Pain was a prominent chief complaint among visitors to the OED (17%) and GED (21%). Approximately a fifth of all drugs used were analgesics , however, in the GED, 51.6% (n = 97) were used for non-pain-related admissions, compared with 33.0% (n = 34) in OED. Opioid usage significantly differed between emergency settings. The GED administered three times as many intravenous opioids (p <0.001), a narrower spectrum of oral and intravenous drugs (p = 0.003) and no rapid-acting opioids, significantly fewer pain adjuvants , and, finally, non-guideline-recommended drugs for pain, such as meperidine and benzodiazepines. Taken together, compared with the GED, the management of cancer-related pain in the OED was more personalized, and characterized by fewer intravenous opioids, enhanced diversity in drug type, route and method of delivery. Efforts should be directed toward reduction of disparities in the treatment of cancer pain in emergency settings.Cancer-related pain constitutes a dominant reason for admission to emergency services, and a significant patient and healthcare challenge. Evidence points to the rising prevalence of opioid misuse in this patient group. We sought to compare drug delivery in an oncology-dedicated emergency department (OED) and a general emergency department (GED) within the same hospital. As such, we obtained patient and drug-related data for OED and GED during a designated three-month period, and compared them using Fisher’s exact test, chi-square tests and the Mann-Whitney test. In total, 584 patients had 922 visits to emergency services (OED  Patients with advanced cancer face unique disease and treatment related complications, and seek unplanned medical care more frequently than the general population . A signiGeneral emergency departments (GEDs) tend to be overcrowded and fast-paced, at-tending to large and heterogeneous populations, and emergency physicians often lack expertise in caring for complex cancer patients or knowledge of the rapidly evolving treatment landscape. Emergency management of patients with cancer by general physicians has been associated with delayed diagnoses, complications, and worse outcomes . In recen = 479; GED n = 443). Patients were matched for age and gender, both groups exhibiting slight male predominance, and mean age was 62.8 and 63.7 in the OED and GED, respectively. Patients were more likely to reside outside of the hospital city, more so in the GED (71.3% vs. 60% p = 0.001), perhaps related to the limited OED opening hours by patient capacity. The discharge rate in the OED was significantly higher, at 71.6%, compared with 44.7% in the GED, however 18.8% of patients in the OED were referred for continued care in the GED (p < 0.001). Patients were more likely to return to the OED, with 38% returning over three times in the designated period compared with 23.5% in the GED (p < 0.001). In the OED, the most frequent diagnosis was gastrointestinal cancer, followed by lung, genitourinary and breast cancer, respectively. Patient characteristics are delineated in Between the dates of April to June 2017 and during the 53 days the OED was open, 584 patients had 922 visits to emergency services (OED p = 0.117). General deterioration and respiratory and gastrointestinal complaints, were also common in both emergency settings. Fewer admissions were required to address nausea/vomiting and hemorrhagic/thromboembolic events. Chief complaints are described in Of ten possible chief complaints, groups were matched for all except admission for invasive procedures, such as paracentesis, which were more commonly performed in the OED, as well as oncological emergencies and neurological symptoms. We previously showed that oncological emergencies and neurological symptoms are more suited for treatment in the GED due to the multidisciplinary environment and availability of complex diagnostic and therapeutic modalities.11 Cancer pain was the most prominent chief complaint in the GED (21%) and second to invasive procedures in the OED (17%), but well balanced between the OED and GED groups . For example, among the oral opioids, the use of oxycodone acetaminophen was more prevalent in GED 51.3% (n = 58) than OED 8% (n = 9); in the OED, enhanced diversity in drug mechanism of action, dosage, schedule (fixed or as needed), and method of delivery (syrup or pill), is evident. Similarly, among the intravenous opioids, the use of morphine was more prevalent in GED 63.1% (n = 41) than OED 16.9% (n = 11), and only physicians in the GED administered meperidine, an opioid not recommended for the treatment of oncological patients. The more modern rapid-onset opioid analgesics were only administered in the OED. On the other hand, the GED and OED showed non-dissimilar administration of non-opioid analgesics, however the total utilization of this drug category was 1.4 times higher in the GED, and dipyrone comprised 44.2% (n = 46), compared with 14.4% (n = 15) in the OED.In total, 1478 drugs were administered in the two emergency settings (OED p < 0.001), with a similar variation in drug distribution between groups. While the OED and GED had similar usage of anti-emetics in total, drug choice in the OED was significantly more diverse (p < 0.001); use of metoclopramide was more predominant in the GED 50.5% (n = 52) than the OED 16.5% (n = 17), as the remaining anti-emetics in the OED were distributed between five drugs. With the exception of bisphosphonates, anticholinergics and granulocyte colony-stimulating factors, all of which target specific oncological indications, drugs in the “other” category were more commonly utilized in the GED, and these included respiratory inhalations, as well as blood pressure, diabetes, clotting and anticonvulsant agents. Of note, anticonvulsants were all used in this analysis for neurological conditions such as epileptic events, and not as pain adjuvants. Resuscitative infusions were used disparately in the two settings (p = 0.004), with higher usage of blood products, electrolytes and dietary supplements in the GED and more fluids in the OED. Pain adjuvants comprised a larger proportion of administered drugs in the OED compared with the GED,  and 67.0% (n = 69) of the total analgesics given in the GED (n = 188) and OED (n = 103), respectively. Put another way, over half of analgesics prescribed in the GED were for patients that did not report pain as a chief complaint (51.6% GED versus 33% OED). The pattern of analgesic delivery for the management of cancer pain mirrors the findings in the rest of the cohort; significantly fewer intravenous opioids were used in the OED while rapid onset opioids were only given in the OED. Moreover, according to the test of difference of proportions, with respect to pain, the use of opioids in the GED was likely to be significantly larger than OED (p = 0.045). Antibiotics and anticoagulants were only delivered in the GED; blood products, electrolytes and fluids were similarly administered. Pain adjuvants comprised more of the drugs delivered in the OED, including antidepressants, antipsychotics, antihistamines and steroids. p = 0.01), while new analgesic agents were used only in OED. No significant differences in pain drug usage were shown for patients presenting with emesis; however, they were more likely to receive adjuvants such as steroids in the OED. A non-significant trend for more opioids was shown in the GED across admission types, including infection, general deterioration, bleeding, neurological problems, and procedures. Finally, admissions for oncological emergencies were more likely to be treated with opioids in the OED than the GED (12.3% vs. 4.6% p = 0.07). Drug utilization by chief complaint mirrored patterns observed for pain admissions. Administration of IV opioids was significantly higher in the GED compared with the OED for patients with gastrointestinal complaints  .The route of drug administration significantly differed between groups. Physicians in the GED were three times more likely to prescribe intravenous opioids than those in the OED, most notably morphine. Morphine is the prototype opioid drug for moderate to severe cancer pain on the third step of the World Health Organization’s (WHO) analgesic ladder. With a large variation in patient response to morphine, studies have not demonstrated its superiority over other opioids in terms of efficacy or tolerability, and it should not be regarded as a “drug of choice” . NeverthDrug delivery in the OED can be characterized by its richer diversity when compared to the GED. The larger variety of oral opioids was presumably tailored to patient needs in the OED, while those in the GED almost always received oxycodone acetaminophen. Rotation among opioids is a useful therapeutic strategy to improve analgesic response or minimize toxicity . This waFinally, the physicians in the GED prescribed nearly double the total amount of drugs for a similar amount of patients. The patterns of drugs use and disparities in practice be-tween the OED and GED hold true both when evaluating patients with pain as a chief complaint, and also when grouping together other chief complaints. This highlights the prevalence and grave significance of the treatment of pain in cancer patients in emergency settings, both when they visit specifically due to their pain, and also when they present for other reasons. Severity and high risk admissions were more likely to be referred to the GED. These, however, did not account for disparities in pain drug usage, as no differences were observed for the high risk “neurological” complaints, while for oncological emergencies, higher opioid administration was actually observed in the OED, further suggesting a targeted treatment for accurate indications.Not all institutions have the capacity, resources and personnel for a dedicated oncology emergency setting. Future directions for this study include the implementation of an educational intervention aimed at general emergency departments. In a prospective study, emergency care teams will undergo a pragmatic training program in supportive care treatment paradigms. Drug delivery practices as well as patient and healthcare satisfaction will be evaluated before and after the intervention. We hypothesize that improved financial and quality care parameters alongside reduced opioid usage due to the enhanced awareness and experience among GED care teams.This study has various limitations. As a single center with limited sample size, the results cannot be generalized. However, electronic medical records were reviewed individually and not automatically to ensure the accuracy of patient data and to account for multiple possible complaints. The analysis may be confounded by patient selection bias, as cases managed in the GED may be more complex that those in the OED, due to type or time of presentation (18.8% referred from OED to GED); however, the dramatic differences in drug utilization appear far greater than those accounted for by this alone. Moreover, a nationwide analysis found that patients with cancer attend emergency services more often during business hours and on weekdays and are more likely to be hospitalized during these times . An addiThe results of this analysis suggest that management of cancer-related pain in oncology-dedicated emergency settings is preferred to general emergency departments. Evidence based drug delivery for appropriate indications, usage of opioids, choice in method and route of drug administration, incorporation of pain adjuncts and diversity in drug choice were all enhanced in the oncology-based setting. Efforts should be directed toward the reduction of disparities in urgent cancer care, and can be achieved by increasing emergency physician knowledge of supportive care treatment paradigms, expanding outpatient symptom management programs, and, finally, the integration of urgent care services in cancer programs. As such, optimized urgent cancer care may contribute to superior patient and healthcare outcomes.A large tertiary referral center for 12 district hospitals, RMC serves approximately 20% of the total population of Israel, and patients with cancer have direct access to inpatient, outpatient, and emergency services covered by national healthcare. Patients presenting during clinic hours visit the OED pending availability of staff, resources and beds, without initial selection or triage; when the OED is filled or closed, they present directly to the main hospital GED, where an oncology consult can be obtained if needed. Open during weekday morning hours (9:00 a.m. until last bed or 12:00 p.m.), the OED is staffed with a designated nurse and oncologist. A palliative care nurse is usually available for consultation. Resources shared with the day care include drugs and fluids for patient administration, while imaging is shared with the GED. After treatment, patients are discharged, hospitalized in the oncology inpatient department, or referred to the GED for more advanced multi-disciplinary evaluation and care.A retrospective electronic medical record review was performed for all patients admitted to the GED and OED during the 3-month period between April 2017 and June 2017. Data for the GED were obtained only for days the OED was open in order to establish similar groups and exclude confounders in weekend or holiday visits. Patients could attend the GED at any hour and needed to have a documented oncology consult. Hematologic malignancies were excluded since they are treated in a separate department at RMC. Patient demographics and disposition  were retrieved from the database. Drug administration was also recorded and divided into specific drug group categories. Cases were assigned “chief complaint” after individual file evaluation by the study team, and could be given more than one assignation, for instance “oncological emergency” and “neurological symptoms”. Patients referred from the OED to the GED were considered in both settings as separate cases but this was taken into account for statistical analysis. The study was approved by the institutional Independent Ethics Committee, registered as 0465-17-RMB and granted a waiver for obtaining patient consent because of its retrospective design.p was <0.05.To assess the difference between drug administration over the emergency setting of interest we implemented a series of chi-square tests or Fisher’s exact tests (when the assumptions of the parametric chi-square test were not met) and nonparametric Mann–Whitney U tests. The results were statistically significant by the standard of the study when


Medical imaging has relied on ultrasound (US) as an exploratory method for decades. Nonetheless, in cell biology, the numerous US applications are mainly in the research and development phase. In this review, we report the main effects on human or mammal cells of US induced by bulk or surface acoustic waves (SAW). At low frequencies, bulk US can lead to cell death. Under specific intensities and exposure times, however, cell proliferation and migration can be enhanced through cytoskeleton fluidization (a reorganization of the actin filaments and microtubules). Cavitation phenomena, frequencies of resonance close to those of the biological compounds, and mechanical transfers of energy from the acoustic pressure could explain those biological outcomes. At higher frequencies, no cavitation is observed. However, USs of high frequency stimulate ionic channels and increase cell permeability and transfection potency. Surface acoustic waves are increasingly exploited in microfluidics, especially for precise cell manipulations and cell sorting. With applications in diagnosis, infection, cancer treatment, or wound healing, US has remarkable potential. More mechanotransduction studies would be beneficial to understand the distinct roles of temperature rise, acoustic streaming and mechanical and electrical stimuli in the field. As . As 4]. requency . Several teams tried to formulate hypotheses and propose models to explain the physical phenomena at play in the biological effects of US. The resonance and shear stress forces could provoke disjunctions between molecular complexes or conformational changes of biomacromolecules. Indeed, the hypothesis presented by Johns suggests that the absorption of US energy by enzymes could lead to their activation. The link between an enzyme and its inhibitor may be broken, or the enzyme may adopt an active conformation on its own. In both cases, the biochemical reactions that the enzyme catalyzes are boosted . Other bCumulative effects of the stress impacted by the resonance on the organelles could also lead to a fatigue phenomenon, which explains the observed cellular damage. Kimmel  develope−2 the most frequently used intensity unit, even if simple and easy to apprehend, does not explain the acoustic field characterization at the studied area. The acoustic shear was rarely taken into consideration in the reviewed studies. Nevertheless, these studies present avenues by which to better understand the physical phenomena at play for low frequencies, or as seen in the next paragraph, for frequencies higher than 10 MHz.The impacts of US depend on physical parameters such as resonance frequency and acoustic pressure, but also on biological parameters such as the cell size, adherence, and type. The frequency, pressure or dose units are not sufficient to comprehend the US effects on cells. A review from 2007  stated tAt high frequencies, the cavitation phenomenon is not observed; moreover, the beamwidth becomes narrower, allowing for a more precise cell stimulation. Technologies using US at frequencies of higher than 10 MHz were developed recently, such as single-cell imaging ,37. We w2+ influx was indeed observed following exposure to US at 193 MHz of human breast cancer or non-cancerous cells, and US of 200 MHz to endothelial cells (HUVEC) [2+ influx, as a function of the invasiveness of human breast cancer cells [2+ concentration changes. A transcriptomic analysis of the genes involved in the piezo channel or the TRP channel is welcomed. The detection of the differences in cell response towards HFUMS could distinguish between non-cancerous and highly invasive cancer cells. Moreover, this kind of stimulation by US showed no impact on cell viability, displaying optimal parameters for potential applications of HFUMS as biosensors [−2. Similar proliferation drops were found at 100 MHz with US only (no LED) [Studies have shown that the permeability enhancement by US at high frequencies, or high frequency microbeam stimulation (HFUMS), seemed to depend on the invasive nature of the cells. Hwang et al. showed that US at 200 MHz increased cell permeability more significantly for human breast non-cancerous cells compared to cancer cells, as evidenced by Rhodamine B reflux . A highe (HUVEC) ,41. Likeer cells . Anotherosensors . In addiosensors ,44. This(no LED) . The autv1.2 channel, which is a type of sodium channel, or human embryonic kidney cells (HEK) modified to express mouse piezo 1 channels. The cells were exposed for 0.7 s to US at a frequency of 43 MHz, and an intensity of 50 or 90 W cm−2. This work confirmed the activation of the piezo channel by the US, more specifically by the acoustic radiation pressure and streaming. The Nav1.2 channel was also activated by the stimulation, albeit only due to thermal heating. Heating can indeed activate or increase the kinetic speed of ion channels. It has to be noted that the temperature rise at play here was only of 0.8 °C. Thus, even a small difference in environmental temperature due to US could impact the cell response.Prieto et al.  conductepp), and pulse duration (tp). The study optimized the parameters for a maximal transfection of 3 kDa dextran molecules, without any significant impact on cell viability in the short (6 h) and long (40 h) term. The optimized parameters were as follows: Vpp = 22 V and tp = 30 µs, or Vpp = 43 V and tp = 10 µs [Given the US effects on the membrane permeability through channel activation, the HFUMS can additionally be used to transfect small molecules, DNA plasmids and RNA messengers. At high frequencies, no microbubble is needed. HFUMS thus facilitates the controlled and local intracellular delivery of chosen molecules. A US-transfection system was developed by Yoon et al. at 150 and 215 MHz and tested on HeLa cells. The size and amount of transfected fluorescent dextran molecules depended on the frequency, the number of electric pulses, the peak-to-peak voltage (Vhe short  h and lo3) chip, on which acoustic waves propagate longitudinally , where only the extreme surface of an elastic material resonates. The SAW are also called Rayleigh waves, in reference to the name of the first scientist to describe them in 1885. The generation of SAW requires the conversion of electrical energy to mechanical energy. A voltage is applied to a metallic interdigitated transducer (IDT) on the surface of a piezoelectric substrate, generally a lithium niobate  ch3 chip, inducing SAW and US (no information was provided about their frequency and intensity) that detached adherent human osteosarcoma sarcoma osteogenic cells (SaOs-2) [A time-dependent detachment of human cells from their growing substrate can be observed when exposed to SAW. Likewise, Stamp et al. applied a power of 300 to 500 mW to a LiNbO(SaOs-2) . They hy(SaOs-2) . Part of(SaOs-2) . Other pA study described different behaviors before the detachment of red blood cells (RBC) depending on their pathological state . For non6 more sensitivity than atomic force microscopy (AFM). SAW could thus be used for the differentiation of cancer and healthy cells, as the elastic modulus might be a possible biomarker for invasiveness or metastatic potential. Single-cell manipulation is a rising field at the intersection of biological sciences, microfluidics, and acoustics. SAW can be used to facilitate cell collision with nanoparticles and to induce cell lysis in very small volumes in microfluidic systems . SAW can−1 [Plasmodium falciparum [A high rate of cell manipulation and sorting can be achieved. A study in 2014 reached a sorting rate of as high as 3000 cells s−1 . Under tlciparum . The autlciparum . SeparatIn 2016, SAW were seen to enhance wound healing, with cells exposed to low powers  for 48 h . Osteobl−2 intensity. In contrast to Stamp’s study, they found a significant preferential alignment in the cell nuclei. They suggested it to be linked to changes in the cytoskeleton, specifically to an increase in actin stress fibers and bundle thickness. The shear stress, estimated to be 3.7 mPa, was thought to be too low to induce such biological impacts and rather, they were attributed to the propagating acoustic waves themselves [In 2020, Brugger et al. conducted a similar experiment, and confirmed the improvement in wound healing using SaOs-2 and canine and human kidney cells . Here, aemselves . The question of whether cell proliferation could be enhanced by SAW is especially pertinent when compared to the impacts of bulk US . SAW couThe study of the acoustic wave’s effects on human and mammal cells is still developing. One major drawback is the lack of standardization between the published works. A primary inconvenience is indeed the difference in US parameters, of either the intensity, the power, or the voltage, especially in the most recent articles on HFUMS or SAW. Considering the wide range of used cell types, a comparison of results from different studies is quite challenging. As shown in Numerous parameters influence these results, however, including cell type, concentration, pathological state, US frequency, intensity, pulse mode, exposure time, and more globally, the dose of exposure, as well as the environmental temperature and shear flow. Large-scale studies focusing on only one parameter would help to develop an understanding of the biological and physical mechanisms of action. This kind of work would contribute to experimental standardization across laboratories, an efficient workload sharing, and the dissemination of systematic results. In the introduction, conventional medical uses of acoustic waves were discussed, with applications in imaging and bone repair. Other forms of imaging such as electrography and ultrasonography rely on ultrasound-induced impacts too, such as the stiffness or elasticity of the targeted tissues. Lithotripsy employs high-amplitude acoustic shock waves to break kidney stones. It has cosmetic applications too, more specifically for laser-tattoo removal . The eff−2 at the focal point with 1 to 1.5 MHz and for <2 h. Clinical studies for uterine fibroid tumors, or prostate cancer, showed its pertinence [In the following paragraph, biomedical applications are discussed with regard to recent advances in understanding the cellular effects of the bulk or surface acoustic waves. For example, high-frequency ultrasounds could enhance medically-assisted reproduction success rates. Surface waves derived from 19 MHz and 2 W stimulation could increase sperm velocity by up to 34% . The undrtinence ,69,70. Hrtinence . Other pThis review summarized the biological outcomes of exposing human or mammal cells to US, and provides leads on the physical phenomena at stake. Even if it is not as emphasized with SAW, US can lead to cell death, damage, or a decrease in their proliferation if the parameters are not well adjusted. Another point of interest for cellular or medical sciences is the possibility of triggering an increase in cell proliferation, migration, and permeability either by inducing changes in the cytoskeleton or ion channel activity. Overall, standardized studies to assess the impact of each physical parameter will be conducted to anticipate specific cell-line responses to US and to design efficient microsystems for biomedical applications of acoustic waves.


The results of this study showed that diameter and height were lower in adult dogs than in senior and geriatrician dogs (p < 0.05). Whereas, sex, body size, and the interaction did not show a significant effect (p > 0.05). Additionally, some images of anisocytosis, polychromasia, and poikilocytosis  were obtained by OM and SEM. Our study provides information about the morphological and morphometry alterations of adult, senior, and geriatrician dogs RBC. This work contributes to future investigations and the diagnosing diseases, where it is necessary to evaluate the morphology of RBC.Red blood cells (RBC) morphologic evaluation through microscopy optical (OM) and SEM, provides information to forecast, evaluate, and monitor the functioning of many organs. Factors, such aging and diseases affect RBC morphology in both, human and animals. SEM is useful to evaluate RBC morphology, although its use in diagnosis and evaluation in dogs is limited, due to the availability and cost. The aim of this research was to assess the normal RBC morphology in adult, senior and geriatrician dogs, clinically healthy by OM and SEM. In addition to evaluating the age effect, sex, body size, and their interaction on erythrocyte morphometry. To carry out the research 152 blood samples were evaluated from dogs of different sexes and body sizes . Three groups were made based on dogs age: group I adults (1–7.9 years old), group II senior (8–11.9 years old), and group III geriatricians (>12 years old). Erythrocyte parameters were evaluated by OM . Per each dog, the parameters of 20 erythrocytes were measured. A total of 2,600 cells were scanned with the AmScope™ Software scale. In addition, the RBC morphology was evaluated by SEM. Statistical analyses used analysis of variance and a general linear model, which allows the comparison of multiple factors at two or more levels ( Red blood cells (RBC) are the most abundant blood cells in the organism, delivering oxygen to body tissues. The count of these vital cells is often the first step done in analyzing a patient's pathological condition , 2. RBC The light microscope has been the most frequent method for the evaluation of the RBC morphology because is an important tool in the detection of diseases in geriatric patients, as well as a quality control measure for automated hematology equipment and as a rapid evaluation of patients in veterinary emergencies –13. HoweThe morphological evaluation of RBC through SEM has been applied mainly in human medicine, in patients with inflammatory diseases, cardiovascular, related to aging, and diabetes –19. SomeFor this reason, it is important to explore other microscopy tools in the field of veterinary research that can assist in the diagnosis and monitoring of diseases in both animals and humans. Besides, to our knowledge, it has not been determined erythrocyte parameters in aging dogs. Therefore, this study aimed to evaluate RBC morphology in the adult dogs (1–7.9 years old), senior dogs (8–11.9 years old), and geriatrician dogs (>12 years old) clinically healthy by OM and SEM. In addition to evaluating the effect of age, sex, body size, and their interaction on erythrocyte morphometry through parameters of RBC .This study was carried out in compliance with the provisions established in the Ethics Regulations for the Use of Animals in Teaching and Research at the Autonomous University of Aguascalientes (CEADI-UAA) Code: DI-PL-NO-37 . A non-eAnimals were assessed as healthy on the basis of a complete physical examination and history. The collection of the medical history and the physical examination were carried out by a veterinarian who specializes in clinical medicine of small species at the Parasitology Laboratory of the Center for Agricultural Sciences of the Autonomous University of Aguascalientes and private clinics. A questionnaire  related All dogs fasted for 8–12 h before blood sampling, and water was offered at libitum. Non-fasted dogs, dogs on medication at the time of blood sampling, or when a significant illness was suspected based on history and observation were excluded from the study. Dogs needed to be free of medication for at least 2 months before inclusion. Preventive medication  was allowed until 2 weeks before the consultation. Females were not pregnant, not lactating, and not in oestrus. All dogs selected for this study were privately owned –30. All ® with EDTA K2, applied by aspersion (BD Franklin Lakes NJ USA) to perform the blood smear analysis.Samples of 500 μl of blood were collected using venipuncture jugular with vacuum tubes BD Vacutainer®, Darmstadt, Germany) and xylol  was placed on them, and they were left to dry for 24 h . Once obtained the blood sample was centrifuged at 2,000 rpm for 10 min to separate the leukocyte layer that was deposited in a 1.5 ml Eppendorf tube, adding glutaraldehyde , to fix them until further analysis. The sample, later, was centrifuged at 6,000 rpm for 1 min, obtaining only the precipitate by decanting the sample. Phosphate buffered saline (PBS) solution 1X  was added to the precipitate, mixed, and allowed to rest for 5 min. This process was carried out three times; then it was added alcohol at 60%, letting the precipitate rest for 10 min. The sample was centrifuged again at 6,000 rpm for 1 min; this process was repeated with alcohol at 70, 80, 90, 96, and 100%. Lastly, 100% of pure acetone was added and fixed in a dark-bottomed aluminum cylinder to later be coated with gold particles in Desk II Denton vacuum equipment , and finally observed in the scanning electron microscope JEOL JSM-5900LV   , 40. Micp < 0.05 was considered significant. We evaluated the distribution of the variables by examining the histograms and using a goodness of fit test (Anderson–Darling) ; Darling) . To deteDarling) .p < 0.05). Morphometric parameters of RBC: diameter, height, and axial ratio represent response variables (dependent), while age, sex, and body size represent factors (independent variables). The interaction between factors was also evaluated. When the data did not meet the normality assumptions and homoscedasticity, we performed a Box-Cox transformation using Minitab's optimal lambda (λ) with a confidence level of 95%. Subsequently, a multiple comparison method (Tukey) was performed with a confidence level of 95%  with a general linear model (GLM), which allows the comparison of multiple factors at two or more levels  based on the recommendations of International Federation of Clinical Chemistry (IFCC) and the Clinical and Laboratory Standards Institute (CLSI)  were calculated using the software Reference Value Advisor  . This soe (CLSI) , 44.A total of 152 blood samples were collected from dogs of different ages: group I adults (1–7.9 years old), group II seniors (8–11.9 years old), and group III geriatricians (>12 years old). Eighty-two dogs were female, and 66 dogs were male. All dogs were grouped according to their body size: 81 small dogs, 25 medium dogs, and 42 large dogs. A variety of small, medium and large dogs were represented in each age group. Nineteen blood samples were excluded: five samples due to the presence of clots, four samples with hemolysis and 10 samples from the statistical analysis because of underlying subclinical diseases. Therefore, only 129 blood samples from clinically healthy dogs were analyzed by light microscopy and 4 blood samples by scanning electron microscopy, as described in In this research were obtained images of the blood smears by light microscopy. A presence of polychromasia  was idenIn Normal lymphocyte morphology was identified in the blood of dogs by light microscopy. p), mean (M), and standard deviation (SD).p = 0.00). The average red cell diameter in adult dogs from 1 to 7.9 years old was 7.56 μm (SD = 0.44), which was significantly lower than the diameter in seniors , and geriatric dogs . Our research showed that diameter increased with age (p = 0.069), body size (p = 0.512), and interaction between age, sex, and body size (p = 0.238) was observed on the diameter.Age had a significant effect on the diameter (with age . No signp = 0.00). M = 7.18 μm, SD = 0.42) was significantly lower than the height of senior dogs  and geriatric dogs . Furthermore, height in senior dogs was significantly lower than height in geriatric dogs (p = 0.027). No effect of sex (p = 0.867), body size (p = 0.335), and interaction between age, sex, and body size (p = 0.414) on height was identified. No statistically significant effect of age (p = 0.56), sex (p = 0.662), body size (p = 0.078), and interaction between age, sex, and body size (p = 0.298) on the axial relationship was identified.Age had a significant effect on height , In particular observed, that abnormally shaped erythrocytes in the blood samples from autistic subjects predominantly featured elliptocytes. While, the NA-NDDs group showed mixed abnormally shaped RBCs, without a predominant erythrocyte shape phenotype, although a slight prevalence of leptocytes was detectable . In paraMorphological changes in RBC have been associated with an increased risk of cardiovascular diseases in human medicine . In inflRBC diameter evaluated in this study from the OM micrographs obtained a mean in adult dogs of 7.56 μm lower than of diameter of senior (7.67 μm) and geriatric dogs (7.72 μm). These results show an effect of age on the erythrocyte diameter. Some authors report that dogs' erythrocyte diameter varies from 6 to 8 μm , 63. An It is important to evaluate the erythrocyte morphology and morphometry, especially in aged dogs, since this undoubtedly favors the diagnosis and prognosis of the aged patient. Optical microscopy is the tool par excellence to evaluate the blood smear, however, it is important to know other visual tools. Some diseases in humans also occur in dogs, therefore, the latter could be used in future research to help evaluate the morphology and RBC parameters by means of optical microscopy and scanning electron microscopy. It is well-known that the dog has contributed to some advances in applied medicine in humans. For this reason, this research encourages researchers in both veterinary medicine and human medicine to explore other diagnostic tools such as scanning electron microscopy.SEM is a tool useful for determining morphological alterations in the membrane of the RBC as indicative of diseases but is not fully accessible in veterinary medicine for economic reasons and knowledge when interpreting the results because the blood circulation occurs in 3D and, it is how the cells look in SEM; whereas the evaluating a smear with MO, when “squashing” the cells change the dimension. Thus, the interpretation differs remarkably, the first exponent is that in SEM the nucleus is not seen and in the case of white blood cells (WBC), the interpretation is quite complicated by not having more than the morphological aspect of the membrane. Scanning electron microscopy has been shown to be a useful tool for detecting morphological changes in aged dogs. Therefore, this study lays the groundwork for continuing the use of electron microscopy as a diagnostic tool in veterinary medicine since it is important to know the effects of some illnesses and aging on the morphology of RBC. This would help clinicians to consolidate patients' reports and to detect diseases in time, as well as to improve their treatment.The original contributions presented in the study are included in the article/The animal study was reviewed and approved by Ethics regulations for the use of animals in teaching and research at the Autonomous University of Aguascalientes Code: DI-PL-NO-37. Written informed consent was obtained from the owners for the participation of their animals in this study.AM-N and AG-B conceived this study, participated in its design, performed coordination, and helped draft the manuscript. TQ-T, AV-F, and MC-R made significant contributions to the conception, design, and analysis of the results. AM-N also carried out laboratory analysis and statistical analysis. All authors contributed to manuscript revision, read, and approved the submitted version.The Autonomous University of Aguascalientes approved and granted funding for TQ-T (Project PIP/SA15–3) for AG-B , which was used in the acquisition of materials and reagents necessary to obtain and process blood samples during the development of this study.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.


Thrombin-antithrombin complex (TAT) is a prethrombotic marker, and its application in ischemic stroke is still uncertain. The purpose of this systematic review and meta-analysis is to evaluate the relationship between plasma TAT and ischemic stroke base on the current evidence.A systematic literature search was conducted for searching the relative studies that investigated the association of TAT and ischemic stroke in PubMed, EMBASE, and Cochrane library databases. Mean difference and 95% confidence interval as the effect sizes were synthesized by random effects model in Review Manager (RevMan) Version 5.4. The heterogeneity was investigated using the chi-square test and the possible sources of heterogeneity were explored by sensitivity analysis and meta-regression. The publication bias was estimated by Egger’s tests.P < 0.0001, I2 = 97.8%). There is a difference of TAT level in the same period among cardioembolic, lacunar, and atherothrombotic stroke , in which the cardioembolic stroke with the highest level. Meanwhile, it is significant of TAT levels among various phases of cardioembolic stroke and the acute phase are markedly elevated . However, no difference was found in the atherothrombotic (P = 0.13) and lacunar stroke (P = 0.34). Besides, the higher TAT level is closely related to the poor prognosis of patients with ischemic stroke, including higher recurrence, mortality, unfavorable recovery , and poor revascularization.A total of 12 eligible studies were included involving 1431 stroke cases and 532 healthy controls, of which six studies were eventually included in the meta-analysis. Plasma TAT in patients with ischemic stroke was significantly higher than that in healthy controls (MD 5.31, 95% CI = 4.12–6.51, This study suggested that plasma TAT levels are different in ischemic stroke subtypes, which are closely associated with the progression and might have an effect on the prognosis.PROSPERO CRD: 42021248787The online version contains supplementary material available at 10.1186/s13643-023-02174-9. More thcts.htm) . Ischemicts.htm) . ThromboIschemic brain damage involves the activation of a series of detrimental signaling cascades, including micro-atheroma, endothelial dysfunction, and inflammation. There is no simple and effective method for early detection other than the detection of narrowed blood vessels by imaging techniques. So, the clinical guidelines suggest that thrombolysis is the most important method in the emergency department under the instruction of multi-mode computed tomography (CT) or magnetic resonance imaging (MRI) neuroimaging once an ischemic stroke occurs . HoweverResearch on some easily available blood biomarkers in ischemic stroke has been reported in a previous review for the diagnosis and differentiation of stroke, including brain natriuretic peptide, matrix metalloproteinase-9, and D-dimer [Elevated TAT has been proven to be associated with several disease studies. There is clear evidence that patients with myocardial infarction were accompanied by mild inflammation with an increase in TAT . The actTherefore, we performed a meta-analysis to clarify whether there are differences in TAT between ischemic stroke subtypes and different responses by splitting the analysis on the timing of the blood draw with ischemic stroke by reviewing the literature. Besides, we did a systematic review to explain the relationship between TAT levels and prognosis reported in the patient groups for helping reduce mortality and better beyond hospital admission management.We performed this systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) . The proA comprehensive search was conducted by two researchers (Peipei Song and Jianqin Xie) from inception to October 13, 2021, in PubMed, EMBASE, Cochrane Library, Web of Science, and Google Scholar. The combination of MeSH and free text terms were used to search in the databases and the strategy of PubMed as follow: (“antithrombins” OR “thrombate III” OR “AT III-protease complex”) AND . The search results were limited to human studies that were written in English, and we also manually searched the references of original articles and reviews. Two authors independently completed the process of literature search and any indistinguishable records were conducted by negotiating with the third party (Chongge You). We showed the database detailed search strategies for the databases in Supplementary Table All studies met the following inclusion criteria and were selected into our systematic review and meta-analysis based: (1) case-control study or cohort study, (2) study investigated the association of plasma TAT levels and strokes, (3) study including stroke subtypes or stages, (4) plasma TAT as one of the outcome indicators was reported in prognosis, (5) if the studies with the same case materials and published by the same authors, only the lasted or largest population will be included. (6) We do not limit the period and language of included studies.The studies were excluded in which they meet the following exclusion criteria: (1) repeated publications, (2) reviews or summaries, (3) non-human studies, (4) incomplete data in the research, and (5) studies measuring TAT level in cerebrospinal fluid or urine.Cardioembolic, lacunar, and atherothrombotic stroke subjects were divided based on the findings of the clinical ancillary examination, such as cerebral angiography, ultrasound examination of carotid vessels, and confirmation of the intracardiac embolization and the evidence of image logical diagnosis. We defined the acute phase (< 24 h), subacute phase (24–48 h), and chronic phase (> 7 days) as the records. Another subgroup was determined according to the methods of TAT measurement.Two authors (Wei Li and Xinying Zhang) independently completed the data extraction and quality assessment. For any indistinguishable record by consulting or talking over the corresponding author. We read the full text for extracting data and further assessment. The baseline characteristics of the literature were extracted by using a well-designed form. The Newcastle-Ottawa Scale (NOS) scale was used to assess the methodological quality of those included the case-control or cohort studies . Each ofP < 0.05 is considered to be statistically significant. We calculated the means and standard deviations in line with the method developed by Hozo et al. [P ≤ 0.05 in comparison among groups or P < 0.1 in comparison within groups. Chi-square test was used to assess the heterogeneity among the included studies, and quantified by the Higgin’s I2 statistic, I2 < 50%, 50% ≤ I2 ≤ 75%, and I2 > 75% were regarded as low, moderate, and high heterogeneity, respectively. Subsequently, a sensitivity analysis was performed when there is the heterogeneity, in which one study at a time was removed and the others analyzed to estimate whether the results could have been affected markedly by a single study. Furthermore, an analysis was performed by meta-regression to searched for sources of heterogeneity. Subgroup analysis was performed according to the different subtypes and phases of ischemic stroke. Egger’s regression tests were used to estimate the publication bias.Two authors (Peipei Song and Jianqin Xie) used the software of StataMP version 16 to synthesize study data, and After retrieving relevant search terms in PubMed, EMBASE, Web of Science, and Cochrane Library databases, a total of 2965 publications were researched, and 4 articles were retrieved from Google Scholar. The PRISMA flow diagram for study inclusion in our meta-analysis was depicted in Fig. A total of ten case-control studies and two cohort studies were incorporated into the systematic review and meta-analysis, including 1431 stroke cases and 532 healthy controls. Six studies were from Japan –22, two All studies were assessed for methodological quality by the Newcastle-Ottawa Scale (NOS). The range of quality scores is 7 to 8 for case-control, with a median of 7.5 (7.5 ± 0.53) . Although there is no difference in atherothrombotic stroke in the result of Supplementary Figure SP = 0.13), and the plasma TAT level was markedly elevated in the acute than that in the subacute and chronic phases. Besides, no significant difference was found in the lacunar stroke which was shown in Supplementary Figure SP = 0.34, I2 = 97.86%), and the highest plasma TAT level is the subacute phase.Meanwhile, we analyzed the differences among different periods in each subtype of ischemic stroke. The cardioembolic stroke was shown in Supplementary Figure We further searched for sources of heterogeneity by meta-regression, and these results are showed in the Supplementary Table A total of six studies have reported the relationship between plasma TAT levels and the prognosis of ischemic stroke prognosis Table . We condP = 0.11, Supplementary Figure SP = 0.7787) regression test.Sensitivity analysis was performed through the elimination method in which one study is removed at a time and the others analyzed to estimate whether the results could have been affected markedly by a single study. However, the results showed that excluding any one study will not affect the results, this analysis confirmed the stability of the results. Another subgroup analysis was performed to explore the source of heterogeneity based on the TAT detection method. There was no significant difference between the groups . Similar to our result, Song, J et al. proved that cardioembolic stroke might be severer and with higher TAT levels than other stroke subtypes [In our study, the results demonstrated that patients with cardioembolic stroke have higher TAT levels than those with atherothrombotic strokes, which suggested that TAT might be able to differentiate cardioembolic stroke from atherothrombotic , which might be related to the mechanism of thrombus formation in the different diseases. This is most commonly due to thrombus formation in a coronary artery [Previous studies have investigated the association between TAT and acute myocardial infarction (AMI), which showed that the highest TAT level is at the subacute phase for those patients with myocardial infarction , 36. Howy artery . The prey artery . ThromboP < 0.001) and acute phases . For those patients admitted to the emergency department, higher plasma TAT levels may alert the clinician that he is more prone to cardiac infarction or earlier stages of disease. Besides, we found that higher TAT levels often indicate higher recurrence [Several published systematic reviews have generated a shred of evidence regarding the role of biomarkers in ischemic stroke. Yan H et al. investigated the correlations of TM and hs-CRP with ischemic stroke . A largecurrence , worse fcurrence , and higcurrence . This hacurrence , 40. ThoIf plasma TAT can be widely developed as one of the physical examination items, it is also a good measure to prevent thrombotic diseases. Currently, the study of comprehensive biomarkers in the stages of ischemic stroke is still in its infancy . The chaOur meta-analysis results showed an important effect of plasma TAT levels on ischemic stroke, and plasma TAT might be involved in the progression and prognosis of ischemic stroke, and it is also helpful in identifying stroke subtypes.We acknowledge limitations in our study. First of all, the number of studies included in our meta-analysis is small, and there are large differences in sample sizes, which may have an impact on statistical analysis and become another source of heterogeneity. Secondly, manual search for relevant reviews may lead to omissions in the literature, which may potentially affect the validity of our results. Finally, due to the lack of research data, the relationship between the severity of ischemic stroke based on the NIHSS scores and TAT has not been analyzed in this meta-analysis, which may be a part worth exploring in the future. Choosing English language articles only is also one of our shortcomings.Additional file 1: Supplementary Table 1. Search strategy for databases.Additional file 2: Supplementary Table 2. The quality of included case-control studies.Additional file 3: Supplementary Table 3. Meta-regression analysis of each study attribute.Additional file 4: Supplementary Figure S1. The level of TAT in cardioembolic stroke among the acute, subacute and chronic phases.Additional file 5: Supplementary Figure S2. The level of TAT in atherothrombotic stroke among the acute, subacute and chronic phases.Additional file 6: Supplementary Figure S3. The level of TAT in lacunar stroke among the acute, subacute and chronic phases.Additional file 7: Supplementary Figure S4. Subgroup analysis of plasma TAT based on the TAT detection method.


The development of high-quality human capital is an important objective that involves value orientations, cultural dimensions and psychological characteristics of activity. This article presents a cross-cultural comparison of value orientations and psychological parameters of activity among youth from Russia, Kazakhstan, and Latvia.The study addressed three questions: (1) Are there values and attitudes related to the readiness for activity among youth in the three countries? (2) Are there any differences between values and parameters of the psychological system of activity in the Russian, Kazakhstani and Latvian samples? (3) What values and attitudes predict the youth’s readiness for activity in each country?University students from Russia, Kazakhstan and Latvia were invited to participate in the study. The study sample was selected according to age, sex and period of living in the country. Value orientations, cultural dimensions and attitudes were measured by the Values Survey Module, World Values Survey questionnaire, The Subjective Evaluation of Basic Values Realisability. Personality Research Form, Quality of Life Enjoyment and Satisfaction Questionnaire, Subjective Happiness Scale, Self-Organisation of Activity Questionnaire, Differential Test of Reflexivity, and Satisfaction with Life Scale questionnaires were applied to evaluate the psychological parameters of activity. To analyse the relationship between value orientations and psychological parameters of activity, we used analysis of variance, Pearson’s correlation coefficient and stepwise linear regression.The cross-cultural variance was established for most values and cultural dimensions in the Russian, Kazakhstani, and Latvian samples, but Personal readiness for activity only differed on the tendency level between the Kazakhstani and Latvian samples. Different values and attitudes accounted for near 57% of the Personal readiness for activity index in Russia and Latvia, but just less than 29% in Kazakhstan.The activity of university students from Russia depends on their need for achievement and level of happiness. In the Kazakhstani and Latvian samples, the most important factor was the quality of life enjoyment and satisfaction index. Traditionally, the definition of social progress and human capital as its part has been based on economic terms . However, a more people-oriented approach has emerged amongst scholars over the last decades. There are a growing number of published studies that focus on high-quality human capital. These aim at exploring social progress index , social Cultural dimensions are supposed to contribute to our better understanding of the interplay between personal and environmental aspects when analysing the problem of high-quality human resource development . EvidencThe studies conducted highlighted the role of young people’s basic values and their subjective evaluation of possibilities to realise these values in their sociocultural environments . BogomazAccordingly, it is captivating to explore cultural dimensions of countries that were recently a single unit. The collapse of the Soviet Union in 1991 generated a unique situation when 15 countries simultaneously started their pathways to building independent national communities . The 30 Today’s young generation in the former Soviet Union countries is an indicator of the social and economic alterations that have occurred since the turbulent turn of the century. Youth is known to be the age category most sensitive to change, so it represents a major research interest in the context of the future trends of social development. A deeper understanding of the cultural context requires a research focus on what is going on in the countries. However, youth’s personal and professional development intertwines with each country’s high-quality human capital from a long-term perspective.Our research includes youth from three ex-Soviet Union countries with different economic and political pathways to building independent national communities: Russia, Kazakhstan, and Latvia. Also noticeable is the geographical differences of these countries: Kazakhstan is in Asia, Latvia is in Europe, and Russia is in both Asia and Europe.Our objectives were to test hypotheses of cross-cultural differences in value orientations and readiness for activity among the Russian, Latvian, and Kazakhstani samples made up of university students. This would allow a differentiated approach to discovering the relationship between these individual personality characteristics and students’ personal and professional development activities. The study addressed three questions: (1) Are there values and attitudes related to the readiness for activity among youth in the three countries? (2) Are there any differences between values and parameters of the psychological system of activity in the Russian, Kazakhstani and Latvian samples? (3) What values and attitudes predict youth’s readiness for activity in each of the countries?We used several existing or specially developed scales to analyse value orientations and attitudes in these three countries and (2) psychological parameters of activity. Value orientations and attitudes included indicators such as traditional values versus secular-rational values (T/S-RV), the need for achievement and affiliation, subjective evaluation of possibilities for basic values realisability in the local settings, quality of life enjoyment and satisfaction and subjective happiness, and cultural values, namely Hofstede’s six dimensions. Psychological parameters of activity include purposefulness, planning, systemic reflection and satisfaction with life, and the personal readiness for activity index, which is the average of the four parameters mentioned. In order to estimate all these psychological characteristics, the study participants were asked to fill out several questionnaires. The internal consistency coefficients  for each dimension are presented for all the subsamples to be analysed and the total sample, respectively, in of utmost importance” to “of very little or no importance”. VSM 2013 Hofstede’s six dimensions of culture values entailed the independent variable values. The dependent variables included the Power distance index (PDI), Individualism index (IDV), Masculinity index (MAS), Uncertainty avoidance index (UAI), Long-term orientation index (LTO), and Indulgence versus restraint index (IVR). A reliability test for the VSM 2013 should be based on the country mean scores; however, the number of countries is insufficient in our case. According to Values Survey Module (VSM 2013) by Hofstede . This cototally disagree” to “absolutely agree”. The scale includes two axes: Traditional values versus Secular-rational values (T/S-RV) and Survival values versus Self-expression values (S/S-EV). In our study, we only used the T/S-RV dimension since the Cronbach’s alpha values for the S/S-EV scale were inadequate for one of the subsamples.World Values Survey questionnaire (WVS) by Inglehart , modifieThe Subjective Evaluation of Basic Values Realisability (SEBVR) technique developed by Bogomaz  developed by hardly ever” to “constantly”. The Q-LES-Q includes five measures: Physical health, Subjective feelings, Leisure time activities, Social relationships, and the Q-LES-Q index.A short version of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) is a self-report instrument by Ritsner and colleagues (2005) in Rasskazova’s adaptation (2012). The questionnaire consists of 17 items with a 5-point response scale from “totally disagree” to “absolutely agree”. However, we used only three items according to the recommendation from Leontiev  was constructed by Leontiev .completely disagree” to “completely agree”.The Self-Organisation of Activity Questionnaire was developed by The Differential Test of Reflexivity (DTR) by The Satisfaction with Life Scale (SWLS), developed by Diener, Emmons, Larsen and Griffin (1985) and adapted by Leontiev and It should be noted that the Self-Organisation of Activity Questionnaire and Differential Test of Reflexivity in a modified version , as described above, as well as the Satisfaction with Life Scale were used to evaluate the study participants’ personal readiness for activity index as an integrative parameter of the psychological system of activity. The personal readiness for activity index is the average of the following indicators: Purposefulness, Planning, Systemic reflection and Life satisfaction, as mentioned above. These transformations were made to develop a research tool adequate to the objective of characterising one’s psychological system of activity via an integrative psychological parameter, namely personal readiness for activity .The study was conducted from 2018 to 2019. The initial sample for establishing the cross-cultural variance consisted of 818 people , aged from 18 to 35 (18.32(2.39) M(SD)). Of these, 550 people participated in the study in Russia; 192 in Kazakhstan; 76 in Latvia. The groups differed significantly in age and sex. To compare the indicators, student age and sex were selected from this sample (18– 26 age range).Table 2) for comparing the factor structure invariance included 601 people  from Russia (n = 344), Kazakhstan (n = 192), and Latvia (n = 65). The mean age of respondents was 20.33 ± 2.20 years  and 54.9% were women . The samples did not differ significantly in age (χ2(2) = 7.01, p = 0.06) and sex .The final sample . In this study, the birth nation does not exclude the respondents, as they might have lived there only for a short period or perhaps were born when their parents stayed in that particular nation and never lived there. The study participants were majoring in various subjects, but this aspect was not in question in this study.The present study was designed based on a snowball sampling technique. The study participants were asked to complete a series of questionnaires, their participation in the study was voluntary. The paper-and-pencil forms were offered in Russian. The university students from Kazakhstan and Latvia who participated in the study could understand the Russian language.The data collected was then statistically treated applying the IBM SPSS Statistics 23. Descriptive analysis and analysis of variance , Pearson’s correlation coefficient and stepwise linear regression were used to compare the subsamples. Correlation analysis was performed to determine a significant relationship between value orientations and activity dimensions. In addition, analysis of variance was done to check if there are any significant differences between the three countries among value orientations and activity dimensions. Finally, regression analysis was performed for the personal readiness for activity index in the countries under study, and the six dependent variables: Traditional values versus Secular-rational values, Need for achievement, Need for affiliation, the SEBVR index, the Q-LES-Q index, Subjective happiness, as well as the respondents’ period of living in their countries. Regression analysis was carried out separately for each subsample under the study. The idea was that psychological variables involved in the study could fully characterise young people’s psychological system of activity, when viewed as predictors of their personal readiness for activity index.Table 3). In general, our findings focus on the relationship between Personal readiness for activity index and Uncertainty avoidance index, Long-term orientation index, Indulgence versus restraint index, Traditional values versus Secular-rational values, Need for achievement, Need for affiliation, SEBVR index, Q-LES-Q index, and Subjective happiness. Power distance index, Individualism index, and Masculinity index were not found to be related to Personal readiness for activity index. However, this relationship could be different in countries yet to be analysed, and more detailed results could be seen in regression analysis.We conducted descriptive statistics (mean and standard deviation) and correlation analysis between value orientations and Personal readiness for activity index for the total sample (n = 601). The results show that out of 13 value orientations, 9 are significantly related to Personal readiness for activity index . While considering the Uncertainty avoidance score of Kazakhstan, it is found to be significantly lower than that of Latvia (p = 0.004). Moreover, the contrast pattern can be seen in Russia (p = 0.00001) and Latvia (p = 0.001), and both have a lower Long-term orientation index than Kazakhstan.The Traditional values versus Secular-rational values indicator is significantly higher in the case of Kazakhstan compared to Latvia (p = 0.000001) and Russia (p = 0.000000000001). Kazakhstan also has a higher Need for achievement dimension than both Russia (p = 0.011) and Latvia (p = 0.006). However, Latvian youth had a significantly lower Need for affiliation dimension than youth in Kazakhstan (p = 0.007) and Russia (p = 0.018). All basic metavalues, such as Metavalue of professional selfrealisation, Metavalue of public self-realisation, Metavalue of vital self-realisation and Metavalue of existential self-realisation, are significantly lower in Russia than in Latvia (p = 0.004 for the SEBVR index) and Kazakhstan (p = 0.00004 for the SEBVR index). The quality of life enjoyment and satisfaction index in Russia is significantly lower than in Kazakhstan (p = 0.00006) and Latvia (p = 0.02) and significantly higher in Kazakhstan than in both Russia and Latvia (p = 0.0001).The parameters of the psychological system of activity show that Purposefulness is significantly lower in Russia than in Kazakhstan (p = 0.012). Satisfaction with life in Latvia is significantly lower than in Kazakhstan (p = 0.00001) and Russia (p = 0.018) and significantly higher in Kazakhstan than in both Russia and Latvia (p = 0.016). The score of the Personal readiness for activity index is higher for youth from Kazakhstan compared to Latvia on a tendency level (p = 0.052).Stepwise linear regression was conducted to identify which value orientations could be significant predictors of Personal readiness for activity index in each country. The Russian sample collinearity tests confirmed the independence of predictor variables , and the assumption of independent errors of residuals was met  in all four models. The Kazakhstani sample collinearity tests confirmed the independence of predictor variables , and the assumption of independent errors of residuals was met  in all four models. The Latvian sample collinearity tests confirmed the independence of predictor variables , and the assumption of independent errors of residuals was met  in all two models.Table 5 demonstrates the overall significance of value orientations and attitudes in Personal readiness for activity across cultures. The need for affiliation is just one significant predictor of Personal readiness for activity index for all samples. The Russian sample regression model  = 53.05, p < 0.000, R2 = 0.391, R2 Adjusted = 0.383) showed that Need for achievement, Subjective happiness, Traditional values versus Secular-rational values and Need for affiliation were significant predictors of Personal readiness for activity index, accounting for 38% of the variance. Similarly, the Kazakhstani sample regression model also showed that Traditional values versus Secular-rational values (T/S-RV), Need for afiliation and, in addition, the Quality of Life Enjoyment and Satisfaction index (Q-LES-Q index) accounted for 29% of the variance in mean scores for Personal readiness for activity index  = 25,70, p < 0.000, R2 = 0.294, R2 Adjusted = 0.285). The Latvian sample regression model showed that the Quality of Life Enjoyment and Satisfaction index (Q-LES-Q index), Need for affiliation accounted for 57% of variance in the indicators concerned  = 41,32, p < 0.000, R2 = 0.579, R2 Adjusted = 0.565).Cross-cultural comparison of university student samples showed that most differences in the countries in question were between Kazakhstan vs Latvia and Russia in both value orientations and attitudes and Personal readiness for activity index. The youth from Kazakhstan differs significantly in the Long-term orientation index (the highest score) and Uncertainty avoidance index (the lowest score) compared to the youth from Russia and Latvia. In other words, Kazakhstan youth follow strict behavioural codes, rules, and laws, whereas Russian and Latvian youth face fewer regulations and reveal more acceptance of different opinions. Kazakhstan youth, to a larger extent, have the present- and past-looking attribute, whereas Russian and Latvian youth demonstrate more the forward-looking attribute. Our data suggests a long-term orientation of Kazakhstan youth, which is consistent with the results of Kazakhstan youth also differ significantly from Russian and Latvian youth in the Traditional vs Secular-rational values indicator that depicts a continuum where the traditional side is associated with the importance of existential security, traditional family ties, and the strong presence of religion and hierarchy. Residents from Latvia more often choose secular-rational values, and residents of Kazakhstan, traditional values, Russian people occupy an intermediate position between them within the Traditional values versus Secular-rational values continuum.Furthermore, the differences between Kazakhstan vs Latvia and Russia connected with personal well-being, such as the quality of life enjoyment and satisfaction scales , subjective happiness and satisfaction with life. This highlights the importance of collectivist and traditional values and feelings of happiness and well-being among the youth of Kazakhstan.In addition, higher scores in purposefulness and personal readiness for activity index in youth from Kazakhstan may also connect with their adherence to traditional values compared to those in Russian and Latvian youth. Such value orientations may result in a desire to follow a certain algorithm to achieve one’s purposes.The study participants from Russia and Latvia have more pronounced individualism dimensions and secular-rational values, but these samples may differ in their motivation. Russian youth seem to be more focused on personal achievements and social support, and they appreciate putting in hard work to achieve goals and the attention of others. Latvian youth showed a higher subjective evaluation of possibilities for realising their basic values in their local settings in the case of Metavalue of professional self-realisation and Metavalue of existential self-realisation. This may signal their greater desire to rely on themselves and a more realistic view of their opportunities.In general, our data reports on the reasonable links between the Personal readiness for activity index and cultural dimensions, value orientations and psychological indicators, such as Uncertainty avoidance index, Long-term orientation index, Indulgence versus restraint index, Traditional values versus Secular-rational values, Need for achievement, Need for affiliation, SEBVR index, Q-LES-Q index, and Subjective happiness. This could mean that active young people feel happier and more satisfied than passive people. A predisposition to secular-rational values, a desire for affiliation and achievement, a long-term perspective, hardiness and mindfulness characterises them. The mechanisms underlying the relationship between well-being dimensions and personality ones in the context of one’s readiness for activity involve psychological factors. One possible explanation is that happy and successful individuals have more freedom to determine their own life pathways and make choices  who do not differ in age or gender were involved in the study concerning the period they had lived in the countries. Our research continues the tradition of cross-cultural studies investigating cultural diversity in the post-Soviet space  and expaOne of the limitations of this study is that all the participants were Russian-speaking young people. Differences probably exist in value orientations and parameters of the psychological system of activity among Kazakhstan and Latvian youth who do not speak the Russian language. The second limitation concerns the generalisability of the findings because of the study design . In order to achieve more robust results in cross-cultural research, the selected samples should include participants from a wider range of social and regional groups.


In older patients receiving general anesthesia, postoperative delirium (POD) is the most frequent form of cerebral dysfunction. Early identification of patients at higher risk to develop POD could provide the opportunity to adapt intraoperative and postoperative therapy. We, therefore, propose a machine learning approach to predict the risk of POD in elderly patients, using routine intraoperative electroencephalography (EEG) and clinical data that are readily available in the operating room.We conducted a retrospective analysis of the data of a single-center study at the Charité-Universitätsmedizin Berlin, Department of Anesthesiology [ISRCTN 36437985], including 1,277 patients, older than 60 years with planned surgery and general anesthesia. To deal with the class imbalance, we used balanced ensemble methods, specifically Bagging and Random Forests and as a performance measure, the area under the ROC curve (AUC-ROC). We trained our models including basic clinical parameters and intraoperative EEG features in particular classical spectral and burst suppression signatures as well as multi-band covariance matrices, which were classified, taking advantage of the geometry of a Riemannian manifold. The models were validated with 10 repeats of a 10-fold cross-validation.Including EEG data in the classification resulted in a robust and reliable risk evaluation for POD. The clinical parameters alone achieved an AUC-ROC score of 0.75. Including EEG signatures improved the classification when the patients were grouped by anesthetic agents and evaluated separately for each group. The spectral features alone showed an AUC-ROC score of 0.66; the covariance features showed an AUC-ROC score of 0.68. The AUC-ROC scores of EEG features relative to patient data differed by anesthetic group. The best performance was reached, combining both the EEG features and the clinical parameters. Overall, the AUC-ROC score was 0.77, for patients receiving Propofol it was 0.78, for those receiving Sevoflurane it was 0.8 and for those receiving Desflurane 0.73. Applying the trained prediction model to an independent data set of a different clinical study confirmed these results for the combined classification, while the classifier on clinical parameters alone did not generalize.A machine learning approach combining intraoperative frontal EEG signatures with clinical parameters could be an easily applicable tool to early identify patients at risk to develop POD. Postoperative delirium (POD) is a common complication and the most frequent cerebral dysfunction after surgery requiring general anesthesia among elderly patients. It manifests as a disturbance of consciousness, attention, perception, memory, and cognition as well as a disruption of the sleep-wake rhythm and can lead to adverse long-term complications such as increased mortality, prolonged hospital stays, and persisting cognitive impairments . We complement the EEG data with clinical patient data that is routinely available in the operating room. Apart from the medication directly connected to the surgery, we only take the American Society of Anesthesiology (ASA) score, the age of the patient, and the duration of the operation into account. On this basis, we aim to develop a robust machine learning model to predict POD, showing that incorporating EEG signatures improves the risk evaluation.To predict the risk of developing POD, we retrospectively analyzed the intraoperative raw EEG files from the single-center study SuDoCo at the Charité-Universitätsmedizin Berlin, Department of Anesthesiology [ISRCTN 36437985]  used by the BIS monitor were recorded , as well as two time-dependent features: the spectral features and the covariance features (explained in detail in Section 2.2.1). The latter two represent a sequence of 2 min time frames of the EEG data. The spectral features contain the frequency spectrum for each time frame, while the covariance features contain multi-band covariance matrices for each time frame. The two time-dependent features are classified separately. For some steps in the preprocessing (Section 2.1) and the classification of the covariance features, we use the Riemannian framework , whether a patient received benzodiazepine (binary), the age (numeric), the length of the operation (numeric), and the ASA score (numeric). The three classifiers corresponding to the categories of features were then combined into a final risk evaluation .We focus on two main types of artifacts: high amplitude artifacts and frequency artifacts. For the first category, we use an amplitude filter, excluding high amplitude artifacts. Since we have different subjects and settings under which the data was recorded, the amplitudes scale differently in different recordings. Hence, we do not define a fixed threshold to exclude the amplitude artifacts but use the 99% quantile of the amplitudes for each patient. The data is re-referenced by the mean (common average reference). Afterward, we apply a bandpass filter (0.3–50 Hz) for the frequency artifacts.After applying the two filters, the data is automatically segmented see . The segAfter z-scoring the data, the estimation of the spectral density or frequency spectrum is done using the Welch method Welch,  for eachFor the covariance features, we use a multi-band signal. To calculate the multi-band signal, we filter the EEG data to the delta (0.3–4 Hz), theta (4–8 Hz), lower alpha (8–12 Hz), higher alpha (12–15 Hz), lower beta (15–20 Hz), higher beta (20–30 Hz) frequency bands. The resulting filtered EEG data in each of the frequency bands is then stacked with the burst suppression timeline. This artificially creates a higher dimensional data set with more channels. The covariance matrices are estimated for each segment using the Oracle Approximating Shrinkage (OAS) method , we use balanced ensemble methods, which can resolve this challenge  and the longest suppression phase.The full overview of the data used can be found in pclassifier for each patient P is based on the probability F be the number of trees, then for the classifiers patient and patient+burst the probability for patient i to develop POD is given by As is typical for random forest classifiers, the probability To combine the three probabilities into a final risk evaluation, we calculatethclassifier that maximizes the g-mean thclassifier can be adjusted to shift = 0.5−thclassifier, resulting in: pcomb improves on the training set when the probabilities are shifted to have an optimal threshold of 0.5 for all classifiers or two out of three. The shifts resulting in the highest AUC-ROC score of pcomb are saved and applied to the test set. If only two probabilities are shifted, the third shift is set to 0. Therefore, Equation (1) can be rewritten as for the probability prediction of the patient+burstsupp, spectral, and the covariance classifier. However, each of these classifiers can have a different optimal threshold for classification because the data is imbalanced and the classifiers are based on different averages taken. The optimal threshold for classification on the training set is the value, that maximizes the true positive rate (TPR) while minimizing the false positive rate (FPR) if every probability below the threshold is classified as negative and every probability above the threshold is classified as positive for POD  to ensure a high negative predictive value (NPV). For the NPV calculated for the final results, the classification threshold is set at 0.5. To retain a better prediction for small values of pclassifier, we set pcomb = pm, if pm < 0.25, with pm = mean(pclassifier) being the common average of the probabilities for all classifiers  with a high enough AUC-ROC on the training set.We chose to use the maximum formulation in the calculation for From the initial 1,277 patients in the SuDoCo study, we excluded 210 patients, due to missing data (98) or EEG files shorter than 20 min after preprocessing (112). Patient characteristics of the included 1,067 patients are given in When the data is trained on the whole data set, there is no apparent benefit of using EEG signatures for the classification. The results shown are the ROC curves and AUC-ROC scores over 10 repeats of a 10-fold cross-validation . The AUCFigure 6. Consequently, if the three groups are trained on separately, the performance of the combined risk evaluation improves for Sevoflurane and Propofol  DAEDALUS  funded by Deutsche Forschungsgemeinschaft . We acknowledge support from the German Research Foundation and the Open Access Publication Fund of TU Berlin.Author SK is an inventor on patents, sold to Medtronic. She reports a grant during the conduct of the study by the German Research Foundation. Author CS is an inventor on patents, she reports grants during the conduct of a study from the European Commission, from Aridis Pharmaceutical Inc., B. Braun Melsung, Drägerwerk AG & Co. KGaA, German Research Foundation, German Aerospace Center, Einstein Foundation Berlin, European Society of Anaesthesiology, Federal Joint Committee and Inner University grants. Grants promoting Science and Education from WHOCC, Baxter Deutschland GmbH, Cytosorbents Europe GmbH, Edwars Lifesciences Germany GmbH, Fresenius Medical Care, Grünenthal GmbH, Masimo Europe Ltd. Phizer Pharma PFE GmbH. Personal fees from Georg Thieme Verlag, Dr. F. Köhler Chemie GmbH, Sintetica GmbH, European Commission, Stifterverband für die deutsche Wissenschaft e.V./Philips, Stiftung Charite, AGUETTANT Deutschland GmbH, AbbVie Deutschland GmbH & Co. KG, Amomed Pharma GmbH, Touch Health, Copra System GmbH, Correvio GmbH, Max-Planck-Gesellschaft zur Förderung der Wissenschaft e.V., Deutsche Gesellschaft für Anästhesiologie & Intensivmedizin (DGAI), Medtronic, Philips Electronics Nederland BV, BMG, and BMBF. Aspect Medical Systems, now Medtronic, funded the initial SuDoCo study were CS was PI. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The remaining 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.


It is known that insufficient physical activity is associated with the risk of hypertension, but the relationship to different physical activity dimensions within hypertension risk remains to be elucidated.The objective of this study is to identify the association between physical activity intensity, frequency, duration, and volume with hypertension risk. Meanwhile, a dose-response experiment is conducted to determine the relationship between physical activity level and hypertension risk.Data came from the 2018 China Health and Retirement Longitudinal Study , which included 14266 participants over the age of 45. Binary logistic regression models were established to assess the associations between different dimensions of physical activity and the risk of hypertension. Restricted cubic spline analysis was used to examine possible non-linear associations between physical activity volume and hypertension risk.For frequency, lower hypertension risk was associated with performing vigorous physical activity 6–7d/w  and moderate physical activity 6–7d/w . No significant association between any light physical activity frequency and hypertension was observed before and after being adjusted. For the duration, lower hypertension risk was observed in performing vigorous physical activity ≥240 min/d  and moderate physical activity ≥240 min/d . For volume, the risks of hypertension in the participants who reported TPA in the 3th and 4th of quantiles were reduced by 18%  and 22% . A non-linear dose-response association between total physical activity and the risk of hypertension was shown among all of the participants (P non-linearity < 0.05).Higher frequency and longer duration of vigorous physical activity or moderate physical activity were significantly associated with a lower risk of hypertension. Higher physical activity levels were associated with a lower risk of hypertension and there was an inverse non-linear dose-response relationship between weekly total physical activity and the risk of hypertension. These findings provide further proof that hypertension could be prevented through increased physical activity. Hypertension is one of the most common chronic diseases worldwide , and it Increased physical activity (PA) was effective in the treatment and prevention of hypertension, this viewpoint has been confirmed by many studies –15. An iFurther investigation of the association between physical activity to hypertension is still required. We hypothesized that higher intensity, frequency, duration and volume of physical activity would each be associated with reduced hypertension risk. Therefore, this study aimed to assess the association of hypertension with various dimensions of PA and to assess whether there were gender and age differences in the dose-response relationship between PA and the risk of developing hypertension.This cross-sectional study was done based on the China Health and Retirement Longitudinal Study (CHARLS) survey in 2018. CHARLS is a nationally representative survey of Chinese middle-aged and elderly people conducted by the National School for Development (China Center for Economic Research) in collaboration with Peking University's Institute for Social Science Survey. The survey covers 450 urban communities and rural areas in 28 provinces, municipalities, and autonomous regions in China. It was approved by the Biomedical Ethics Review Committee of Peking University , and informed consent was required of all participants.To be included in this study, participants (age ≥ 45 years) should have complete data on physical activity record, gender, place of residence, marital status, educational level, sleep status, smoking status, drinking status, annual income, hypertension record. Participants younger than 45 years or with missing data for any of the above will be excluded.post hoc analysis of sample power using G Power 3.1, the present study population provided a statistical power of 0.99.Among 19,752 participants in 2018, we excluded 226 participants aged < 45 years, 5,243 participants with missing hypertension diagnoses data, 12 participants with missing sleep data, and 5 participants with missing smoking data. Finally, 14,266 participants were included in this cross-sectional study. Based on the A modified version of the validated International Physical Activity Questionnaire Short Form (IPAQ-SF)  was usedHypertension was defined based on self-reported medical history and measurement of blood pressure (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg). Participants were asked the question “Have you been diagnosed with hypertension by a doctor?” We considered that the individual had hypertension when the response was “yes”.Covariates in the present study were age, sex , marital status , education , residency , smoking status , drinking frequency  and sleep duration , annual income .t-test. Binary logistic regression analysis was used to explore the associations between various dimensions of PA and the risk of hypertension, while adjusting for potential confounders. Model 1 was adjusted for demographic characteristics ; Model 2 was further adjusted for health-related behaviors . A restricted cubic spline (RCS) was used to assess the dose-response relationship between the risk of hypertension and PA, using the 25th, 50th, and 75th percentiles of the TPA as fixed knots. The RCS models were adjusted for age, sex, marital status, education, residency, smoking status, drinking frequency and sleep duration. Analyses stratified by sex and age were conducted. Missing data were imputed using multiple imputation by chained equations. To test the robustness of the results, we performed a sensitivity analysis with imputed data. All tests were two-tailed, and a probability value of p < 0.05 was considered statistically significant. Graph Pad prism 8 was used to draw cubic splines.The software STATA16.0 was used for data processing and analysis. Categorical variables were expressed as counts and percentages and were compared using the Pearson's chi-squared test. Continuous data are expressed as mean ± SD and analyzed with Student's P < 0.001), sex (P = 0.006), marital status (P < 0.001), smoking status (P < 0.001) and annual income (P = 0.019). However, there was no significant difference in drinking frequency, residency, education, and sleep duration between participants with and without hypertension . Compared with non-hypertensive participants, hypertensive patients had lower weekly TPA. Women and older adults had lower weekly TPA (ekly TPA .P < 0.01). The reduction in the risk of hypertension in participants with TPA in second quantile was not statistically significant before and after adjustment (P > 0.05). In addition, an inverse association between the TPA level and the risk of hypertension was observed in all three models (P for trend < 0.001).Lower risk of hypertension was observed in participants spending 30–119 min  or over 240 min per day  for VPA. Spending 120–239 min  or over 240 min  on MPA each time was correlated with smaller odds of hypertension. Participants performing over 240 min LPA each time had a lower risk of hypertension . After adjusting for age, sex, marital status, education, residency, smoking status, drinking frequency and sleep duration, spending over 240 min on VPA each time and over 240 min on MPA each time was correlated with smaller odds of hypertension .As shown in Missing values were imputed by multiple imputation, 19,466 participants were included in the sensitivity analysis. A non-linear dose-response relationship between TPA and the risk of hypertension was similar to the main analysis .This cross-sectional study evaluated the association between the risk of hypertension with various dimensions of PA in middle and older-aged Chinese people. Several important findings of the current study include: (1) Higher frequency and longer duration of VPA or MPA were significantly associated with a lower risk of hypertension. (2) There was an inverse association between TPA and risk for hypertension. (3) A non-linear dose-response relationship between TPA and the risk of hypertension was observed in all participants, the downward hypertension risk flattened when TPA was approximately 4500 MET-minutes/week. (4) There were sex and age differences in the dose-response relationship between physical activity and hypertension risk.Intensity, frequency, and duration of PA are important factors affecting the benefits of PA. We found that VPA and MPA were associated with a lower risk of hypertension after adjustment for covariates. The result is consistent with those of previous studies, moderate-to-vigorous PA is beneficially associated with many health statuses . HoweverIn terms of duration, the physical activity guidelines recommend that adults should do at least 150–300 min MPA per week, or 75–150 min. VPA per week for substantial health benefits . Taylor-Our result shows an inverse association between TPA level and the risk of hypertension, which is consistent with previous research , 33. ImpIt is worth noting that sex and age differences were found in the dose-response relationship between physical activity and hypertension risk. A linear dose-response relationship between PA and hypertension was observed in the male population. No significant dose-response relationship was found in female participants, which was consistent with the findings of Haapanen et al. . PhysicaThis study has the strength of including a representative sample of middle-aged and older adults in the Chinese population, which increased the statistical power. We conducted subgroup analyses based on age and sex to explore whether a difference in association could be observed in subgroups with a different age or sex. Furthermore, the sensitivity analyses have confirmed the robustness of this study's findings. This study has some limitations. First, because of the cross-sectional design, the cause-effect relationships between PA and the risk of hypertension not be determined. Further longitudinal studies are needed to determine the direction of causality for these associations. Second, questionnaire-based assessments of physical activity may be subject to recall and social desirability bias. Although the IPAQ is widely used, validation studies have shown poor agreement with objective measures . Third, It is expected that the prevalence of hypertension will continually increase in the future as the Chinese population ages rapidly. Our findings reinforce a growing body of independent evidence that supports the effectiveness of moderate-to-vigorous-intensity physical activity in preventing and managing the risk of hypertension. This study also has significant practical implications. We analyzed the associations between multiple dimensions of physical activity and the risk of hypertension, and found gender and age differences in the dose-response relationship between accumulated physical activity over the week and the risk of hypertension. This may provide more detailed guidance for the prevention and control of hypertension in different populations. Physical activity as a non-pharmacological intervention has been shown to be effective in reducing the risk of hypertension. Objective measurement of physical activity should be considered and incorporated into the management of hypertensive patients.The results of this study assessed associations between different dimensions of PA and the risk of hypertension. After adjustment for potential confounders, higher frequency and longer duration of VPA or MPA were significantly associated with a lower risk of hypertension. Higher PA levels were associated with a lower risk of hypertension and there was an inverse dose-response relationship between weekly TPA and the risk of hypertension. When TPA reached approximately 4500 MET-minutes per week, the risk of hypertension in the overall population decreased by 19%, while continued increases in PA did not appear to produce any further marked reduction in the risk. These findings provide further proof that hypertension could be prevented through increased PA.https://g2aging.org.Publicly available datasets were analyzed in this study. This data can be found at: The studies involving human participants were reviewed and approved by the Biomedical Ethics Review Committee of Peking University. The patients/participants provided their written informed consent to participate in this study.LZ, YL, and WF designed the research. LZ, WF, NX, XY, and MW performed all the statistical analysis. LZ, WF, YL, and XW interpreted the data analysis. LZ, WF, YC, YL, and XW wrote the manuscript with critical input from YL. All authors read and approved the final manuscript.This work was supported by the Jiangsu Provincial Natural Science Foundation of China , the Xuzhou Natural Science Foundation , and the Natural Science Foundation of the Jiangsu Education Institutions of China .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.