Antenatal depression and anxiety are highly prevalent conditions that have been associated with increased risk for myriad adverse outcomes. Current literature exploring the connection between antenatal mental health and gestational diabetes mellitus (GDM) is limited, presenting conflicting evidence. We sought to evaluate the association between antenatal depression/anxiety (DEP-ANX) and GDM using population-based, administrative data, accounting for aspects of preconception mental health.In this population-based retrospective cohort study, we included all singleton births in British Columbia, Canada from April 1, 2000, to December 31, 2014. We identified instances of DEP-ANX from outpatient and inpatient records that included relevant diagnostic codes and stratified our cohort by preconception DEP-ANX persistence. Logistic regression models were run to estimate odds of GDM given antenatal DEP-ANX. Models were adjusted for the birthing person’s socio-demographics and pregnancy characteristics. Using an expanded cohort, we ran conditional logistic regression models that matched birthing people to themselves (in a subsequent pregnancy) based on discordance of exposure and outcome.Out of the 228,144 births included in this study, 43,664 (19.1%) were to birthing people with antenatal health service use for DEP-ANX. There were 4,180 (9.6%) cases of GDM among those antenatal exposure to DEP-ANX compared to 15,102 (8.2%) among those without exposure (SMD 0.049). We observed an unadjusted odds ratio (OR) of 1.19 (95% CI: 1.15 – 1.23) and fully adjusted OR of 1.15 (95% CI: 1.11 – 1.19) overall. Apparent risk for GDM given antenatal DEP-ANX was highest among the no DEP-ANX history stratum, with a fully adjusted OR of 1.24 (95% CI: 1.15 – 1.34). Associations estimated by matched sibling analysis were non-significant (fully adjusted OR 1.19 [95% CI: 0.86 – 1.63]).Results from this population-based study suggest an association between antenatal DEP-ANX and GDM that varied based on mental health history. Our analysis could suggest that incident cases of DEP-ANX within pregnancy are more closely associated with GDM compared to recurring or chronic cases.The online version contains supplementary material available at 10.1186/s12884-022-05002-5. Depression and anxiety are highly prevalent among individuals of reproductive age –3, and nGDM is a unique subtype of diabetes mellitus (DM), indicated by glucose intolerance first detected during pregnancy. GDM has been shown to pose significant risks to perinatal health, increasing the likelihood of hemorrhage, preeclampsia, and operative delivery –14. InstCurrent literature investigating the link between antenatal DEP-ANX and GDM is limited, and presents conflicting evidence regarding the significance and magnitude of this association , 20–26. In this study, we aimed to incorporate preconception mental health into a study of how antenatal depression/anxiety influences risk for GDM. We hypothesized that compared to those without history of DEP-ANX, individuals with chronic histories would have higher odds of GDM related to antenatal DEP-ANX, given increased exposure to chronic stress and its cumulative effects  , 34.We conducted a population-based, retrospective cohort study of all live births in British Columbia (BC), Canada from April 1, 2000, to December 31, 2013. Birthing person data were collected from 10-years preconception through delivery. Population Data (PopData) BC created our cohort through the BC Perinatal Data Registry (BCPDR) , containEthics approval for our use of deidentified administrative data was approved by the University of British Columbia Behavioural Research Ethics Board. Data access was approved by the Data Stewards. Both approvals include a waiver of informed consent from participants. All inferences, opinions, and conclusions drawn are those of the authors and do not reflect opinions or policies of the Data Stewards.Our cohort included singleton births to birthing people with complete record of neighborhood-based income quintiles and final gestational age (GA). We excluded births to individuals who had pre-existing DM, and/or any record of health service use with diagnostic codes corresponding to bipolar disorder, schizophrenia, psychosis, or mania  by subtracting final GA (reported in the BCPDR) from the offspring’s date of birth (DOB), then subtracting two weeks. Final GA is approximated by the BCPDR based (in order of accuracy) on earliest ultrasound, last menstrual period, or newborn examination. We defined pregnancy as the period between the DOC and DOB, and preconception periods  using the approximate DOC.Mental health measures. Depression and anxiety were classified as a single exposure, DEP-ANX, due to high rates of co-occurrence  ), no DEP-ANX history group (Model 2 aOR 1.18 [95% CI: 0.86 – 1.63]), and any DEP-ANX history group (Model 2 aOR 1.02 [95% CI: 0.90 – 1.16); however, the direction of association remained positive in all three cases.In this population-based, retrospective cohort study, we found a modest association between antenatal DEP-ANX and GDM that differed in effect size based on preconception mental health. Overall, individuals with antenatal DEP-ANX that had no history of DEP-ANX appeared to be at higher risk for GDM than those with an episodic or chronic, continuous history. While these relationships were attenuated, they largely remained statistically significant after adjusting for socio-demographics and pregnancy characteristics in our original and expanded cohort. Matched sibling pairs analysis resulted odds ratios of similar magnitude among those with no DEP-ANX, but the association was no longer statistically significant and thus we cannot rule out residual confounding as an explanation for the associations in the main cohort.The positive association between DEP-ANX and GDM is consistent with prior literature. Several observational studies have demonstrated significant associations between antenatal DEP-ANX and GDM of varying effect size, reporting increased risks between 52 – 300% from unadjusted and adjusted analysis , 28, 49.We observed a slightly larger effect size in the associations between GDM and incident DEP-ANX vs. recurring or chronic DEP-ANX, highlighting the potential role of GDM-induced stress in the development of antenatal DEP-ANX. GDM diagnosis has been previously shown to be a significant stressor, with lasting impacts on the birth person’s physical and emotional well-being . While wRegardless of the mechanism connecting antenatal DEP-ANX and GDM, and even in the case of residual confounding, our findings suggest that DEP-ANX and GDM often co-occur and emphasize the importance of ongoing prenatal screening for both GDM and DEP-ANX, particularly among those without a history of either condition. Differences in association based on preconception DEP-ANX persistence may be due to diagnostic bias that delays DEP-ANX treatment among those with discontinuous or no history of DEP-ANX. Further, more regular preconception interactions with mental health services may facilitate easier access to mental health care during pregnancy, thereby mitigating the effects of antenatal DEP-ANX or preventing DEP-ANX recurrence in response to a GDM diagnosis. This points to the importance of addressing barriers to mental health services, particularly during pregnancy, and the value of providing consistent mental health care throughout a birthing person’s life.Stratification by persistence of preconception DEP-ANX is a novel approach not previously used to understand the relationship between DEP-ANX and GDM. By accounting for variation in preconception DEP-ANX, we were able to report association between mental health history (DEP-ANX) and GDM in a way that sheds light on the potential mechanisms connecting these conditions. Future work is needed to understand how preconception mental health might affect prenatal trajectories of both antenatal DEP-ANX and GDM. Additionally, research that can more precisely explore themes of mental health care access, diagnostic biases, and symptom severity could help elucidate the underlying mechanism linking GDM and DEP-ANX.This study is strengthened by its use of population-based administrative datasets and operationalization of more granular definitions for understanding individual DEP-ANX histories. This more nuanced approach allowed for deeper exploration of the relationship between DEP-ANX and GDM. Our study also possessed key limitations. Compared to included individuals, those who were excluded from our study (largely due to not having lived in the province for 5-years preconception) tended to be of lower socioeconomic status with more limited records of overall health status, potentially affecting generalizability of our findings. We did not have access to pharmacy data, prohibiting us from evaluating the role of psychotropic medication in the observed association. Additionally, our definitions for DEP-ANX relied on treatment records filed with provincial health, thus omitting data from individuals seeking care from providers outside BC’s universal health coverage  and those with under- or un-treated DEP-ANX. Omission of these data may have caused some misclassification of DEP-ANX persistence and/or antenatal DEP-ANX, particularly for those with chronic histories who may have well-established treatment regimens outside of the health system.Our use of data for 10-years preconception despite applying a registration criterion for 5-years preconception may have also introduced misclassification, specifically for individuals who experienced DEP-ANX prior to 5-years preconception but were not living in the province at that time. This is unlikely to be associated with GDM status, though, and would therefore bias toward the null. Our inability to determine whether GDM preceded antenatal DEP-ANX made interpreting results more challenging. As we do not have date of diagnosis for GDM in the BCPDR and cannot assume that the first DEP-ANX diagnosis code reported in health services data represents actual onset of DEP-ANX, we cannot determine which diagnosis came first. Finally, we cannot rule out the possibility of residual confounding related to both socioeconomic factors that are known to be important determinants of mental health during pregnancy and to yet unmeasured factors that contribute to both GDM and antenatal DEP-ANX.Results from this population-based retrospective cohort study suggest an association between antenatal DEP-ANX and GDM that varied based on mental health history. Our analysis could suggest that incident cases of DEP-ANX within pregnancy are more closely associated with GDM compared to recurring or chronic cases. These findings present a novel perspective on the relationship between DEP-ANX and GDM.Additional file 1.


POCUS is an important tool for the diagnostic approach in the primary care setting already before the start of the SARS-CoV-2 pandemic.Portable devices are useful in monitoring the clinical evolution of patients with infection from SARS-CoV-2 at home.The ultrasonographic features can help the general practice physicians to evaluate the presence of lung involvement and to diagnose complications from the SARS-CoV-2 infection involving districts such as the cardiovascular system.The SARS-CoV-2 pandemic is considered one of the most critical global health emergencies in the last century. The diagnostic approach to the novel coronavirus disease (COVID-19) and its possible complications through a point-of-care-ultrasound (POCUS) evaluation could represent a good solution in the primary care setting. POCUS is a non-invasive technique that can be used outside hospitals to screen COVID-19 patients and their complications safely. Moreover, it offers several applications of diagnostic evaluation not only on lung parenchyma but also to search disease complications, such as the cardiovascular system, even at the patients' home. This narrative review aims to analyse the literature and provide data to primary care physicians engaged in monitoring and treating patients with SARS-CoV-2 infection. Healthc1.1.We performed a literature search on public databases  from December 2019 through November 2021, focussing on articles relating to the use of POCUS in COVID-19 in the primary care setting in terms of diagnostic, therapeutic strategies and risk stratification algorithms. The use of POCUS to assess COVID-19 pathological findings and complications in adult and paediatric patients were searched.COVID-19 AND primary care AND ultrasound OR bedside ultrasound OR POCUS;SARS-CoV-2 AND primary care AND ultrasound OR bedside ultrasound OR POCUS;novel coronavirus disease AND primary care AND ultrasound OR bedside ultrasound OR POCUS.Search terms were:1.2.vs an urban teaching hospital, showing that scanning patients at the primary care level reduce the number of hospital scans, out- and in-patients visits and emergency admissions. Although costs are higher in the outpatient service than the hospitals, the total average costs are lower because of the avoidance of hospital admission [POCUS is a valuable tool in primary care setting, capable of refining diagnostic and therapeutic pathways, therefore contributing to better patient outcomes. However, its integration into the primary care setting requires caution due to the differences between primary care and other treatment settings . Wordswodmission . Steinmedmission  pointed n = 334) or positive (n = 220) experience of being examined with POCUS by the GP. Despite this, there is a large variety in primary care physicians' access to home ultrasound. Andersen et al. [Moreover, Andersen et al.  have shon et al.  showed t2.POCUS is a non-invasive technique to screen COVID-19 patients safely, using the correct disinfection protocol of the ultrasound transducer . It is a2.1.The diagnosis of SARS-CoV-2 infection is reached by nasopharyngeal swab with RT-PCR (reverse-transcriptase polymerase-chain-reaction). This method shows a good accuracy in detecting the presence of SARS-CoV-2 infection, with a relevant sensitivity , and it 2.2.During the COVID-19 outbreak, patients with COVID-19 were managed according to well-defined pathways from primary care services to COVID-19 hospitals. In the COVID-19 Hospitals, Triage or Pre-Triage Units were located outside the Emergency Department, with different levels of organisation, but constituted mainly by dedicated physicians, paramedics and adequate equipment, with the ability to perform rapid tests, RT-PCR tests, serologic testing and ultrasound, since POCUS has been suggested as a tool in the early diagnosis and follow-up of COVID-19 patients .Studies on clinical manifestations of COVID-19 with POCUS imaging include several findings, but most of them are not specific for COVID-19. The BLUE protocol, developed in 2008, allows quick differential of patients presenting in the ED with acute respiratory failure . The pan2.3.Concerning cardiovascular management, POCUS is widely used to assess the presence of previous heart disease and monitor clinical cardiological developments in the clinical context of COVID-19. The ultrasonographic approach gives the physicians of primary care and COVID-19 hospitals the opportunity to evaluate the cardiovascular system and screen the thromboembolic risk. The latter is known to be significantly increased in COVID-19 due to the endothelial damage, recurring in particular to CUS of lower limbs veins. Both cardiac and vascular ultrasound monitoring could be applied in primary care by experienced GP or specialists, even though existing POCUS guidelines are based mainly on hospitalised patients and may not apply to general practice .multiorgan POCUS and LUS show a maximum efficacy compared to any other imaging technique available in the guide of adequate ventilatory support;LUS is considered more effective than X-ray and on au pair with CT to provide a guide to the appropriate clinical approach;multiorgan POCUS shows greater efficacy than LUS alone in guiding the correct clinical approach.The ultrasonographic evaluation could also be precious in monitoring hospitalised patients with COVID-19 as a decision-making tool in ventilatory support and fluid therapy strategies. Moreover, if compared to ARDS, COVID-19 shows some peculiar characteristics that have led to the identification of two phenotypes , which cMoreover, regarding the application of POCUS to fluid therapy management, the ultrasonographic evaluation has yet been widely used before the pandemic in the critically ill patient (e.g. VExUS score ) and has3.3.1.The lower airways represent the main target of infection for the SARS-CoV-2 virus. The study of the lung parenchyma through CT examination typically shows bilateral interstitial pneumonia with irregular asymmetrical lesions, mainly distributed in the peripheral portion . This diThe typical ultrasound features of lung involvement from COVID-19 ,32 are tMoreover, the physicians could also find consolidations, suspected signs of bacterial superinfection and the presence of complications as pleural effusion, more frequently present in patients with a suggestive history of cardiovascular disease .Some imaging scores have been used to define the extension of lung damage. The LUS score is a semiquantitative parameter of the severity of pulmonary impairment, and it is based on the presence of alterations such as B-lines, pleural line abnormalities and lung consolidations. Lichter et al.  have fouIn this setting, it is important to compare LUS and traditional radiology imaging, in particular chest X-ray and lung CT scan, in the diagnosis of COVID-19 pneumonia and management of COVID-19 patients . As mentHowever, LUS is operator-dependent and clinicians should receive a specific training and there is not a standardised protocol for LUS. CT imaging provides instead a high diagnostic accuracy even if the use of radiations limit its use in some populations such as paediatrics and it is not a bedside technique for the diagnosis at patients’ home. A recent meta-analysis has demonstrated a significant higher diagnostic accuracy of LUS versus traditional chest X-ray (86.4% (95%CI: 72.7–93.9) vs 80.6% (95%CI: 69.1–88.6), respectively), confirming the importance of LUS for the diagnosis of COVID-19 pneumonia. Among all techniques, however, chest CT demonstrates the highest specificity to detect lung damage from the SARS-CoV-2 infection (80.0% (95%CI: 74.9–84.3) ,38.r = 0.65, p < .001) [r = 0.953, p < .0001) [Another point which has confirmed the importance of LUS in the assessment of COVID-19 pneumonia is the demonstration that LUS correlates well with the visual scoring at CT ( < .001) . Moreove< .0001) .3.2.patients with pre-existing cardiovascular diseases who have a predisposition to a higher risk of death and worse outcomes if affected by COVID-19, for example, heart failure and atrial fibrillation ,21;patients with COVID-19 showing a tendency to develop cardiovascular complications;some drugs tested in the treatment of the infection that could have cardiovascular side effects;p < .001), meanwhile RVD was not  [during the pandemic, great interest has been raised regarding the role and safety of angiotensin-converting enzyme (ACE) inhibitors and sartans in correlation with COVID-19 . Echocar = .404) .Cardiac involvement in COVID-19 disease has been evaluated since the early days of the pandemic, with a wide area of interest involving:n = 901), the echocardiogram was abnormal in 46%, and 13% had cardiac disease with high-grade severity. Independent predictors of ventricular abnormalities included high natriuretic peptides, cardiac troponin and severity of COVID-19 symptoms. The echocardiographic exam changed patient management in 33% of cases. In fact, the echocardiographic data changed the management of disease-specific therapy in 42% of cases (171/405) in terms of therapy for heart failure, acute coronary syndrome, pulmonary embolism or tamponade, and initiating antibiotics in the presence of endocarditis. The echocardiographic data also changed the level of patient care by 8% (32/405) and guided titration of haemodynamic support in 13% (51/405).COVID-19 patients tend to develop pulmonary hypertension associated with hypoxic vasoconstriction of the pulmonary bed, even in the early stages of the disease. In a prospective study of 1216 COVID-19 individuals , 667 (55p = .005) and in patients who had elevated cardiac biomarkers compared with patients without these laboratory findings .All these changes in terms of patient management were reported more frequently in patients with a history of cardiac disease (38% vs 32% compared with those without pre-existing cardiac disease; In conclusion, cardiac POCUS is a valuable tool to evaluate patients with COVID-19 and suspected cardiac impairment. Also, an operator with a standard level of expertise can early recognise the most important signs of cardiac damage and provide a hospital admission, in particular for those subjects who have a pre-existing cardiac disease and advanced age .4.A debated topic during the pandemic was the use of POCUS in the evaluation of pulmonary involvement from COVID-19 in mildly symptomatic patients at home isolation. In Italy, this monitoring was carried out by physicians called "USCA", that is an acronym for Special Continuity Care Units ,46, but Focussing on Italian experience, the USCA doctors were activated from primary care physicians to specifically evaluate at home the COVID-19 patients see . PhysiciThe need to use POCUS at home, also thanks to the born of these home health units, has been largely promoted, for obvious technical needs, with a consequent widespread diffusion of portable ultrasound devices. The accuracy of portable devices was a hot topic even before the pandemic . They haThe use of POCUS has demonstrated a precious role in monitoring the possible clinical evolution of patients . All theEven in the setting of paediatrics, the ultrasound evaluation of the paediatric patient with COVID-19 has played an essential role since the beginning of the pandemic. In childhood and in the paediatric population, SARS-CoV-2 infection generally produces mild symptoms, though in a small percentage of cases, it can cause severe disease with the need for admission to intensive care and, on rare occasions, can give a fatal outcome . POCUS cHand-held ultrasound is playing a key role in the diagnosis and management of patients COVID-19 due to its versatility, availability and its inherent advantages in infection control and staff safety . Rapid p5.POCUS has been considered an important tool for the diagnostic approach in the primary care setting already before the start of the SARS-CoV-2 pandemic, which has acted as a trigger for an already existing trend, managing to breakdown some methodological and practical resistances and spreading ultrasound clinical investigation .Moreover, the strong diffusion of portable ultrasound equipment has opened new horizons, in particular in terms of primary care health services at patients' homes and to manage special populations, as pregnant women .Before pandemics, authors had already shown the diagnostic importance and usefulness of ultrasound in general medicine, showing that POCUS scans were reported to have a higher diagnostic accuracy, indicating that POCUS could reduce health care costs, even if there were still some uncertainties about the quality of ultrasound portable scans and about training . It is aThe pandemic from COVID-19 is offering new perspectives and resources, regarding challenges and opportunities deriving from new technology. For example, promising studies have shown that nanotechnologies medicine could be applied to fight the ongoing pandemic . Taking 6.The use of POCUS through portable devices has shown to have a role in monitoring the possible clinical evolution of patients with infection from SARS-CoV-2. The ultrasonographic features are helpful to manage SARS-CoV-2 patients in the primary care setting and can help the physicians to evaluate the presence of lung involvement and to diagnose complications from the SARS-CoV-2 infection involving the cardiovascular system. The use of ultrasound in primary care is establishing itself and opens up new scenarios with perspectives also thanks to the possible application of emerging technologies.


SARS-CoV-2 pandemic is one of the most critical pandemics during human civilization. Several therapeutic strategies for COVID-19 management have been offered; nonetheless, none of them seems to be sufficiently beneficial. In effect, vaccines have been proffered as a viable option. The critical issue now is to concentrate on protecting individuals against illness through immunization. One of the causes for concern among the researchers, physicians, and generally the whole community from the onset of vaccination has been the adverse effects  that may be observed after the injection of the COVID-19 vaccine. In some countries, such concerns have even resulted in the temporary or permanent discontinuation or abandonment of the application of some vaccines . By evaluating rigorous studies published on this subject, the present article is aimed at identifying the association between blood clot incidence and COVID-19 vaccination. Various methods for producing the COVID-19 vaccines are analyzed, along with their possible pros and cons as well as common and rare side effects, especially VITT and blood clots. Finally, the differences of various vaccines on thrombotic events, WHO recommendations for VITT treatment, and blood clots statics are discussed. In Dece2In the early days of the COVID-19 pandemic, some antibacterial drugs  as well as some systemic corticosteroids  were used to control the disease, but were later limited due to the ineffectiveness or widespread side effects . CurrentOverall, no conclusive and definitive cure has yet been discovered for SARS-COV-2. Therefore, the development of practical medicine and vaccines for the treatment and control of SARS-COV-2 is a priority.3Based on the information obtained from the Centers for Disease Control and Prevention (CDC), approved COVID-19 vaccines will have several benefits for preventing COVID-19. Vaccination aims to suppress the prevalence of COVID-19. In general, it may also protect uninfected individuals against infected ones by interrupting the chain of transmission; therefore, it will be quintessential for hampering the pandemic . Vaccina4The efficacy and impact of the vaccine on the SARS-CoV-2 pandemic are complex, and numerous possibilities could occur following the deployment. Since hospitalization and critical-care admissions put a tremendous burden on the healthcare organizations, the protection capability of a vaccine upon severe disease and mortality is the most substantial endpoint. The promising effect of vaccines on the population can be observed if the vaccination is sufficiently effective in older adults . Vaccination now is widely distributed, including for people who are most susceptible to COVID-19. Admittedly, vaccines do not improve the clinical course but relieve the SARS-CoV-2 transmissibility .5A very brief overview of the potential primary vaccines will be provided with a focus on the vaccines’ safety and influence records in the following sections.5.1The mechanism behind the mRNA vaccination is that mRNA is an intermediary messenger that must be converted into an antigen after being delivered into host cells via multiple pathways. Pfizer and Moderna, as potential candidates for COVID-19 mRNA vaccines, exert their effect via injecting SARS-CoV-2 spike protein-encoding mRNA directly into the host cell. Although pure mRNA has been swiftly degraded over the last decade, various technical progressions in transfer systems and RNA carriers have enabled fast and secure uptake of mRNA into the cytosol, where ribosomes transform mRNA into a protein that could trigger an immunological reaction . Theoret5.2The global requirement for mass immunization against the COVID-19 pandemic is the main impetus for developing adenovirus vector vaccines . Phase IDifferent adenoviruses are utilized as vectors in modern COVID-19 vaccines for the mentioned vaccines; nonetheless, the primary manufacturing platforms and mechanism of action are the same in all of them. For example, Janssen is based on a human adenovirus, whereas Oxford vaccination is based on a chimpanzee (ChAdOx1) adenovirus. The Oxford approach used a chimpanzee virus to decrease the impact of human adenovirus antibodies over time. The SARS-CoV2 Spike protein gene is produced as DNA; then, the synthesized DNA is inserted into the DNA genome of adenoviruses, substituting a crucial adenovirus gene (E1) for virus replication; adenovirus cannot multiply. After this change, it cannot initiate a complete infection cycle as a result of this alteration. However, it may penetrate cells and show the inserted unfamiliar gene to make the S protein of Coronavirus . High do5.3The organism’s purified protein extracts – usually administered together with an adjuvant to elevate the immune response – are a more traditional method of advancing in vaccines. So far, only NVX-CoV2373 has passed the third phase of the clinical trials . Novavax5.4The available inactivated vaccines made by China, the Indian vaccine named Bharat Biotech , and Valneva vaccine in development by the European Union all are created using very comparable and well-established technology. Generated in Vero cells, the virus is chemically inactive and is purified to varying degrees, with adjuvants added. In all situations, beta-propiolactone (BPL) is used to attenuate the virus . New res6Some side effects have been reported after receiving COVID-19 vaccines, most of which are short term and resolve after a few days without any medical intervention. However, some more severe side effects have also been reported.The findings by the Brighton Collaboration as well as other previous studies on vaccines’ side effects are briefly mentioned here: various types of strokes like nonhemorrhagic and hemorrhagic, encephalomyelitis, appendicitis, immune thrombocytopenia, Bell’s palsy, acute myocardial infarction, anaphylaxis, deep vein thrombosis, pulmonary, myocarditis or pericarditis, disseminated intravascular coagulation, and narcolepsy .7Common side effects after receiving the first dosage of COVID-19 vaccine include about 63.7% injection site tenderness, 54.2% injection site pain, 53.1% fatigue, nearly 52.6% headache, 44.2% malaise, 44.0% myalgia, about 33.6% pyrexia and feverishness, and 7.9% fever >38 °C .Flu-like symptoms such as joint and muscle pain or headache are common side effects and could last for 1–2 days after vaccination . In SoutVaccination has several side effects such as sudden pain in the chest, abdomen, headache, and dizziness. If side effects continue or recur after 3 days, further medical diagnostics should be performed to rule out thrombosis .8In a clinical trial study in the United Kingdom and Brazil, only 168 participants  experienced severe adverse effects. Seventy-nine participants who had serious side effects had received ChAdOx1 of-19, and 89 of them had received MenACWY .8.18.1.1There have been reports of allergic reactions including anaphylaxis. The most common adverse reactions to vaccination are local reactions and mild symptoms. Recently, 4.5 per million reports of anaphylaxis have been identified after the administration of both doses .8.1.2Neurological symptoms that emerge after the vaccine administration include headache, myalgia, dizziness, muscle spasm, and paresthesia. Sporadic symptoms such as tremors, diplopia, tinnitus, dysphonia, epilepsy, and reactivation of herpes zoster appear after vaccination .A case of transverse myelitis was identified 14 days after receiving the ChAdOx1 nCoV-19 booster vaccine, which is thought to have occurred potentially due to vaccination . Two add8.1.3Due to the incidence of some instances of DIC and CVT, on March 15, 2021, the European Union put out a motion to temporarily cease the vaccination by AstraZeneca as a precaution, pending the EMA verdict . AccordiThe specialists on the Committee examined the reports of nine deaths with DIC and CVST recorded by the Member States, most of them being younger than 55 years and women . Recentl8.1.4Factually, the number of confirmed deaths after vaccination is very limited. The majority of them are caused by other reasons  rather than the vaccine ,38. PatiChest or back pain, breathlessness, shoulder swelling or coldness, blurred vision, extreme and deteriorating headache following vaccination, intermittent bleeding, several minor bruising, red or purple stains, and under skin blood blisters are all signs that may signify a clot caused by the COVID-19 vaccine, according to EMA . Anaphyl9In this section, we first look at a syndrome that clinically resembles postvaccination thrombotic thrombocytopenia. Then, we will review the WHO guideline for the treatment of VITT, and in the end, we will discuss the blood clots statics.9.1HIT is characterized by unusually severe thrombotic events accompanied by thrombocytopenia. Thrombocytopenia is caused by rogue antibodies directed against platelet factor 4 (PF4), which causes massive platelet aggregation and thrombosis and a reduction in the platelet count resulting in bleeding. As a consequence, patients may experience both severe thrombosis and severe bleeding .In a molecular view, platelet-activating antibodies’ transitory generation of the IgG class – which detects the multimolecular set of the cationic platelet factor 9 (PF4) coupled with poly-anionic heparin – causes heparin-induced thrombocytopenia (HIT), a pro-thrombotic adverse medication event .Heparin-induced thrombocytopenia (HIT) is a pro-thrombotic adverse medication event caused by the transient formation of platelet-activating antibodies from the IgG class, which recognizes multimolecular complexes of (cationic) platelet factor 9 (PF4) coupled with (poly-anionic) heparin. Heparin administration can result in the formation of HIT antibodies since heparin can act as a hapten, and hence, it is recognized by the immune system ,45. PlatApart from heparin, other poly-anions  can cause adaptive changes in PF4 required to reveal the HIT antigen. Furthermore, in the absence of additional poly-anions, significant PF4 binding to platelets may result in HIT antigen(s) exposure. In the latter case, poly-anions on the platelet area are likely to increase the proximity of PF4. This issue demonstrates that antigens could be impacted by factors other than heparin administration called autoimmune HIT (A-HIT). These factors could be bacterial wall ingredients or trauma-induced nucleic acid unleash , platelet-derived poly-anions, or the AstraZeneca COVID-19 vaccination .9.2Occasional cases of thrombotic thrombocytopenia caused by the resistance of platelet-activating antibodies against PF4 may happen after inoculation with ChAdOx1 n-Cov-19. The clinical sight of moderate-to-severe thrombocytopenia and thrombotic consequences at uncommon locations happening 1–2 weeks after immunization with ChAdOx1 n-Cov-19 against SARS-CoV-2 indicates a syndrome that clinically mimics severe heparin-induced thrombocytopenia. According to one study, five patients infected by venous thrombosis and thrombocytopenia 7–10 days after injecting the first AstraZeneca dose of adenoviral vector vaccine showed significant levels of antibodies to platelet factor 4-poly-anion complexes, without any prior heparin exposure. Antibodies to SARS-CoV-2 nucleocapsid protein were negative in all five individuals. Thus, the previous infection with SARS-CoV-2 could be deemed to have been highly unlikely. In a population of about 130,000 vaccinated individuals, only five cases of VITT were observed. The clinical parameters compared to those of immune system heparin-induced thrombocytopenia were distinguished within the vaccine-induced resistant thrombotic thrombocytopenia patients. Scientists conjecture that these complications are vaccine-induced thrombotic thrombocytopenia (VITT), an infrequent vaccine-related form of spontaneous heparin-induced thrombocytopenia .10The pathogenic mechanism of VITT, which the German Greifswald Company recently explained by Andreas Greinacher, is similar to heparin-induced thrombocytopenia (HIT). In this complication, IgG-type antibodies cause a pro-thrombotic condition that detects multimolecular complexes between the cationic platelet factor 4 and the anionic heparin and trigger platelet activation via the FcRIIA receptor. However, this syndrome is unusual since it occurs in immunized people with COVID-19 who have not received any heparin therapy during their lives. For the formation of this prothrombotic condition, known as “spontaneous” or autoimmune HIT, some explanations can be provided. It has recently been discovered that factors except heparin can produce a progressive syndrome with clinical and laboratory characteristics that closely mimic HIT. The mentioned factors include certain highly sulfated and highly negatively charged oligosaccharides  . A HIT-lFurthermore, PF4 binds directly to bacteria, forming a neo-antigen recognized by anti-PF4/heparin or anti-PF4/poly-anion antibodies. This will result in immune complexes that are important in antibacterial host defense. Many scientists have been researching COVID-19, and they have found nonplatelet-activating and platelet-activating anti-PF4/heparin antibodies. The aforementioned mechanisms of two antibodies could also be implicated in the antiviral response to SARS-CoV-2 infection .11The inflammatory stimulation of the immunization or vaccination activates anti-PF4 antibodies, which cross-reacts with PF4 and platelets in the cases of VITT syndrome. It has been discovered that AstraZeneca COVID-19 vaccination increased the reactivity of VITT patients’ serum with platelets, implying the interactions between the vaccine and platelets or the vaccine and PF4 .A theory could be buttressed by adenovirus utilized as a vector in AstraZeneca vaccine: the affinity of adenovirus for PF4 is high and can activate platelets. Free DNA in the vaccination might be a cause of these PF4-reactive antibodies. Previously, it has been demonstrated that DNA and RNA create multimolecular PF4 complexities that fasten antibodies against heparin-induced thrombocytopenia and induce antibodies. Based on what is mentioned, other adenovector vaccines such as Janssen (J&J) and Sputnik V may be potent for causing VITT. Other reports have indicated a similar mechanism; the records state that there may be a link between adenovector vaccines and blood clots .There might be an essential connection between the SARS-COV2 Spike protein itself or similar molecules, with side effects in the body . Soluble Spike protein has been shown to negatively affect endothelial cells, such as a severe inflammatory response. Furthermore, there are numerous viruses with Spike surface protein in the bloodstream. In practice, all cases of critical SARS-CoV-2 infections (COVID-19) may be exposed to the death danger after thromboembolic events. Even pseudoviruses with Spike protein on their face produce severe inflammatory responses in the tissues and endothelial cells, showing the risk of this protein when it is present systemically. Therefore, different formulations and posttranscription modifications  may cause similar heparin–PF4 complex and trigger immune response . The pos12According to several cases, young women who use hormonal contraceptives are more likely to experience harm and adverse reactions to the vaccines . It can 13At first glance, the VITT recognition seems comparatively straightforward. However, numerous immune thrombocytopenia cases have been reported following the injection of Moderna and Pfizer vaccines. It is worth noting that other clinical conditions also can raise anti-PF4 antibodies in the blood  .The evidence indicates that venous or arterial thrombosis might occur in uncommon sites such as the brain or stomach in specific individuals, with clinical signs appearing 5–20 days after immunization. If followed by thrombocytopenia, this event can lead to an adverse impact of the preceding COVID-19 vaccination . Because14In the following section, the vaccines whose injection has been officially reported to be accompanied by VITT and blood clots in the receivers will be discussed.14.1ChAdOx1 nCoV-19  is a low-cost and easy-to-store vaccine manufactured by the Oxford University and AstraZeneca. It also has been the most controversial COVID-19 vaccine due to the diverse reports of thrombosis following its administration . The thr14.2BNT162b1 (known as Comirnaty) produced by BioNTech and Pfizer is the first authorized COVID-19 vaccine and the first vaccine utilizing mRNA technology in the vaccine history . This va14.3mRNA-1273 or Moderna COVID-19 vaccine is one of the other mRNA-based vaccines, which is produced by Moderna company . A study14.4Ad26.COV2 , which was approved by the United States Food and Drug Administration (US-FDA) in February 2021, is one of the most controversial COVID-19 vaccines. According to various reports, rare and unknown types of thrombosis have been witnessed ,63. Simi14.5A study by Liu et al.  targeted15Anti-PF4-heparin and PF4-polyanion antibodies can be tested alone or together using a commercially approved method. However, false-negative results are possible in some rapid immunoassays and chemo-luminescence tests. ISTH guidelines recommend affirmation employing a functional test such as carbon 14-labeled serotonin discharge measure. The preliminary assessment of suspected VITT ought to incorporate a total blood cell tally, D-dimer and fibrinogen levels, PF4-polyanion ELISA, and imaging . OverallAlternative causes of thrombocytopenia and thrombosis must be considered and examined regardless of (autoimmune) HIT and VIPIT test results. Several thrombotic microangiopathy syndromes such as antiphospholipid syndrome, immunological thrombotic-thrombocytopenic purpura or atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria, and underlying malignant  illnesses are only a few examples that can be counted .16VITT treatment must be based on clinical and laboratory analyses. That said, this can be modulated depending on the case condition. Intravenous immunoglobulin, glucocorticoids, and anticoagulation are significant parts of VITT therapy. Platelet-mediated activation of the Fcγ receptor is inhibited by high-dose intravenous immunoglobulin . The resAnticoagulant alternatives must include nonheparin anticoagulants that are utilized for heparin-induced thrombocytopenia therapy. A compelling experiment has ruled out the heparin-dependent increase of platelet activation . Althoug17World Health Organization has constantly observed the TTS occurrence after COVID-19 vaccination and provides some recommendations, advises, and caution for VITT patients in its published guideline named “Guidance for clinical case management of thrombosis with thrombocytopenia syndrome (TTS) following vaccination to prevent coronavirus disease (COVID-19)”  based onWHO also recommends that for preventing exposure to the antigen, patients who have reported VITT should not receive the same vaccine as the booster dose. It also strongly advises against the use of heparin-based drugs and vaccination with adenovirus vector-based vaccines in individuals with a history of HIT . Recentl18Although there is a connection between some COVID-19 vaccines and blood clots, it is not suggested to break on vaccination. Researchers at a new pre-print study from Oxford University have demonstrated that the rate of CVST AstraZeneca vaccination compared with the rate of CVST associated with COVID-19 is 8–10. This research was based on a U.S. health database and provided cogent evidence demonstrating the benefits of vaccines over and above its risks. All crucial information on COVID-19 vaccines is summarized in 19Adenovirus vector vaccines  seem to be responsible for developing vaccine-induced immune thrombotic thrombocytopenia. However, it is not entirely understood what exactly triggers the immune system to cause VITT. That said, there are some speculations about DNA/RNA-PF4 complex, Spike protein itself, and transcription complexities that describe the occurrence of thrombotic thrombocytopenia syndrome reasonably. In addition, some factors like the patient’s underlying disease or age/sex and hormonal situation of the patient are effective in the management and treatment of VITT. All in all, it appears that first and foremost, physicians should review the testes’ results of anti-PF4-heparin and PF4-polyanion antibodies. Assessment of D-dimer and fibrinogen levels, as well as imaging methods, may also be helpful for medical doctors in evaluating suspected VITT patients. WHO has recommended the use of IVIG and/or nonheparin-based anticoagulants in individuals who are suffering from TTS after the COVID-19 vaccination. It has also generally  advised against the use of heparin, platelet infusion, and steroid treatment in such patients. It should also be noted that although there is a connection between blood clots and COVID-19 vaccination, statistics and data have provided cogent proof that the occurrence of blood clots in COVID-19 is up to 10 times more common than the vaccines’ injection.


Zoonotic transmission of SARS-CoV-2 from infected humans to other animals has been documented around the world, most notably in mink farming operations in Europe and the United States. Outbreaks of SARS-CoV-2 on Utah mink farms began in late July 2020 and resulted in high mink mortality. An investigation of these outbreaks revealed active and past SARS-CoV-2 infections in free-roaming and in feral cats living on or near several mink farms. Cats were captured using live traps, were sampled, fitted with GPS collars, and released on the farms. GPS tracking of these cats show they made frequent visits to mink sheds, moved freely around the affected farms, and visited surrounding residential properties and neighborhoods on multiple occasions, making them potential low risk vectors of additional SARS-CoV-2 spread in local communities. Nidovirales, family Coronaviridae  than adults . Mean time spent in neighborhoods was also higher for juveniles (TN = 141.25 min) than adults (TN = 28.89 min), but the difference was not significant . Conversely, adults had larger mean values for home visits (HV = 47.0) and mean time spent near homes (TH = 2083.89 min) than juveniles (HV = 22.5 and TH = 762.50 min), but those differences were not significant . The only activity variable between adults and juveniles that clearly did not show much difference was mean neighborhood visits .GPS data were recovered from 13 of the 15 cats collared for GPS tracking . AnalysiThere were no significant differences detected in means of activities between males and females or between uninfected cats and those positive for SARS-CoV-2 RNA by PCR or that had antibody reactive to SARS-CoV-2. On average, cats with detectable SARS-CoV-2 RNA roamed 12.40 ha of area near mink farms where they spent 239.17 min in infected mink sheds during 8.0 visits, spent 1763.33 min at homes during 43.83 visits, and spent 33.33 min in neighborhoods over 0.67 visits. On average, cats with antibody reactive with SARS-CoV-2 roamed 12.72 ha of area near mink farms where they spent 286.00 min in infected mink sheds during 8.60 visits, spent 1580.00 min at homes during 34.20 visits, and spent 40.0 min in neighborhoods over 0.80 visits .The 15 cats captured and GPS tagged in this study were located on three farms and considered free-roaming and not completely feral because of their tendencies to remain close to the mink farming operations, presumably to take opportunistic meals of mink feed in and around the mink sheds and to prey on rodents and other wildlife in and around the farming operations ,35. The Of the 15 cats captured and fitted with GPS collars, only 13 returned to the area or remained close enough to the base stations enabling wireless download of the data. The GPS loggers were attached to break away collars, so it is possible the two cats without data left the area and did not return, or the collars on these cats fell off or were otherwise removed. The GPS data collected from the other 13 cats revealed that infected cats frequently entered the mink sheds, moved through surrounding properties, and spent large amounts of time in multi-house neighborhoods where they could potentially encounter and have contact with other free-roaming cats, domestic pets, livestock, and peridomestic wildlife. One actively infected cat (C15) roamed over 50 ha while spending over 3 hours in neighborhoods while three other cats, all with detectable SARS-CoV-2 RNA on their fur, spent anywhere from 4–65 h visiting around homes. None of these three cats with detectable SARS-CoV-2 RNA on their fur were considered actively infected with SARS-CoV-2 and these findings represent environmental contamination only; there is no evidence that pet fur can serve as a fomite for SARS-CoV-2 transmission .An age bias was detected with respect to activity by the cats in and around the mink farms. Juvenile cats were more likely to visit mink sheds and spend more time in the sheds. One possible explanation for this difference may be the readily available food source. Mink were fed a meat paste daily, which was deposited on top of the cage where younger cats would have easy access to an opportunistic meal. Research on social hierarchy and feeding in feral and free-roaming cats in Italy reported that juvenile cats were allowed to feed before the adults ,42, whicOn average, juveniles spent more time in neighborhoods than did the adults and adults had more home visits and spent more time near homes, but neither of these measurements were statistically significant, perhaps again, due to the small sample size. Regardless of the significance with these age biases, the data clearly show that these infected free-roaming cats are dispersing from the SARS-CoV-2-infected mink farms, traveling as far as 1.8 km to nearby properties with homes and to multiple home neighborhoods, and spending large amounts of time there.The phylogenetic analysis of the SARS-CoV-2 sequences from one infected cat oral swab sample and numerous mink samples on Utah farms revealed that the same virus was circulating in both species in August. The larger analysis A did conMephitis mephitis) and Bushy-tailed woodrats (Neotoma cinerea) were found to be susceptible to SARS-CoV-2 infection and shed virus in respiratory secretions [Like humans, the potential of these free-roaming cats to shed SARS-CoV-2 and infect other animal species, including peridomestic and endangered wildlife, is also of concern ,16. Deercretions .An important concern from a One Health perspective is spillover into domestic animals or wildlife that could result in the establishment of a competent secondary zoonotic wildlife reservoir  or the eIn summary, the results of this study demonstrate the susceptibility of free-roaming cats to infection with SARS-CoV-2 through their activities on infected mink farms. Furthermore, the results demonstrate the capacity of a SARS-CoV-2-infected cat to extend the potential risk of viral transmission to household pets, peri-domestic animals, wildlife, and into surrounding homes and multi-home neighborhoods over broad distances.


Objective: Brain ischemia leads to the accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER) lumen and consequently, ER stress. To help cells restore ER function, a series of adaptive stress response pathways, collectively termed the unfolded protein response (UPR), are activated. We have previously demonstrated that the UPR pathway initiated by ATF6 is pro-survival in transient ischemic stroke. However, the effect of ATF6 activation on the outcome after permanent ischemic stroke remains unknown. Here, we addressed this knowledge gap.Method: sATF6-KI mice with functional short-form ATF6 (sATF6) predominantly expressed in forebrain neurons were subjected to two ischemic stroke models: photothrombotic stroke and permanent middle cerebral artery occlusion (pMCAO). Both short-term and long-term functional outcomes were evaluated. Changes in neuroinflammation and cerebrovascular density after pMCAO were also assessed.Results: Compared to littermate controls, sATF6-KI mice performed significantly better in open field, cylinder, and foot fault tests on day 1 or 3 after photothrombotic stroke. However, on days 7 and 14 after stroke, the performance of these functional tests was not significantly different between groups, which is likely related to mild brain damage associated with this stroke model. Thus, to evaluate the long-term effects of ATF6 activation in permanent stroke, we turned to our pMCAO model. We first found that on day 4 after pMCAO, functional outcome was better, and infarct volumes were smaller in sATF6-KI mice vs controls. Next, the 15-day stroke outcome study indicated that compared to control mice, sATF6-KI mice consistently exhibited improved performance in neurologic scoring, tight rope test, and tape removal test, after pMCAO. Moreover, sATF6-KI mice showed higher vascular density and lower activation of both astrocytes and microglia around stroke regions on day 16 after pMCAO.Conclusions: Here, we presented the first evidence that activation of the ATF6 UPR branch is protective in permanent ischemic stroke, which further supports the therapeutic potential of targeting the ATF6 pathway in stroke. Every year, approximately 800,000 people in the US have a stroke, and about 87% of these strokes are ischemic in nature  negatively impact the function and structure of existing proteins, and the synthesis and maturation of new proteins. This leads to the accumulation of unfolded and misfolded proteins in the ER, and activation of the UPR.One promising cerebroprotective strategy for stroke is to leverage cellular self-healing mechanisms that have been refined over time by nature , activating transcription factor-6 (ATF6), and inositol-requiring enzyme-1 , folding catalysts , and ERAD components . These genes are also upregulated in neurons after activation of ATF6 signaling . sATF6 has a nuclear localization sequence that guides the translocation of sATF6 into the nucleus where sATF6 acts as a potent transcription factor to regulate gene expression. Both To examine the role of ATF6 signaling in the brain, we previously developed a conditional and tamoxifen-inducible sATF6 knock-in mouse line, sATF6-MER  to generate sATF6-MER; Emx1-Cre mice (sATF6-KI). In sATF6-KI mice, sATF6 is FLAG-tagged and is constitutively expressed and present in the cytoplasm of neurons. To activate ATF6 signaling, sATF6-KI mice received a 5-day tamoxifen treatment, which triggered nuclear translocation of sATF6, leading to ATF6-dependent gene expression . The conditional and inducible sATF6 knock-in mouse line, sATF6-MER, was maintained in the lab  was drilled in the skull above the MCA. The MCA trunk was then permanently ligated with a silk suture proximal to the cortical branch to the rhinal cortex.Permanent MCAO (pMCAO) was performed essentially the same as described previously  was suspended in corn oil (Sigma-Aldrich). Mice were treated with 100 mg/kg tamoxifen by oral gavage once daily for 5 days. The stroke surgery was performed 2 days after tamoxifen treatment. In the long-term study, we resumed tamoxifen treatment at the same dose beginning on day 4 poststroke and continuing once every other day thereafter until 15 days after stroke.All tests were performed in a blinded manner. Reference data for behavioral tests were presented in This 48-point scoring system was used to evaluate neurologic deficits after stroke, and has been described in detail previously / × 100%.This test was performed as previously described, with slight modifications , and its motion was recorded for a total of 10 min. The travel distance was calculated by an automated animal behavior analysis system (CleverSysTopscan 3.0).This test was performed as previously described , as described previously  were obtained using a Leica cryostat. Images were captured on a Zeiss Axio Imager Z2 motorized fluorescence microscope (Carl Zeiss MicroImaging).Lectin labeling was performed as previously reported  staining method  in the ipsilateral or contralateral cortex and striatum . The mean values of GFAP and Iba1 fluorescence intensity and vascular density were calculated as the percentage of ipsilateral/contralateral ROI.Immunofluorescence staining was performed on frozen tissues, as described previously , Mann-Whitney U test (neurologic scores), or by two-way ANOVA with Holm-Sidak post-hoc . Data are presented as mean ± SD or the median (neurologic score), as shown in the figures. The level of significance was set at p < 0.05.All data analyses were performed using Prism 8 . Infarct volume (short-term) or neurologic score (long-term) was used to determine the group size for each experiment. Statistical analysis was assessed by unpaired Student’s The PT stroke model has been widely used in experimental stroke research due to the simplicity of the procedure and excellent long-term survival rates. Since deficits in motor function are common in stroke patients, our PT model targets the right M1 primary motor cortex region, which leads to left limb movement disorder in the mouse.For five consecutive days, sATF6-KI and littermate control mice were orally treated with tamoxifen to induce translocation of sATF6-MER from the cytosol into the nucleus where ATF6-dependent genes are then activated  or Iba1 (a microglia marker). Using GFAP-stained brain sections, we found that sATF6-KI mice had significantly larger striatal areas than control mice, indicating less striatal atrophy . As expeHere, we performed the first experimental study to demonstrate that activation of the ATF6 pathway improves not only the acute outcome but also long-term outcome after permanent ischemic stroke.Proteins are the key biologic molecules that perform most of the work in cells. Thus, proteostasis is essential to cell health and survival. Indeed, misfolded or damaged proteins are dysfunctional, and are prone to form aggregates, which can be toxic and cause cell death. To maintain or restore proteostasis, a complex protein quality control network functions in subcellular components that are involved in the biogenesis of proteins, especially the cytoplasm and ER. In the cytoplasm, heat shock proteins (HSPs) are the major protein chaperones. Under physiologic conditions, HSPs fold newly synthesized proteins, while under stress conditions, they are required to prevent protein aggregation, mediate protein disaggregation, and remove dysfunctional proteins and protein aggregates. Among these HSPs, cytosolic HSP70 plays a vital role in restoring proteostasis in pathologic states  and NIH grants NS099590 and HL157354.


Self-care behaviour is fundamental in preventing hypertension in the general population. According to the Health Belief Model, health beliefs and perceptions influence the success in adopting disease prevention strategies. While factors influencing hypertension self-care behaviour have been examined previously in patient populations, they have not been assessed in the general community.This was a cross-sectional study conducted between 12 June 2020 to 26 July 2021. An online survey was administered via email and social media to Malaysians in the Selangor and Kuala Lumpur communities. Respondents were over 18 years old, without a formal diagnosis of hypertension. The survey evaluated hypertension knowledge, Health Belief Model constructs, self-care behaviour frequency, and motivators and barriers to self-care behaviour. Multiple linear regression was performed to determine the main predictors of self-care behaviour, and descriptive statistics were used to characterise motivators and barriers of each self-care behaviour.p < 0.001) and perceived barriers  significantly influenced self-care behaviour. Maintaining a healthy diet, regular physical activity and blood pressure checks need to be improved in the community, particularly in reducing salt and calorie intake. Lack of time, limited choices and laziness are the biggest challenges that need to be tackled in adopting a healthy diet and an active lifestyle in the community. Many are ignorant towards their health status, therefore, do not prioritize blood pressure screenings, suggesting a need to enhance community blood pressure checks for early diagnosis of hypertension.Only health motivations (β = 0.217, Motivations and barriers were the main determinants of self-care behaviour in the Selangor and Kuala Lumpur community. Targeting these aspects of self-care behaviour should be considered when developing interventions and education programmes tailored to local cultural, environmental and personal factors, to more effectively reduce the hypertension prevalence and burden. Cardiovascular disease (CVD) is the leading cause of death worldwide, with most deaths attributed to coronary heart disease or stroke . HyperteHere, hypertension self-care behaviours is defined as behaviours which help to control blood pressure and deter the onset of hypertension. These behaviours include various lifestyle modifications such as daily intake of less than 5 g salt and at least five servings of fruits and vegetables, reducing fat intake, regular physical activity, limiting alcohol consumption, practicing non-smoking, and regular monitoring of blood pressure –8. RegulEvidence-based development of interventions framed within a validated theoretical model are preferable to those without since they are often more clinically relevant and cost effective . DespiteWith respect to understanding the success or failure of disease prevention strategies and screening, the Health Belief Model (HBM) is widely applied today, despite its conception in the 1950’s . The HBMThis cross-sectional study evaluated predictive strength of six factors  in regards to hypertension self-care behaviour in a convenience sample of the Malaysian community.Ethical approval was approved by the Science and Engineering Research Ethics Committee (SEREC) at the University of Nottingham Malaysia (ref: PT110520). Electronic consent was obtained from all participants before starting the anonymous online survey. Participants who denied consent were redirected to the end of the survey. Additional information regarding the ethical, cultural, and scientific considerations specific to inclusivity in global research is included in the Supporting Information .Participants were recruited from 12 June 2020 to 26 July 2021 through distribution of the online survey link, via email and social media. The inclusion criteria was Malaysian adults aged 18 years and above, no formal diagnosis of hypertension, and residing in Selangor or Kuala Lumpur. During provision of electronic consent, a series of yes-or-no questions evaluating the participants’ understanding of their participation in the study and their eligibility were asked. Those that were ineligible were automatically redirected to the end of the survey.a priori F test with the following assumptions: effect size = 0.15, margin of error = 5% and number of predictors = 5. Following this, the minimum sample size required to detect a power of 95% was estimated to be 138. Assuming a 10% rate of non-completion of the full survey, the target sample size was 151.Sample size was estimated using G* Power version 3.1.9.4 adopting an The survey instrument was informed by the Health Belief Model (HBM)  and admiPerceived severity was measured by a single item  with a 3-point ordinal scale response option . Perceived benefits was measured by two items  with a 3-point ordinal scale response option on capability . Self-efficacy was measured by three items .th grade reading level. Response options use a 4-point ordinal scale with increments of agreement or compliance with each statement . Hence, higher scores indicate higher levels of self-care behaviour etc. The original 20-item tool was modified by omitting five statements that were irrelevant to a non-hypertensive group (such as “take your blood pressure medication”). This left a total of 15 statements about self-care behaviour concerning five broad categories: salt and calorie intake, fruit and vegetable intake, physical activity, alcohol intake and blood pressure screening. For each statement, participants were asked about their current health behaviour (how frequent?), its health motivation (how important?) and any perceived barrier (how difficult?). Participants were asked to select a maximum of three options from three to five pre-existing motivations  or three to five barriers  or they were able to write down an additional factor not on the list. The pre-existing options were based on responses in previous studies conducted in Malaysian populations [Health motivations, perceived barriers and current self-care behaviours were measured by the Hypertension Self-Care Profile (HTN-SCP) . Each HTulations , 33, 34.ulations –38. For Knowledge about hypertension was assessed using items taken from Oliveria et al (2005)  and tranSocio-demographic assessments included age, sex, ethnicity, body mass index (BMI), level of education, and household income.Statistical analysis was carried out using SPSS version 27.0. The sample was described using descriptive statistics of perceived severity, health motivation, perceived barriers, self-efficacy and hypertension knowledge that influence self-care behaviour.p < 0.05 was considered as statistically significant in this study.To determine which factors predicted self-care behaviour, multiple linear regression was performed. Kaiser-Meyer-Olkin (KMO) (> 0.5) and Bartlett’s test (p < 0.05)  was usedThere were 260 respondents, but 22 did not complete the survey, indicating a completion rate of 91.5%. After excluding these from the data set, this left a total of 238 for analysis. Participant demographics is summarised in Participants understood the severity of hypertension , the benefits of controlled blood pressure  and the ability to prevent hypertension, indicated by self-efficacy , and had reasonably good hypertension knowledge , . Mean scThe mean score for self-care behaviour was 39.3 (SD = 8.2) out of 60. Categorizing self-care behaviours into five broad categories showed that practicing reduced salt and calorie intake (rarely/sometimes = 81.5%) was the most challenging in the Selangor and Kuala Lumpur communities . Consumi2 = 0.487, F  = 38.541, p < 0.001). Thus, 48% of the variation in self-care behaviour was explained by the six measured predictors. Considering the individual contributions to self-care behaviour, only health motivations and perceived barriers significantly contributed to the outcome  indicated significant predictors of self-care behaviour , overarching all diet and physical activity-based self-care behaviours, excluding regular blood pressure measurements . Self-caBarriers to maintaining a healthy diet by controlling salt and calorie intake, or consuming adequate fruits and vegetables were similar. Common barriers included the lack of time prepare healthy foods due to busy schedule, the lack of healthy food options at work place or eating out, and to a lesser extent the cost of healthy foods . For redThe lack of time to exercise (72.2%) and laziness (72.2%) were the greatest barrier to regular physical exercise . Lack ofTo our knowledge, this study is one of the first of its kind to evaluate determinants of self-care behaviour for hypertension prevention in the general community based on the HBM. The present study showed that perceived barriers and health motivations were the strongest determinants of self-care behaviour in a convenience sample. We also observed that although participants knew that self-care behaviours could maintain health and prevent diseases, they were unable to practice these behaviours regularly due to various identified barriers.Self-care behaviour for blood pressure management is similar for both treatment and prevention of hypertension in terms of lifestyle modifications, where only medication adherence is specific to hypertensive patients. The HBM was selected as the framework of this study as it is particularly well suited to health conditions that can be prevented or ameliorated through individual action and so hypertension is an excellent candidate , 40–42. Previous studies demonstrated that at least five HBM predictors were significantly associated with self-care behaviour in blood pressure management in hypertensive patients , 40, 41.Our study demonstrated that knowledge about hypertension was not associated with self-care behaviour. This was inconsistent with previous studies reporting a positive influence of knowledge about hypertension on blood pressure control , 43. A lIt was unsurprising that perceived barriers had the strongest influence on self-care behaviour for hypertension prevention in the present study as it has been consistently reported as the strongest predictor in behaviours for disease prevention, followed by perceived benefits , 21, 28.In our study, maintaining a low salt and healthy diet, regular blood pressure check and regular physical activities were the main issues in the self-care behaviour for hypertension prevention although most respondents knew that these behaviours could improve health and prevent disease in general. Our study showed a low frequency of self-care behaviour especially in reducing salt intake, which were consistent with another study which reported that 79% of respondents exceeded the recommended amounts set by local and international health guidelines . Other nIn our study, approximately 50–60% of participants practiced regular physical activity and consumed adequate intake of fruits and vegetables. Urbanization is known to cause adverse health effects from reduced energy expenditure due to increased sedentary lifestyle, and shift to a high fat, high energy diet , 54. TheEarly stages of hypertension are typically asymptomatic, therefore many are unaware that they have high blood pressure , 58. RegThe results should be interpreted with caution due to the small sample size, relatively young and middle-aged population and limited to a defined geographical area around the capital city of Malaysia. The cross-sectional nature of the study also indicated that causal inference is limited. Further studies covering different regions or specific communities should be conducted for development of targeted or personalised hypertension prevention interventions. Health motivations, perceived barriers and frequency of hypertension self-care behaviour were measured using the same survey tool (HTN-SCP) based on consistent scoring system with 15 items for each predictor, while the other HBM predictors were evaluated with as few as a single item to minimise the length of the survey. HBM predictors evaluated by only one to three items such as perceived severity, perceived benefits and self-efficacy may not have been measured effectively. Hence, lack of standardization in measurement of each predictor for hypertension self-care behaviour may have introduced some bias in the generated model. Motivators and barriers to smoking cessation were also not evaluated. This poses further opportunities to investigate motivators that encourage non-smoking and uncover barriers to smoking cessation in a relatively well-educated and financially-able population.Health motivations (importance of self-care behaviour) and perceived barriers (difficulty in conducting self-care behaviour) were important determinants of preventive hypertension self-care behaviour in the Selangor and Kuala Lumpur community. Perceived barrier had stronger influence on self-care behaviour than perceived motivations. An alarming majority did not practice reduced salt and calorie intake albeit the strong relationship between sodium intake and hypertension development. Frequency of physical activity, fruit and vegetable intake and regular blood pressure monitoring were also inadequate. Cultural, environmental and personal factors contributed to the challenge in practicing these behaviours. Therefore, hypertension prevention intervention or strategies should focus on targeting barriers and motivations of self-care behaviour, particularly barriers against adopting a healthy diet, regular physical activity and blood pressure screenings. More importantly, development and execution of these preventive interventions or strategies require action and cooperation from both government policy makers and the community to reduce the prevalence and burden of hypertension.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S1 Appendix(DOCX)Click here for additional data file.S1 Checklist(DOCX)Click here for additional data file.