Burnout has been recognized as a serious health problem. Nurses as a professional group are at a high risk of burnout occurrence, especially when facing burden associated with the COVID-19 pandemic. Despite evidence that higher job demands lead to burnout, there is less known about the indirect effect of job demands and resources on burnout via surface acting. Using the JD-R framework, this study examined how job demands and resources affected burnout among Polish nurses and whether these relationships are mediated by surface acting and moderated by coping with the workload.A sample of 270 nurses from the biggest hospital in Southern Poland filled out an online questionnaire at the time between the fourth and the fifth wave of the COVID-19 pandemic in Poland. The Polish adaptations of Oldenburg Burnout Inventory (OLBI), Organizational Constraints Scale (OCS), Interpersonal Conflict at Work Scale (ICAWS), Areas of Worklife Survey (AWS), and Emotional Labor Scale (ELS) were used. Mediation and moderation analyses were carried out in the SPSS macro-PROCESS.Surface acting partially mediated the positive association between organizational constraints and interpersonal conflict at work and burnout, as well as the negative association between the perceived organizational support and burnout. Coping with workload moderated the direct effect of organizational constraints on burnout via surface acting.The findings enrich the knowledge of the mediating and moderating mechanisms to explain the association between job demands, resources and burnout among nurses. There have been proposed interventions concerning increasing organizational support, effective emotional regulation of management education and psychological training regarding adequate coping strategies which could help reduce or prevent the occurrence of burnout in this professional group. The World Health Organization (WHO) recognizes occupational burnout as a result of chronic stress experienced in the workplace consisting of three dimensions: the feeling of loss, negative feelings concerning work and the mental distance toward it, as well as reduced professional effectiveness . Nurses The situation of Polish nurses in terms of burnout seems to be even worse as the study of Uchmanowicz et al.  reportedThe already high prevalence of burnout among nurses in ordinary times became an even more serious concern during the current COVID-19 pandemic due to the emergence of new stressors at their workplace, such as the high death rate of COVID-19 patients, the increased number of overtime shifts, the fear of not getting the appropriate medical equipment  or the possibility of COVID-19 transmission and the infection of family members , 13. AccAccording to the Job Demands-Resources theory (JD-R), occupational burnout is a long-term effect of stress caused by prolonged excessive job demands and insufficient resources to deal with these job demands effectively –18. BurnDifferent studies conducted among nurses which applied JD-R theory confirmed that such stressors, as excessive workload , 24 thirOrganizational constraints are related to situations or things that prevent employees from translating ability and effort into a high level of job performance. These include faulty equipment, incomplete or poor information flow, as well as interruptions by others . Garcia-In the current study interpersonal conflicts are considered in the context of theory of social relations which seems to be relevant within the context of hospital as a work organization . InterpeH1:Job demands will have direct effects on burnout with organizational constraints and interpersonal conflict at work having a positive association with burnout.With regard to job resources, social support has been acknowledged as an important resource which influences of an individual’s perception of threatening situation at work . OrganizH2:Organizational support as a job resource will be directly negatively associated with burnout.Baka and Prusik  indicateH3:Job demands will indirectly affect burnout via surface acting, indicating the mediating effect of surface acting on the relation between organizational constraints, interpersonal conflict at work and burnout.With respect to the relationship between perceived organizational support and emotional labor, previous studies demonstrated that the high level of organizational support leads to high levels of effort in deep acting, whereas in the case of feeling a low level of organizational support, nurses simply choose a less effortful way, i.e., surface acting, to perform emotional labor , 50. TheH4:Surface acting will mediate the relationship between organizational support and burnout.Apart from job resources, the JD-R model recognizes personal resources, for instance coping strategies, which are expected to buffer the undesirable impact of job demands on strain . Coping H5:Coping with workload will moderate the direct path in the mediation process of organizational constraints on burnout through surface acting. These relations will be weaker for nurses with higher capabilities of coping with workload.There are no studies exploring the burnout level among Polish nurses specifically during COVID-19 pandemic so far. However, according to the research by Szwamel et al.  which enThe late wave of COVID-19 pandemic in Poland has taken place in the end of 2021 and at the beginning of 2022. Despite of full access to vaccination, the situation paradoxically seemed to be quite dramatic, especially because of very high rate of death due to COVID-19. For example, on 29 December has been reported the highest rate of death during the whole pandemic period – 795 persons passed away this day . MoreoveThis cross-sectional study was conducted in the University Hospital of Cracow, the largest hospital in Southern Poland. The survey was conducted from 3 January to 6 February 2022. An online survey was created using the Qualtrics platform and link for the study, which was sent to all hospital nurses. The inclusion criteria applied related to a nurse and female gender of the respondent. Participation in the research was completely voluntary and anonymous.At the beginning of the survey, the participants were informed about the general purpose of the study, while also the fact that the study is non-invasive and the results would be analyzed anonymously. It was also explained that they could withdraw from the study by closing the web browser without their responses being recorded. The participants provided their written consent prior to participating in this study. The contact details of the person responsible for the project was provided in case they wished to obtain additional information or had any questions concerning the study.n ≥ Z2*p(1 − p)/d2, where n is size sample, Z is the z score for α = 0.05 (=1.96), p is prevalence of disease in population and d is the margin of error. We included a correction for a finite population in the calculations. For this, we used formula: nadj = Nn/(N + n − 1)  . Based o+ n − 1) , 5% margThe Polish adaptation  of the OThe Polish adaptation  of the 1The Polish adaptation  of 4-iteRewards (four items) and Fairness (six items) from Areas of Worklife Survey (AWS) developed by Leiter and Maslach  has been estimated by using the Polish adaptation  of two s Maslach . POS is  Maslach . Perceiv Maslach . ResponsWorkload from Areas of Worklife Survey (AWS) by Leiter and Maslach , interpersonal conflict at work (ICAW); job resources – perceived organizational support (POS), coping with workload (CWW), as well as surface acting (SA) and occupational burnout (OB) were analyzed using descriptive statistics. Correlations were verified by Pearson’s correlation coefficients. To verify the mediating effects of SA in the association between JD-R and burnout, Hayes’ PROCESS macro 4.0 programme was used. Analysis of mediating effects was performed by inputting Model 4, 95% confidence interval (CI), and 5,000 as the bootstrap sample size. The moderated direct effect of CWW on the relationship between OC and OB through SA was tested by using PROCESS macro (Model 5). Finally, all analyses were controlled for the socio-demographics of nurses, including the work experience, workplace, education level, marital status and number of children. A statistically significant mediating effect was confirmed if the CI of the indirect path did not include 0.P-values less than 0.05 were considered statistically significant.The Shapiro-Wilk normality test was applied to consistency of the residual (error) distribution with the normal distribution for each linear model. In the model diagnostics, we also checked the occurrence of multicollinearity between independent variables, based on tolerance (≥0.1 and variance inflation factor (VIF) < 10. Moreover, the Durbin–Watson value was used to assess autocorrelation of errors . To avoid multicollinearity problems in model with moderation  we appliSD = 12.2). Most of the participants were in a relationship (71.5%) – both in terms of marital or informal ties. It is worth mentioning that this group is divided into half in terms of the participants’ number of children – 51.1% did not have any child, while 37% had 1 or 2 children. Another important characteristic of the research group is their educational level – the vast majority of respondents obtained a higher degree diploma (88%). In terms of work experience, less than half of the sample (41.1%) had worked in the nursing profession for at least 16 years, while a quarter of the research group had worked as a nurse for no more than 2 years.A group of 270 participants took part in the study. As shown in In M = 2.47; SD = 0.38) and surface acting . Furthermore, the sample reported the average level of job demands, while perceived organizational support (job resource) was relatively high . Pearson correlations analyses showed that both organizational constraints and interpersonal conflict at work were positively associated with burnout  and surface acting, i.e., OC , ICAW . By contrast, perceived organizational support and coping with workload had a negative correlation with burnout, i.e., POS , CWW , as well as with surface acting, i.e., POS , and CWW .The next stage of the analysis was to measure the descriptive statistics in the case of all the variables. The results are presented in t = 6.572, p < 0.001). When the mediating variable surface acting was put into the model with covariates, the direct effect of OC on OB was still significant , indicating that SA partially mediated the association between OC and OB. The bootstrapped standardized indirect effect on the path from OC to OB through SA was significantly different from 0 .t = 6.538, p < 0.001). The direct path between ICAW and OB remained significant  when SA and the covariates were included in the model, indicating the partial mediation of SA in the association between ICAW and OB. Bootstrapping results showed an indirect effect of 0.0116  through surface acting.t = −7.855, p < 0.001). When surface acting with covariates were added, the direct effect of POS on OB was still significant , indicating partial mediation. The indirect effect of POS on OB through SA was significantly different from 0 . These findings support hypotheses 1, 2, 3, and 4.t = 2.7188, p < 0.001), and the product of organizational constraints and coping with workload had negative significant effect on burnout , indicating that CWW moderated the direct effect of OC on OB.In our research model  we hypotbsimple = 0.003, t = 0.670, p = 0.504). As the coping with workload decreased to the middle (M) and low level (M-1SD), role of organizational constraints had a positive effect on burnout and the effect was increasing gradually , indicating that with the improvement of coping with workload level, the positive effect of organizational constraints on burnout was decreasing gradually. These findings confirm hypothesis 5.Further simple slope analysis results are shown in The mediating effect of surface acting in the relation between OC and OB was 16% (0.0032/0.0194), while the mediating effect of SA in the relation between ICAW and OB was 21% (0.0116/0.0551). In turn, the mediating effect of SA in the relation between POS and OB was 13% (−0.0042/−0.0317). This implied that interpersonal conflict at work had more of an influence on the burnout of nurses through surface acting compared with the other two analyzed associations.This study explored how job demands and resources affected burnout among nurses and whether these relationships are mediated by surface acting and moderated by coping with workload. Our findings turned out to be consistent with the JD-R theory, thus confirming hypotheses 1 and 2.The health-impairment process was indicated by the significant positive association between organizational constraints, interpersonal conflict at work and burnout among nurses. These findings are consistent with previous studies supporting the positive relationship between job demands and burnout in terms of both organizational constraints , 70 and With respect to the relationship between organizational support considered to be a job resource and burnout, we found its significant negative association. This finding is in line with a previous study according to which the perception of a pleasant working environment and the sense of receiving organizational care could reduce burnout among medical staff . AlthougRegarding hypotheses 3 and 4, our study demonstrated that surface acting has a partial mediating effect on the positive relationship between both analyzed job demands and organizational support and burnout. In other words, higher organizational constraints and conflicts at work are associated with an increase in surface acting, which is in turn associated with an increase in burnout. This finding is consistent with a previous study of Gilardi et al.  in whichBy contrast, as demonstrated, a higher level of perceived organizational support is related to a decrease in surface acting, which in turn is associated with a decrease in burnout among Polish nurses. Several explanations for such an effect could be proposed. As Chou et al.  showed, With respect to hypothesis 5, our study indicates that coping with workload moderated the direct path in the mediation process of organizational constraints on burnout through surface acting among Polish nurses. This is consistent with the buffering impact of job and personal resources on the relationship between job demands and burnout postulated by the JD-R model . In the It is worth mentioning a few contributions of our study. First, to the best of our knowledge, so far no studies have investigated the mediating role of surface acting between organizational constraints and interpersonal conflict at work (job demands) which are regarded as very important stressors among nursing staff , 29. ThuAlthough the results of the study deepen our understanding concerning the mediating and moderating effects in associations between job demands and burnout among nurses from Central-Eastern Europe, there are several limitations which should be listed. Firstly, our sample consisted of nurses from only one hospital and only females, therefore future studies may take into account a more representative sample of nurses to draw better conclusions about JD-R, burnout and surface acting. We recommend conducting studies on bigger samples and analyse nurses, including both females and males, recruited from many Polish hospitals, located both in big cities, as well as small cities. Secondly, since we analyzed cross-sectional data, our results should be interpreted with caution, as we reported associations between job demands, resources and burnout, yet we cannot confirm causal relations. This limitation may be addressed by the collection and analysis of longitudinal data, e.g., data obtained during pandemic and in post-pandemic period. Thirdly, in our research model we did not include any personal traits, such as, for instance self-efficacy or ego-resiliency, which, according to research, affect JD-R and burnout among nurses , 25. ThuThis is the first study relating to the burnout level of Polish nurses during the COVID-19 pandemic. The findings enrich our knowledge on the mediating and moderating mechanisms in order to explain the association between job demands, resources and burnout among nurses during the latest wave of the COVID-19 pandemic. We confirmed that job demands, such as interpersonal conflict at work and organizational constraints significantly increase burnout, both directly and indirectly by means of surface acting, whereas, job resources, such as organizational support, decrease it. Moreover, perceived organizational support has a direct negative impact on burnout, as well as an indirect effect via a decrease in surface acting.Our results suggest that when nurses experience high job demands, strengthening organizational support and coping with workload could help alleviate burnout. It is important especially in the context of COVID-19 pandemic, during which many nurses perceived their workplace as potentially harmful and dangerous. As previous studies reported, organizational support during COVID-19 pandemic was associated with lower level of anxiety , lower bThe original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.This study was reviewed and approved by the Jagiellonian University Bioethics Committee .GW: research idea, research design, conceptualization, literature review, data collection, data interpretation, draught manuscript, and revision of work. AW: conceptualization, project administration, work supervision, revision of work, and funding. IB: data interpretation, visualization, and revision of work. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Plasmodium vivax malaria on the executive and cognitive functions of elderlies, in the Brazilian Amazon. A cohort study was conducted to evaluate executive and cognitive functions one week (T0), two months (T2) and eight months (T8) after the malaria episode. Mini-Mental State Examination (MMSE), Beck Depression Inventory II (BDI-II), Clock Drawing Test (CDT), Wechsler adult intelligence scale (WAIS-III), and Wisconsin Card Sorting Test (WCST) were used to assess executive and cognitive functions. One hundred-forty elderlies were enrolled . P. vivax malaria was associated with impairment of the executive and cognitive functions in elderlies for up to 8 months after acute P. vivax malaria. Prior history of malaria, recurrences and higher parasitemia were independently associated with various surrogates of executive and cognitive impairment. With the increase in life expectancy, elderlies living in malaria endemic areas will deserve more attention from health authorities, to guarantee improvement of their quality of life in the tropics.The exact path leading to cognitive impairment that goes beyond malaria is unclear, but it appears to be the result of interactive factors. Time of exposure to disease and recurrences are potentially major determinant variables. Cognitive impairment is described mainly in children, rarely in adults. The disease in high endemic areas usually does not affect elderlies, because of acquired immunity over time. However, this population is relatively more frequently sick in lower endemic areas, such as in the Amazon. This study assessed the effect of  Plasmodium vivax infection1. Although predominant globally, for a long time it was believed that P. vivax malaria was always associated with benign disease2. However, in recent decades, severe cases and deaths from P. vivax malaria have been reported3. The main complications of severe P. vivax malaria include pulmonary edema, severe acute respiratory syndrome, acute renal failure, severe anemia, hemorrhage, acidosis, and disseminated intravascular coagulation5. Cerebral malaria (CM), a potentially fatal condition associated with P. falciparum infection, has also been reported in P. vivax mono-infection in children, but is rare6.Approximately a third of the global population is at risk for P. falciparum (CMF), which could be a potential cause of short- and long-term neurological and cognitive deficit in Subsaharan African children7. Few studies documented the effects of CMF on adults’ cognitive performance and none of these studies tested all the five facets of cognition  making it difficult to identify patterns of cognitive impairment.A few studies address the association between malaria and cognition, particularly after the acute phase of the disease, during convalescence. Those few studies usually focus on cognition following the development of CM triggered by 8. Patterns of cognitive impairment may differ between children and adults, with age of exposure to disease being an important variable, as well as repetitive infections9.The exact path leading to cognitive impairment that goes beyond CM is unclear, but it appears to be the result of many potentially interactions. There are many risk factors, such as anemia, multiple infections, hippocampal dysfunction, damage to sub-cortical white matte, neurotoxins released from infected red blood cells, which may damage cortical areas of the brain, and cytokine stormP. vivax14 or P. falciparum malaria16, in non-severe malaria, the impact on adults is not well addressed, especially in vivax malaria. Four studies investigated the impact of infection due to non-severe vivax malaria on cognition. A study conducted in Sri Lanka and determined the short-term impact of malaria on the cognitive performance of 571 schoolchildren (ages 1–8 years)10. Oliveira-Ferreira et al.11, in a cross-sectional study carried out in the city of Careiro, Amazonas, with 198 students (aged 6–14 years) identified impairment in school performance. Brasil et al.12, in a study on the Marajó Island, Pará, with 17 schoolchildren (aged 2–10 years) demonstrated that children with a history of vivax malaria presented significant impairments in the cognitive, affective, instrumental domains (problem solving in activities of daily living) and in verbal comprehension . Tapajós et al.13, in a study with 219 schoolchildren (aged 2–7 years) in the community of Brasileirinho, Manaus, Amazonas, revealed that vivax malaria is a risk factor for low cognitive development.Thus, although few studies evaluate the cognitive impairment of children after P. vivax malaria on executive and cognitive functions in such age group, in the Brazilian Amazon, where about 89,3% of malaria cases are caused by P. vivax in 201914. Thus, due to the lack of knowledge on the subject and local epidemiological issues, it was decided to study exclusively P. vivax infection.To our knowledge, there is no report on the assessment of cognition in elderlies after malarial infection, especially vivax malaria. This study assessed the effect of Fundação de Medicina Tropical Dr Heitor Vieira Dourado (FMT-HVD) (CAAE: 71396317.7.0000.0005). All participants were informed about the objectives and risks of participation and signed informed consent terms. This study was conducted in accordance with the principles of the Declaration of Helsinki and the guidelines of Good Clinical Practice of the International Harmonization Conference.This study was approved by the Human Research Ethics Committee of This was a cohort study, with selection of malarial exposed and non-exposed without malaria, in which executive and cognitive functions were evaluated during an 8-month follow-up. Elderlies’ evaluations were performed during the first week after malaria infection (T0), two months (T2) and eight months (T8) later.15. The non-exposed group consisted of elderlies in the same age group, without malaria in the last six months of the interview, living in the same locality as the cases. Participants with any history of neurological or psychiatric impairment were not included in the study.The study was carried out from February 2018 to November 2020 at FMT-HVD, a reference institution for infectious diseases in Manaus, Amazonas State. After malaria diagnosis by thick blood smear, patients aged ≥ 60 years, both genders, were invited to participate. In case of interest in participating in the study, they received a domiciliary visit during the first week after the diagnosis. Vivax malaria patients were treated according to the Brazilian malaria treatment protocol1. All participants (exposed and unexposed) were instructed to seek the care unit if they manifested symptoms. In addition, all participants were followed in online official Malaria Epidemiological Surveillance Information System . At the time of assessment of executive and cognitive functions, in T2 and T8, peripheral venous blood was collected for assessment of asymptomatic infection by molecular techniques For DNA extraction, the miniblod Qiagen Kit was used, according to the manufacturer's instructions. Qmal Taqman PCR was used to detect Plasmodium spp. in DNA samples, as previously described16. Malaria recurrences over the study period have been confirmed in Sivep-Malária. Patients diagnosed with malaria were treated according to the Brazilian Ministry of Health's treatment guidelines.Thick blood smears were performed for the malaria diagnosis Clique ou toque aqui para inserir o texto. in all symptomatic patientsHepatitis C, HIV and syphilis were also investigated by serological rapid tests (Abbot) performed according to the manufacturer's recommended instructions, as potential concomitant causes of cognitive impairment at T0. At T2 and T8, blood samples were also collected to assess blood glucose and hemoglobin measurements, as uncontrolled diabetes and anemia are also potential confounders.17. Instruments used and their respective domains evaluated are summarized in Supplementary Table Participants answered to the socio-demographic cognition assessment form  at T0. At T2 and T8, MMSE, CDT, Beck depression inventory II (BDI-II instruments), subtests  of the Wechsler adult intelligence scale (WAIS-III), and Wisconsin Card Sorting Test (WCST) were applied. Global cognitive and executive functions were assessed by tests validated for the Brazilian population. The Addenbrooke’s cognitive examination III (ACE-III), a standard cognitive assessment, was undergoing validation during the study period18. BDI-II is a widely used self-report inventory measuring the severity of depression through 21-items19. CDT measures cognitive assessment and is used in the investigation of the impairment of some cognitive skills such as visual-constructive functions, visuo-spatial functions, symbolic and graphomotor representation, auditory language, semantic memory, and executive functions20.MMSE is an instrument that assesses mental state, more specifically the symptoms of dementia, through questions that assess orientation in time and place, registration and evocation of words, attention and ability to simple calculations, language, and visual constructive capacity21. As a measure of executive functions (EFs), the Working Memory Index (WMI) was used in these studies and was obtained through the weighted score of the subtests, digits in direct order and digits on the back, arithmetic and sequential numbers and letters. The correlation of their results with brain location has been the subject of many studies and has contributed significantly to the understanding of the action of the prefrontal cortex, specifically as dorsolateral and ventromedial subregions22.The WAIS-III is an advanced cognitive assessment instrument used to assess intellectual ability in adults and is composed of several subtests that measure different aspects of intelligence23. It evaluates strategic planning, organized search, the use of feedback from the environment to change cognitive strategies, the direction of behavior to achieve goals and the modulation of impulsive responses. The WCST assessment, therefore, can be used to assess and identify cognitive impairments and neurological conditions related to the frontal region of the brain that has deficits23. In this study, the WCST scores: "number of trials administered", "total number of errors"," trials to complete the first category", and "learning to learn", were not considered. The first three are redundant and the last one has the power to bias studies24.WCST is an internationally recognized instrument for assessing EFs and is frequently adopted in neuropsychological assessmentsP. falciparum in adults25. For the general population, the prevalence was assumed to be 6.1%26. Thus, considering a test of differences in proportions between two groups of the same size, 90% of power and 5% alpha error, 244 participants were required (122 per group). Adding 15% of losses, the final sample size was ~ 280 participants. Sample calculation was performed using software and R, version 4.0.5 27. Interim analysis was scheduled after the inclusion and follow-up of 140 patients.The sample size calculation assumed a 20% prevalence of cognitive impairment due to infection caused by Normal distribution was assessed for variables with the Shapiro–Wilk test. Differences between baseline characteristics were evaluated by ANOVA, for continuous variables with normal distribution, Wilcoxon rank-sum test for continuous variables not normally distributed, and Pearson's Chi Squared test was applied for categorical variables. Multivariate analysis included age, sex, and education variables, as well as depression (expressed by BDI-II indicators).3. Previous univariate analysis was performed for multivariable variable selection. Variables with a p-value lower than 0.2 were included. All analyses were conducted in Stata 13.0 .The main and subgroup analyzes were performed with Poisson regression. The main analyzes compared executive and cognitive fucntions between subjects with malaria and without malaria. Additional subgroup analysis was performed for malaria patients considering three variables: (1) malaria episodes before enrollment; (2) recurrences between T0 and T8; and parasitemia higher than the median number of parasites/mmOut of 470 subjects, 140 were considered eligible (70 exposed and 70 non exposed) . However, in the multivariate analysis, no differences were found , even though the marginal significance indicated a trend in worst performance in the exposed group. Otherwise, the malaria group had worse performance in cognitive  and executive functions , both at T2 and T8, independently of age, sex, education and depression  and T8 (WCST categories: p < 0.05) . In this study, we used tools with different sensitivities, which resulted in different results regarding the determination of cognitive and executive functions. However, it is important to emphasize that screening tests MMSE and CDT have high specificity and are used to signal mild cognitive impairment and a maximum number of suspected psychological processes and are suitable to safely exclude false positives. The other tests used WCST and (WAIS/WMI) are high sensitivity instruments and used to confirm any psychological condition and confirm true positives, and are used to signal mild cognitive impairment and a maximum number of suspected psychological processes8 and cytomegalovirus (CMV)37, HIV41, and bacteria, such as Chlamydia pneumoniae8 and Helicobacter pylori8 and Lyme neuroborreliosis42 have been associated with cognitive impairment. In older adults with pneumonia and urinary tract infection, for example, the risk of cognitive loss is about 1.4 times higher and previous episodes are positively associated with cognitive loss43. Inflammatory reactions have been highly related to cognitive decline and risk of dementia44. Inflammatory cytokines produced by the nervous system act on neural substrates to produce behavioral symptoms that can be related to cognitive changes45. Thus, like the diseases, vivax malaria is capable of significantly altering cognitive and executing functions for up to 8 months, which, in turn, may affect the quality of life of the elderly.Infections by herpes simplex virus type 1 (HSV-1)46. In the elderlies, we observed similar effects up to 8 months after the malaria episode. Parasitemia at T0, number of previous and recurrent malaria had a negative impact on cognition and executive functions.In children, parasitemia, the number of previous and recurrent malaria has a negative impact on cognition and executive functions, with a cumulative negative effect on school performance being observedPlasmodium berghei ANKA (PBA) strain, are a valuable tool for understanding the cognitive and neurological outcomes associated with this condition48. Studies with an animal model are focused on seeking to understand mainly the cognitive and neurological mechanisms, based on the implementation of CM. Neuroinflammation after PBA infection of mice influences neurotrophin expression, which impairs hippocampal neurogenesis and increases hippocampal cell death. This is associated with impaired memory, but specifically short-term memory after the CM course48. Inflammation of the central nervous system, because of CM, determines the release of inflammatory cytokines, which affect neurogenesis and reverberate in cognitive defects49. The study organized by Azevedo-Quintanilha et al. revealed that αDβ2 integrin deletion alters the natural course of experimental severe malaria, demonstrating previously unrecognized activities of a key leukocyte integrin in the immunoinflammatory responses that mediate brain involvement50. In non-severe malaria, the cognitive impairment mechanisms are not known, but they may be associated with cytokine storms during acute infection51, the production of neurotoxins by infected red blood cells52, impaired coagulation that can impact the correct oxygen supplementation to the tissues of the central nervous system53, anemia54, multiple infections55.The cognitive mechanisms underlying malaria remain poorly understood and experimental models of severe malaria, particularly the murine model using the Plasmodium vivax can be associated with neurological and vascular impairment56. The predilection for reticulocytes, marked proinflammatory responses, and the reversible microvascular dysfunction typically associated with P. vivax infection may explain the pathogeny of CM in malaria vivax59. Vascular congestion, hypoperfusion, and localized hypoxia in CM occurs mainly in the occipital and parietal lobes, this in turn has important reflexes in visuospatial deficit63. In the present work, visuospatial deficits were evaluated with the MMSE and CDT tools and the exposed group's performance was worse than non-exposed group. Executive functions and visuospatial skills are two interrelated cognitive processes and these deficits, which are associated with a decline in the performance of daily activities65.67. Since only the patients exposed in this study had previous malaria, they are in an endemic area, where CQ has been the treatment of first choice for many years and low CQ resistance is defined, we consider that CQ may potentially play an important role in altering neurocognitive functions. CQ is reported as an inhibitor of autophagy in a variety of diseases, including Alzheimer's disease and cerebral ischemia. After inducing brain trauma, treatment with CQ significantly suppressed neuronal autophagy and reduced levels of expression of inflammatory cytokines, interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α), in the hippocampus of the mouse (81) and this can reduce cognitive impairment. In contrast, patients treated with CQ (cases) showed worsening cognition and executing functions68. However, the half-life of the drug is highly unlikely to explain the long-term cognitive impairment seen in our patients at T8.It must be considered that chloroquine (CQ) used for the treatment of vivax malaria may have as an adverse event psychiatric and nervous system disorders, which may reflect on changes in cognitive and executive functions during the treatment of vivax malariaIn this study, we did not assess other potential co-infections associated with malaria or underlying diseases that could potentially interfere with cognition. A systematic approach to addressing these confounders would be important, however, the clinical and pre-clinical follow-up of these patients to define potential confounders was hampered in this study population, especially due to home care and to the fact that they present at the hospital unit exclusively for the malaria diagnosis. The use of secondary information from SIVEP is also an important limiting factor. Although the groups exposed and not exposed to malaria were selected from the same transmission area, other variables were not properly paired. The adjustment of variables not properly paired were included in multivariate analyzes and had no impact on cognition alone. Attention and language were evaluated by instruments of low sensitivity.P. vivax infection, and that factors such as number of previous malaria cases, recurrence, and parasitemia are important predictors of executive impairment in the second and eighth months after infection. In the context of a rapidly ageing population and the high rates of transmission of vivax malaria in subtropical and tropical areas, where vivax malaria is endemic, malaria can contribute with a substantial negative impact on cognition and executing functions that reflect on the life quality. This, in turn, adds to the deleterious events of the normal ageing process . The revelations obtained in this study should serve as a notice to the policy makers and professionals involved in the healthcare and improvement of the elderlies’ quality of life, considering that this population is vulnerable to cognitive damage.Our results suggest that malaria promotes cognitive, executive, and functional decline in the elderly population for up to 8 months after Supplementary Tables.


E. coli mutants carrying deletions of the ADP-heptose biosynthesis genes became hypersensitive to a wide range of antibacterial drugs: DNA gyrase inhibitors, protein biosynthesis inhibitors , RNA polymerase inhibitors (rifampicin), and β-lactams (carbenicillin). In addition, it was found that inactivation of the gmhA, hldE, rfaD, and waaC genes led to dramatic changes in the redox status of cells: a decrease in the pool of reducing NADPH and ATP equivalents, the concentration of intracellular cysteine, a change in thiol homeostasis, and a deficiency in the formation of hydrogen sulfide. In “deep rough” mutants, intensive formation of reactive oxygen species was observed, which, along with a lack of reducing agents, such as reactive sulfur species or NADPH, leads to oxidative stress and an increase in the number of dead cells in the population. Within the framework of modern ideas about the role of oxidative stress as a universal mechanism of the bactericidal action of antibiotics, inhibition of the enzymes of ADP-heptose biosynthesis is a promising direction for increasing the effectiveness of existing antibiotics and solving the problem of multidrug resistance.Impaired lipopolysaccharide biosynthesis in Gram-negative bacteria results in the “deep rough” phenotype, which is characterized by increased sensitivity of cells to various hydrophobic compounds, including antibiotics novobiocin, actinomycin D, erythromycin, etc. The present study showed that  As a result, there was an increase in membrane permeability for hydrophobic substances and an enhancement in cell sensitivity to various hydrophobic compounds, including antibiotics novobiocin, actinomycin D, erythromycin, etc. . A,8. AE. cA detailed study of mutants with a violation of different stages of LPS synthesis has not been carried out, just as the supersensitivity mechanism of these mutants to various antibiotics remains unclear.gmhA, hldE, rfaD, gmhB, waaC, and waaF on the redox status of cells, their production of hydrogen sulfide, cell viability, and cellular sensitivity to different antibiotics was evaluated.The interest in a more detailed study of LPS synthesis mutants is primarily due to practical considerations. Increased sensitivity to antibiotics makes them promising targets for the search for small-molecule inhibitors which can be used as new antibacterial drugs that enhance the action of traditional antibiotics. In this study, the effect of deletion of the genes E. coli strains used in the present study are listed in gmhA, hldE, gmhB, rfaD, waaC, and waaF deletion strains of E. coli was produced according to the method of Datsenko and Wanner [E. coli. To obtain strains, antibiotics were added at 30 μg/mL (for chloramphenicol) and 100 μg/mL (for ampicillin). A solid medium was prepared using 1.5% agar. All reagents used in the work produced by Sigma-Aldrich, St. Louis, MO, USA, unless otherwise stated.d Wanner . The pri7 cells per 1 mL. Cell suspensions were aligned according to optical density, and a series of 6 consecutive tenfold dilutions was prepared. Then the cells were placed on solid media containing various concentrations of antibiotics. To determine the viability of bacterial cells, suspensions were incubated in the presence of lethal doses of antibiotics and then plated on solid media for counting colony-forming units (CFU) [Overnight cultures were inoculated into a LB broth and grown at 37 °C to ~2 × 10ts (CFU) .Cells were grown in a complete medium to an optical density of 0.4 and then washed twice with phosphate-buffered saline (1xPBS), centrifuged, the supernatant was removed, and cells were resuspended in 100 μL of PBS. Cell parameters were analyzed using flow cytometry on a BD LCR Fortessa flow cytometer . The cell population for analysis was selected according to the parameters of forward (FSC) and side scattering (SSC), which characterize the size and granularity of cells.E. coli cells was assessed by the level of reactive oxygen species (ROS) and intracellular thiols, a significant part of which is intracellular reduced glutathione (GSH). The ROS level was assessed using the dye Dihydrorhodamine 123 (DHR123)  [The percentage of dead cells in the cell population was assessed using propidium iodide , which was added to the cells at a concentration of 10 μg/mL per minute before the start of the analysis. Propidium iodide penetrates the cells with a damaged membrane and, after binding to DNA, has a bright fluorescence in the red region of the spectrum. The redox status of MA, USA) , which wMA, USA) . Cells wCells were grown in 10 mL of LB medium at 37 °C to an optical density of 0.4 and collected by centrifugation. The concentration of reductive NADPH equivalents was determined using the High Sensitivity NADPH Quantitation Fluorometric Assay Kit  on a Tecan Spark tablet reader. The obtained values were related to the optical density of the culture. Data were obtained from three independent experiments.The amount of ATP in cells was determined by the luminescent method using the ATP Detection Assay Kit  on a Tecan Spark tablet reader. One hundred microliters of overnight culture were inoculated with 10 mL of fresh LB medium and grown to an optical density of 0.4. Cells were destroyed by ultrasound. Debris was removed by centrifugation. The resulting extracts were transferred to a plate with the reaction mixture, and the luminescence was immediately measured at a wavelength of 535 nm. Three independent repeats were prepared for each sample.2S production in wild-type (wt) and mutant cells, the lead acetate detection method was used [2 were affixed to the inner wall of a cultural tube, above the level of the liquid culture of wild-type or mutant bacteria. Overnight cultures were diluted at 1:500 in LB and incubated for 16–18 h at 37 °C with aeration. Stained paper strips were scanned and quantified with an Alpha Imager . The results were normalized per ODs.To detect Hwas used . Paper s4. The suspension was centrifuged, and the pH of the supernatant was adjusted to 8.5 by adding KOH. Potassium perchlorate was removed by centrifugation. Samples were treated with 50 mM DTT. The reaction mixture consisted of 500 µL of the sample and 500 µL of Gaitonde’s reagent . A calibration curve was built using the known concentrations of cysteine. The assigned values were related to the OD600 of the culture. Data were obtained from three independent experiments.Intracellular cysteine was determined in cell extracts by the method of Gaitonde . Bacterip) less than 0.05 were considered significant. Statistical analysis was performed using the GraphPad Prism 9.1.2 software .The data are shown as mean ± standard deviation measures from triplicate values obtained from 3–4 independent experiments. The statistical difference between experimental groups was analyzed by one-way ANOVA with Tukey correction for multiple comparisons. Probability values  of antibiotics and plated on a solid medium for further CFU counting . SurvivagmhA, hldE, rfaD, and waaC sensitize E. coli cells to all the studied classes of antibiotics, while ∆waaF exhibits very moderate sensitivity, and the ∆gmhB mutant does not differ from wild-type bacteria.Deletions of hldE gene induced maximal oxidative stress  increase in the thiol group level in E. coli. In cells with a deletion of waaF, the increase in thiols was less pronounced (less than 2 times). At the same time, the amounts of thiols in the ∆gmhB mutant did not differ from wild-type bacteria  differ sharply in the redox status of the cells from the wild-type bacteria . The cofactors ATP, NADH, and NADPH constitute the core of an intricate biochemical network, the operation of which must be clearly regulated in changing environmental conditions. Reducing equivalents of NADPH are the main electron donors in the redox reactions and are essential for many anabolic reactions to occur. One of the main sources of NADPH formation in a bacterial cell is the oxidative branch of the pentose phosphate shunt. In addition, it is in this metabolic pathway that the precursor of ADP-heptose, sedoheptulose 7-phosphate, is formed.gmhA,hldE, rfaD, and waaC, there was a significant decrease in the level of NADPH compared to the wild-type strain  encoded by the mstA gene [Previously, it was shown that the level of endogenous Hcysteine , as it istA gene .2S generation in the gmhA, hldE, rfaD, and waaC mutants is due to a low level of intracellular cysteine content, we performed a quantitative determination of this amino acid in living cells   a, the inD, waaC) b.E. coli cells against the background of impaired LPS biosynthesis. The results of this work clearly indicate that the level of sensitivity of different mutants to antibiotics correlates well with a decrease in the intracellular content of NADPH, ATP, and cysteine, the generation of hydrogen sulfide, thiol levels, and an increase in the intracellular ROS. In the strains ∆gmhA, ∆hldE, ∆rfaD, and ∆waaC with high sensitivity, there is a dramatic increase in ROS, one type of which is superoxide  [gmhB is practically the same as the wild-type strain. In these strains, changes in redox status and other measured parameters were not as considerable. This is due to the fact that ∆gmhB does not lead to a complete disruption of ADP-heptose synthesis due to the presence of homologous enzymes. The gmhB gene product  is an enzyme belonging to the phosphatase class. Several similar enzymes are present in E. coli cells, for example, the imidazoleglycerol-phosphate dehydratase/histidinol-phosphatase HisB involved in histidine biosynthesis, according to the literature [gmhB deletion defect. In addition, there are phosphatases involved in the central carbon metabolism, the activity of which is critical for cell viability; therefore, it is not possible to completely block this stage of ADP-heptose biosynthesis [gmhB and ∆rfaD populations was detected. Furthermore, the outer membrane integrity is monitored by the envelope stress response system, which initiates the activity of genes and enzymes involved in membrane remodulation. The loss of GmhB activates periplasmic serine endoprotease DegP production, resulting in porin OmpF degradation [The results obtained reveal that strong oxidative stress develops in peroxide . On the s costs) ,23. The ynthesis ,25. Howeradation . ChangeswaaF secretes large amounts of colanic acid, this biosynthetic pathway can deplete ATP [waaF strain can be explained by changes in the functioning of the respiratory chain [waaF . Cysteine, along with hydrogen sulfide and other low-molecular-weight thiols form an important regulatory system that maintains the redox balance of the bacterial cell and its resistance to stress. Cysteine, being in the external environment mainly in the oxidized form (cystine), is transported into the cell, where it undergoes rapid recovery. Cystine is present in bacterial cells in trace amounts that cannot be detected [2S generation (2S in mutants, a complete LB medium was used. Under these conditions, an important contribution to the intracellular pool of cysteine is made by its transport in the form of cystine, which is a component of the LB environment and is carried out with the participation of specific transporters tcyP and tcyJ [gmhA, ∆rfaD, and ∆waaC mutants, which indicates an imbalance in central metabolism (hldE leads to the conservation of ATP compared to other deep-rough mutants, since this enzyme catalyses the ATP-dependent addition of phosphate in the first position to D-glycero-manno-heptose 7-phosphate and subsequent transformation of D-glycero-β-D-manno-heptose 1-phosphate into ADP-L-glycero-β-D-manno-heptose.Furthermore, an increase in the number of reduced thiol groups also indicates significant changes in the metabolism of reactive sulfur species in LPS mutants (∆detected . Currentdetected ,35. On tdetected . As a reneration , which, and tcyJ . This exand tcyJ . This prand tcyJ . Previouand tcyJ . Accorditabolism . It is pE. coli cells occur when the gmhA, hldE, rfaD, and waaC genes are deleted (Thus, a change in the normal structure of the LPS of the cell wall of gram-negative bacteria not only leads to a violation of its barrier functions but also significantly affects the key protective mechanisms. Redox imbalance of deep-rough mutants deprives cells of the opportunity to form an adequate response to oxidative stress caused by the antibacterial drugs. The most significant changes in redox homeostasis in  deleted  and thes deleted . In the Helicobacter pylori and Mycobacterium tuberculosis [Previously, attempts were made to create inhibitors of the LPS biosynthesis enzyme ,7,9,38. rculosis ,40. Base


Bubo bubo) at 14 nests in the Judea region, Israel. A total of 9461 prey items were identified and although mammals and birds dominated, there were also reptiles, amphibians, and invertebrates. The gradient of diversity of mammalian prey decreased from west to east; and avian prey increased correspondingly. The index of prey species diversity had no relationship with breeding success. The prey-base of the Eagle Owls helped identify the changes in geographic distributions of several species. The Eagle Owl’s diet emphasizes its generalist foraging habits, but pairs may be species-specific specialists. This adaptation is especially important in a fast-developing and congested country like Israel and probably allows the species to subsist in the region.We studied the diet and breeding success of Eagle Owls (Bubo bubo) have been suggested to vary at different latitudes. However, it is still unclear whether and how these relationships exist at lower latitudes outside of Europe. We therefore studied the diet and breeding success of Eagle Owls during four breeding seasons at 14 nests in the Judea region, Israel. Of a total of 9461 prey items were identified; mammals  and birds  predominated the prey-base. We found that the gradient of diversity of the mammalian prey decreased from west to east; and avian prey increased from east to west. The index of species diversity, H’ for all prey, had no relationship with breeding success. The prey-base of the Eagle Owls helped identify the changes in geographic distributions of several species. Marbled polecat (Vormela peregusna), especially threatened, appear to be relatively abundant, as are brown rats (Ratttus norvegicus) which were previously considered to be restricted to the coastal regions. In addition to Egyptian fruit bats (Rousettus aegyptiacus), the Eagle Owls also preyed on nine different species of insectivorous bats, several of which appear to have enlarged their geographic distribution within Israel. The Eagle Owl’s diet emphasizes its generalist foraging habits, but pairs may be species-specific specialists. This adaptation is especially important in a fast-developing and congested country like Israel, because a generalist hunting strategy probably allows the species to subsist in the region.The diet and breeding success of Eagle Owls ( Bubo bengalensis, [Tyto alba, [B. bubo, hereafter EO; [Raptors, as apex predators, are excellent bioindicators of their environment and the changes occurring in them whether by natural causes or owing to anthropogenic activities . Howeveralensis, ; barn owto alba, ,10 whileto alba, ,12). Thuto alba, ,14,15. Yto alba, . This isto alba, ,14,15, after EO; ).Erinaceinae Sppl. [Hystrix indica; [The diet of the EO can be extremely diverse, comprising many different species of mammals and birds, but also reptiles, amphibians, fish, carrion, and invertebrates ,20,21,22ae Sppl. ,29,30,31 indica; ) are speThe most common method of studying the diet of a wide range of species is by collecting and dissecting pellet contents. However, the subject of the reliability of pellet analyses is also questioned . AlthougEO breeding has been well studied in Europe with some studies concentrating on habitat characteristics ,36,37, pB. b. interpositus, which is known to breed in southern Europe and the Levant [In Israel, the subspecies of EO is e Levant . The spee Levant  EO is co2 area of the Judea region of Israel  and owl territories were identified by searching on foot in suitable habitats to detect EO activity , while Overall, 14 nests were monitored for pellets and prey remains: six of the nest sites were monitored in all four years, four nest sites for three years, one nest site for two years, and five nest sites for one year. We successfully collected pellets and prey remains from a cumulative of 43 nesting attempts in the four-year study period; 2006 (N = 10 nests), 2007 (N = 11 nests), 2008 (N = 11 nests), and 2009 (N = 11 nests). Both pellets and remains were collected so as to ensure that the sampling was not biased to small or large prey ,47. PreyIn order to calculate the relative percentage for each species, we calculated the average of the range of the body mass and multiplied by the number of individuals identified in the prey remains ,34. PreyH’ denotes the index of species diversity , s the number of species, and ip the proportion of total samples belonging to ith.The biodiversity of prey at each nest was expressed as Shannon–Wiener diversity index:p-value for Shapiro–Wilk test was >0.05), while number of nestlings significantly deviates from the assumed theoretical normal distribution (p = 0.0023). In all cases, we used the Pearson coefficient for measurements of correlation.To test for differences in H’ between particular groups  we used one-way ANOVA. The normality of residuals coming from one-way ANOVA analysis was tested by the Shapiro–Wilk test, while Bartlett test was used as test of homogeneity variance. The Shapiro–Wilk test was also used to check that all dependent variables are in accordance with the normal distribution. If one of the above assumptions  were not met, we used a non-parametric alternative to ANOVA, i.e., the Kruskal–Wallis test. All H’ indices showed accordance with the normal distribution  found at nests as well as separately for avian (H’birds) and mammalian prey . All H’ indices (for numbers and biomass of prey) and the number of nestlings did not differ between years . Furthermore, number of nestlings was also independent of nest geographical localization . However, we found a relationship between the number of prey, i.e., mammals and birds . We used H’  as the dependent variable, and longitude and latitude as explanatory variables. To test the significance of slope in the model, we used the t-test. We considered p < 0.05 as statistically significant. The statistical analyses were performed using R. 4.1.2.The mean number of nestlings was similar between the 2006 , 2007 , 2008 , and 2009 breeding seasons . We calculated + 0.39 SE) were monitored during the 2006–2009 breeding seasons , followed by 23.83% birds , 1.90% arachnids , 0.94% reptiles , 0.42% insects , and 0.01% amphibians , Egyptian’s fruit bat , Tristram jird , Southern white-breasted hedgehog , blind mole rat , black rat , brown rat ; and four avian species, namely the Western jackdaw , rock pigeon , chukar partridge , and hooded crow . The only reptile species of significance was the javelin sand boa ; and of the Arthropoda was the large-clawed scorpion .Even though 111 prey species were identified, only the following seven mammal species made up more than 1% of the diet: Günther’s vole (Predation on mesopredators (large carnivorous vertebrates) made up 3.0% of the diet including four species of Strigiformes , three species of Falconiformes , and six species of Carnivora .1,41 = 1.52, p = 0.22; H’bird F1,41 = 0.34, p = 0.56; H’mammal F1,41 = 2.14, p = 0.15, The H’ for all prey, mammal, and birds did not have an effect on the number of nestlings , while longitude was not significant . The opposite relationship was found for H’birds. In this case, latitude was positively associated with this index  but we also found decreased H’birds from east to west . For H’mammals, we found that this index decreased from south to north , while longitude was not significant .However, all H’ indexes changed linearly with longitude, while for the latitude we found no such relationship . Based o1,41 = 0.45, p = 0.50; H’bird F1,41 = 0.89, p = 0.34; H’mammal F1,41 = 4.07, p = 0.051. However, we found, similar to the H’ of numbers of prey, that biomass diversity index decreased from south to north , while longitude was not significant . Avian biomass index showed an opposite relationship. In this case, this index increased from south to north , while longitude was not significant . Mammalian biomass index also decreased from south to north , and from west to east .The biomass Shannon–Wiener diversity indices for all prey, mammal and birds had not effect on the number of nestlings , was a surprise since they are a great distance away from their known distribution within the country. This is the first evidence for the species in the Judea region. Moreover, the marbled polecat (Vormela peregusna) is the smallest mammalian predator in Israel and is listed as Endangered in Israel and as Vulnerable in the International Union for the Conservation of Nature (IUCN) Red List [Another species that was a surprise to us because of its relatively high abundance at the EO nests was the Middle East blind mole-rat . The maN = 572; , which iRed List . The speRed List ,63. The Bats typically make up a very small percentage of the diet of EO in Europe due to their small size and fast flight . They aEgyptian fruit bats do not have many predators in Israel and were in the past declared as agricultural pests, while extensive campaigns were conducted by the Ministry of Agriculture to eradicate the species from the 1950s till the late 1980s ,67. RoosRhinolophus ferrumequinum; N = 38) is listed as Endangered in Israel [Eptesicus serotinus), a Mediterranean species listed as Endangered in Israel, is a sign that the species exists in the Judea region where it was considered to be extinct by the authorities. Two other bat species that appear to have enlarged their geographic distribution within Israel are the European free-tailed bat (Tadarida teniotis) and the Desert long-eared bat (Otonycteris hemprichi). Finding the Naked-rumped Tomb bat (Taphozous nudiventris) suggests its change in distribution from the Syrian-African Rift Valley towards the interior regions of Israel. Similarly, the Egyptian Tomb bat (Taphozous perforatus), a species of African origin and found only around the Dead Sea depression and considered extremely rare in Israel, appears to be extending its geographic range towards the Mediterranean. The same is also true for the Egyptian slit-faced bat (Nycteris thebaica) and the Greater mouse-tailed bat (Rhinopoma microphyllum), and this is the first evidence of these species from central Israel.In addition to Egyptian fruit bats, the EO also preyed on nine different species, albeit in small numbers, especially of the insectivorous bats. The aforementioned campaign by the agricultural community on the fruit bats invariably also negatively affected all the other bat species. The Greater Horseshoe bat  because the known distribution of the species is further north and to the west of our study area, i.e., in the coastal regions from Caeserea to the sand dunes of the western Negev, and finding them in the prey items is evidence of their distribution also further inland in the Judea region. Similarly, the finding of Desert hedgehogs (Paraechinus aethiopicus) was also a surprise because their known distribution is much further to the south in the Negev Desert and to the East in the Judean Desert. Now, we have evidence that the species also occurs in the Judean region of Israel.White-breasted hedgehogs made up 7.6% of the diet (biomass 4.2%), of the prey taken by EO in Israel. This is similar to Europe, where hedgehogs comprised on average 5.8% of the diet (range 0.1–13%) ,31,59,69Even though EO are considered super-intraguild predators, and predated upon 18 different species of mesopredators, these species only made up a small percentage of the owls’ overall diet , which is in agreement with other studies ,20,21,22Especially of interest is the predation by EO on the larger raptors, namely the Long-legged buzzard (LLB) and Short-toed Eagle (StE). We have observed not only nestlings  being taken from their nests in both the raptor species, but three cases  where the EO also killed and brought the carcass of the brooding female to feed its nestlings at the nest site. Following the installation of closed-circuit television (CCTV) cameras in recent years, this phenomenon has been substantiated in real time whereby EO have been documented nest-robbing nestlings as well as hunting adults in the nest site.Unlike some of the European studies, from comparable biomes, wherein Lagomorphs comprised a major part of the diet (27–89%) and sustained EO populations ,71,72,73There is a need for further studies to determine whether the relatively high breeding success in central Israel is related to prey abundance and/or the owls’ ability to be opportunistic hunters. Future studies should try to understand at the micro- and macro-scales the influences of habitat characteristics on the prey-base available to the EO. Further, in light of the relatively high number of diurnal and nocturnal raptors included in their prey-base, it will be of interest to understand the influence EO have on the other raptorial species in the vicinity of their breeding site or hunting territory.Further, although we have attempted to collect all pellets and prey remains at each of the visits to the nests , we did In conclusion, our study, based on a large sample size of prey remains and pellets, demonstrates the generalist hunting behavior of the Eagle Owls and the opportunistic manner in which they appear to take their prey. We have also shown that there is a latitudinal gradient in the prey-base with mammals being predominant to the west, which is complimentarily compensated by an increasing proportion of avian prey. We assume that this generalist and flexible manner of hunting prey is a strategy that allows this apex predator to subsist in the human-congested and well-developed region of central Israel.


Vegetable protein intake negatively correlated with the incidence of diabetes in non-drinkers (odds ratio (OR): 0.208; 95% confidence interval (95% CI): 0.046–0.935; p = 0.041). Furthermore, animal fat intake positively correlated with the incidence of diabetes in non-drinkers . Therefore, vegetable protein and animal fat intakes in combination with drinking habits need to be considered for the prevention of diabetes.Although nutrient intake and alcohol consumption are both closely associated with the incidence of diabetes, their interrelationships remain unclear. Therefore, we herein have investigated the interrelationships among nutrient intake, alcohol consumption, and the incidence of diabetes using longitudinal data. This study included 969 residents ≥40 years living in Japan. In 2011 and 2012, a baseline study was conducted using questionnaires on basic demographics, diabetes, nutrient intake, and lifestyle habits. In 2018 and 2019, a follow-up study was performed using questionnaires and medical records on diabetes. Two-way analysis of covariance (two-way ANCOVA) was used to test the interactions of drinking habits and diabetes incidence on nutrients intake. The prospective relationship between nutrient intake at baseline and the incidence of diabetes in the follow-up stratified by drinkers and non-drinkers was evaluated using multiple logistic regression analysis. Interactions were observed for vegetable protein intake ( The prevalence of type 2 diabetes (DM2) is rapidly increasing worldwide and is estimated to reach 592 million individuals by 2035 . AccordiTherefore, the relationship between nutrient intake and the risk of diabetes remains unclear. This may be attributed to the involvement of other factors such as lifestyle habits, including alcohol consumption, which may affect nutrient intake and diabetes. Since alcohol produces more than twice as much energy as the same amount of carbohydrates or protein, excessive alcohol consumption has been proposed as a risk factor for diabetes ,25. ManyAlthough nutrient intake and alcohol consumption are both considered to be closely associated with the incidence of diabetes, this interrelationship has not yet been examined in detail, particularly using longitudinal data.Therefore, the present study investigated the interrelationships among nutrient intake—including protein, fat, and carbohydrates—alcohol consumption, and the incidence of diabetes, and compared prospective relationships between nutrient intake and the incidence of diabetes between non-drinkers and drinkers using longitudinal data from a general population in Japan.The Shika study, which examines the health status of community-dwelling residents living in Shika town, has been conducted since 2011. The town is located in the center of the Noto Peninsula in Ishikawa Prefecture, Japan, and had a total population of 23,208 in July 2011. The present longitudinal study was conducted utilizing data from the Shika study.The target population of the present study was residents ≥40 years living in model districts in the town. In 2011 and 2012, a baseline study was conducted using questionnaires on basic demographics, diabetes, nutrient intake, and lifestyle habits. In 2018 and 2019, a follow-up study was performed using questionnaires and medical records from hospitals on diabetes.Among 2264 eligible residents in the baseline study, 1948 were analyzed . Of these, 1670 individuals were eligible for the follow-up study after the exclusion of 200 deaths, 35 relocations in the town, and 43 moving out of the town. Following the exclusion of 554 individuals who did not respond to the follow-up study or had no medical information (follow-up rate of 66.8%), 1116 individuals were eligible. A total of 969 individuals were ultimately included in analyses after the exclusion of 46 individuals with diabetes at baseline, 10 with an over- or under-reported nutritional intake, and 91 with missing data.The present study was conducted with the approval of the Ethics Committee of Kanazawa University (No. 1491). Written informed consent was obtained from all participants prior to data collection.Regarding diabetes in the baseline study, participants were asked if they were currently being treated for diabetes. Concerning the incidence of diabetes in the follow-up period, medical record information on diabetes was collected thorough a medical record collecting system, which we constructed in four hospitals in the study area. In parallel with the system, we used questionnaires asking whether participants had been diagnosed with diabetes by a physician.Nutrient intake was estimated using the brief self-administered dietary history questionnaire (BDHQ). The BDHQ provides information on the average daily frequency of consumption of 58 food and beverage items in the past month. These 58 items were selected from foods or drinks commonly consumed in Japan, mostly based on the food list of the Japanese National Health and Nutrition Survey ,31. The 2). Smoking was categorized into two groups: current non-smokers (non-smokers and ex-smokers) and current smokers. Regarding leisure-time physical activities, we used the following question: “How many times a week do you exercise?”. The response options included: (1) daily; (2) 5–6 days a week; (3) 3–4 days a week; (4) 1–2 days a week; (5) none.Data on sex, age, height, weight, smoking, drinking habits, leisure-time physical activities, and the diagnosis of hypertension were obtained using questionnaires. Body mass index (BMI) was calculated by dividing weight (kg) by height squared , adjusted for age, BMI, leisure-time physical activities, hypertension, magnesium, and alpha-tocopherol, was used. Two-way ANCOVA was used to test the interactions of drinking habits and diabetes incidence on nutrients intake. Age, BMI, leisure-time physical activities, hypertension, magnesium, and α-tocopherol were used as covariates. The Bonferroni post hoc test was used for nutrients that showed interactions to test differences in nutrient intake between the diabetes and non-diabetes incidence groups stratified by drinkers and non-drinkers. The prospective relationship between nutrient intake and the incidence of diabetes stratified by drinkers and non-drinkers was examined using multiple logistic regression analysis. The covariates were age, BMI, leisure-time physical activities, hypertension, magnesium, and alpha-tocopherol, and each nutrient was entered separately for each analysis.All analyses were stratified by sex. Between males and females, unpaired Student’s p < 0.05 for all analyses.Statistical Package for Social Science  version 27 was used for these analyses. The significance of differences was set at p = 0.021). BMI was significantly higher in males than in females (p < 0.001). The percentages of subjects who were smokers (p < 0.001), drinkers (p < 0.001), and with frequent leisure-time physical activities (p = 0.047) were significantly higher in males than in females. No significant differences were observed in the incidence of diabetes in the follow-up study between males and females, although it was slightly higher in males (p = 0.053). The prevalence of hypertension did not significantly differ between males and females. Regarding comparisons of nutrient intake, the intakes of animal protein (p < 0.001), vegetable protein (p < 0.001), animal fat (p < 0.001), vegetable fat (p < 0.001), and carbohydrates (p < 0.001) were significantly higher in females than in males.p = 0.035), while no significant differences were observed in females. In males, BMI was slightly higher in the diabetes incidence group than in the non-diabetes incidence group (p = 0.092), while no significant differences were noted in females. The percentages of smokers, drinkers, those with frequent leisure-time physical activities, and the prevalence of hypertension did not significantly differ between the diabetes and non-diabetes incidence groups in both sexes. Furthermore, mean nutrient intake did not significantly differ between the diabetes and non-diabetes incidence groups in both sexes.p = 0.003) in males. Interactions of diabetes incidence and drinking habits on vegetable protein (p = 0.023) and animal fat intake (p = 0.016) were found in males.p = 0.040). In contrast, no significant differences were observed between the two groups for the drinking group.The results of Bonferroni post hoc tests for the non-drinking group showed that the intake of vegetable protein was significantly lower in the diabetes incidence group than in the non-diabetes incidence group (p = 0.048) in the diabetes incidence group than in the non-diabetes incidence group, while no significant differences were observed between the two groups for the drinking group.In the non-drinking group, the intake of animal fats was significantly higher (p = 0.041). Likewise, a positive correlation was noted between animal fat intake and the incidence of diabetes in the non-drinking group .In other words, the incidence of diabetes was found to be frequent when vegetable protein intake was lower and animal fat intake was higher only in non-drinkers.The present study examined the interrelationships among nutrient intake, alcohol intake, and the incidence of diabetes utilizing longitudinal data from a general population of middle-aged and elderly Japanese individuals. We also compared the prospective relationship between nutrient intake and the incidence of diabetes between non-drinkers and drinkers. The results obtained showed an interaction of drinking habits and the incidence of diabetes on nutrient intake, demonstrating the preventive effects of vegetable protein intake and the promotive effects of animal fat on the incidence of diabetes in male non-drinkers.Previous studies reported that a higher intake of vegetable protein was associated with a reduced risk of DM2 ,20. A loA cohort study that followed 21,523 people in Australia for approximately 12 years and a meta-analysis integrating 11 cohort studies found an inverse relationship between vegetable protein intake and the development of DM2 in females ,21. AnotNumerous studies have reported a relationship between alcohol consumption and the incidence of diabetes. Since alcohol produces more than twice as much energy as the same weight of carbohydrates or protein, excessive alcohol consumption has been proposed as a risk factor for diabetes ,34. HoweAnimal fats mainly contain SFAs. The PREDIMED study, a prospective cohort study that followed 3349 Spanish individuals for 3 to 4 years, reported that higher intakes of animal fats and SFAs were associated with an increased risk of DM2 . In addiThe present results demonstrated the interactions of drinking habits and animal fat intake with the incidence of diabetes, and a logistic regression analysis stratifying drinkers and non-drinkers showed that a low animal fat intake was protective against the development of diabetes in male non-drinkers only. By taking drinking habits into consideration as a third factor, our results were consistent with the former studies for non-drinkers and with the latter studies for drinkers. Almost the same discussion as to the association between vegetable protein intake and diabetes incidence can be applied for animal fat intake.The lack of similar results for vegetable protein and animal fat intakes in females may be due to the small number of female drinkers examined in the present study.The mechanisms by which vegetable protein, animal fat, and alcohol intake affect the development of diabetes remain unclear. Previous findings have suggested that the amino acid composition of vegetable protein increased the efficiency of amino acid metabolism, thereby reducing the risk of DM2 . HoweverSeveral mechanisms have been proposed for the increased risk of diabetes with a high animal fat intake. The fatty acid composition of structural membrane lipids may affect insulin sensitivity. For example, the higher SFAs content of membrane phospholipids was previously shown to increase insulin resistance and the risk of developing diabetes ,41,42. FFoods containing vegetable protein include beans and their processed products, cereals, and vegetables ,44. In aThe strengths of the present study include its longitudinal design, which allowed prospective and causal relationships between nutrient intake and the incidence of diabetes to be established. In addition, evaluations of the incidence of diabetes were supplemented by the medical records of hospitals to ensure objectivity. Moreover, the participation rate at baseline was high, which may have excluded selection biases. However, this study had several limitations that need to be addressed. Dietary data were subjective because the intake frequencies of foods or food groups were based on a self-administered questionnaire, which may lead to recall biases. In addition, the calculation of nutrients intake did not account for changes in nutrients composition due to cooking, such as heating. Furthermore, protein data from the nutrient calculations were not analyzed in detail other than vegetable and animal categories. Likewise, we could not use more detailed categorized data for fats because they have not been adequately validated. Moreover, supplements were not included in the calculation, although they were included as a question item. The influence of bioactive substances , which are abundant in vegetables, was also not examined. Furthermore, for some participants, source information on the incidence of diabetes was only self-reported and not corroborated by medical information. Additionally, the questionnaire for the assessment of diabetes has not been tested for reproducibility or validity, although we utilized medical information whenever possible. Finally, the follow-up rate was low, which may have led to withdrawal biases.The present study showed that a higher intake of vegetable protein and a lower intake of animal fat were prospectively associated with a lower incidence of diabetes in male non-drinkers. Considering vegetable protein and animal fat intakes in combination with drinking habits might be important for the prevention of diabetes incidence.


Bibliometric analysis was designed to investigate a systematic understanding of developments in exercise and osteoporosis research over the past 20 years.Relevant publications from the Web of Science Core Collection were downloaded on April 26, 2022. CiteSpace, VOSviewer, and the online bibliometric analysis platform were used to conduct this scientometric study.A total of 5518 publications were in 1202 academic journals with 137405 co-cited references in by 5637 institutions from 98 countries/regions. The country leading the research was the USA. The University of Melbourne was the most active institution. Osteoporosis International was the most productive journal concerning exercise and osteoporosis research. According to the burst references, “low-level vibration,” “high-frequency” and “resistance exercise” have been recognized as the hotspots research in the domain. The keywords co-occurrence analysis identified “skeletal muscle,” “sarcopenia” and “mesenchymal stem cell” as the important future research directions.This study was the first comprehensive metrological and statistical analysis of exercise and osteoporosis research over the past 20 years. Our findings would provide guidance to understand the research frontiers and hot directions in the near future. According to the Global Burden of Disease (GBD) Study 2019,Over the years, there has been a growing interest in the benefits of exercise for people with osteoporosis. At adolescence, physical exercise is clearly an effective way to increase the peak bone mass . A sedenBibliometrics is a quantitative statistical tool used to analyze published literature. It has been applied to assess citation counts and collaboration in countries, institutions, journals, and authors, and to predict keyword trends of research activities over time . In receFull records and cited references of articles were downloaded from the Web of Science Core Collection (WoSCC) database, which included Social Science Citation (SCI)-EXPANDED. A complete online search was carried out on 26 April 2022. Our search strategy was as follows : Title =2 for further bibliometric analysis. The impact factor (IF) and Quartile in category of journals were obtained from the 2021 Journal Citation Reports .Two investigators (FL and WX) independently conducted the primary search. Before reaching a consensus, any disagreements were discussed. The collected data included publication counts, titles, authors, countries, institutions, journals, highly cited articles and keywords. The WoSCC data were converted to txt format and imported into CiteSpace V5.8.R3 SE, 64bit , VOSviewer 1.6.18  and the Online Analysis Platform of Literature MetrologyClinicalTrials.gov. The annual publication trend was represented by Microsoft Excel 2019 .CiteSpace is usually applied to visualize and analyze the publications. In our research, CiteSpace was utilized to, respectively, identify the productive authors, institutions, co-cited authors, co-cited references, references and keywords with the strongest citation bursts, as well as the related visual networks. In the networks, links between nodes represent the relationship of cooperation or co-citations and the different node size and colors represent different items and years, respectively . Besidesn = 407), indicating that exercise and osteoporosis research has become a hotspot and captures global research attention now.The systematic search identified 5518 publications met the inclusion criteria between 2002 and 2021, including 4655 articles and 863 reviews. The annual publication trend was shown in To identify productive countries/regions and institutions leading the research in this field, further analysis of publications in different countries and institutions was conducted. The top 10 countries/regions and institutions were shown in The top 10 institutions were distributed in five countries. Of these, three were from the Canada, three were from USA, two were from Australia and the remaining two were from China and Sweden. A total of two institutions published more than 100 papers: Univ Melbourne and Univ Toronto . The mern = 53) and ranked first, followed by Harri Sievanen (n = 40) and Julie A Pasco (n = 32). In most cases, cross-cooperation can promote productivity of a certain study. The merged co-authorship network map is shown in n = 979) and ranked the first, followed by Cummings SR (n = 677), Frost HM (n = 475), Cyrus Cooper (n = 415) and Turner CH (n = 401).The number of publications produced by one author is able to represent the degree of research activity and contribution in the field. As shown in n = 438, 7.94%, IF = 4.507) published the most documents in this field, followed by Bone  and Journal of Bone and Mineral Research . Among the top 20 most prolific journals, Journal of Bone and Mineral Research had the highest IF. Furthermore, eleven journals were classified as Q2 and five were classified as Q1. As for the research domain of these journals, nine were classified into orthopedics. A total of 5518 publications were published in 1202 academic journals. The top 20 most prolific and co-cited journals were listed in Q = 0.7205, S = 0.8842). It can be seen that 17 major cluster labels were marked, including osteosarcopenia, irisin, calcium, peripheral quantitative computed tomography, accelerometer, sarcopenia, microgravity, vitamin d supplementation, whole body vibration, biochemical markers of bone turnover, obesity, sclerostin, older men, body mass, juvenile idiopathic arthritis, bulimia and male athlete triad. Furthermore, we also provided the timeline view for the major clusters in The co-citation and clustered network map were identified by CiteSpace from 137405 references in a hierarchical order. There were 908 nodes and 1983 links in the network map . The netClinicalTrials.gov between 2020 and 2022  was caused by the paper entitled “The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendation” authored by Weaver et al.  appeared in 2018, followed by “x ray absorptiometry” (n = 17.68), indicating the importance of skeletal muscle of osteoporosis. The recent keywords with citation bursts occurred in 2018 were “inflammation,” “adipose tissue,” “skeletal muscle” and “fat mass.” Furthermore, these keywords also continued to 2021.The top 25 keywords with citation bursts were presented in This study visualized research articles in exercise and osteoporosis research from 2002 to 2021. A total of 5518 papers were in 1202 academic journals with 137405 co-cited references in by 5637 institutions from 98 countries/regions. The annual output of the publications was slowly increasing over the past 20 years, indicating that an increase in researcher interest in this field. In the 1970s, Aloia et al.  observedAdequate nutrition is identified as a strategy to counteract osteoporosis, particularly with regard to vitamin D, calcium and protein intake. It is necessary to achieve adequate nutrition for maximizing the skeletal benefits of exercise.Exercise is generally recognized as an important mechanical stimulus for the development and maintenance of bone health and quality, but not all exercise interventions exert positive effect on bone mass. As seen from the clusters of co-cited publications and keyword analysis, the researches of exercise interventions were largely concentrated in aerobic exercise, whole-body vibration (WBV), high-impact exercise, weight-bearing exercise and resistance exercise. Astronauts experience more bone loss per month than the loss on Earth in postmenopausal women per year . Due to It is worth mentioning that osteoporotic fracture, a major complication of osteoporosis, is associated with substantial morbidity and mortality. The clustered network map of keywords analysis reflected the relationship between fracture and exercise. The majority of non-vertebral fractures occur from a fall, there is strong evidence that exercise could reduce falls, which primarily involve balance and functional exercises . AlthougAnother trend in exercise and osteoporosis research is the shift from postmenopausal women to different age groups and other populations with diseases. To our knowledge, the majority of previous research is clinical trials that focused on postmenopausal women. The results of this bibliometric analysis indicate that exercise is recommended for the prevention of osteoporosis at all stages of life, such as children, young, adolescent and old people. The skeleton of growing children is particularly sensitive to exercise, exercise in adolescence and early adulthood can significantly increase peak bone mass . An inteMechanical loading from physical exercise imposes an anabolic stimulus on bone. The mechanical signal was observed to promote both proliferation of mesenchymal stem cell (MSC) and capacity for osteogenic differentiation . RecentlA wide variety of techniques are available to evaluate BMD. The most widely used are dual energy X-ray absorptiometry (DXA), which only measures bone mass and areal BMD. However, there are many technical limitations in the application of DXA for measurements  and the ClinicalTrials.gov. In addition, only English documents were considered. Therefore, the data may not be comprehensive enough.To the best of our knowledge, our study based on bibliometric tools, including CiteSpace, VOSviewer, and the online bibliometric analysis platform, analyzed the knowledge base and research hotspots on exercise and osteoporosis research. However, this study had several limitations. The data were only retrieved from the WoSCC database. The clinical trials were only searched from Our study firstly provides a bibliometric analysis of exercise and osteoporosis research from the publications over the past 20 years. According to our findings, the foci of research on exercise and osteoporosis has changed in multiple dimensions, including different types of exercise interventions, different age groups, the related mechanism and the method for measuring BMD. High-impact exercises or resistance exercises combined with high-impact training have a more beneficial effect that should be promoted in a preventative approach for improving bone mass. Further work is required to explore the ideal exercise interventions at different stages of life. The crosstalk impact between skeletal muscle and bone following exercise provides a new method for the mechanisms governing bone mass in the context of exercise. Overall, researchers could clearly understand the fundamental knowledge, and benefit from the analysis of research hotspots and frontiers. Our results will provide helpful clues for future research directions and scientific strategies in this field.The original contributions presented in this study are included in the article/FL and WX designed the study. FL and YH drafted the manuscript. JX revised the manuscript. FL and ZL analyzed the data. All authors contributed to the article and approved the submitted version.


As an optional regional anesthesia approach, pericapsular nerve group (PENG) block has been successfully utilized to manage pain for hip surgeries without affecting motor function. The present meta-analysis aimed to verify the efficacy of PENG block for postoperative analgesia in patients undergoing hip surgery.I2. Statistical analysis was performed using Review Manager 5.4.A total of 497 academic articles were identified after a systematic search in the databases of PubMed, Embase, Web of Science, and Cochrane Library up to 25 August 2022. The primary outcome was postoperative 24-h morphine consumption. Secondary outcomes included the time of the first request for rescue analgesia, static and dynamic pain scores 6 and 24 h after surgery, and incidence of postoperative nausea and vomiting (PONV). We calculated mean differences (MDs) with 95% confidence intervals (CIs) for postoperative 24-h morphine consumption, time of the first request for rescue analgesia, static and dynamic pain scores 6 and 24 h after surgery, and odds ratios (ORs) with 95% CIs for incidence of PONV. The chi-square test was used for heterogeneity analysis, and heterogeneity was assessed by P = 0.08] and the time of the first request for rescue analgesia  between the PENG block and control groups. PENG block did not reveal a significant difference in 6 h   and 24 h ,  static and dynamic pain scores compared with other nerve block methods. Moreover, the two groups have a similar risk of PONV .Numerous electronic databases were searched, and finally, nine studies were identified. There was no significant difference in morphine consumption during the postoperative 24 h [MD: −2.57, 95% CI: , This review shows that PENG block can act as an alternative multimodal analgesia for hip surgery, and compared with the other kinds of nerve block, there was no significant difference in the postoperative analgesic effect of PENG block.Supplementary Datasheet 1, identifier: CRD 42022356496. Approximately 1.6 million people worldwide suffer a hip fracture each year, and this number is increasing by 25% every 10 years, as the population continues to grow . In the In view of the inconsistent results of these RCTs, we carried out a systematic review and meta-analysis to identify the effects of PENG block, with a focus on the analgesic effects compared with other peripheral nerve blocks in participants after hip surgery.This meta-analysis was planned and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist . The aut*”) AND . Appropriate adjustments were made when searching the database and if the full-text article was available. The search strategies for each database are included in the We searched the electronic databases of PubMed, Embase, Web of Science, and Cochrane Library from the establishment of the database to 25 August 2022. The process of searching was systematically executed by two researchers (L.Y. and X.S.), independently, without language, publication year, journal, or region restrictions. The following search terms were used: (“PericapsulAny studies that met the following criteria were included: (1) RCTs; (2) studies that included adult patients with hip surgery; (3) studies that compared the effect of PENG block with that of other peripheral nerve blocks; and (4) studies that reported postoperative pain-related outcomes. Conversely, the following types of articles were excluded: (1) non-randomized studies; (2) studies that compared the effect of PENG block with sham block; and (3) studies in which numerical data related to postoperative analgesia were not available. When there were any differences of opinion between the two authors selecting the included studies, a senior author (H.L.) was involved and made the final decision.Two authors (L.Y. and X.S.) independently examined and screened the final enrolled RCTs and collected the following data: first author, publication year, country, sample size, type of surgery, type of anesthesia, treatment of PENG block group, treatment of control group, and primary outcome. Medians, interquartile ranges, and ranges were approximated as means and standard deviations using the quantile estimation method and the Box-Cox method of McGrath et al.  as well The primary outcome was postoperative 24-h intravenous morphine equivalent doses, which was defined as the sum of analgesic drug conversion to intravenous morphine consumption over 24 h postoperatively. The secondary outcome included the time of the first request for rescue analgesia, the static and dynamic pain scores at 6 and 24 h after surgery, and the incidence of PONV. Pain score is defined as a participant's reported feeling of discomfort using an 11-point visual analog scale (VAS) or a numerical rating scale (NRS) . PONV is defined as a discomfort sensation in which the participant has the impulsion to vomit or is forced to expel the stomach contents from the mouth .Two authors (L.Y. and X. S.) independently evaluated the risk of bias and quality of evidence. The risk of bias was assessed by using the Cochrane Risk of Bias tool for randomized trials, based on seven aspects: random sequence generation, allocation concealment, blinding of participants, blinding of outcome assessors, incomplete outcome data, selective reporting, and other potential bias; risk levels were categorized as low, unclear, or high . The GRAp-value was < 0.05 and the 95% CI did not include 1 for OR and 0 for the MD, the difference was considered statistically significant. The chi-square test was used for heterogeneity analysis, and heterogeneity was assessed by I2. When the I2-values were < 25%, 25–50%, and >50%, the heterogeneity levels corresponded to low, medium, and high. A decision was made to use a random effect model due to the anticipated heterogeneity in this study. The sensitivity analyses were performed, removing one study at a time and combining the other studies, to assess whether a single study significantly affected the pooled results.Meta-analysis was performed using Review Manager 5.4 (Cochrane Collaboration). The data used were the mean differences (MD) and odds ratio (OR), presented as 95% confidence intervals (CI). When the Data presented in the original literature were used as the primary source for extraction; when data were not shown, we contacted the authors for more information. As a final resort, when mean and SD values were not reported for an outcome    , indicatI2 = 0%, P = 0.13]   , indicatI2 = 5%, P = 0.57)  . The senDuring this meta-analysis and systematic review, we evaluated the role of PENG block in the effectiveness of postoperative analgesia after hip surgery. We did not find any significant difference in PENG block in postoperative pain-related indicators and PONV compared with other nerve block techniques. Statistically, PENG block seemed to be as effective as other types of nerve blocks for alleviating pain after hip surgery. We note that the pooled result of postoperative 24-h morphine consumption in published relevant meta-analysis is inconsistent with ours . Due to Traditionally, regional nerve block in hip surgery is performed using femoral nerve or fascia iliaca block. While partially effective, these blockade methods lead to a decrease in muscle strength . In the We performed a sensitivity analysis for each comparison; some pooled results were reversed, and the heterogeneity decreased significantly. The studies rejected by the sensitivity analysis were reviewed, and we found that the reasons for rejection included some bias risks that were unclear , the stySeveral limitations exist in the present study. First, because the number of RCTs is not yet adequate and the evaluation methods of muscle strength index vary greatly, data types include dichotomous variables and continuous variables. We do not perform a quantitative analysis comparing the PENG block to control groups in preventing quadriceps weakness. Second, in several measurements, moderate to high heterogeneity was observed. Due to the small number of RCTs included for each pooled outcome, only the static pain scores 6 h postoperative were successfully analyzed in subgroups. The results of the subgroup and sensitivity analyses together showed that the study by Choi et al.  was the a priori (More and more researchers believe that it is inappropriate to go back and re-select fixed effect or random effect models after knowing the size of the heterogeneity . Comparea priori . Third, In summary, PENG block provides an effective analgesic, similar to other peripheral nerve blocks in hip surgery. Considering that PENG block can better preserve motor function, it can be used as a promising regional anesthetic technique to replace other nerve blocks in hip surgery. At the same time, we encourage more relevant research to update this meta-analysis.The original contributions presented in the study are included in the article/LY conceived and designed the study. LY and XS performed the literature search and drafted the manuscript. HL was responsible for providing methodology and manuscript editing. All authors critically revised the manuscript and approved the final version for submission.