Genomic alterations and enormous monoclonal immunoglobulin production cause multiple myeloma to heavily depend on proteostasis mechanisms, including protein folding and degradation. These findings support the use of proteasome inhibitors for treating multiple myeloma and mantle cell lymphoma. Myeloma treatment has evolved, especially with the availability of new drugs, such as proteasome inhibitors, into therapeutic strategies for both frontline and relapsed/refractory disease settings. However, proteasome inhibitors are generally not effective enough to cure most patients. Natural resistance and eventual acquired resistance led to relapsed/refractory disease and poor prognosis. Advances in the understanding of cellular proteostasis and the development of innovative drugs that also target other proteostasis network components offer opportunities to exploit the intrinsic vulnerability of myeloma cells. This review outlines recent findings on the molecular mechanisms regulating cellular proteostasis pathways, as well as resistance, sensitivity, and escape strategies developed against proteasome inhibitors and provides a rationale and examples for novel combinations of proteasome inhibitors with FDA-approved drugs and investigational drugs targeting the NRF1 (NFE2L1)-mediated proteasome bounce-back response, redox homeostasis, heat shock response, unfolding protein response, autophagy, and VCP/p97 to increase proteotoxic stress, which can improve the efficacy of antimyeloma therapy based on proteasome inhibitors.

• MeSH
• Drug Resistance, Neoplasm MeSH
• Proteostasis * drug effects   MeSH
• Proteasome Inhibitors * therapeutic use   pharmacology   MeSH
• Humans MeSH
• Multiple Myeloma * drug therapy   metabolism   MeSH
• Antineoplastic Agents * therapeutic use   pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Musculoskeletal disorders, affecting as many as 1.3 billion people worldwide, are the leading cause of disability and impose a substantial health and socioeconomic burden. Despite the high prevalence of these conditions, translational research in this field is far from optimal, highlighting the need for stronger collaboration between basic and clinical scientists. This paper, authored by members of the basic and clinical action groups of the European Calcified Tissue Society (ECTS) and endorsed by the Board of the ECTS, examines the key barriers to effective translational research in musculoskeletal diseases, including clinician workload, differences in professional language and culture, physical distance between research sites, and insufficient interdisciplinary funding. Through interviews with eight institutional managers across five European countries, we observed that in some institutions, the collaboration between basic scientists and clinicians was regarded as no concern (but with room for improvement), and in most institutions it was recognised as a serious issue. We found consensus on the importance of collaboration yet identified discrepancies in the provision of structural and financial support. Based on these findings, we propose strategic initiatives to bridge the gap between basic and clinical research. Suggested measures include dedicated translational funding, integrated research facilities, collaborative scientific forums, strategic collaborations, establishment of physician-scientists, and, finally, bringing basic and clinical researchers together in the same building or even in a combined department. Notable successes, such as the development of the anti-osteoporotic drugs, romosozumab and denosumab, underscore the value of a coordinated approach and exemplify how shared insights between laboratory research and clinical practice can lead to impactful therapeutic advances. Moving forward, we advocate for institutional commitments to foster a robust translational research environment, as well as tailored funding initiatives to support such efforts. This paper serves as a call for discussion and action to enhance interdisciplinary cooperation to advance musculoskeletal medicine and improve outcomes for patients with debilitating musculoskeletal diseases.

• MeSH
• Biomedical Research organization & administration   MeSH
• Cooperative Behavior MeSH
• Humans MeSH
• Musculoskeletal Diseases * therapy   MeSH
• Translational Research, Biomedical * MeSH
• Research Personnel MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH

Objectives. The digital era has enhanced the possibility of working flexibly, which provides employees with many advantages (e.g., greater autonomy). However, on the other hand, they tend to work longer and faster, which is accompanied by higher levels of work pressure, strain, and stress. In line with the Job Demands-Resources theory, the aim of this cross-sectional study was to explore the relationship between workload and well-being (engagement, burnout) and to test the moderating role of promotion and prevention job crafting (JC) strategies in this relationship in the context of flexible work. Sample and settings. Data were collected online. The research sample consisted of 309 participants, working in a flexible working arrangement, preferably through a partial or full-time home office. Statistical analyses. Correlational, hierarchical regression and moderation analysis were performed. Results. Higher level of workload and prevention JC was positively related to higher burnout. Promotion JC had a positive effect on work engagement, whereas prevention JC related to engagement negatively. Contrary to our assumption, a higher level of promotion JC increased the negative effect of workload on work engagement. The effect of workload on burnout was moderated by the level of prevention JC. Specifically, burnout increased with workload at all levels of prevention JC, but the rate of increase was highest at low levels of prevention JC. The mitigating role of promotion JC between workload and burnout, as well as the effect of prevention JC on the relationship between workload and engagement, have not been confirmed. Conclusion. The findings underscore the intricate and sometimes unexpected interactions between JC strategies, workload, engagement, and burnout in flexible work settings. Future research should further investigate these dynamics, particularly the surprising impact of promotion JC under higher workload in flexible environments, to gain a clearer understanding of how various approaches can be refined to enhance employee well-being and performance. Limitations. Cross-sectional design, the size and diversity of the research sample and the use of self-assessment tools.

BACKGROUND: During the COVID-19 pandemic, the majority of patients received ambulatory treatment, highlighting the importance of primary health care (PHC). However, there is limited knowledge regarding PHC workload in Europe during this period. The utilization of COVID-19 PHC indicators could facilitate the efficient monitoring and coordination of the pandemic response. The objective of this study is to describe PHC indicators for disease surveillance and monitoring of COVID-19's impact in Europe. METHODS: Descriptive, cross-sectional study employing data obtained through a semi-structured ad hoc questionnaire, which was collectively agreed upon by all participants. The study encompasses PHC settings in 31 European countries from March 2020 to August 2021. Key-informants from each country answered the questionnaire. Main outcome: the identification of any indicator used to describe PHC COVID-19 activity. RESULTS: Out of the 31 countries surveyed, data on PHC information were obtained from 14. The principal indicators were: total number of cases within PHC (Belarus, Cyprus, Italy, Romania and Spain), number of follow-up cases (Croatia, Cyprus, Finland, Spain and Turkey), GP's COVID-19 tests referrals (Poland), proportion of COVID-19 cases among respiratory illnesses consultations (Norway and France), sick leaves issued by GPs (Romania and Spain) and examination and complementary tests (Cyprus). All COVID-19 cases were attended in PHC in Belarus and Italy. CONCLUSIONS: The COVID-19 pandemic exposes a crucial deficiency in preparedness for infectious diseases in European health systems highlighting the inconsistent recording of indicators within PHC organizations. PHC standardized indicators and public data accessibility are urgently needed, conforming the foundation for an effective European-level health services response framework against future pandemics.

• MeSH
• COVID-19 * epidemiology   MeSH
• Humans MeSH
• Cost of Illness MeSH
• Pandemics MeSH
• Primary Health Care MeSH
• Cross-Sectional Studies MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Cyprus MeSH

Ethiopia increased the availability of latrines notably, but the sanitation facilities rarely meet hygienic standards. Therefore, the market-based sanitation (MBS) programme has been implemented across the country for nearly a decade to expand the market and boost the demand for hygienic sanitation products and services. While it does not seem that the MBS would bring any notable change in sanitation conditions so far, its implementation challenges are not adequately understood. To address this gap, this article delves into the grassroots-level implementation of MBS in the Wolaita zone. The study relies on qualitative data gathered through interviews with various stakeholders, examining both demand- and supply-side challenges. Some issues identified were external to MBS implementation, such as high inflation and an unstable political and security situation in Ethiopia. Additionally, the study reveals that more general deficiencies of the Ethiopian health extension program, including the stress and discouragement of local change agents (health extension workers, health development army members) due to workloads and low remuneration, have adversely impacted MBS delivery. The implementation of MBS has also not effectively addressed the affordability of hygienic sanitation products. On the supply side, economic constraints and organizational inefficiencies have hindered the development of the sanitation market, preventing it from reaching a critical mass. Our research suggests that MBS alone will not suffice to improve sanitation in Ethiopia.

• MeSH
• Health Promotion MeSH
• Sanitation * MeSH
• Health Personnel MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Ethiopia MeSH

Cíle: Zhodnocení úrovně psychické pracovní zátěže a kvality života u sester v České republice pomocí dostupných standardizovaných dotazníkových metod v průběhu pandemie covidu-19. Metodika: Byla provedena průřezová epidemiologická studie, a to v době samotné pandemie v roce 2021. Bylo provedeno dotazníkové šetření u 450 sester. Byly použity dva standardizované dotazníky, a to Meisterův dotazník na subjektivní vnímání psychické zátěže a dotazník SF-36 na kvalitu života. Výsledky: Analyzováním míry psychické zátěže se ukázalo, že jednotlivé škály psychické zátěže (přetížení, monotonie, nespecifický faktor a celková zátěž) významně (p < 0,05) a negativně (r < 0) korelují s kvalitou života v každé doméně. Nejvyšší stupeň psychické zátěže se zjistil u sester pracujících na vyčleněných odděleních a místech určených pro pacienty s covidem, pohotovostech a na jednotkách intenzivní péče. Závěry: Pandemie covidu-19 měla negativní vliv na celkový chod zdravotnictví z hlediska nepřipravenosti na tuto situaci. Nejvíce postihla pracovníky pracující přímo s nakaženými pacienty. Je proto potřeba se v budoucnu na podobnou zátěž lépe a koordinovaně připravovat.

Objectives: The assessment of the level of work-related stress and quality of life among nurses in the Czech Republic throughout the utilisation of available standardised questionnaire methods during the COVID-19 pandemic. Methodology: A cross-sectional epidemiological study was conducted during the pandemic year of 2021. A questionnaire was administered to 450 nurses. Two standardised questionnaires were employed: Meister's questionnaire for subjective assessment of work-related mental load and the SF 36 questionnaire for quality of life. Results: Through the analysis of the level of mental strain, it became apparent that individual scales of mental strain (overload, monotony, nonspecific factors and overall strain) significantly (p < 0.05) and negatively (r < 0) correlated with quality of life in each domain. The most severe level of mental strain was identified among nurses working in designated COVID-19 patient departments, emergency departments, and intensive care units. Conclusion: The COVID-19 pandemic negatively impacted the overall function of healthcare, primarily due to the lack of preparedness for such scenarios. Health care workers directly caring for infected patients were affected the most. Therefore, there is a need to thoroughly prepare for similar straining situations in the future.

• MeSH
• COVID-19 * MeSH
• Quality of Life MeSH
• Humans MeSH
• Pandemics MeSH
• Workload psychology   MeSH
• Surveys and Questionnaires MeSH
• Stress, Psychological * MeSH
• Nurses * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH

Ošetrovateľstvo sa zameriava na podporu zdravia, prevenciu ochorení a starostlivosť pri fyzických, či mentálnych ochoreniach, ktoré postihujú ľudí v každom veku. Sestry celosvetovo tvoria takmer polovicu pracovnej sily v zdravotníctve a poskytujú takmer 80 % praktickej starostlivosti. V mnohých prípadoch sú sestry často prvým zdravotníckym pracovníkom a niekedy aj jediným, s ktorým pacienti prichádzajú do kontaktu. V súčasnosti majú sestry vyššiu prevalenciu muskuloskeletálnych ochorení súvisiacich s výkonom ošetrovateľskej praxe. Tieto ochorenia majú značný vplyv na ich zdravie a sú príčinami práceneschopnosti a invalidity.

Nursing focuses on health promotion, disease prevention and care for physical or mental illnesses that affect people of all ages. Nurses make up almost half of the healthcare workforce worldwide and provide almost 80 % of practical care. In many cases, nurses are often the first healthcare professional, and sometimes the only one, that patients come into contact with. Currently, nurses have a higher prevalence of musculoskeletal diseases related to the performance of nursing practice. These diseases have a significant impact on the health of nurses and are the causes of sickness absence and disability.

• MeSH
• Ergonomics methods   MeSH
• Occupational Health MeSH
• Workload MeSH
• Stress, Psychological MeSH
• Physical Exertion MeSH
• Nurses MeSH

Príspevok sa zaoberá vplyvom generačnej diverzity na pracovnú záťaž sestier. V článku vychádzame z najnovších poznatkov a dostupných informácií, ktoré sa venujú generačnej teórii. Uvádzame charakteristiku jednotlivých generačných kohort s dôrazom na pracovnú záťaž. Cieľom článku je priniesť nové poznatky zamerané na generačnú diverzitu a jej možný vplyv na pracovnú záťaž sestier.

The article deals with the impact of generational diversity on nurses' workload. The paper is based on the latest knowledge and available information, which are devoted to the generational theory. We present the characteristics of individual generational cohorts with an emphasis on workload. The aim of the article is to bring new knowledge focused on generational diversity and its possible impact on nurses' workload.

• MeSH
• Behavior and Behavior Mechanisms MeSH
• Interpersonal Relations MeSH
• Attitude MeSH
• Workload MeSH
• Intergenerational Relations MeSH
• Nurses MeSH

Úvod: Pracovné prostredie sestier charakterizujú viaceré rizikové faktory, ktoré výrazne môžu ovplyvniť prežívanie, fyzické i psychické zdravie a spokojnosť s prácou. Pracovná spokojnosť môže mať významný vplyv na kvalitu starostlivosti o pacientov a na celkovú výkonnosť zdravotníckych zariadení. Pracovnú spokojnosť často ovplyvňujú problémy, ako je pracovná záťaž, nedostatok personálu, nedostatočná organizácia práce, nedostatočná podpora od nadriadených a iné. Uvedené aspekty sú tie, ktoré častokrát vedú k syndrómu vyhorenia. Pokiaľ nespokojnosť s pracovnými podmienkami a riziko syndrómu vyhorenia pretrváva, mnohokrát to vedie k pracovnej migrácii. Cieľom výskumu bolo zistiť vzťah medzi vybranými faktormi pracovného prostredia sestier a ich pracovnou spokojnosťou a rizikom syndrómu vyhorenia. Materiál a metódy: Výskumnú vzorku tvorilo 263 sestier, ktoré poskytujú ošetrovateľskú starostlivosť geriatrickým pacientom. Priemerná dĺžka praxe sestier v geriatrii bola 10,31 rokov. Na zber údajov bol použitý dotazník rizika syndrómu vyhorenia (SMBM) a dotazník vlastnej konštrukcie zameraný na záťažové a problematické pracovné situácie na pracovisku a na pracovnú spokojnosť sestier. Výsledky: Medzi faktory pracovnej záťaže, ktoré významne korelujú s pracovnou spokojnosťou, patria pracovné podmienky, organizácia práce (pracovný čas, množstvo víkendov, veľa práce za vymedzený čas, práca nad rámec svojich kompetencií), nedostatočné materiálno-technické zabezpečenie. S rizikom syndrómu vyhorenia korelujú najmä pracovné podmienky, organizácia práce, atmosféra a vzťahy na pracovisku. S pracovnou záťažou ani rizikom syndrómu vyhorenia výrazne nekoreluje finančné ohodnotenie, sociálne výhody, osobnostný rozvoj, kariérny rast. Záver: Zvyšujúca sa pracovná záťaž, zvyšujúce sa nároky na sestry, nedostatočná organizácia práce, nedostatok personálu vedú k zdravotným problémom, pracovnej nespokojnosti a syndrómu vyhorenia, čo vedie sestry k odchodu zo zamestnania alebo zmene pracoviska, a to nielen v rámci Slovenska, ale aj do zahraničia.

Objectives: The working environment of nurses is characterized by several risk factors that can significantly affect survival, physical and psychological health and job satisfaction. Job satisfaction can have a significant impact on the quality of patient care and the overall performance of healthcare facilities. Job satisfaction is often affected by problems such as workload, lack of staff, insufficient work organization, insufficient support from superiors, and others. The mentioned aspects are the ones that often lead to burnout syndrome. If dissatisfaction with working conditions and the risk of burnout persist, it often leads to labor migration. The aim of the research was to determine the relationship between selected factors of the nurses‘ work environment and their job satisfaction and the risk of burnout. Material and Methods: The research sample consisted of 263 nurses, who provide nursing care to geriatric patients. The average length of practice of nurses in geriatrics was 10.31 years. The burnout syndrome risk questionnaire (SMBM) and self-constructed questionnaire focused on burdensome and problematic work situations at the workplace and job satisfaction of nurses were used for data collection. Results: Among the workload factors that are significantly correlated with job satisfaction include working conditions, work organization (working hours, number of weekends, a lot of work in a limited time, work beyond the scope of one’s competences), insufficient material and technical security. Working conditions, work organization, atmosphere and relationships at the workplace are mainly correlated with the risk of burnout. Financial compensation, social benefits, personal development, career growth are not significantly correlated with workload or the risk of burnout. Conclusion: Increasing workload, increasing demands on nurses, insufficient organization of work, lack of staff lead to health problems, job dissatisfaction and burnout syndrome, which leads nurses to leave their jobs or change workplaces, not only within Slovakia, but also in abroad.

• MeSH
• Adult MeSH
• Geriatric Nursing * MeSH
• Middle Aged MeSH
• Humans MeSH
• Working Conditions * psychology   statistics & numerical data   MeSH
• Job Satisfaction MeSH
• Workload psychology   MeSH
• Burnout, Professional prevention & control   MeSH
• Surveys and Questionnaires MeSH
• Nurses psychology   statistics & numerical data   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Geographicals
• Slovakia MeSH

Background: The paper deals with older workers and the issue of combining informal care for family members with paid employment, which is increasingly important in the light of socio-demographic changes in society - namely demographic ageing and the lengthening of working life. The topic is highly relevant to the group of non-medical healthcare professions studied, as they combine care in the professional and domestic spheres. Purpose of the research: The aim of the research is to point to gender inequalities in how the combination of formal and informal care impacts the work and personal spheres of (pre-) retirement-age nonmedical healthcare workers. Methods: The article is based on the analysis of 36 qualitative interviews with nonmedical healthcare workers in Czechia. We used thematic analysis and approached the issue of (un)doing gender from a social constructivist perspective. Results: The results suggest that women and men in nonmedical healthcare professions face differences in relation to the double care burden in older age. Women are more likely to be affected by a combination of dual care, which has implications for their workload, financial remuneration, etc., whereas men are under greater pressure to perform at work, which becomes increasingly difficult at older ages. Conclusion: Gendered character of double care has implications for gender inequalities in mental and physical health and for the gender pension gap.

• MeSH
• Epidemiologic Factors MeSH
• Gender Role * MeSH
• Middle Aged MeSH
• Humans MeSH
• Nursing Care organization & administration   MeSH
• Caregivers * economics   organization & administration   MeSH
• Surveys and Questionnaires MeSH
• Interviews as Topic MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH