 4 kHz and of 16.33 +/- 13.89 dB at 8 kHz. The results of left ear audiometry were very close to those of right ear in both groups of subjects. The linear regression analysis yielded almost identical positive correlation between the time spent at the job and hearing damage, with correlation factor r = +.55 for the right and left ear at 4 kHz. The noise was measured at the Opatija Fire Station. Several measurements were performed: on the premises where firefighters are exposed to so-called communal noise, measurements at 2 m of the fire truck when sirens are sounded, noise measurements in driver's cab when sirens are sounded, and the noise made by motor water pump used in firefighting. Also, measurements were performed on the spot, i.e. at the working place of parking lot employees in the center of Rijeka where they stay most of the time, and on the street by the parking lot. It may be concluded that noise-induced hearing damage in firefighters is a major problem in this working population, their physical and mental condition being very good, which is to be expected of the groups of operatives on whom the lives of "ordinary" people often depend. Hearing damage is the only weak point of firefighters, although fairly mild to moderate at higher frequencies, so medical experts in cooperation with their chiefs should persuade them to wear hearing protection, which could be discomforting in firefighting operations. Firemen are employed mainly at a young age when their hearing is normal. A parallel may be drawn with the military. Professional soldiers who are physically perfectly fit, at periodical medical examinations are often assessed as "limited service" due to hearing damage, although their hearing was good when they started the career. Hearing in the young population is generally good, in Primorje-Gorski Kotar County the average hearing level is 10 dB at all routine frequencies on audiometry, so hearing damage is not among illnesses that might cause difficulties to young recruits. To conclude, to preserve good hearing in both young and experienced firefighters, the Hearing Preservation Program should be more strictly implemented in the Primorje-Gorski Kotar County.
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Pérdida Auditiva Provocada por Ruido/diagnóstico , Ruido en el Ambiente de Trabajo/efectos adversos , Enfermedades Profesionales/diagnóstico , Adulto , Audiometría , Incendios , Humanos , MasculinoRESUMEN
BACKGROUND: Psychiatric disorders are not compatible with carrying firearms or with driving a car. Persons with such disorders are often not employed and are persistent in demanding invalidity pensions, but some of them also insist on holding on to the mentioned licenses. In such cases, where persons are already in possession of firearms and driving licences, it never occurs to them, that they should surrender their permits back. AIM Pointing to the importance of OM controlling firearm/car driving licenses. CASE REPORTS: This paper discusses the problem of three cases that should be widely recognised as it is potentially life-threatening to other people. The first is the case of a war veteran in retirement with PTSD that had his application for firearms licence rejected by the authorities. The second is the case of a labourer who suffers from a depressive disorder, temporarily incapable of work. The third is the case of a war veteran, a chronic alcoholic with toxic epilepsy, who is applying for invalidity retirement but wants to keep his driving license. CONCLUSION: Occupational medicine assess every single worker by applying advanced methods and psycho tests that enable a thorough assessment of work capacity and fitness for carriage of firearms, driving as well as the assessment of psychiatric disorders, which are the most delicate to assess.
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Differentiation therapy of acute promyelocytic leukemia with all-trans retinoic acid represents the most successful pharmacological therapy of acute myeloid leukemia (AML). Numerous studies demonstrate that drugs that inhibit mechanistic target of rapamycin (mTOR) and activate AMP-kinase (AMPK) have beneficial effects in promoting differentiation and blocking proliferation of AML. Most of these drugs are already in use for other purposes; rapalogs as immunosuppressants, biguanides as oral antidiabetics, and 5-amino-4-imidazolecarboxamide ribonucleoside (AICAr, acadesine) as an exercise mimetic. Although most of these pharmacological modulators have been widely used for decades, their mechanism of action is only partially understood. In this review, we summarize the role of AMPK and mTOR in hematological malignancies and discuss the possible role of pharmacological modulators in proliferation and differentiation of leukemia cells.
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Proteínas Quinasas Activadas por AMP/metabolismo , Leucemia Mieloide Aguda/tratamiento farmacológico , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Proteínas Quinasas Activadas por AMP/química , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/metabolismo , Aminoimidazol Carboxamida/uso terapéutico , Ensayos Clínicos como Asunto , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Metformina/metabolismo , Metformina/uso terapéutico , ARN Interferente Pequeño/metabolismo , ARN Interferente Pequeño/uso terapéutico , Ribonucleósidos/metabolismo , Ribonucleósidos/uso terapéutico , Transducción de Señal/efectos de los fármacos , Sirolimus/análogos & derivados , Sirolimus/metabolismo , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR/químicaRESUMEN
Abstrat A 50-year-old female patient suffering from a severe form of epidermolysis bullosa acquisita (EBA) took legal action against the Croatian Pension Insurance Institute (CPII) in an attempt to overturn their assessment that she was no longer capable of working as a seamstress but still capable of doing administrative jobs. Her claim was that she was not capable of doing any job at all. She was first diagnosed EBA in 2000, and the disease progressed slowly with intermittent remissions. In 2012, skin erosions appeared on her feet, followed by the loss of all toenails and lesions and infiltrations on the tongue and oral mucosa. Her whole body was covered in oozing wounds, she was in pain, and parts of her skin would stick to fabric while changing clothes or bandages. The most recent findings showed oesophageal stricture. She can consume only liquid food and is on the waiting list for receiving a feeding tube. The occupational health expert witness confirmed that the patient was generally incapable of work and was fighting her life. The judge and CPII lawyers fully accepted this report and the earlier assessment was overturned. To avoid incompetent assessments of working (in)capacity in the future, CPII and similar institutions should engage occupational medicine specialists to work in their assessment teams.
Asunto(s)
Epidermólisis Ampollosa Adquirida , Medicina del Trabajo/legislación & jurisprudencia , Medicina del Trabajo/métodos , Reinserción al Trabajo/legislación & jurisprudencia , Índice de Severidad de la Enfermedad , Croacia , Estudios de Evaluación como Asunto , Femenino , Humanos , Persona de Mediana EdadRESUMEN
The aim of this research is to find out whether the firefighter manpower is adequate to the requirements in the field under the most severe conditions. It also attempts to test whether firefighters' working ability corresponds to their age. To that purpose 220 Croatian firefighters from the Littoral Mountainous county, 99 professional firefighters from the city of Rijeka, 45 professional firefighters from its suburbs and 76 volunteer firefighters from the suburbs were submitted to load test, fitness test--stepping on the bench for three minutes, repetitive power test--sit-ups lasting 1 minute, and a leap-explosive power test. The fitness test was repeated carrying Drdäer's respiratory apparatus PSS 100 with compressed air, so respiratory values were compared before and after the burden of the respiratory apparatus. The results have shown that professional firefighters from the city have the mean increased body mass index (BMI) 26, and professionals from the suburbs BMI 27. In spite of the increased body mass they showed good fitness, spirometric values before and after the load showed neither restrictive nor obstructive ventilation difficulties, which indicates a good condition of cardio respiratory system and also adequate protective equipment. The initial hypothesis has been confirmed: with age, equipped with personnel does not necessarily mean operative equipment, because linear regressive analyses have shown a negative correlation coefficient in relation to repetitive and explosive power. Also, on the average somewhat younger volunteer firefighters are stronger in performing the repetitive power test (p < 0.05) compared to professional firefighters. Occupational medicine should suggest administrative health measures to improve the accelerated retirement plan and shorten the shifts so that all available firefighters could instantaneously be included in the field intervention.
Asunto(s)
Incendios , Trabajo de Rescate , Evaluación de Capacidad de Trabajo , Carga de Trabajo , Adolescente , Adulto , Factores de Edad , Índice de Masa Corporal , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Aptitud Física , Estrés Psicológico/psicologíaRESUMEN
The total of 178 firefighters from the Littoral Mountainous County, the Republic of Croatia, have undergone psychotestings in three groups--99 professionals from city Rijeka, 44 professionals from suburb and 35 volunteers from suburb. The scores of PSS 10 Cohen Stress Perception Scale, COPE questionnaire, STAI X1 anxiety test as condition and STAI X2 anxiety test as trait personality and Beck Depression Inventory were analyzed. The results have shown that firefighters do not suffer from negative effects of stress. There is slight anxiety as condition in city firefighters and medium anxiety as trait personality in all firemen. All firefighters are often problem-oriented, need only occasionally compassion of environment and sometimes react by avoiding to face stress. They differ significantly by depression (p < 0.001), which is negligible in relation to ordinary population. "Working anxiety", i.e. medium anxiety which is a distinctive trait of their personality becomes the necessary initiator of functioning in the most difficult working conditions.